A Phase 1 Clinical Trial to Evaluate the Safety and Pharmacokinetics of VRC-HIVMAB075-00-AB (VRC07-523LS) in the Sera and Mucosae of Healthy, HIV-1-Uninfected Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
 
PROTOCOL 
HVTN 128 
A phase 1 clinical trial to evaluate the safety and 
pharmacokinetics of VRC-HIVMAB075-00-AB (VRC07-
523LS) in the sera and mucosae of healthy, HIV-1–
uninfected adult participants 
DAIDS DOCUMENT ID 38523 
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(S) PROVIDED BY 
Dale and Betty Bumpers Vaccine Research Center (VRC), NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
September 18, 2018 
FINAL 
HVTN 128 
Version 1.0 
 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 2 of 132 
Contents 
1 Ethical considerations ....................................................................................................5 
2 IRB/EC review considerations .......................................................................................7 
2.1 
Minimized risks to participants ......................................................................7 
2.2 
Reasonable risk/benefit balance .....................................................................7 
2.3 
Equitable participant selection .......................................................................8 
2.4 
Appropriate informed consent ........................................................................8 
2.5 
Adequate safety monitoring ...........................................................................8 
2.6 
Protect privacy/confidentiality .......................................................................8 
3 Overview ......................................................................................................................10 
3.1 
Protocol Team ..............................................................................................13 
4 Background ..................................................................................................................14 
4.1 
Rationale for trial concept ............................................................................14 
4.2 
VRC07-523LS ..............................................................................................19 
4.3 
Trial design rationale ....................................................................................22 
4.4 
Plans for future product development and testing ........................................24 
4.5 
Preclinical safety studies of VRC07-523LS .................................................24 
4.6 
Preclinical PK and challenge studies of VRC07-523LS ..............................26 
4.7 
Clinical studies of VRC07-523LS ................................................................26 
4.8 
Potential risks of study products and administration ...................................30 
5 Objectives and endpoints .............................................................................................34 
5.1 
Primary objectives and endpoints ................................................................34 
5.2 
Secondary objectives and endpoints ............................................................34 
5.3 
Exploratory objectives ..................................................................................35 
6 Statistical considerations ..............................................................................................36 
6.1 
Accrual and sample size calculations ...........................................................36 
6.2 
Randomization .............................................................................................39 
6.3 
Blinding ........................................................................................................39 
6.4 
Statistical analyses ........................................................................................40 
7 Selection and withdrawal of participants .....................................................................45 
7.1 
Inclusion criteria ...........................................................................................45 
7.2 
Exclusion criteria ..........................................................................................48 
7.3 
Participant departure from study product administration or withdrawal .....51 
8 Study product preparation and administration .............................................................55 
8.1 
Study product regimen .................................................................................55 
8.2 
Study product formulation ...........................................................................55 
8.3 
Study product storage ...................................................................................55 
8.4 
Preparation of study products .......................................................................56 
8.5 
Administration ..............................................................................................58 
8.6 
Acquisition of study products ......................................................................59 
8.7 
Pharmacy records .........................................................................................59 
8.8 
Final disposition of study products ..............................................................59 
9 Clinical procedures ......................................................................................................60 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 3 of 132 
9.1 
Informed consent ..........................................................................................60 
9.2 
Pre-enrollment procedures ...........................................................................62 
9.3 
Enrollment visit ............................................................................................64 
9.4 
Infusion visits ...............................................................................................65 
9.5 
Follow-up visits ............................................................................................66 
9.6 
Mucosal sampling ........................................................................................68 
9.7 
HIV counseling and testing ..........................................................................71 
9.8 
Contraception status .....................................................................................72 
9.9 
Urinalysis .....................................................................................................72 
9.10 Assessments of Solicited AEs ......................................................................72 
9.11 Visit windows and missed visits ..................................................................74 
9.12 Early termination visit ..................................................................................74 
9.13 Pregnancy .....................................................................................................74 
9.14 HIV infection during the study .....................................................................75 
10 Laboratory ....................................................................................................................76 
10.1 HVTN CRS laboratory procedures ..............................................................76 
10.2 Total blood volume ......................................................................................76 
10.3 VRC07-523LS concentrations .....................................................................76 
10.4 ADA detection assays ..................................................................................76 
10.5 ADA functional assay ..................................................................................77 
10.6 Monoclonal antibody reaction assays ..........................................................77 
10.7 Exploratory studies .......................................................................................77 
10.8 Specimen storage and other use of specimens .............................................77 
10.9 Biohazard containment .................................................................................78 
11 Safety monitoring and safety review ...........................................................................79 
11.1 Safety monitoring and oversight ..................................................................79 
11.2 Safety reporting ............................................................................................80 
11.3 Safety pause and prompt PSRT AE review..................................................83 
11.4 Review of cumulative safety data ................................................................84 
11.5 Study termination .........................................................................................84 
12 Protocol conduct ..........................................................................................................85 
12.1 Social impacts ..............................................................................................86 
12.2 Emergency communication with study participants ....................................86 
13 Version history .............................................................................................................87 
14 Document references (other than literature citations) ..................................................88 
15 Acronyms and abbreviations........................................................................................90 
16 Literature cited .............................................................................................................92 
Appendix A Sample informed consent form ....................................................................98 
Appendix B Approved birth control methods (for sample informed consent form) ......119 
Appendix C Sample consent form for use of samples and information in other studies 120 
Appendix D Table of procedures (for sample informed consent form) ..........................124 
Appendix E Laboratory procedures ................................................................................125 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 4 of 132 
Appendix F Procedures at HVTN CRS ..........................................................................127 
Appendix G HVTN low risk guidelines for the US ........................................................129 
Appendix H Adverse events of special interest (AESI) ..................................................131 
Appendix I Protocol Signature Page .............................................................................132 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 5 of 132 
1 
Ethical considerations 
It is critical that universally accepted ethical guidelines are followed at all sites 
involved in the conduct of clinical trials. The HIV Vaccine Trials Network 
(HVTN) has addressed ethical concerns in the following ways: 
• HVTN trials are designed and conducted to enhance the knowledge base 
necessary to find new methods for the prevention of 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) and/or other Good Clinical Practice 
(GCP) guidelines. 
• HVTN 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 and 
prevention clinical trials. 
• HVTN 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 HVTN research sites to ensure community input. 
• HVTN 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. 
• Participants who become HIV-infected during the trial are referred to medical 
practitioners to manage their HIV infection and to identify potential clinical 
trials they may want to join. 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 HVTN provides 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. 
• Prior to implementation, HVTN trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration.  
• HVTN trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 6 of 132 
• The HVTN designs its research to minimize risk and maximize benefit to both 
study participants and their local communities. For example, HVTN 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. HVTN protocols also include careful 
medical review of each research participant’s health conditions and reactions 
to study products while in the study.  
• HVTN 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 HVTN trials are able to conduct other 
critical research in their local research settings. 
• The HVTN values 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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 7 of 132 
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 HVTN 
Investigator welcomes IRB/EC/RE questions or concerns regarding these research 
requirements. 
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 study product 
administration and collecting information regarding side effects for several days 
post study product administration; (d) having staff properly trained in 
administering study procedures that may cause physical harm or psychological 
distress, such as blood draws, study product administrations, HIV testing and 
counseling and HIV risk reduction counseling; (e) providing HIV risk reduction 
counseling and checking on contraception use (for persons assigned female sex at 
birth); and (f) providing safety monitoring. 
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.  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 8 of 132 
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 HVTN as part of its entering 
the HVTN. The HVTN requires a signed consent document for documentation, in 
addition to chart notes or a consent checklist. 
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 9). Safety is 
monitored daily by HVTN clinical staff and routinely by the HVTN 128 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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 9 of 132 
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 HVTN 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 HVTN. In 
some cases, a comparable confidentiality agreement process may be acceptable. 
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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 10 of 132 
3 
Overview 
Title  
A phase 1 clinical trial to evaluate the safety and pharmacokinetics of VRC-
HIVMAB075-00-AB (VRC07-523LS) in the sera and mucosae of healthy, HIV-
1–uninfected adult participants 
Primary objective(s) 
• To evaluate the safety and tolerability of VRC07-523LS administered at 
10 mg/kg intravenous (IV) infusion every 4 months 
• To evaluate the safety and tolerability of VRC07-523LS administered at 
30 mg/kg IV infusion every 4 months 
• To determine whether multiple infusions of VRC07-523LS reach and 
maintain detectable levels in the mucosa 
• To correlate levels of VRC07-523LS in serum and the mucosa  
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. 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. 
Table 3-1 Schema 
Group 
N* 
Route 
VRC07-
523LS Dose 
Product administration  
schedule 
D0 
D112 
D224 
W0 
W16 
W32 
1 
12 
IV 
10 mg/kg 
X 
X 
X 
2 
12 
IV 
30 mg/kg 
X 
X 
X 
Total 
24 
 
 
 
 
 
IV = intravenous infusion 
N* = number of participants receiving at least one product infusion 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 11 of 132 
Participants 
24 healthy, HIV-1–uninfected volunteers aged 18 to 50 years; 24 study product 
recipients 
Design 
Multicenter, randomized, unblinded trial 
Duration per participant 
12 months of scheduled clinic visits followed by biopsy safety contact 2 weeks 
after the last scheduled clinic visit 
Estimated total study duration 
17 months (includes 5 months for enrollment, and 12 months of scheduled visits) 
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) 
Core operations 
HVTN Vaccine Leadership Group/Core Operations Center, Fred Hutchinson 
Cancer Research Center (Fred Hutch) (Seattle, Washington, 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) 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 12 of 132 
• Vaccine Research Center – Immunology Testing Laboratory (Gaithersburg, 
Maryland, USA) 
• Dartmouth College (Hanover, New Hampshire, USA) 
Study sites 
HVTN Clinical Research Sites (CRSs) to be specified in the Site Announcement 
Memo 
Safety monitoring 
HVTN 128 PSRT; HVTN Safety Monitoring Board (SMB) 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 13 of 132 
3.1 
Protocol Team 
Protocol leadership 
Chair 
Stephen Walsh 
Brigham & Women’s 
Hospital 
617-525-8418 
swalsh@bwh.harvard.edu 
Statistician 
Ollivier Hyrien 
SCHARP, Fred Hutch 
206-667-5780 
ohyrien@fredhutch.org 
Co-chair 
Maria Lemos 
Fred Hutch 
206-667-2221 
mlemos@fredhutch.org 
Medical officer 
Jane Baumblatt 
DAIDS, NIAID 
301-761-7754 
jane.baumblatt@nih.gov 
Protocol Team leader 
Carmen Paez 
HVTN Core, Fred Hutch 
206-667-2881 
cpaez@fredhutch.org 
Laboratory lead 
Maria Lemos 
Fred Hutch 
206-667-2221 
mlemos@fredhutch.org 
Other contributors to the original protocol 
Core medical monitor 
Carmen Paez 
HVTN Core, Fred Hutch 
Clinical safety specialist 
Maija Anderson 
HVTN Core, Fred Hutch 
Study product 
developer 
representatives 
Julie Ledgerwood 
VRC 
Clinical trials 
manager 
Shelly Ramirez 
HVTN Core, Fred Hutch 
 
Lucio Gama 
VRC 
Clinical data manager 
Claire Chapdu 
SCHARP, Fred Hutch 
Laboratory protocol 
operations manager 
On Ho 
HVTN Laboratory 
Program, Fred Hutch 
Program and portfolio 
manager 
Lisel Koepl 
SCHARP, HVTN 
Regulatory affairs 
associate 
Laurie Rinn 
HVTN Core, Fred Hutch 
SDMC Associate director 
of lab science 
April Randhawa 
SCHARP, Fred Hutch 
Clinic coordinator 
Elvin Fontana-Martinez 
Brigham & Women’s 
Hospital 
Julie Czartoski 
Seattle CRS 
Statistical research 
associate 
Xue Han 
SCHARP, Fred Hutch 
Community Advisory 
Board (CAB) members 
Tasia Baldwin 
Seattle CAB 
Protocol development 
manager 
Ramey Fair 
HVTN Core, Fred Hutch 
 
Ray Allmond 
Cleveland CAB 
Community engagement 
unit representative 
Gail Broder 
HVTN Core, Fred Hutch 
DAIDS protocol 
pharmacist 
Oladapo Alli 
DAIDS, NIAID 
240-627-3593 
Community 
educator/recruiter 
Kim Louis 
Seattle CRS 
 
Justine Beck 
DAIDS, NIAID 
Technical editor 
Richa Chaturvedi 
HVTN Core, Fred Hutch 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 14 of 132 
4 
Background 
4.1 
Rationale for trial concept 
Although the identification and implementation of diverse disease prevention 
strategies have decreased the number of newly diagnosed HIV infections, 
HIV/AIDS continues to be a global health burden. UNAIDS estimates that there 
were 1.8 million new HIV infections worldwide in 2017 (4). While many 
countries have made progress toward leveling HIV prevalence over the last few 
years, micro-epidemics of infection continue to occur in nearly all regions, even 
in countries possessing the full toolkit of proven prevention approaches (5-8). 
Furthermore, limitations of current methods and interventions including side 
effects, cost, and individual compliance highlight the importance of the 
development of a safe, effective, durable, and innovative biomedical option. 
Ultimately, an effective vaccine will be necessary to better control the HIV 
pandemic (9, 10). 
An alternative approach to prevention and/or treatment of infectious diseases is 
passive administration of antibodies (Ab), a strategy that has been employed for 
more than 100 years against diverse disease targets and that is still used for 
hepatitis A and B prophylaxis (11, 12) and for postexposure prophylaxis (PEP) 
against rabies, measles, varicella zoster, and other infectious diseases (13). 
Palivizumab, a mAb 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 (14). 
Over the past several years, there has been a concerted and notably successful 
effort to isolate broadly neutralizing antibodies (bnAbs) against HIV-1 from 
chronically infected donors (15-31). Subsequent research has provided 
considerable insight into the sites these antibodies target on HIV-1 and their 
functionality (ie, the mechanisms by which they neutralize the virus) (18, 19, 28, 
32). This research has informed efforts to design recombinant protein 
immunogens that can elicit such antibodies (33-36), prompting optimism that 
vaccines that elicit bnAbs against HIV-1 can be developed (34, 37). In addition, 
the availability of bnAbs against HIV opens the exciting possibility of antibody-
mediated prevention (AMP) of HIV infection. 
4.1.1 
Rationale for mucosal sampling 
Since the majority of HIV infections worldwide are the result of sexual exposure, 
the vagina/cervix, rectum/distal colon, or penis are crucial areas in the disease 
transmission process. The colon and cervix are lined by a columnar epithelium, 
which protects a large pool of potential HIV target cells, including activated 
CD4+ T cells, dendritic cells, and macrophages. In contrast, the vagina and penis 
have stratified epithelium, protecting a less dense concentration of HIV target 
cells. Thus, whereas receptive anal sex has the highest probability of HIV-1 
transmission (0.4-3.38%), receptive vaginal sex is associated with intermediate 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 15 of 132 
transmission probability (0.018-0.150%), and transmission probability is lowest 
for insertive penile exposure (0.003-0.009%) (38-40). 
The central role of mucosal sites in transmission and early infection underscores 
the need for prevention approaches that protect mucosal sites from infection. 
Humoral and cellular immune responses in mucosal compartments have been 
analyzed by the HVTN in vaccine trials as well as in recent and ongoing mAb 
trials. 
Among the vaccine trials that have gathered data from mucosal samples were 
HVTN 069 and HVTN 076. During HVTN 069 (41), participants at the Seattle 
site were offered enrollment into a companion mucosal study. HVTN 076 was 
specifically designed to evaluate mucosal responses to the vaccine regimen of a 
large-scale phase 2b efficacy study that was being conducted in parallel, namely 
HVTN 505 (42). As it would have been challenging to perform in-depth mucosal 
evaluations within the framework and risk profile of the large-scale vaccine 
efficacy trial, a scientifically and operationally sound approach was to conduct a 
smaller scale study looking at the congruent intervention in a stringently designed 
phase 1 study that allowed the consistent evaluation of mucosal samples. 
Similarly, in parallel with the large-scale efficacy AMP studies (HVTN 
703/HPTN 081 and HVTN 704/HPTN 085) to assess whether a passively 
administered bnAb VRC01 can prevent HIV-1 infection in adults at risk, it is 
desirable to gather in-depth data on the distribution and persistence of bnAbs in 
mucosal secretions and tissues. In contrast to efficacy trials, where mucosal 
biopsies are not feasible to perform because of potential alterations in risk of 
infection due to the procedure itself, phase 1 studies present an opportunity to 
collect relevant data in human mucosal tissues. In HVTN 104, a phase 1 study 
that preceded the ongoing AMP studies (43), an ancillary study was created to 
obtain mucosal tissue samples from participants who received VRC01. Using 
Singulex technology, it was possible to detect VRC01 in sera, rectal secretions 
and biopsies, cervical secretions and vaginal biopsies at days 3-14 post 2nd/3rd 
infusions (see Figure 4-1). The antibody was functional and capable of providing 
increased resistance to Bal26 HIV-1 challenges (neutralization 
IC80 = 0.17 mcg/mL) in infused participants, but not in controls (Figure 4-2 
preliminary data provided by J. McElrath, R. Astronomo and M. Lemos). 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 16 of 132 
 
Figure 4-1 Levels of VRC01 in rectal and genital compartments of HVTN 104 participants 
collected 3-14 days post 2nd or 3rd infusion with 10 mg/kg (purple) or 30 mg/kg IV VRC01 
antibody (teal). Significant differences were observed in comparisons between serum and 
rectal secretions, serum and rectal tissue, and serum and vaginal tissue. P values for 
comparisons based on Dunn’s posthoc analysis are shown (Preliminary data provided by J. 
McElrath, R. Astronomo and M. Lemos). 
 
Figure 4-2 Ex-vivo explant infection of rectal and vaginal biopsies from HVTN 104 
participants (collected 3-14 days post 2nd or 3rd infusion with 10 mg/kg or 30 mg/kg IV 
VRC01 antibody) or controls (not receiving infusions). Total HIV replication is measured by 
the nanoluciferase production of Bal26 HIV-1 on days 3-21 with 1x106 viral particles. P value 
is Mann-Whitney test for the average of biopsies from a single donor (Preliminary data 
provided by J. McElrath, R. Astronomo and M. Lemos). 
In HVTN 116 (NCT02797171), an ongoing trial in US and South African sites, 
mucosal secretion samples and biopsies are being obtained to compare serum, 
mucosal pharmacokinetics (PK), and functionality of VRC01 and VRC01LS 
across several infusions at multiple timepoints (see Table 4-1). HVTN 116 is a 
phase 1 multicenter, randomized, open-label trial. It was designed to evaluate the 
safety, pharmacokinetics, and anti-viral activity of VRC01 and VRC01LS in the 
serum and mucosa of healthy, HIV-uninfected adults. The study opened to accrual 
in March 2017, and as of May 15, 2018, 79 participants have been enrolled. There 
have been no safety pauses, no related Serious Adverse Events (SAEs), and 
product administrations have been generally well tolerated. Mucosal secretion 
sampling and biopsy procedures have also been generally well tolerated. The 
current mucosal biopsy collection schedule in HVTN 116 for Groups 1-3 is 
shown below in Table 4-2 and for Groups 4-5 in Table 4-3. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 17 of 132 
Table 4-1 HVTN 116 schema 
Group 
Treatment 
Infusion schedule (Months) 
N 
M0 
M2 
M3 
M4 
M6 
Group 
1 
VRC01  
10 mg/kg  
23 
IV 
Infusion 
IV 
Infusion 
 
IV 
Infusion 
IV 
Infusion 
Group 
2 
VRC01  
30 mg/kg  
23 
IV 
Infusion 
IV 
Infusion 
 
IV 
Infusion 
IV 
Infusion 
Group 
3 
VRC01LS  
30 mg/kg 
7 
IV 
Infusion 
 
IV 
Infusion 
 
IV 
Infusion 
Group 
4 
VRC01  
30 mg/kg  
16 
IV 
Infusion 
 
 
 
 
Group 
5 
VRC01LS  
30 mg/kg 
10 
IV 
Infusion 
 
 
 
 
Table 4-2 HVTN 116 mucosal biopsy collection schedule for Groups 1-3 
Tissue 
Function 
Visit 2 
(Baseline) 
Visit 14 
(Month 6) 
Visit 15 
(Month 7) 
Visit 16 
(Month 9) 
Visit 17 
(Month 
12) 
Visit 18** 
(Month 
15) 
Visit 19** 
(Month 
18) 
Rectal 
# of Bx and 
Use 
Ab levels 
1 
1 
1 
1 
1 
1 
1 
IHC 
1 
1 
1 
1 
1 
1 
1 
Infectivity 
3 
3 
3 
3 
3 
3 
3 
Total = 
35*/25 
5 
5 
5 
5 
5 
5 
5 
Ectocervical 
# of Bx and 
Use 
Ab levels 
1 
1 
1 
1 
1 
1 
(1)*** 
IHC 
1 
1 
1 
1 
1 
1 
(1)*** 
Infectivity 
2 
2 
- 
- 
- 
- 
- 
Total = 
16*/14 
4 
4 
2 
2 
2 
2 
(2)*** 
Vaginal 
# of Bx and 
Use 
Ab levels 
1 
1 
1 
1 
1 
1 
(1)*** 
IHC 
1 
1 
1 
1 
1 
1 
(1)*** 
Infectivity 
3 
3 
3 
3 
3 
2-3 
2-3 
Total = 
24*/22 
5 
5 
5 
5 
5 
4-5 
(2-5)*** 
* Number of samples refers to Group 3 
** Visits only apply to group 3 
*** These samples will only be collected if the participant has missed prior collection 
visit(s), in order to maintain the total number of biopsies indicated in the “Function” 
column 
 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 18 of 132 
Table 4-3 HVTN 116 mucosal biopsy collection schedule for Groups 4-5 
Tissue 
Function 
Visit 4 
(0 mo) 
Visit 5 
(1 mo) 
Visit 9 
(3 mo) 
Visit 12 
(4.5 mo) 
Visit 14 
(6 mo) 
Visit 16** 
(9 mo) 
Visit 17** 
(12 mo) 
Rectal 
# of Bx and 
Use 
Ab levels 
1 
1 
2 
2 
1 
2 
1 
IHC 
1 
1 
- 
- 
1 
- 
1 
Infectivity 
- 
- 
- 
- 
- 
- 
- 
Total = 
14*/10 
2 
2 
2 
2 
2 
2 
2 
Ectocervical 
# of Bx and 
Use 
Ab levels 
1 
1 
2 
2 
1 
2 
1 
IHC 
1 
1 
- 
- 
1 
- 
1 
Infectivity 
- 
- 
- 
- 
- 
- 
- 
Total = 
14*/10 
2 
2 
2 
2 
2 
2 
2 
Vaginal 
# of Bx and 
Use 
Ab levels 
1 
1 
2 
2 
1 
2 
1 
IHC 
1 
1 
- 
- 
1 
- 
1 
Infectivity 
- 
- 
- 
- 
- 
- 
- 
Total = 
14*/10 
2 
2 
2 
2 
2 
2 
2 
* Number of samples refers to Group 5 
** Visits only apply to group 5 
Preliminary results from HVTN 116 indicate that functional antibody is detectable 
in mucosal compartments 2 and 6 weeks post-multiple infusions (VRC01 or 
VRC01LS in groups 1, 2, and 3 in Table 4-1). At baseline, rectal samples from all 
participants were susceptible to challenge with Bal26, 1086 and Du422.1 HIV-1 
viral strains. After three infusions, ex-vivo challenges of rectal explants with 
Bal26 (neutralization IC80 = 0.17 mcg/mL) were partially protected from HIV-1 
challenge, whereas ex-vivo challenges of rectal explants with HIV-1 1086 
(neutralization IC80 = 3 mcg/mL) and Du422.1 (neutralization 
IC80 < 45 mcg/mL) were susceptible to infection (Figure 4-3 preliminary data 
provided by J. McElrath, R. Astronomo and M. Lemos). The inhibition of Bal26 
replication waned over time. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 19 of 132 
 
Figure 4-3 Ex-vivo explant infection of rectal biopsies from HVTN 116 participants collected 
at baseline, and weeks 2, 6, and 14 post third infusion of 10 mg/kg VRC01 IV, 30 mg/kg 
VRC01 IV or 30 mg/kg VRC01LS. Total HIV replication is measured by the nanoluciferase 
production of B.Bal26, 1086, or Du422.1 HIV-1 at days 3-21 post challenge. Triangles 
represent the mean of 1-3 biopsies per participant. Infusion arms are blinded at this stage of 
the trial (Preliminary data provided by J. McElrath, R. Astronomo and M. Lemos). 
4.2 
VRC07-523LS 
The Vaccine Research Center (VRC), at the National Institute of Allergy and 
Infectious Diseases (NIAID), one of the National Institutes for Health (NIH), has 
developed several different HIV-1–specific mAb. Among them is VRC07-523LS, 
a highly potent and broadly neutralizing HIV-1 human mAb that targets the HIV-
1 CD4 binding site. A similar antibody, VRC01, also targeting the CD4 binding 
site, is currently in clinical trials under IND 113,611 [prevention indication] and 
IND 126,001 and IND 126,664 [therapeutic indication]. VRC01 was originally 
isolated from a subject infected with HIV-1 for more than 15 years whose 
immune system controlled the virus without anti-retroviral therapy (44). Through 
advances in B-cell immunology, cloning, and structure-guided optimization 
techniques, numerous HIV-1 neutralizing mAbs, including VRC07 (“07” denotes 
sequential numbering when discovered), VRC07-523 (“523” denotes sequential 
numbering when engineered variant generated), and later VRC07-523LS (“LS” 
denotes 2 specific amino acid mutations), were isolated and subsequently 
engineered to have potency and breadth greater than those of antibodies identified 
earlier (45). 
The VRC07 (wild-type) heavy chain was identified by 454 deep sequencing based 
on its similarity to the VRC01 mAb and paired with the VRC01 (wild-type) light 
chain (45). The engineered mutations that together define the 523 designation that 
increase the breadth and potency compared to VRC07 are a glycine to histidine 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 20 of 132 
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 (45). The LS mutation was 
introduced by site-directed mutagenesis and changed a methionine to leucine (L) 
and an asparagine to serine (S) (M428L/N434S, referred to as LS) in the C-
terminus of the heavy chain constant region. The LS mutation increases the 
binding affinity for the neonatal Fc-receptor (FcRn), resulting in increased 
recirculation of functional IgG (46, 47), thus increasing plasma half-life. 
In vitro, VRC07-523LS was found to be 5-to 8-fold more potent than VRC01 (see 
Figure 4-4), as well as broader, 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 (45). Furthermore, VRC07-523LS displayed minimal levels of 
autoreactivity. VRC07-523LS was shown to have a prolonged half-life over 
VRC07 by about 2-fold (45) in non-human primates (NHPs). 
 
Figure 4-4 VRC07-523LS neutralizes a higher fraction of HIV-1 isolates at a lower 
concentration than VRC01 (data courtesy of Kshitij Wagh and Bette Korber). 
4.2.1 
Rationale for Testing VRC07-523LS 
In vivo proof-of-concept studies have shown that VRC07-523LS is about 5-fold 
more potent than VRC01LS in Rhesus macaques at preventing SHIV infection 
following a mucosal challenge. VRC07-523LS has a longer half-life (9.8 days) 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 21 of 132 
than VRC07 (4.9 days) following a single dose of mAb at 10 mg/kg administered 
by the IV route (45). 
The increased neutralization potency in vitro and prolonged half-life of VRC07-
523LS correlate with improved protection against SHIV infection in vivo in 
animal studies (Figure 4-5) suggesting a potential role for this bnAb for 
prevention of HIV-1 infection in humans (45). 
 
Figure 4-5 (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 
(45). 
When administered IV at a single dose of 10 mg/kg in cynomolgus macaques, the 
half-life of VRC07-523LS was about 12 days (Figure 4-6B), and it persisted at 
least 28 days (final collection point) in rectal and vaginal secretions and tissues 
(see the Investigator’s Brochure (IB) for further details). When administered SC 
at a single dose of 10 mg/kg in rhesus macaques, the half-life of VRC07-523LS 
was about 14 days and it persisted at least 49 days (final collection point) in 
rectal, vaginal, and nasal secretions (see the IB for further details). Furthermore, 
complete protection from SHIV-SF162P3 challenge was demonstrated with a 
single dose of VRC07-523LS at 20 mg/kg administered IV. (Figure 4-6A). See 
the IB for further details. 
(A) VRC07-523LS (20 mg/kg IV) 
(B) VRC07-523LS (10 mg/kg IV) 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 22 of 132 
 
Figure 4-6 (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. (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. 
Repeated administration of VRC07-523LS will permit further understanding of 
the mucosal antibody levels, their accumulation after repeated dosing, and the 
consequences of any antidrug responses, if they were to develop. 
4.3 
Trial design rationale 
Given that HIV-1 is acquired through sexual exposure, the concentration and 
function of antibodies in the rectal and genital mucosae following systemic 
administration are potentially key to the effectiveness of the passive 
immunoprophylaxis approach. While phase 1-2a studies have collected limited 
samples to measure VRC01 and VRC01LS antibody levels in human mucosal 
secretions, there are no data on mucosal VRC07-523LS antibody levels or 
distribution in human mucosal tissues. Hence, this study presents a crucial 
opportunity to examine VRC07-523LS levels in both mucosal secretions and 
tissues. 
The HVTN 127/HPTN 087 trial, which opened in February, 2018, is planned to 
enroll a total of 100 healthy, HIV-uninfected adult participants who will receive 
multiple injections of VRC07-523LS administered via the IV or SC routes. 
HVTN 127/HPTN 087, version 2.0 dated March, 2018 includes an IM arm with 
24 participants, of whom 20 will receive VRC07-523LS, and 4 placebo, and 
shortens the interval of infusions to four months for all doses (Table 4-4). The 
primary objectives of the study are to assess safety and tolerability of repeated IV, 
SC, or IM administrations of VRC07-523LS, and to characterize serum levels 
over time for different doses, schedules, and routes and methods of 
administration. Additional objectives include building a population PK model of 
VRC07-523LS, and determining whether antidrug antibodies (ADA) emerge in 
response to repeated administrations of the antibody.  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 23 of 132 
Table 4-4 HVTN 127/HPTN 087 amended 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. 
In parallel with the HVTN 127/HPTN 087 trial, it is desirable to gather in-depth 
data on the distribution and persistence of VRC07-523LS in mucosal secretions 
and tissues when delivered by IV infusion. The HVTN 128 mucosal study will 
investigate concentrations and distribution of the VRC07-523LS antibody in 
mucosal tissues that are common sites of HIV exposure, and compare these to 
paired serum levels. This mucosal study can help us in understanding the 
underlying biological tenets of AMP, particularly with respect to mucosal 
challenge. 
A critical aspect of the VRC07-523LS mucosal study will be the collection of 
mucosal secretions and tissues in all participants. Collections will include serum, 
rectal secretions and biopsies in men and women; cervicovaginal secretions as 
well as cervical and vaginal biopsies in women, and semen from men. The 
proposed time points will provide the opportunity to estimate VRC07-523LS peak 
and trough levels and accumulation. The mucosal specimens will be collected as 
outlined in Table 9-1 and Table 9-2. 
To correlate VRC07-523LS levels in secretions and sera, we plan to assess 
VRC07-523LS levels in secretions and sera at peak and trough timepoints (Table 
9-1 and Table 9-2). The genital and rectal secretion and biopsy sampling at 
baseline is designed to evaluate participant anatomical suitability for biopsy 
collections, before they have received their first VRC07-523LS administration. 
Baseline biopsies and secretions will be used as negative controls in the 
comparisons of VRC07-523LS levels post product administration. Serum 
collections will also serve to test anti-drug antibodies (ADA) at these timepoints. 
The collection of biopsies and secretions after mAb delivery will serve to assess 
and compare biodistribution in mucosal compartments at the different mAb doses 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 24 of 132 
at peak and trough timepoints. These timepoints were selected to evaluate the 
similarity and differences between VRC07-523LS and VRC01LS kinetics (Figure 
4-7 A and B). Lastly, a collection at 16 weeks following last mAb administration 
(W48) will serve to assess the possibility of increased dosing intervals of VRC07-
523LS.  
4.3.1 
Dose, route, and schedule 
The VRC07-523LS doses and intervals in this trial are based on human studies of 
VRC01 (43, 48) and VRC01LS (49), preclinical and clinical studies of VRC07-
523LS. The data collected in the proposed study could be combined with the data 
obtained in VRC 605 and in other trials of VRC07-523LS, including HVTN 
127/HPTN 087, to further inform population PK modeling of VRC07-523LS in 
both serum and mucosal sites as described in section 6.4.4.1. The doses were 
chosen to increase the likelihood of detection of the mAb in the mucosal biopsy 
and secretion samples. The IV route is necessary to deliver these higher doses 
given the concentration of the mAb. 
The rationale for the doses in this trial is also supported by serum PK data from 
the initial VRC01LS trials. The repeated doses of 10 mg/kg and 30 mg/kg have 
been used in HVTN 116 for the detection of mucosal VRC01 and VRC01LS, and 
have shown partial protection against Bal26 in rectal tissue infectivity assays at 
weeks 2-14 (Figure 4-3). This suggests those antibodies can reach the mucosa and 
have detectable functionality. As VRC01LS has less potency and breadth than 
VRC07-523LS, we have extended the assessment to 16 weeks, to evaluate the 
trough of a triannual dosing schedule. 
4.4 
Plans for future product development and testing 
HVTN 128 is the next step in the characterization of VRC07-523LS. The 
information obtained is expected to inform further study of VRC07-523LS and its 
biodistribution in mucosal compartments. Additional upcoming Phase 1 trials plan 
to test VRC07-523LS as part of combination mAb regimens. As combinations of 
bnAbs targeting distinct regions of Env may be needed to successfully protect 
against sexual transmission of the diverse circulating strains of HIV-1, this 
information will contribute greatly to the design of future bnAb efficacy trials. 
4.5 
Preclinical safety studies of VRC07-523LS 
4.5.1 
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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 25 of 132 
strongly to cardiolipin. VRC07-523LS was also tested for cross-reactivity against 
a panel of various nuclear antigens using a licensed systemic lupus erythematosus 
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 (45). 
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), mAb binding to cytoplasmic sites generally is 
considered of little to no toxicologic significance. See the IB for further details. 
4.5.2 
In vivo toxicology studies 
4.5.2.1 
Repeat dose IV and SC toxicity study in Sprague-Dawley rats 
A repeat dose IV and SC toxicity study 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 which 
had had 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 IB for further details. 
4.5.2.2 
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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 26 of 132 
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. 
4.6 
Preclinical PK and challenge studies of VRC07-523LS 
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 4-6A). 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 IB for further details. 
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 (45). 
4.7 
Clinical studies of VRC07-523LS 
4.7.1 
VRC 605 
A phase 1, dose-escalation study of VRC07-523LS, the VRC 605 protocol 
(NCT03015181), is currently 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 
(q3 months) of 5 mg/kg SC and 20 mg/kg IV VRC07-523LS (Table 4-5). 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 27 of 132 
Table 4-5 VRC 605 study schema 
Group 
Participants 
Administration Schedule 
Day 0 
Week 12 
Week 24 
1 
4# 
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. 
Study objectives include evaluating the safety and tolerability of the study 
regimen and the pharmacokinetics of each dose level; determining the presence or 
absence of detectable ADA to VRC07-523LS; and evaluating for evidence of 
functional activity of VRC07-523LS. 
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. 
There have been no SAEs and no safety pauses for adverse events (AEs). Overall, 
15 of 25 participants (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 4 AE was for a drug induced 
liver injury likely caused by fluoxetine. This participant was independently 
evaluated by the NIH hepatology consult service and product administrations 
were discontinued due to the concomitant illness. While the participant was being 
followed for safety, her liver enzymes decreased, but then increased again after 
being started on citalopram, which reinforced that the original event was likely 
incited by an underlying sensitivity to selective serotonin reuptake inhibitor 
(SSRI) medications. Six (6) mild to moderate AEs were assessed as related to 
study product, including mild dizziness, mild abdominal pain, and 4 infusion 
reactions (1 mild and 3 moderate, reported for 2 participants). All AEs assessed as 
related to the study product have resolved without residual effects. 
Two (2) participants developed infusion reactions shortly after IV product 
administration. Symptoms were typical of infusion reactions observed with other 
mAbs. No atypical symptoms or delayed symptoms were seen. One participant 
enrolled in the 40 mg/kg IV group experienced a moderate infusion reaction with 
chills, rigors, fever, myalgia, and headache beginning 15 minutes after completion 
of the infusion. The participant was treated with acetaminophen and ibuprofen. 
All symptoms resolved within 12 hours. A separate participant in the 20 mg/kg IV 
group experienced infusion reactions (n = 2 moderate, n = 1 mild) after each 
product infusion. The participant experienced nausea, chills, rigors, malaise, 
tachycardia, headache, myalgia (mostly back), and arthralgia (mostly hips and 
knees). Symptoms began 15 minutes to 1 hour after completion of each product 
administration and completely resolved within 12 hours. The participant was 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 28 of 132 
treated with acetaminophen and ibuprofen. Otherwise, product administrations 
have been generally well tolerated. 
For solicited local reactions in the week after VRC07-523LS administrations, one 
of 17 participants (5.9%) who received the product by IV administration reported 
mild bruising at administration site, and 5 of 8 participants (62.5%) who received 
the product SC reported mild pain/tenderness at the injection site. 
For solicited systemic AEs reported to have occurred within 3 days after product 
administration, 4 of 17 participants (23.5%) receiving VRC07-523LS IV reported 
mild or moderate systemic reactogenicity symptoms. The reported symptoms 
were malaise (n = 2 mild, n = 1 moderate), myalgia (n = 2 mild, n = 1 moderate), 
mild headache (n = 2), and moderate chills (n = 2). Five (5) of 8 participants 
(62.5%) receiving VRC07-523LS SC reported mild systemic reactogenicity 
symptoms: malaise (n = 3), myalgia (n = 2), headache (n = 3), chills (n = 1), 
nausea (n = 1), and joint pain (n = 2). 
Figure 4-7 displays interim VRC07-523LS PK results in VRC 605. 
 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 29 of 132 
 
A 
 
B 
 
C 
 
Figure 4-7. Interim VRC 605 PK results for VRC07-523LS with VRC01LS comparators. (A) 
Single administration of 5 mg/kg IV; all administrations completed. (B) Single administration 
of 5 mg/kg SC; all administrations completed. (C) Repeated administrations of 20 mg/kg IV 
every three months; all administrations completed. VRC07-523LS shows stable kinetics 
following repeat administrations. 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 30 of 132 
4.7.2 
HVTN 127/HPTN 087 
As of July 31, 2018, 24 participants have been enrolled in the IV administration 
arms of HVTN 127/HPTN 087, 8 in Group 1 (2.5 mg/kg), 8 in Group 2 (5 
mg/kg), and 8 in Group 3 (20 mg/kg). No SAEs and only one mild product-related 
AE (injection site pruritus in an SC recipient) have been identified to date. 
4.8 
Potential risks of study products and administration 
There is limited human experience with administration of VRC07-523LS. VRC 
605 was already 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 
HVTN 127/HPTN 087. In addition, the similar CD4-binding site mAb VRC01 
has been given to more than 3000 adults and 60 infants in several phase 1 and 
phase 2b clinical trials. More than 10,000 infusions of 10 mg/kg and 30 mg/kg 
VRC01 have been given to HIV-uninfected adults in HVTN 703/HPTN 081 
[NCT02568215] and HVTN 704/HPTN 085 [NCT02716675]. 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 (50). Most infusion reactions appear to result from antibody-antigen 
interactions resulting in cytokine release (50). Administration of mAbs may have 
a risk of severe reactions, such as acute anaphylaxis, serum sickness, angioedema, 
bronchospasm, hypotension, and hypoxia, the generation of ADAs; 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 (50) or with 
the use of murine mAbs, which have a risk of eliciting human anti-mouse 
antibodies (51). 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 (52). 
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 (52). 
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 (51). 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 31 of 132 
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 (53). Supportive treatment may also be indicated for 
some signs and symptoms. 
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 (48). 
• No hypersensitivity reactions or cytokine release syndrome symptoms were 
reported in HVTN 104 (48). 
• 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 related AEs has been Grade 1 (for 
17 events) and Grade 2 (for 6 events, including 2 infusion reactions). 
• Serious reactions associated with mAb administration, such as acute 
anaphylaxis, serum sickness, ADAs, and increased risk of infections have not 
been observed to date in trials of VRC01-class mAbs. 
There is a possibility that receipt of the study product will cause a reactive result 
on some currently available HIV test kits, especially if testing occurs close to 
study product administration timepoints (see Section 9.7.1). 
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. Blood drawing may also cause anemia. 
Risks of IV Infusion: The placement of an IV 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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 32 of 132 
prevented by the use of aseptic technique in the pharmacy and universal 
precautions during product administration. 
Risks of biopsy and secretion collections: Collection of cervicovaginal secretions 
using menstrual cups or sponges can cause momentary discomfort during 
speculum or menstrual cup insertion and, in some cases, minor bleeding. 
Collection of rectal secretion samples using a rectal balloon sampling device can 
cause momentary discomfort during anoscope insertion and, in some cases, minor 
bleeding. Collection of semen can be embarrassing for the participant.  
Possible complications of biopsies are bleeding and infection. These 
complications are rare and risks of these complications will be minimized by 
careful hemostasis by the clinicians and detailed education of the participants to 
report bleeding and/or fever after the procedures. As biopsies create breaches in 
mucosal integrity, the risk of HIV infection - if exposed - is potentially increased 
during wound healing. Therefore (and to allow for undisturbed wound healing) an 
abstinence period is required of the participants after each biopsy. Healing of the 
superficial wounds in mucous membranes caused by these shallow, small (~2-
4mm) biopsies is rapid; by 5-14 days, healing is expected to be complete (in 
cervicovaginal tissue and within 3 days in rectal tissue) (54). 
In the proposed schedule, a minimum of 21 days between biopsy collections will 
be adhered to, and repetitious biopsies are not assumed to increase the risk as 
compared to a single biopsy. More than 300 biopsy collections have been 
performed at the Seattle HIV Vaccine Trials Unit in the past two years and thus 
far not a single complication has occurred. In MTN 007, 7 rectal biopsies have 
been collected three times within one month, respectively, in 65 volunteers. One 
participant (1.5%) reported grade 1 hematochezia, two participants (3.1%) 
reported grade 1 painful defecation, and three participants (4.6%) reported grade 1 
anal pruritus (55). As the biopsies create superficial wounds in mucous 
membranes, healing is rapid. By 5-14 days, cervical healing is expected to be 
complete (54). 
A review of 34 studies in which 8,330 cervical and vaginal biopsies were taken 
concluded that cervical and vaginal biopsies taken among special populations, 
including women living in high HIV prevalence areas, are also safe and well 
tolerated (56). As of May 15, 2018, HVTN 116 has conducted 472 rectal biopsy 
collections, 280 cervical biopsy collections and 339 vaginal biopsy collections in 
a total of 79 enrolled participants. One female could not undergo complete 
collections due to a vagal reaction after the first biopsy collection; one reported 
embarrassment after vaginal collection, and one stinging from silver nitrate. Two 
participants reported rectal discomfort after anoscope insertion but tolerated the 
collections. There have not been any terminations to date due to discomfort with 
the procedures. Cervical and vaginal biopsies in one female participant were 
permanently discontinued due to recurring vaginitis of unclear etiology. 
Regarding procedure-related events during HVTN 116, to date there has been one 
pre-syncopal event after the collection of vaginal/cervical/rectal biopsies that 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 33 of 132 
resolved on its own; one report of minimal rectal bleeding discovered when 
wiping with toilet paper that resolved on its own; two reports of constipation (one 
treated with medication and another resolved on its own), and one report of rectal 
pain that resolved on its own. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 34 of 132 
5 
Objectives and endpoints 
5.1 
Primary objectives and endpoints 
Primary objectives 1:  
• To evaluate the safety and tolerability of VRC07-523LS administered at 
10 mg/kg IV infusion every 4 months 
• To evaluate the safety and tolerability of VRC07-523LS administered at 
30 mg/kg IV infusion every 4 months 
Primary endpoint 1:  
• Local and systemic Solicited AE signs and symptoms, laboratory measures of 
safety, Unsolicited AEs, SAEs, AEs of special interest (AESI) and rates of 
discontinuation 
Primary objectives 2:  
• To determine whether multiple infusions of VRC07-523LS reach and 
maintain detectable levels in the mucosa 
• To correlate levels of VRC07-523LS in serum and the mucosa 
Primary endpoints 2:  
• Levels of VRC07-523LS in genital and rectal secretions, as well as cervical, 
vaginal, and rectal tissues at the collection timepoints 
• Levels of VRC07-523LS in serum out to Week 48, 16 weeks after the last 
product administration 
5.2 
Secondary objectives and endpoints 
Secondary objective 1: 
• To compare dose regimens of VRC07-523LS delivery for their ability to 
sustain mucosal mAb levels at serial timepoints post repeat administration 
Secondary endpoint 1: 
• Levels of VRC07-523LS in genital and rectal secretions and tissue at 
specified timepoints 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 35 of 132 
Secondary objectives 2: 
• To determine whether ADA can be detected in serum 
Secondary endpoint 2: 
• Serum concentration of ADA in each group measured at multiple timepoints 
from baseline through the final study visit 
5.3 
Exploratory objectives 
Exploratory objective 1: 
To assess the acceptability and tolerability of repeat mucosal sampling, including 
secretions and biopsies, for application in future studies 
Exploratory objective 2: 
To develop predictive mucosal population pharmacokinetic models of VRC07-
523LS administered IV 
Exploratory objective 3: 
To conduct analyses related to furthering the understanding of HIV, monoclonal 
antibodies, immunology, vaccines, and clinical trial conduct 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 36 of 132 
6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target accruing a total of 24 healthy, HIV-1–uninfected adult 
participants in two treatment groups, with 12 participants assigned to each group. 
In Group 1, all study participants will receive three IV administrations of VRC07-
523LS at the 10 mg/kg dose level. In Group 2, all study participants will receive 
three IV administrations of VRC07-523LS at the 30 mg/kg dose level.  
In both groups, the three infusions will be administered every 16 weeks. 
Participants will be randomly assigned to either one of the groups. Groups 1 and 2 
will open to randomization at the same time. 
In Groups 1 and 2, every study participant will be followed for 12 months 
(including 8 months of product administration plus 4 months of follow-up) from 
the day of first product administration. 
To ensure balance in the trial of both sexes assigned at birth, the trial will enroll at 
least and approximately 50% of participants assigned female sex at birth. 
Randomization will be stratified by assigned sex at birth to ensure balance within 
each treatment group. 
The times at which samples will be collected are listed in Table 9-1 and Table 9-2 
for each mucosal site and the blood. 
Since enrollment is concurrent with the first biopsy sample collection, all 
participants will provide some data regarding tolerability of mucosal sample 
collections. For analyses of VRC07-523LS levels in serum and mucosa and of 
data from ADA assays, it is possible that data may be missing for various reasons, 
such as participants terminating from the study early, problems in shipping 
specimens, or high assay background. Immunogenicity data from 17 phase 1 and 
2 phase 2a HVTN vaccine trials, which began enrolling after June 2005 (data 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. 
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. All participants who receive at least one 
product administration will be included in this analysis. The ability of the study to 
detect SAEs 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 = 12, there is 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 37 of 132 
at least 90% chance of observing at least 1 event if the true rate of such an event is 
17.5% or more; and there is at least 90% chance of observing no events if the true 
rate is 0.87% or less. For both groups combined (n = 24), there is at least 90% 
chance of observing at least 1 event if the true rate of such an event is 9.2% or 
more; and there is at least 90% chance of observing no events if the true rate is 
0.43% 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 12 and 24 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. 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
groups of size 12 and 24 for a range of true event rates 
True event rate (%) 
arm size 
0 events 
1+ events 
2+ events 
1 
12 
0.89 
0.11 
0.01 
24 
0.79 
0.21 
0.02 
4 
12 
0.61 
0.39 
0.08 
24 
0.23 
0.77 
0.42 
10 
12 
0.28 
0.72 
0.34 
24 
<0.02 
>0.98 
0.89 
20 
12 
0.07 
0.93 
0.73 
24 
<0.01 
>0.99 
>0.99 
30 
12 
0.01 
0.99 
0.91 
24 
<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 (CI) for the true rate of an AE based on the 
observed data. Table 6-2 shows the 2-sided 95% CIs for the probability of an 
event based on a particular observed rate. Calculations are done using the score 
test method (57). If none of the 12 participants in either Group 1 or Group 2 
experiences a safety event, the 95% 2-sided upper confidence bound for the true 
rate of such events in the population is 24.2%. If none of the 24 participants 
enrolled in Groups 1 and 2 experiences a safety event, the 95% 2-sided upper 
confidence bound for the true rate of such events in the population is 13.8%. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 38 of 132 
Table 6-2 Two-sided 95% CIs based on observing a particular rate of safety endpoints for 
groups of size 12 and 24 
Observed event rate 
(number of events / sample size) 
95% CI (%) 
0/12 
[0 ; 24.2] 
1/12 
[1.5 ; 35.4] 
2/12 
[4.7 ; 44.8] 
0/24 
 [0 ; 13.8] 
1/24 
 [0.07 ; 20.2] 
2/24 
 [2.3 ; 25.8] 
6.1.2 
Sample size calculations for serum and mucosal levels 
One of the primary objectives of the study includes assessing the association 
between the levels of VRC07-523LS measured in serum and in mucosal 
secretions and tissues at various sites. Measurements will be collected in all 24 
participants before the first infusion as well as at several timepoints following the 
first infusion. The primary statistical analysis will estimate associations between 
blood and mucosal levels within timepoints. These primary analyses will be 
conducted irrespective of dose (ie, data from Groups 1 and 2 will be combined) as 
well as within each treatment group. Additional analyses, secondary in nature, 
will evaluate association between the levels of VRC07-523LS in serum and in 
mucosal samples within each birth sex. 
The power of the study to detect a significant association between the levels of 
VRC07-523LS (possibly transformed) measured in serum and in any given 
mucosa site is shown in Table 6-3 for several values of Pearson’s linear 
correlation coefficient (r) and sample sizes (n). We anticipate that the primary 
correlation analysis will be based on samples of sizes n = 12 and n = 24. The 
secondary correlation analysis will be performed on samples of sizes that are 
expected to range between n = 5 and n = 15. 
In an analysis combining all 24 participants from Groups 1 and 2, the study has 
more than 72% power to detect a significant association between measurements if 
the true value of the correlation coefficient is 0.5 or higher. If the true value of the 
correlation coefficient is 0.6 or higher, the power of the study is greater than or 
equal to 89.8%. 
With 12 participants (eg, in any primary analysis assessing association within a 
particular treatment group, or in any secondary analysis within a particular birth 
sex combining both groups), the study has almost 77% power to detect a 
significant association between measurements if the true value of the correlation 
coefficient is 0.7 or higher. 
With 6 participants (as in any secondary correlation analysis restricted to a 
specific sex assigned at birth and conducted within a particular treatment group, 
assuming balance in treatment groups), the study has more than 77% power to 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 39 of 132 
detect a significant association between measurements if the true value of the 
correlation coefficient is 0.9 or higher. 
Additional calculations are reported in the Table that account for 40% to 60% 
birth sex imbalance within groups. These calculations assumed a two-sided test at 
the 5% significance level. They were based on Cohen’s method and used an 
arctanh transformation of the correlation coefﬁcient defined by 𝑍′ =
𝑎𝑟𝑐𝑡𝑎𝑛ℎ⁡(𝑟) + 𝑟/(2(𝑛−1)) (58). 
Table 6-3 Statistical power (in percent) to detect a significant association between serum 
and mucosal VRC07-523LS levels as a function of the sample size (n) for multiple true 
values of the correlation coefficient (r) 
True correlation 
coefficient (r) 
Sample size (n) 
5 
6 
7 
9 
12 
15 
24 
0.3 
8.2 
9.1 
10.1 
12.5 
16.0 
19.6 
30.3 
0.4 
10.7 
12.7 
14.8 
19.3 
26.0 
32.6 
50.6 
0.5 
14.5 
18.0 
21.7 
29.2 
40.0 
49.9 
72.6 
0.6 
19.9 
25.7 
31.6 
42.9 
57.6 
69.4 
89.8 
0.7 
28.0 
36.9 
45.4 
60.3 
76.7 
86.9 
98.1 
0.8 
40.5 
53.3 
64.2 
80.0 
92.4 
97.4 
99.9 
0.9 
62.0 
77.2 
87.0 
96.2 
99.4 
>99.9 
>99.9 
6.2 
Randomization 
Participants will enroll in the study at the first biopsy collection. Only participants 
who remain in the trial after the completion of the first biopsy visit will be 
randomized. 
Accrual will continue until 24 participants have received first product 
administration. 
The randomization sequence will be obtained by computer-generated random 
numbers and provided to each HVTN CRS through the SDMC via a Web-based 
randomization system.  
Groups 1 and 2 will be randomized simultaneously. 
The randomization will be stratified by assigned sex at birth and done in blocks to 
ensure balance across both groups. 
6.3 
Blinding 
Participants and site staff will be unblinded as to participant treatment group 
assignments. VRC07-523LS concentration and ADA assessments will be 
performed in a blinded fashion. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 40 of 132 
6.4 
Statistical analyses 
This section describes the final study analyses, unblinded as to treatment arm 
assignment. 
All analyses pertaining to safety and drug levels objectives of the study will be 
conducted with an intent-to-treat analysis that includes all randomized individuals 
per their randomization allocation. Additional analyses will be performed that 
account for the actual infusions and dose levels that each participant received. 
Analyses will be performed using SAS and R. Other software may be used to 
perform additional exploratory analyses. Unless otherwise stated, all tests will be 
two-sided and performed at a 5% significant level. In particular, no formal 
multiple comparison adjustments will be employed for multiple safety endpoints. 
6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, 
VRC07-523LS concentrations, and laboratory measurements for primary, 
secondary, and exploratory 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 participants who received at least 1 partial or complete administration of 
VRC07-523LS will provide some safety data. 
6.4.3.1 
Solicited AEs 
The number and percentage of participants experiencing solicited AEs, either 
signs or symptoms, will be tabulated by severity 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 administration 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. 
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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 41 of 132 
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 
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  
Boxplots 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 
boxplot will show the first quartile, the median, and the third quartile. Outliers 
(values outside the boxplot) 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 9.10) will be tabulated by treatment arm for each 
postadministration timepoint. Reportable clinical laboratory abnormalities without 
an associated clinical diagnosis will be included in the tabulation of AEs 
described above. 
6.4.3.4 
Reasons for discontinuation of study product administration 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. 
6.4.3.5 
Acceptability of study product or procedure 
Acceptability of study product administration and infusion procedures will be 
tabulated by reason and treatment arm. 
6.4.4 
Analysis of antibody level endpoints 
6.4.4.1 
General approach 
The second primary objectives of the study are to determine whether levels of 
VRC07-523LS in mucosa are detectable, and to correlate levels of VRC07-523LS 
in serum and mucosal sites. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 42 of 132 
In the primary statistical analysis, data from randomized participants will be used 
according to the initial randomization assignment regardless of how many 
administrations they received. Additional analyses may be performed, limited to 
participants who received all scheduled administrations per protocol. Assay 
results that are unreliable, from specimens collected outside of the visit window, 
or from HIV-infected participants postinfection may be excluded. Participants 
enrolled in this study will be recruited from a population at low risk of HIV 
infection. In the unlikely event of an HIV infection, since the exact date of 
infection is unknown, any assay data from blood draws or biopsy and secretion 
collections 4 weeks prior to an infected participant’s last seronegative sample and 
thereafter may be excluded. If an HIV-infected participant does not have a 
seronegative sample postenrollment, then all data from that participant will be 
excluded from the analysis. Biopsy and secretion collections will be discontinued 
in HIV-infected participants. 
For continuous assay data (eg, levels of VRC07-523LS in serum and mucosa), 
graphical and tabular summaries of the distributions by treatment arm and 
timepoint will be made. Scatterplots and measures of association (eg, Spearman’s 
rank and Pearson’s linear correlation coefficients) and their 95% CIs will be 
constructed within each timepoint for every pair of serum and mucosa drug levels. 
Regression models may be used to describe association between two variables 
(eg, VRC07-523LS levels measured in a mucosal site versus VRC07-523LS 
levels in the serum), potentially adjusting for important confounders if needed. 
Independent samples (eg, VRC07-523LS levels measured in different treatment 
groups) may be compared using nonparametric tests (eg, Wilcoxon rank-sum or 
Mann-Whitney tests), whereas paired samples (eg, VRC07-523LS levels 
measured in mucosal secretions before and after the first drug administration) will 
be compared using Wilcoxon’s signed rank test. If the normality assumption 
appears satisfied, two-sample t-tests with unequal variances, or parametric 
analysis of variance (ANOVA), or analysis of covariance (ANCOVA) adjusting 
for important covariates, may be used instead of the nonparametric tests when 
comparing independent groups. Likewise, the comparison of paired samples may 
be accomplished using one-sample t-tests. An appropriate data transformation (eg, 
logarithmic) may be applied prior to hypothesis testing to better satisfy analysis 
assumptions. For the analysis of correlation between two continuous assay 
variables over time, cross-correlation of the two variables with different time lags 
may also be calculated and visually displayed. Similar analyses stratifying by sex 
assigned at birth will be performed. Inference from these analyses will have 
limited power due to the small sample sizes of the groups. 
The analysis of categorical variables derived from assay measurements (eg, 
whether VRC07-523LS levels are above a limit of detection or prebaseline levels) 
will be performed by tabulating the frequency of each category for each assay by 
group at each timepoint at which an assessment is performed. Frequencies will be 
presented with their corresponding 95% CI estimates calculated using the score 
test method (57). 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 43 of 132 
More sophisticated analyses of drug-level data and other assay data collected over 
time employing repeated measures methodology that is valid under the missing at 
random (MAR) assumption (for example, mixed effects models) may be utilized 
to incorporate outcome responses over several timepoints and to account for 
subject heterogeneity. 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. Generalized linear models for response rates 
may use a binomial error distribution and for continuous endpoints, a normal error 
distribution. All models will consider including as covariates all available 
baseline predictors of the missing outcomes. 
Additional exploratory analyses will develop population PK models of VRC07-
523LS in serum and mucosal sites, 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 sex at birth). 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 will be excluded from the analysis. 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.  
The proposed models will describe the PK 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 may suffice to 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. PK data on 
VRC07-523LS from other trials (eg, HVTN 127/HPTN 087) may be combined 
with PK data from HVTN 128 to avoid identifiability issues in these analyses. 
More details of the statistical analysis approaches will be described in a separate 
Statistical Analysis Plan document.  
6.4.5 
Analyses 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, 
drug level or functional endpoint assessments. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 44 of 132 
6.4.5.1 
Safety analyses 
During the course of the trial, analyses of safety data will be prepared 
approximately every 4 months during the main study for review by the SMB. Ad 
hoc safety reports may also be prepared for SMB review at the request of the 
HVTN 128 PSRT. The HVTN leadership must approve any other requests for 
safety data prior to the end of the scheduled follow-up visits. 
6.4.5.2 
Anti-VRC07-523LS and other Laboratory Assessments 
Generally, analysis of a primary laboratory endpoint may be performed when all 
participants have completed the corresponding visit and data are available for 
analysis from at least 80% of these participants. The Laboratory Program will 
review the analysis report prior to distribution to the protocol chairs, DAIDS, 
product developer, and other key HVTN members and investigators. Distribution 
of reports will be limited to those with a need to know for the purpose of 
informing future trial-related decisions. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 45 of 132 
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 HVTN 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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 46 of 132 
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 low risk of HIV exposure 
through the last required protocol clinic visit. See Appendix G for US Low risk 
guidelines. 
Laboratory Inclusion Values 
Hemogram/Complete blood count (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 feminizing hormone therapy 
for more than 6 consecutive months should be assessed for eligibility using the 
hemoglobin parameters for persons 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). 
16. Negative Hepatitis B surface antigen (HBsAg)  
17. Negative anti-Hepatitis C virus (anti-HCV) antibodies, or negative HCV 
polymerase chain reaction (PCR) if the anti-HCV is positive 
Urine 
18. Normal urine: 
• Negative or trace urine protein 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 47 of 132 
Reproductive Status 
19. Volunteers who were assigned female sex at birth: negative serum or urine beta 
human chorionic gonadotropin (β-HCG) pregnancy test performed prior to biopsy 
collection and/or study product administration.  
20. Reproductive status: A volunteer who was assigned female sex at birth must: 
• Agree to use effective contraception 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 128 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); 
▪ Tubal ligation 
• Or be sexually abstinent until at least 4 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 
Mucosal Specimen Collection 
22. Volunteers 21 years of age and older who were assigned female sex at birth: 
Pap smear (verified by medical records) is required within: 
• the 3 years prior to enrollment with the latest result reported as normal or 
ASCUS (atypical squamous cells of undetermined significance), OR  
• the 5 years prior to enrollment, with the latest result reported as normal, or 
ASCUS with no evidence of high risk HPV. 
If no Pap smear was done within the last 3 years (or within the last 5 years, if high 
risk HPV testing was performed), the volunteer must be willing to undergo a Pap 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 48 of 132 
smear with the result reported (verified by medical records) as normal or ASCUS 
prior to sample collection. 
23. Willing to have mucosal secretions and tissue biopsies collected at several 
timepoints 
24. Willing to abstain from sexual intercourse for the required period after each 
biopsy collection 
7.2 
Exclusion criteria 
General 
1. Weight > 115 kg  
2. Blood products received within 120 days before first study product 
administration unless eligibility for earlier enrollment is determined by the HVTN 
128 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-HVTN HIV antibody testing during the planned 
duration of the 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 128 PSRT will 
determine eligibility on a case-by-case basis. 
7. Previous receipt of humanized or human monoclonal antibodies (mAbs), 
whether licensed or investigational; the HVTN 128 PSRT will determine 
eligibility on a case-by-case basis. 
8. Previous receipt of monoclonal antibodies against HIV 
Immune System  
9. Immunosuppressive medications received within 30 days before first 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 < 20 mg/day and length of 
therapy < 14 days) 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 49 of 132 
10. Serious adverse reactions to VRC07-523LS formulation components 
(sucrose, histidine, and sorbitol; see Section 8.2), including history of 
anaphylaxis and related symptoms such as hives, respiratory difficulty, 
angioedema, and/or abdominal pain. 
11. Immunoglobulin received within 90 days before first infusion unless eligibility 
for earlier enrollment is determined by the HVTN 128 PSRT 
12. 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) 
13. Immunodeficiency 
Clinically significant medical conditions  
14. 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 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 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 below. 
15. 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, Solicited AEs, or a volunteer’s 
ability to give informed consent 
16. 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 50 of 132 
17. Current anti-tuberculosis (TB) therapy 
18. Asthma other than mild, 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 moderate/high dose inhaled corticosteroids, or 
• In the past year has 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. 
19. Diabetes mellitus type 1 or type 2. (Not excluded: type 2 cases controlled with 
diet alone or a history of isolated gestational diabetes.) 
20. 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. 
21. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or 
platelet disorder requiring special precautions) 
22. 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) 
23. 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 51 of 132 
24. Asplenia: any condition resulting in the absence of a functional spleen 
25. History of hereditary angioedema, acquired angioedema, or idiopathic 
angioedema. 
Mucosal Specimen Collection 
26. A rectal condition (for rectal biopsies), such as an active infection or 
inflammation of the colorectal area (eg, an HSV-2 outbreak or inflamed 
hemorrhoids or colitis/diarrhea), internal hemorrhoids, or any other condition 
noted during screening rectal exam via anoscope or in medical history that in the 
opinion of the clinician represents a contraindication to mucosal sampling.  
27. For those who were assigned female sex at birth (for vaginal and cervical 
biopsies), any condition noted during pelvic exam via speculum or in medical 
history that in the opinion of the clinician represents a contraindication to mucosal 
sampling (eg, bacterial vaginosis). 
28. An active genital tract condition, such as an active infection or inflammation of 
the genital tract (eg, genital sores or ulcers, penile or abnormal vaginal discharge, 
genital warts that are symptomatic or requiring treatment) or any other condition 
that in the opinion of the clinician represents a contraindication to mucosal 
sampling. 
29. Hysterectomy or bilateral oophorectomy 
30. Menopause 
31. Current use of anticoagulants 
7.3 
Participant departure from study product administration 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 will be delayed. 
Refer to the HVTN 128 Study Specific Procedures (SSP) for further guidance 
regarding which procedures to conduct in these instances. 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 
▪ Receipt of systemic glucocorticoids (eg, prednisone or other 
glucocorticoids) or other immunomodulators (other than nonsteroidal anti-
inflammatory drugs [NSAIDs]) 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 52 of 132 
• Preinfusion 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 (PI) (or designee) to require delay or withdrawal from the study 
product administration schedule. The investigator may consult the HVTN 128 
PSRT. 
• Pregnancy: study product administration will be stopped while a participant is 
pregnant. If the participant is no longer pregnant (as defined by two 
consecutive negative tests) 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 128 PSRT. 
Study product should not be administered outside the visit window period 
specified in the HVTN 128 SSP. 
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 administration may 
be granted with the unanimous consent of the HVTN 128 PSRT) 
• 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: 
▪ HIV infection 
▪ Any grade 4 local or systemic Solicited or Unsolicited AE that is 
subsequently considered to be related to study product; 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 53 of 132 
▪ 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 128 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 
▪ Clinically significant hypersensitivity or mAb reaction including but not 
limited to type 1 hypersensitivity reaction, urticaria, or serum sickness 
associated with study product. Consultation with the HVTN 128 PSRT is 
required prior to subsequent infusion following any hypersensitivity 
reaction associated with study product 
• Investigator determination in consultation with Protocol Team leadership (eg, 
for repeated nonadherence to study staff instructions) 
Participants discontinuing study product administration for reasons other than 
pregnancy and HIV infection 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 (see HVTN 128 SSP). 
Participants who become pregnant during the study should be encouraged to 
participate in follow-up visits (see Section 9.13). Participants diagnosed with HIV 
infection during the study should be encouraged to participate in follow-up visits 
(see Section 9.14).  
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 HVTN CRS 
is not possible, 
• HVTN CRS determines that the participant is lost to follow-up,  
• Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff), or 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 54 of 132 
• Any condition where termination from the study is required by applicable 
regulations. 
7.3.5 
Delaying tissue biopsy and mucosal secretion collections for a 
participant 
An individual participant’s biopsy and mucosal secretion collections may be 
delayed in certain circumstances as described in Section 9.6. In addition to all 
mucosal collections, sexually transmitted infection (STI) and hormonal panel 
testing will be stopped while a participant is pregnant. If the participant is no 
longer pregnant (as defined by two consecutive negative tests) or breast-feeding 
and mucosal collections can be performed within an appropriate visit window, 
collections may resume with unanimous consent of the HVTN 128 PSRT. 
Furthermore, if a participant receives a live attenuated vaccine other than 
influenza vaccine within 10 days prior to any tissue biopsy or mucosal secretion 
collection, mucosal sampling may be delayed and collections may resume with 
unanimous consent of the HVTN 128 PSRT. 
7.3.6 
Discontinuing tissue biopsies for a participant 
An individual participant’s tissue biopsy collections will be permanently 
discontinued under certain circumstances, including: 
• Increased risk of HIV infection, as indicated by: 
▪ New diagnosis of chlamydia, gonorrhea, syphilis, or any other disease 
that, in the clinician’s opinion may indicate an increased risk of HIV 
infection 
▪ Change in HIV risk behavior (see Appendix G) 
• HIV infection 
• Any medical condition that presents a contraindication for biopsies (eg, a 
condition requiring anticoagulants), in consultation with the HVTN 128 PSRT 
• Investigator determination in consultation with the HVTN 128 PSRT and/or 
Protocol Team leadership  
• The participant is no longer willing to provide biopsy specimens 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 55 of 132 
8 
Study product preparation and administration 
HVTN 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 IB 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) 10 mg/kg to be 
administered IV at weeks 0, 16, and 32. 
Group 2 
Treatment 2 (T2): VRC07-523LS (VRC-HIVMAB075-00-AB) 30 mg/kg to be 
administered IV at weeks 0, 16, and 32. 
8.2 
Study product formulation 
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. 
8.3 
Study product storage 
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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 56 of 132 
minimum of 30 minutes and may be held at room temperature for up to 8 hours 
prior to product preparation. 
8.4 
Preparation of study products 
Prior to preparation of the first dose, 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). 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 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 infusion 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 40 General Chapter / General Tests and Assays / 
Physical Tests and Determinations / <797> Pharmaceutical Compounding – 
Sterile Preparations, and should follow the requirements of their country, their 
institution, and their pharmacy regulatory authority regarding these procedures. 
8.4.1 
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. 
The following instructions apply to thawing VRC07-523LS. 
1. Thaw vial(s) for a minimum of 1 hour at controlled room temperature 
(maximum 27°C) after removing from the freezer.  
2. Keep the material at room temperature during the entire preparation period 
until use, up to the maximum storage times described in Section 8.3. 
3. Prior to preparation for administration, vials should be swirled for 30 seconds 
with sufficient force to resuspend any visible particles yet avoiding foaming. 
DO NOT SHAKE THE VIALS. If particles are observed, return the vials to 
2°C to 8°C storage. If the particles dissolve within the maximum storage times 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 57 of 132 
described in Section 8.3 for 2°C to 8°C storage, the vials may be used for 
product preparation. If the particles continue to be observed, do not use the 
vialed product for IV administration. 
4. If the thawed material is not administered within 24 hours of thaw, follow the 
storage information provided in Section 8.3. 
8.4.1.1 
Intravenous infusion preparation instructions (T1 and T2): 
1. Calculate the total milligrams of VRC07-523LS required based on the 
participant’s weight (in kg) and the randomized treatment group of either 
10 mg/kg or 30 mg/kg. Remove the total number of vials required from 
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 8.4.1. 
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 0.9% Sodium Chloride 
Injection, USP 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 0.9% Sodium Chloride Injection, USP, please 
refer to the Study Products Considerations section of the HVTN 128 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 for 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 10 mg/kg or 30 mg/kg and 
the total amount (mg) of VRC07-523LS added to the 0.9% Sodium 
Chloride Injection, USP 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 58 of 132 
• Final volume of the IV container (bag/glass bottle) 
• For IV administration 
• 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 (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. 
8.5 
Administration 
8.5.1 
VRC07-523LS Intravenously 
For Groups T1 and T2 
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 8.4 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. The mL/hr infusion rate may vary based on 
the total volume needed to administer a full dose.  
A 1.2 micron in-line filter infusion set must be used for IV product 
administration. In-line filters must comply with the specifications described in the 
HVTN 128 SSP. When the in-line filter is added to the tubing, prime the 
administration set with 0.9% Sodium Chloride Injection, USP. HVTN CRS staff 
may prime the administration set with VRC07-523LS only during a shortage of 
0.9% Sodium Chloride Injection, USP. At the end of product administration, flush 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 59 of 132 
the administration set with about 30 mL or appropriate volume of 0.9% Sodium 
Chloride Injection, USP. 
8.6 
Acquisition of study products 
VRC-HIVMAB075-00-AB (VRC07-523LS) is provided by the VRC/NIAID. 
Filter needles, in-line filter infusion sets and 0.9% Sodium Chloride for Injection, 
USP should be obtained by the site. Please refer to the study product 
considerations section of the HVTN 128 SSP for product specific reference 
numbers. 
Once an HVTN CRS is protocol registered, the pharmacist can obtain study 
products from the NIAID Clinical Research Products Management Center 
(CRPMC) by following the ordering procedures outlined in the Pharmacy 
Guidelines and Instructions for DAIDS Clinical Trials Networks. 
8.7 
Pharmacy records 
The HVTN 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. 
8.8 
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 study sponsor. The 
procedures are included in the Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks.  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 60 of 132 
9 
Clinical procedures 
The schedule of clinical procedures is shown in Appendix F. 
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 HVTN 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 an HVTN study. Informed consent 
encompasses all written or verbal study information HVTN CRS staff provide to 
the participant, before and during the trial. HVTN CRS staff will obtain informed 
consent of participants according to HVTN 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, HVTN 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. 
An HVTN CRS may employ recruitment efforts prior to the participant 
consenting. For example, some HVTN 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. HVTN 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.” HVTN 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 HVTN 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, HVTN CRS staff can continually screen 
potential participants and, when needed, proceed quickly to obtain protocol-

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 61 of 132 
specific 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 B. 
Each HVTN 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 B. The consent form(s) must be developed in 
accordance with requirements of the following: 
• HVTN CRS’s IRB/EC and any applicable REs, 
• HVTN CRS’s institution, and 
• Elements of informed consent as described in Title 45, CFR Part 46 and 
Title 21 CFR, Part 50, and in ICH E6, Good Clinical Practice: 
Consolidated Guidance 4.8.  
Study sites are strongly encouraged to have their local CABs review their site-
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 document 
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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 62 of 132 
Participants must verbalize understanding of all questions answered incorrectly. 
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 enrollment biopsy collection on day 14. 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 G); 
• 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; skin; and pelvic 
and/or rectal exam; 
• 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 
• Pap smear (only for volunteers 21 years or older who were assigned female 
sex at birth and who have not had a Pap smear performed within the last 3-5 
years; for specific requirements see Section 7.1) 
• Laboratory tests , including: 
▪ Screening HIV, 
▪ HBsAg, 
▪ Anti-HCV Abs, 
▪ CBC with differential , 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 63 of 132 
▪ Chemistry panel (ALT, creatinine), 
▪ Syphilis, 
▪ Urine dipstick (urinalysis if indicated; see Section 9.9), 
▪ Urine or serum pregnancy test (volunteers who were assigned female sex 
at birth);  
▪ Chlamydia/gonorrhea (for all participants) 
▪ Trichomonas vaginalis (for participants providing cervicovaginal samples) 
▪ Bacterial vaginosis (for participants providing cervicovaginal samples) 
▪ Yeast (for participants providing cervicovaginal samples, only when 
clinically indicated) 
• 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 9.7 
• 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 study 
If a participant screens for an HVTN study at the same HVTN 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). 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 64 of 132 
9.3 
Enrollment visit 
Enrollment is simultaneous with baseline biopsy collection on day –14. At the 
baseline biopsy visit, cervical, vaginal, and/or rectal biopsies and mucosal 
secretion specimens will be collected. These samples will serve as baseline 
controls and will help to assess both the participants’ acceptability of the biopsy 
procedures and their fitness to continue with mucosal biopsy collections. 
Participants with conditions not amenable to biopsy sampling, not willing to 
continue in the trial after these baseline biopsies have been performed, or not able 
to provide mucosal secretions, will not be randomized. Participants not willing to 
continue in the trial after these baseline biopsies have been performed may be 
replaced. 
Randomization will occur after the mucosal collection. The HVTN CRS requests 
the randomization assignment via a Web-based randomization system. In general, 
the time interval between randomization and infusion should not exceed 4 
working days. However, circumstances may require a participant’s infusion visit 
to be changed. This may exceed the 4-day randomization time limit. At the 
enrollment biopsy collection visit, the following procedures are performed: 
• 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 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 (see Section 
9.2); 
• Assessment of any new or unresolved Unsolicited AEs/intercurrent illnesses; 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth); 
• Risk reduction counseling (see Section 9.7) 
• For participants capable of becoming pregnant, pregnancy prevention 
assessment (see Sections 9.2 and 9.7) 
• Social impact assessment 
• Specimen collection (including mucosal and biopsy samples as described in 
Section 9.6); 
• Laboratory tests (see Appendix E), including: 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 65 of 132 
▪ Blood hormone panel (estradiol and progesterone [assigned female sex at 
birth only]) 
• Confirm that participants received HIV test results from previous visit. If not, 
provide test results and post-test counseling as appropriate. 
9.4 
Infusion visits 
At all infusion visits, the following procedures are performed before study 
product administration: 
• 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 any new or unresolved Unsolicited AEs/intercurrent illnesses 
(as described in Section 11.2.2); 
• Assessment of concomitant medications (Section 9.2); 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth).  
• Blood collection (see Appendix E) 
• Mucosal secretion collection at infusions 2 and 3 only (see Section 9.6 and 
Appendix E). 
Following completion of all procedures in the preceding list, and if results 
indicate that infusion may proceed, infusion is administered (see Sections 8.4 and 
8.5). 
Administration of all infusions during an infusion visit must be accomplished 
within 1 calendar day. 
Immediately following infusion, the participant remains in the clinic for 
observation. See the HVTN 128 SSP for details regarding infusion visit protocols 
and subsequent infusion observation and Solicited AE assessment procedures 
(Section 9.10) that HVTN CRSs must follow. The HVTN CRS will make 
arrangements to be in contact with the participant during the Solicited AE period 
(as described in Section 9.10 and the HVTN 128 SSP). 
The following procedures may be performed prior to, during, or following first 
infusion (see Appendix E and Appendix F): 
• HIV infection assessment; 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 66 of 132 
• Risk reduction counseling (see Section 9.7); 
• For participants capable of becoming pregnant, pregnancy prevention 
assessment (see Sections 9.2 and 9.7); 
• Administration of behavioral risk assessment questionnaire; 
•  Mucosal sampling acceptability 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); 
• Administration of the social impact assessment questionnaire (types of 
impacts assessed involved personal relationships, health insurance, life 
insurance, educational or employment opportunities, housing, immigration, or 
travel); 
For management of mAb reactions see the HVTN 128 SSP. The following 
procedures should be performed after a mAb reaction:  
• mAb reaction clinical assessment 
• mAb reaction blood collection. 
9.5 
Follow-up visits 
Procedures will be performed at scheduled follow-up visits as specified in 
Appendix D and Appendix F: 
• 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; or 
• Complete physical examination (performed at last scheduled clinic visit), 
including height, weight, vital signs, and clinical assessments of head, ears, 
eyes, nose, and throat; neck; lymph nodes; heart; chest; abdomen; extremities; 
neurological function; skin; and pelvic and/or rectal exam ; 
• Risk reduction counseling (as described in Section 9.7); 
• Pregnancy prevention assessment (as described in Section 9.2 and 9.8); 
• Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if the participant has 
experienced any new social impacts as a result of trial participation); 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 67 of 132 
• 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); 
• Assessment of new or continuing concomitant medications (as described in 
Section 9.2); 
• Assessment of new or unresolved AEs/intercurrent illnesses or AESIs (as 
described in Section 11.2.2 and Appendix H; 
•  Mucosal sampling acceptability questionnaire 
• Behavioral risk assessment questionnaire 
• HIV diagnostic testing (see Section 9.7); 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; 
• Specimen collection (including mucosal sampling as described in Section 
9.6); 
• Clinical laboratory tests, including: 
▪ CBC with differential, 
▪ Chemistry panel (see Section 9.2), 
▪ Blood hormone levels (estradiol and progesterone) for participants 
assigned female sex at birth only 
▪ Urine dipstick (urinalysis if appropriate; see Section 9.9), 
▪ Chlamydia/gonorrhea (for all participants) 
▪ Trichomonas vaginalis (for participants providing cervicovaginal samples 
when clinically indicated) 
▪ Bacterial vaginosis (for participants providing cervicovaginal samples, at 
indicated visits and when clinically indicated. See Appendix E) 
▪ Yeast (for participants providing cervicovaginal samples, when clinically 
indicated) 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Pregnancy test result required prior to biopsy collection. 
CRS staff will contact study participants for a safety contact at Week 50 (see 
Appendix E and Appendix F). 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 68 of 132 
9.6 
Mucosal sampling 
Mucosal secretion and biopsy samples will be collected at the timepoints 
indicated in Appendix D. All participants in this trial will have consented to 
mucosal specimen collections. Participants assigned male sex at birth will provide 
semen, rectal secretions, and rectal biopsies. Participants assigned female sex at 
birth will provide cervicovaginal and rectal secretions, as well as cervical, vaginal 
and rectal biopsies. Small (~2-4 mm) tissue biopsies are obtained from the vagina 
and ectocervix using a speculum and from the rectum by anoscopy by 
experienced clinicians. The product administration and biopsy collection 
schedules per mucosal compartment and visit are described in detail in Table 9-1, 
and also outlined in Appendix D; however, fewer samples may be taken based on 
the judgment of the performing clinician. The number of biopsies collected per 
mucosal compartment and visit is shown in Table 9-2. Following the first product 
administration, a participant may decline all or some of the mucosal biopsies or 
secretion collections, but they should be encouraged to continue with any 
collections that they deem acceptable until the end of the trial. 
Table 9-1 HVTN 128 Sampling and product administration schedule 
 
D 14 
W 2 
D0 
W0 
D14 
W2 
D112 
W16 
D126 
W18 
D224 
W32 
D238 
W34 
D336 
W48 
Product Administration 
 
X 
 
X 
 
X 
 
 
Blood collection 
X 
X 
X 
X* 
X 
X* 
X 
X 
Rectal, cervicovaginal  
and seminal secretion 
collection 
X 
 
X 
X* 
X 
X* 
X 
X 
Cervical, rectal, and 
vaginal biopsy collection 
X 
 
X 
 
 
 
X 
X 
* Specimen collections to be done prior to the infusion 
 
Table 9-2 Biopsy and secretion specimen totals 
 
D 14 
W 2 
D14 
W2 
D112 
W16 
D126 
W18 
D224 
W32 
D238 
W34 
D336 
W48 
Total 
Rectal 
biopsies 
2 
2 
 
 
 
2 
2 
8 
Cervical 
biopsies 
2 
2 
 
 
 
2 
2 
8 
Vaginal 
biopsies 
2 
2 
 
 
 
2 
2 
8 
Semen 
1 
1 
1 
1 
1 
1 
1 
7 
Cervical 
secretions 
2 
2 
2 
2 
2 
2 
2 
14 
Rectal 
secretions 
1 
1 
1 
1 
1 
1 
1 
7 
• At each biopsy visit, prior to biopsy, participants must be confirmed to be 
low-risk for HIV infection. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 69 of 132 
• Participants will regularly be tested for gonorrhea and chlamydia. 
Additionally, participants who were assigned female sex at birth will be tested 
for trichomoniasis and bacterial vaginosis at indicated visits and may be tested 
for hyphae/budding yeast (when clinically indicated) as outlined in Appendix 
D. In addition to the predefined testing timepoints, such tests may be 
performed at any time according to the clinicians’ discretion. Test results will 
be provided to participants and all participants who test positive for 1 or more 
of these infections will receive counseling, as well as treatment or referral for 
treatment as appropriate. Sample collection will not be performed or may be 
deferred to a later date within the visit window if a contraindication to 
sampling (eg, active STI) is present (as indicated below). 
• If biopsy or secretion collections are delayed, they should be performed as 
soon as possible, within the visit window. Specimens should not be collected 
outside the visit windows specified in the HVTN 128 SSP. The participant 
should resume the collection schedule with the next collection unless there are 
circumstances that require further delay or permanent discontinuation of 
collections. 
Rectal secretions and/or biopsy sampling 
• For participants assigned female sex at birth and capable of becoming 
pregnant, a pregnancy test must be performed and be negative prior to any 
rectal mucosal sampling. 
• Rectal sampling will not be performed (or may be deferred to a later date 
within the visit window) if there is a contraindication to rectal biopsy or 
secretion sampling, such as an active infection or inflammation of the 
colorectal area (such as an HSV-2 outbreak or inflamed hemorrhoids or 
colitis/diarrhea).  
Additional biopsy-specific criteria 
• Biopsies will be collected a minimum of 21 days from previous rectal 
biopsies.  
• Participants must not have taken antithrombotic medications (except ASA and 
NSAIDs) for 5 days prior to the procedure. If a participant is taking these 
medications for medical reasons, biopsies should not be collected and these 
medications should not be interrupted. 
• Participant should not currently be taking anticoagulants. For participants with 
recent anticoagulant use, a CRS clinician must consult with the HVTN 128 
PSRT for approval prior to collecting any tissue biopsies. 
• Participants should not have receptive anal sex and/or insert any foreign 
object or substance into the rectum for 5 days after biopsy samples have been 
collected; 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 70 of 132 
• Participants should contact the clinic if they experience an excessive amount 
of bleeding, have a temperature of more than 38.1°C (100.5°F), experience 
chills, or have pain that is not improving. 
Cervicovaginal secretion and/or biopsy sampling 
• Participants who are age 21 or older must report having had a Pap smear 
within the 5 years prior to enrollment, with the latest result reported as 
normal, or ASCUS (atypical squamous cells of undetermined significance) 
with no evidence of high-risk HPV; if high-risk HPV testing was not 
conducted, the participant must report having had a Pap smear within the 3 
years prior to enrollment, with the latest result reported as normal or ASCUS. 
Pap smear results must be verified by medical records.  
• 
 For a participant who is capable of becoming pregnant, a pregnancy test must 
be performed and confirmed negative prior to biopsy sampling. For 
cervicovaginal secretion sampling, a pregnancy test must be done on the same 
day but can be performed prior to or after sampling.  
• Cervicovaginal mucosal secretions cannot be collected during menstruation 
but should be performed as soon as possible, within the visit window.  
• Cervicovaginal biopsies may be collected within the visit window during 
menses at the clinician’s discretion. 
• Cervicovaginal secretions or biopsy sampling will not be performed (or may 
be deferred to a later date within the visit window) if a participant has an 
active genital tract infection or lesion at the scheduled timepoint.  
• Additional biopsy-specific criteria: 
▪ Biopsies will be collected a minimum of 21 days from previous cervical 
and vaginal biopsies.  
▪ Participants must not have taken antithrombotic medications (except ASA 
and NSAIDs) for 5 days prior to the procedure. If a participant is taking 
these medications for medical reasons, biopsies should not be collected 
and these medications should not be interrupted. 
▪ Participant should not currently be taking anticoagulants. For participants 
with recent anticoagulant use, a CRS clinician must consult with the 
HVTN 128 PSRT for approval prior to collecting any tissue biopsies. 
▪ Participants should not have receptive vaginal sex and/or insert any 
foreign object or substance into the vagina for 7 days after biopsy 
samples have been collected; 
▪ Participants should contact the clinic if they experience an excessive 
amount of bleeding, have a temperature of more than 38.1°C (100.5°F), 
experience chills, or have pain that is not improving. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 71 of 132 
Semen sampling 
• Semen sampling will not be performed (or may be deferred to a later date 
within the visit window) if a participant is known to have an active genital 
tract infection at the scheduled timepoint. 
9.7 
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 current HVTN 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. Potential and enrolled participants identified as HIV-infected will be 
referred for medical treatment, counseling, and management of the HIV infection. 
With respect to enrolled participants who become HIV-infected, see Section 9.14.  
It is theoretically possible that an anti-HIV mAb may suppress viral replication, 
which can reduce the ability to detect HIV, even if a person is actually infected.  
An anti-HIV mAb is not likely to directly reduce or inhibit the assays used to 
detect HIV-1 infection. 
9.7.1 
Study product-related seroreactivity 
Tests of human plasma containing VRC07-523LS have been conducted using a 
variety of commercially available HIV test kits. At high plasma concentrations, 
reactive or indeterminate results have been observed on some test kits. See the 
HVTN 128 SSP for further detail. Thus, there is a possibility that receipt of the 
study product will cause a reactive result on some currently available HIV test 
kits, especially if testing occurs close to study product administration timepoints.  
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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 72 of 132 
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. 
9.8 
Contraception status 
Contraception status is assessed and documented at every scheduled clinic visit 
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. 
9.9 
Urinalysis 
Dipstick testing may be performed in the clinic or the lab, as long as the required 
elements (glucose, protein, and hemoglobin) are tested. The examination is 
performed on urine obtained by clean catch. 
If the screening dipstick is transiently abnormal due to menses or infection, 
document this issue in the participant’s source documentation. For infection, 
provide appropriate treatment and/or referral. Following resolution, repeat the 
dipstick. 
Follow-up urinalysis should be deferred if a participant is menstruating, but 
should be performed as soon as possible. If a follow-up dipstick is abnormal due 
to a participant’s menstrual period, document in the comment section of the case 
report form (CRF) and repeat the dipstick once the participant is no longer 
menstruating. A micro-urinalysis is not required. 
See relevant section of the Ab Manual of Operations (MOP) for further details. 
9.10 
Assessments of Solicited AEs 
For all participants, baseline assessments are performed before and Solicited AE 
assessments are performed after each study product administration. 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, July 2017, except 
as noted in Section 11.2.2. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 73 of 132 
The Solicited AE assessment period is 3 full days following each study product 
administration per the assessment schedule shown in Table 9-3. Participants are 
instructed to record symptoms using a Participant Diary. The site staff and the 
participant will be in contact after the 3-day Solicited AE assessment period, or 
sooner if indicated. See the Ab MOP for further details. In general, a participant 
who self-reports any poststudy product administration reaction 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 9-3. 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 study product 
administration and 3 full days after), or those meeting SAE/Unsolicited AEs 
requiring expedited reporting according to DAIDS criteria, are recorded on an AE 
Log. 
Table 9-3 Schedule of Solicited AE assessments 
Day 
Time 
Performed by 
0a 
Baseline: before infusion 
HVTN CRS clinician 
 
Early: 25-60 minutes after infusion 
HVTN CRS clinician 
 
Between early assessment and 11:59pm 
day 0 
HVTN CRS clinician or 
participant 
1-3b 
Between 12:00am and 11:59pm on the 
respective day 
HVTN CRS clinician or 
participant 
a Day of infusion 
b New or unresolved Solicited AEs present on day 3 are followed until resolution 
9.10.1 
Assessment of systemic and local symptoms 
Systemic symptoms to be assessed as Solicited AEs in this trial include increased 
body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, 
nausea, urticaria, non-exertional dyspnea, non-exertional tachycardia (assessed by 
HVTN CRS staff, not by the participant), generalized pruritus, facial flushing, and 
unexplained diaphoresis. Local symptoms include pain and/or tenderness at the 
infusion site. The daily maximum severity reached for each symptom during the 
assessment period is reported (see Ab MOP). 
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 
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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 74 of 132 
9.10.2 
Assessment of infusion site 
Typical infusion site reactions are erythema/redness and induration/swelling. The 
maximum diameter for all infusion/injection site reactions are recorded. 
All infusion site reactions are monitored until resolution. Areas with diameters 
greater than 5 cm are followed daily; otherwise, the frequency of follow-up is 
based on clinician judgment. 
9.11 
Visit windows and missed visits 
Visit windows are defined in HVTN 128 SSP. For a visit not performed within 
the window period, a Missed Visit form is completed. 
If a participant misses a scheduled visit, the HVTN CRS staff should attempt to 
bring the participant in as soon as possible to complete the required safety 
assessments and other procedures. See the HVTN 128 SSP for more details. 
If a missed visit required study product administration or if study product 
administration must be permanently discontinued, please refer to Section 7.3.2 
and Section 7.3.3 for resolution. 
9.12 
Early termination visit 
In the event of early participant termination, site staff should consider if the 
following assessments are appropriate: a final physical examination, Mucosal 
sampling acceptability questionnaire, safety contact, clinical laboratory tests 
(including urine dipstick, CBC with differential, and chemistry panel), pregnancy 
testing, social impact assessment, and HIV test. See relevant section of the Ab 
MOP for further details. 
9.13 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more 
infusions of study product will be given. During pregnancy, no more STI testing, 
hormonal panel testing, biopsy collections, and mucosal collections will be 
conducted. 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. 
If the participant is no longer pregnant (as defined by two consecutive negative 
tests) or breast-feeding and study product administration and mucosal collections 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 75 of 132 
can be performed within an appropriate visit window, these may resume with 
unanimous consent of the HVTN 128 PSRT. 
See relevant section of the Ab MOP for further details 
9.14 
HIV infection during the study 
If a participant becomes HIV infected during the course of the study, no 
additional study product will be administered. In addition, no more STI testing, 
hormonal panel testing, biopsy collection, and mucosal secretion collections will 
be conducted. Participants will be encouraged to continue scheduled study visits 
up to 16 weeks following their last study product administration. Follow-up 
duration for participants diagnosed with HIV infection may be adjusted in 
consultation with the CRS investigator and the HVTN 128 PSRT (eg, to avoid 
interference with participant initiation into HIV treatment). At postinfection 
follow-up visits, only specimens required for protocol-specified safety laboratory 
tests, urinalysis, and pregnancy tests will be collected (see Appendix E and 
Appendix F). 
See relevant section of the Ab MOP for further details. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 76 of 132 
10 
Laboratory 
10.1 
HVTN CRS laboratory procedures 
The HVTN 128 Site Lab Instructions and SSPs 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 D. For tests performed 
locally, the local lab may assign appropriate tube types. 
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 D. 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 levels will be measured in serum, semen, cervicovaginal 
secretions, rectal secretions, and mucosal tissue lysates prepared from cervical, 
vaginal, and rectal biopsies collected at the designated timepoints. A quantitative 
immunoassay will be used to determine the concentration of VRC07-523LS. 
Ultra-sensitive bead-based analyses enable a broad dynamic range and higher 
sensitivity (eg, for the anti-idiotype mAb, 5C9, the lower limit of quantification is 
approximately 50 pg/mL). The operational sensitivity of the quantitative assays 
with respect to the various sample specimens will be determined for the clinical 
grade VRC07-523LS mAb used for this study. VRC07-523LS levels may be 
normalized relative to total protein and/or total IgG concentrations. Hemoglobin 
measurements may be used to perform quality control of mucosal secretions. 
10.4 
ADA detection assays 
A tiered testing approach will be used to identify and characterize ADAs that may 
arise. Anti-VRC07-523LS antibody detection assays (screening, confirmatory, 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 77 of 132 
and/or titration) will be performed on serum samples from study participants at 
indicated timepoints.  
10.5 
ADA functional assay  
A functional ADA assay will be used to characterize any positive activity that is 
observed in the ADA detection assays. Functional activity will measure a 
reduction in VRC07-523LS neutralizing activity against a qualified virus in the 
TZM-bl assay.  
10.6 
Monoclonal antibody reaction assays 
To investigate mAb reactions, serum samples collected after the onset of reaction 
may be tested to measure levels of certain markers (eg, tryptase, complement 
components (C3 and C4), and cytokines). ADA detection and functional assays, 
as described above, may be performed on serum samples taken prior to the study 
product administration associated with the reaction. Refer to the HVTN 128 SSP 
for more information. 
10.7 
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, samples may be used to perform additional assays to support 
standardization and validation of existing or newly developed methods. 
10.8 
Specimen storage and other use of specimens  
The HVTN stores 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, mAbs, the immune system, and other 
diseases. This could include genetic testing and, potentially, 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 IRB/EC of 
the researcher requesting the specimens, and the HVTN 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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 78 of 132 
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 
HVTN CRS in a Web-based tool that documents their current decisions for other 
use of their specimens. The HVTN will only allow other research to be done on 
specimens from participants who allow such use.  
HVTN 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. 
10.9 
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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 79 of 132 
11 
Safety monitoring and safety review 
11.1 
Safety monitoring and oversight 
11.1.1 
HVTN 128 PSRT 
The HVTN 128 PSRT is composed of the following members: 
• DAIDS medical officer representative 
• Protocol chair and co-chair 
• Protocol Team leader 
• Core medical monitor 
• Clinical safety specialist 
The clinician members of the HVTN 128 PSRT are responsible for decisions 
related to participant safety. 
The Protocol Team clinic coordinator, clinical data manager, study product 
developer representative, clinical trial manager, and others may also be included 
in HVTN 128 PSRT meetings. 
11.1.2 
HVTN SMB 
The SMB is a multidisciplinary group consisting of biostatisticians, clinicians, 
and experts in HIV prevention and drug research that, collectively, has experience 
in the conduct and monitoring of prevention 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 128 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 
SDMC 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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 80 of 132 
• Providing reports of clinical data to appropriate groups such as the HVTN 128 
PSRT and HVTN SMB (see Section 11.1.2); 
11.1.4 
HVTN Core roles and responsibilities in safety monitoring 
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 128 PSRT AE review criteria (see Section 11.3); 
• Notifying HVTN CRSs and other groups when safety pauses or planned holds 
are instituted and lifted (see Section 11.3); 
• Querying HVTN CRSs for additional information regarding reported clinical 
data; and 
• Providing support to the HVTN 128 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 must 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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 81 of 132 
product/procedure(s). See the Ab MOP and SSP for further detail regarding 
Solicited and Unsolicited AEs. 
The study Unsolicited AE reporting period is from study enrollment of a trial 
participant to completion of the safety contact two weeks after the last biopsy 
collection at Week 50. 
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 
128 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); 
• Monoclonal antibody reactions (see HVTN 128 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) and (2), 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. 
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 Members’ site 
(https://members.hvtn.org/protocols/hvtn128). 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 (their local time) to confirm that the email has been received and reviewed. 
If email service is not available, the HVTN CRS should notify clinical safety staff 
of the event by telephone, then submit CRFs. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 82 of 132 
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 product for which expedited reporting are required is: 
• 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. 
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). 
HVTN CRS Investigators of Record/designees will submit AE information and 
any other relevant safety information to their IRBs/ECs in accordance with 
IRB/EC requirements. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 83 of 132 
11.3 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all enrollment and study product 
administration with the product 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 128 PSRT AE review are summarized in Table 11-1. Study product 
administrations 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 128 
PSRT, participant safety may be threatened. Criteria for an individual 
participant’s departure from the schedule of study product administrations are 
listed in Section 7.3. 
Table 11-1 AE notification and safety pause/AE review rules 
Event and 
relationship to study 
products 
Severity 
HVTN 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, 2, 
or 1 
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/hvtn128). 
b HVTN CSS or HVTN Core designee 
c Does not include the following subjective Solicited AEs symptoms (infusion site pain and/or tenderness, 
fatigue/malaise, myalgia, arthralgia, chills, headache, non-exertional dyspnea, generalized pruritus, facial 
flushing, and unexplained diaphoresis). 
For all safety pauses, HVTN Core notifies the HVTN 128 PSRT, HVTN 
Regulatory Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), DAIDS 
Regulatory Affairs Branch (RAB), DAIDS Safety and Pharmacovigilance Team 
(SPT), and participating HVTN CRSs. When an immediate safety pause is 
triggered, HVTN Core notifies the SMB.  
Once a trial is paused, the HVTN 128 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 HVTN CRSs, HVTN Regulatory Affairs, DAIDS PAB, 
DAIDS RAB, and DAIDS SPT of the decision regarding resumption or 
discontinuation of study product administrations. Based on the HVTN 128 PSRT 
assessment, DAIDS RAB notifies the FDA as needed. 
If an immediate HVTN 128 PSRT notification or prompt HVTN 128 PSRT AE 
review is triggered, HVTN Core notifies the HVTN 128 PSRT as soon as possible 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 84 of 132 
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 128 PSRT AE review cannot be completed within 72 hours of notification 
(excluding weekends and US federal holidays), an automatic safety pause occurs. 
The HVTN requires that each HVTN 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). HVTN CRSs must also follow all applicable RE reporting requirements. 
In addition, all other AEs are reviewed routinely by the HVTN 128 PSRT (see 
Section 11.4.2). 
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 HVTN CRSs. 
Events are tracked by internal reports until resolution.  
11.4.1 
Daily review 
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 128 PSRT AE review criteria. 
11.4.2 
Weekly review 
During the study product administration phase of the trial, the HVTN 128 PSRT 
reviews clinical safety reports on a weekly basis and conducts calls to review the 
data as appropriate. After the infusions and the following safety visit are 
completed, less frequent reporting and safety reviews may be conducted at the 
discretion of the HVTN 128 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 HVTN CRS clinic coordinator for verification. 
11.5 
Study termination 
This study may be terminated early by the determination of the HVTN 128 PSRT, 
FDA, NIH, Office for Human Research Protections (OHRP), or study product 
developer(s). In addition, the conduct of this study at an individual HVTN CRS 
may be terminated by the determination of the IRB/EC and any applicable RE. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 85 of 132 
12 
Protocol conduct 
This protocol and all actions and activities connected with it will be conducted in 
compliance with the principles of GCP (ICHe6), and according to DAIDS and 
HVTN policies and procedures as specified in the HVTN Manual of Operations, 
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; 
• Quality control; 
• Protocol monitoring and compliance; 
• Advocacy and assistance to participants regarding negative social impacts 
associated with 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 or HVTN standards or require 
additional instructions (eg, instructions for randomization specific to this study) 
will be described in the Ab MOP and HVTN 128 SSP.  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 86 of 132 
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 F). A social harm that is 
reported by the participant and judged by the investigator of record 
(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 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 HVTN 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 HVTN CRS must notify the IRB/EC and any applicable RE of the matter as 
soon as possible. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 87 of 132 
13 
Version history 
The Protocol Team may modify the original version of the protocol. 
Modifications are made to HVTN protocols via clarification memos, letters of 
amendment, or full protocol amendments.  
The version history of, and modifications to, Protocol HVTN 128 are described 
below. 
Protocol history and modifications 
Date: September 18, 2018 
Protocol version: 1.0 
Protocol modification: 
 
Original protocol 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 88 of 132 
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 128 Special Instructions. Accessible through the HVTN protocol-
specific website. 
• HVTN 128 Study Specific Procedures (SSP). Accessible through the HVTN 
protocol-specific website. 
• HVTN 128 Site Lab Instructions. Accessible through the HVTN protocol-
specific website. 
• HVTN Manual of Operations. Accessible through the HVTN website. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 89 of 132 
• Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
http://www.iata.org/publications/dgr/Pages/index.aspx 
• Lab assay algorithm (available upon request) 
• International Council on 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 
• Participants’ Bill of Rights and Responsibilities. Accessible through the 
HVTN 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/regulations-and-policy/regulations/45-cfr-
46/index.html 
See Section 16 for literature cited in the background and statistics sections of this 
protocol. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 90 of 132 
15 
Acronyms and abbreviations 
Ab 
 
antibody 
Ab MOP  
Antibody Manual of Operations 
ADA 
 
antidrug antibodies 
AE 
 
adverse event 
AESI 
 
adverse event of special interest 
AMP 
 
antibody-mediated prevention 
ANOVA  
analysis of variance 
aPTT 
 
activated partial thromboplastin time 
ART 
 
antiretroviral therapy 
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 
CI 
 
confidence intervals 
CRF 
 
case report form 
CRPMC 
 
NIAID Clinical Research Products Management Center 
CRS 
 
clinical research site 
DAERS 
 
DAIDS Adverse Experience Reporting System 
DAIDS 
 
Division of AIDS (US NIH) 
DHHS 
 
US Department of Health and Human Services 
EAE 
 
expedited AE 
EC 
 
Ethics Committee 
EIA 
 
enzyme immunoassay 
ELISA 
 
enzyme-linked immunosorbent assay 
FDA 
 
US Food and Drug Administration 
Fred Hutch 
Fred Hutchinson Cancer Research Center 
GCP 
 
Good Clinical Practice 
HBsAg 
 
hepatitis B surface antigen 
HCV 
 
hepatitis C virus 
HIPAA 
 
Health Insurance Portability and Accountability Act 
HIV 
 
human immunodeficiency virus 
HVTN 
 
HIV Vaccine Trials Network 
IB 
 
Investigator’s Brochure 
ICH 
 
International Council on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IHC 
 
immunohistochemical 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 91 of 132 
IND 
 
Investigational New Drug 
IoR 
 
investigator of record 
IRB 
 
Institutional Review Board 
IUD 
 
intrauterine device 
IV 
 
intravenous 
mAb 
 
monoclonal antibody 
MAR 
 
missing at random 
MOP 
 
Manual of Operations 
NHP 
 
nonhuman primate 
NIAID 
 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
 
US National Institutes of Health 
OHRP 
 
US Office for Human Research Protections 
PAB 
 
DAIDS Pharmaceutical Affairs Branch 
PCR 
 
polymerase chain reaction 
PEP 
 
postexposure prophylaxis  
PI 
 
Principal Investigator 
PK 
 
pharmacokinetic 
PSRT 
 
Protocol Safety Review Team 
RAB 
 
DAIDS Regulatory Affairs Branch 
RE 
 
regulatory entity 
RSC 
 
DAIDS Regulatory Support Center 
SAE 
 
serious adverse event 
SCHARP  
Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
 
statistical and data management center 
SMB 
 
Safety Monitoring Board 
SPT 
 
DAIDS Safety and Pharmacovigilance Team 
SSP 
 
study specific procedures 
STI 
 
sexually transmitted infection 
SUSAR 
 
suspected unexpected serious adverse reaction 
TB 
 
tuberculosis 
UNAIDS  
The Joint United Nations Programme on HIV/AIDS 
UW-VSL  
University of Washington Virology Specialty Laboratory 
VRC 
 
Vaccine Research Center (NIAID) 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 92 of 132 
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 Global Report: Report on the global AIDS epidemic [Internet]. 
2017. Available from: 
www.unaids.org/sites/default/files/media_asset/20170720_Data_book_2017_
en.pdf. 
5. 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/. 
6. UNAIDS. Global Report: Report on the global AIDS epidemic 2013. 2013 
2013. Report No.: UNAIDS / JC2502/1/E. 
7. UNAIDS WipwUa. Global Report on HIV Treatment 2013: Results, Impact 
and Opportunities. 2014 6/2014. 
8. UNAIDS. Local Epidemics Issues Brief. 2014 2014. 
9. Fauci AS, Marston HD. Ending AIDS--is an HIV vaccine necessary? N Engl 
J Med. 2014;370(6):495-8. 
10. Gray GE, Laher F, Lazarus E, Ensoli B, Corey L. Approaches to preventative 
and therapeutic HIV vaccines. Curr Opin Virol. 2016;17:104-9. 
11. Winokur PL, Stapleton JT. Immunoglobulin prophylaxis for hepatitis A. Clin 
Infect Dis. 1992;14(2):580-6. 
12. 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 93 of 132 
13. 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. 
14. Simoes EA. Immunoprophylaxis of respiratory syncytial virus: global 
experience. Respir Res. 2002;3 Suppl 1:S26-33. 
15. 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. 
16. 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. 
17. 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. 
18. 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. 
19. 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. 
20. 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. 
21. 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. 
22. 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. 
23. 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 94 of 132 
24. 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. 
25. 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. 
26. 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. 
27. 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. 
28. 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 
neutralization in selected HIV-1 infected individuals. PLoS Pathog. 
2010;6(8):e1001028. 
29. 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. 
30. 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. 
31. 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. 
32. 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. 
33. Walker LM, Burton DR. Rational antibody-based HIV-1 vaccine design: 
current approaches and future directions. Curr Opin Immunol. 
2010;22(3):358-66. 
34. 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 95 of 132 
35. 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. 
36. Kwong PD, Mascola JR. Human antibodies that neutralize HIV-1: 
identification, structures, and B cell ontogenies. Immunity. 2012;37(3):412-
25. 
37. 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. 
38. Vittinghoff E, Douglas J, Judson F, McKirnan D, MacQueen K, Buchbinder 
SP. Per-contact risk of human immunodeficiency virus transmission between 
male sexual partners. Am J Epidemiol. 1999;150(3):306-11. 
39. Boily MC, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, et al. 
Heterosexual risk of HIV-1 infection per sexual act: systematic review and 
meta-analysis of observational studies. Lancet Infect Dis. 2009;9(2):118-29. 
40. Jin F, Jansson J, Law M, Prestage GP, Zablotska I, Imrie JC, et al. Per-
contact probability of HIV transmission in homosexual men in Sydney in the 
era of HAART. AIDS. 2010;24(6):907-13. 
41. Koblin BA, Casapia M, Morgan C, Qin L, Wang ZM, Defawe OD, et al. 
Safety and immunogenicity of an HIV adenoviral vector boost after DNA 
plasmid vaccine prime by route of administration: a randomized clinical trial. 
PLoS ONE. 2011;6(9):e24517. 
42. Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, 
et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 
2013;369(22):2083-92. 
43. Mayer KH, Seaton KE, Huang Y, Grunenberg N, Isaacs A, Allen M, et al. 
Safety, pharmacokinetics, and immunological activities of multiple 
intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, 
VRC01, administered to HIV-uninfected adults: Results of a phase 1 
randomized trial. PLoS Med. 2017;14(11):e1002435. 
44. 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. 
45. 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 96 of 132 
46. 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. 
47. 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. 
48. 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. 
49. Gaudinski MR, Coates EE, Houser KV, Chen GL, Yamshchikov G, Saunders 
JG, et al. Safety and pharmacokinetics of the Fc-modified HIV-1 human 
monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in 
healthy adults. PLoS Med. 2018;15(1):e1002493. 
50. 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. 
51. 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. 
52. 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. 
53. Vogel WH. Infusion reactions: diagnosis, assessment, and management. Clin 
J Oncol Nurs. 2010;14(2):E10-E21. 
54. Hasselrot K, Cheruiyot J, Kimani J, Ball TB, Kaul R, Hirbod T. Feasibility 
and safety of cervical biopsy sampling for mucosal immune studies in female 
sex workers from Nairobi, Kenya. PLoS ONE. 2012;7(10):e47570. 
55. McGowan I, Hoesley C, Cranston RD, Andrew P, Janocko L, Dai JY, et al. A 
phase 1 randomized, double blind, placebo controlled rectal safety and 
acceptability study of tenofovir 1% gel (MTN-007). PLoS ONE. 
2013;8(4):e60147. 
56. Thurman A. Safety of Cervical and Vaginal Biopsies in Microbicide and 
Contraceptive Research. 2015. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 97 of 132 
57. Agresti A, Coull BA. Approximate is better than "exact" for interval 
estimation of binomial proportions. Am Stat. 1998;52(2):119-26. 
58. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed: 
Lawrence Erlbaum, Hillsdale NJ; 1988. 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 98 of 132 
Appendix A 
Sample informed consent form 
A phase 1 clinical trial to evaluate the safety and pharmacokinetics of VRC-
HIVMAB075-00-AB (VRC07-523LS) in the sera and mucosae of healthy, HIV-
1–uninfected adult participants 
Protocol number: HVTN 128 
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) and [Insert site name] are doing a 
study to test an 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). 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 24 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 study VRC07-523LS antibody safe to give to people? 
• Are people able to take the study antibody without becoming too 
uncomfortable? 
• How much of the antibody remains in the body as time passes? 
• How much of the antibody is found at the rectum, vagina, and penis? 
• How does the body’s response to the antibody change depending on the 
amount and timing of the doses? 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 99 of 132 
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. This 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 used only 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 alone 
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 13 times higher than those used in 
this study. 
As of July 2018, VRC07-523LS has been given by injection or by intravenous 
infusion (IV)  in ongoing clinical trials at the NIH Clinical Center and in a 
multisite study. In the VRC 605 study, 25 participants have received the antibody 
by injection or by intravenous infusion (IV). In the HVTN 127/ HPTN 087 
clinical trial, VRC07-523LS has been given by IV infusion to 24 people (8 people 
have received a low dose, 8 people have received a medium dose, and 8 people 
have received a high dose of the antibody). So far, the study antibody has not 
made people too uncomfortable or caused serious health problems. Two people 
who got the study antibody by infusion had chills, fever, nausea, body aches, 
rapid heartbeat, and headache. These feelings went away within 12 hours.  
General risks of antibodies similar to VRC01: 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 100 of 132 
As of July 2018, 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 3000 adults and 
60 infants have gotten those study products. 
In a previous study, one person who got VRC01 by injection had a rash. One 
person had a brief fainting spell several hours after getting VRC01 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 a 
study antibody. 
Many of these studies are still going on and we don’t know which people got the 
study antibodies 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. 
VRC07-523LS and VRC01 may have other side effects that we do not know 
about yet. 
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, diarrhea, racing heartbeat, chest pain, or swelling in the lip, tongue, throat 
or face.  
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.  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 101 of 132 
These rare side effects and reactions have not been seen in other studies with 
VRC07-523LS or similar experimental antibodies.  
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 assess how easy it might be to start an IV 
• Rectal and/or pelvic exam 
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, chlamydia, gonorrhea, Trichomonas vaginalis, 
bacterial vaginosis, hepatitis B, and hepatitis C. We will ask you about 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 102 of 132 
medications you are taking. We will ask you about behaviors that might put you 
at risk for getting HIV. 
If you were assigned female sex at birth, we will test you for pregnancy. If you 
were assigned female sex at birth and are 21 years or older, you must have had a 
Pap smear within the last 3 to 5 years with the most recent result being normal. 
We will need to request a copy of your Pap smear result. If you have not had a 
Pap smear within the last 3 years and would like to get one, we will tell you where 
you can get one. 
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 were assigned female sex at birth and could 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 at least 21 days prior to enrollment through the last required 
protocol 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: 
8. You will come to the clinic for about 9 scheduled visits for just under one 
year. 
We will ask you to come to the clinic about 14 days before the first infusion for 
tissue collections that will be compared with tissue collections taken after 
infusions. This is to see how much study product gets into the tissues. You’ll 
come again within about 2 weeks after each infusion to draw your blood. We will 
do this so that we can look at how your body responds to the study product. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 103 of 132 
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). 
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 participants assigned 
female sex at birth 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 antibody by IV infusion.  
There are 2 groups in this study. All people in both groups will get the study 
antibody by IV. The amount of antibody is different in each of the 2 groups. 
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 60 minutes each. 
Which group you are in is completely random, like flipping a coin. We have no 
say in which group you are assigned to. Neither will you. We can tell you which 
group you are assigned to. 
11. We will give you the study products on a schedule. 
You will be in one of 2 groups. Both groups will get an IV infusion 3 times during 
the study, about every 4 months. You will get a different dose depending on 
which group you are in. 
Participants in Group 1 will get the lower dose. Participants in Group 2 will get 
the higher dose. 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 104 of 132 
 
 
Group 
Route 
Dose 
IV schedule 
First infusion 
4 months later 
8 months later 
1 
IV 
Lower 
X 
X 
X 
2 
IV 
Higher 
X 
X 
X 
You will have to wait in the clinic for about an hour after the first IV infusion and 
for about half an hour after the other IVs 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 infusion to ask how you have 
been feeling. Contact the clinic staff if you have any issues or concerns after 
getting an infusion. If you have a problem, we will continue to check on you until 
it goes away. 
12. In addition to giving you the study products, 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 were assigned female sex at birth 
• 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 17 mL and 100 mL (2 tablespoons to 1/2 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 105 of 132 
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.  
13. We will also collect semen, rectal fluid and tissue, cervical fluid and cervical 
and vaginal tissue samples from you. 
We want to see if the antibodies get to the parts of the body where people may be 
exposed to HIV: their rectum, vagina, and penis. We will take samples from these 
areas.  
We will ask you to avoid some activities before we collect these samples. This 
will help make sure your samples give accurate lab readings. There are also some 
activities we will ask you to avoid after collecting the samples that are described 
below. 
We will ask all participants assigned male sex at birth to provide semen as well as 
rectal fluids and tissue. We will ask all participants assigned female sex at birth to 
provide cervical and rectal fluids as well as cervical, rectal and vaginal tissues. 
Site: localize measurement units throughout the following sections as needed. 
Semen collections (for persons assigned male sex at birth) 
You will provide semen at the clinic. We will ask you to ejaculate into a plastic 
cup, which we will give to you.  
For the 2 days before semen collection, we will ask you to follow these 
instructions: 
• Do not ejaculate, or have oral, vaginal, or anal insertive sex, 
• Do not use anything with lubricants,  
• Do not put saliva (your own or someone else’s) on your penis. 
Rectal fluid collections (for all participants) 
We will collect rectal fluid by first placing a plastic tube about 2 cm wide (a little 
less than an inch) into your rectum to hold it open. The tube will go in about 6½ 
cm (about 2½ inches). A small balloon will be placed through the tube and into 
the rectum. The balloon will stay in for less than a minute. The balloon will be 
inflated to about half the size of a chicken egg after it is inside your rectum, and 
deflated before it is removed.  
For the 2 days before we collect your rectal fluid, we will ask you to follow these 
instructions:  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 106 of 132 
• Do not have receptive anal intercourse,  
• Do not put anything into your anus, including cleaning products (creams, gels, 
lotions, pads, etc.), lubricant, enemas or douches (even with water), 
• Do not use any anti-inflammatory creams in or around your anus, 
• We will not collect rectal fluid if we think you may have an anal or rectal 
infection. You should tell us if your rectal area is sore. 
Rectal tissue collections (for all participants) 
We will collect small samples of tissue about the size of half a grain of rice from 
the lining of your rectum. These are called rectal biopsies. We will collect 2 
biopsies at 4 different visits. To take the samples, we will place a plastic tube 
about 2 cm wide (a little less than an inch) into the anus to view the lower part of 
the rectum. You may feel some discomfort, but the biopsies are almost always 
painless. It will take 5 to 10 minutes.  
You may see blood in your first few stools. This is normal after a biopsy. If you 
think the bleeding is excessive, contact your study clinician immediately. 
For the 5 days before we collect your rectal tissues, we will ask you not to take 
medicines that thin your blood or prevent blood clots. These medicines are called 
NSAIDS, and common examples include Ibuprofen (brand name Advil®) and 
Naprosyn (brand name Aleve®). 
For the 2 days before we collect your rectal tissues, we will ask you to follow the 
same instructions as above. In addition, we will ask you to follow these 
instructions after the procedure:  
• Do not have rectal sex and/or insert any foreign object or substance into the 
rectum for 5 days after biopsy samples have been collected; 
• You should call the clinic if you have a lot of bleeding, have a temperature of 
more than 38.1°C (100.5°F), experience chills, or have pain that is not getting 
better. 
Cervical fluid collections (for persons assigned female sex at birth) 
We will collect cervical fluids by using either a soft sponge inserted into the 
opening of your cervix, or by using a disposable menstrual cup inserted into your 
vagina. If we use a soft sponge to collect cervical fluids, we will insert a speculum 
(a device that holds your vagina open) into your vagina and place the sponge in 
the opening of the cervix. This is similar to getting a pap smear. If we use a 
menstrual cup, we will explain how to insert it into your vagina. You may insert it 
before you come to the clinic. You will wear it for up to 6 hours and remove it at 
the clinic. You will insert a second menstrual cup at the clinic and wear it for 10-

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 107 of 132 
15 minutes. If you are uncomfortable doing any of this on your own, you may 
come to the clinic and we will help you.  
For the 2 days before we collect your cervical fluid, we will ask you to follow 
these instructions:  
• Do not use any spermicide, lubricants, douche (even with water), or 
medication in or around your vagina;  
• Do not have vaginal intercourse or insert anything into your vagina; 
• Using a vaginal ring for contraception is fine and can continue to be used. 
You will need to remove it for a few hours before the procedure. The clinic 
staff can explain this to you. 
We will not collect cervical fluid if you are menstruating, or if we think you may 
have a cervical or vaginal infection. If you are menstruating, we may ask you to 
return to collect this sample at another time. 
Cervical and vaginal tissue collections (for persons assigned female sex at birth) 
We will collect small samples of tissue about the size of half a grain of rice. We 
will collect up to 2 cervical and 2 vaginal biopsies at 4 different visits. We will 
insert a speculum into your vagina. A speculum is a metal or plastic tool that 
looks like a bird’s beak. It is used to help open your vagina a few inches.  
After the speculum is put into your vagina, the cervix and vaginal wall will be 
cleaned with a clean cotton ball or swab.  
Biopsies will be taken with clean forceps. Forceps are a metal tool to help get the 
tissue from inside your vagina and cervix. You may feel cramping, pain or 
discomfort. We will check to make sure that there is no bleeding from where the 
biopsies are taken. If there is bleeding, we will use a medication to stop it. One 
type of medication, silver nitrate, has a gray color. You may see gray flecks in 
your vaginal discharge after the biopsy. This is normal. The procedure will take 
about 10 minutes. 
For the 5 days before we collect your cervical and vaginal tissues, we will ask you 
not to take medicines that thin your blood or prevent blood clots. These medicines 
are called NSAIDS, and common examples include Ibuprofen (brand name 
Advil®) and Naprosyn (brand name Aleve®). 
For the 2 days before we collect your cervical/vaginal tissue, we will ask you to 
follow the same instructions as above. In addition, we will ask you to follow these 
instructions after the procedure:  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 108 of 132 
• Do not have vaginal sex and/or insert any foreign object or substance, 
including tampons, into the vagina for 7 days after biopsy samples have been 
collected; 
• Participants should contact the clinic if they experience a large amount of 
bleeding, have a temperature of more than 38.1°C (100.5°F), experience 
chills, or have pain that is not improving.  
• Using a vaginal ring for contraception is fine and can continue to be used. 
14. 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.  
15. We will test your samples to see how your immune system responds to the 
study antibody. 
We will send your samples (without your name) to labs approved by the HVTN 
for this study, which are located in the United States. 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. 
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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 109 of 132 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 
16. When samples are no longer needed for this study, the HVTN wants to use 
them in other studies and share them with other researchers.  
These samples are called “extra samples”. The HVTN will only allow your extra 
samples to be used in other studies if you agree to this. You will mark your 
decision at the end of this 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 sell my samples and information? No, but the HVTN 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. 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 HVTN or 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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 110 of 132 
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.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, 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 contribute to this study.  
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. 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. 
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. 
17. We will do our best to protect your private information. 
Site: 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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 111 of 132 
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. 
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 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] 
Site: 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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 112 of 132 
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. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
Site: The text below may not be deleted or changed, per FDA requirement. It’s OK to 
remove the box around it. 
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. 
18. We may stop your IV infusions 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 IV infusions.  
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 infusions, we may ask you to stay in the study to complete other 
study procedures. 
19. We will stop your IV infusions and most sample collections 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 113 of 132 
20. If you get infected with HIV during the study, we will stop your infusions and 
most sample collections, and we will help you get care and support. 
We will encourage you to stay in the study for up to 16 weeks if you choose. We 
will discuss your study options with you. 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.  
Other Risks 
21. 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:  
In this study, we will do some routine medical procedures. These are taking blood 
from you. These procedures can cause bruising, pain, fainting, soreness, redness, 
swelling, itching, a sore, bleeding, blood clot, and (rarely) muscle damage or 
infection where the needle was inserted. Taking 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. 
Risks of taking rectal and genital fluids and tissues: 
We will ask you to stop some activities before and after we collect these samples. 
You may find this inconvenient. These sample collections may cause some 
anxiety, temporary discomfort, and embarrassment. We will try to make you as 
comfortable as possible. 
All biopsies may cause a small amount of bleeding, which usually stops on its 
own. In rare cases, excess bleeding or infection may occur from a biopsy. If you 
need care, we will tell you about the care we can give you here. We will also tell 
you about care we can help you get elsewhere. 
Until the areas where the biopsies were taken heal, you may be at increased risk 
for HIV or other sexually transmitted infection (STI) infection if you are exposed. 
Most people heal within 5 to 14 days, but some may take longer. 
Personal problems/discrimination/testing HIV antibody positive: 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 114 of 132 
Some people who join HVTN 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 have used 
several common HIV antibody tests to test samples of blood containing different 
amounts of the study antibody. Very high VRC07-523LS levels in the blood can 
cause positive or uncertain results on a few brands of HIV tests. Such high levels 
might exist for a short time after a person gets the study antibody. This means that 
for a few days after getting the antibody, certain HIV tests might say a person is 
infected with HIV when they really aren’t. 
For this reason, 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:  
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.  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 115 of 132 
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 
22. The study may not benefit you. 
We do not know whether getting the study antibody might 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.  
This study may help in the search for a vaccine to prevent HIV. However, if the 
study antibody or a vaccine later becomes approved and sold, there are no plans to 
share any money with you.  
Your rights and responsibilities 
23. 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 
24. 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.  

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 116 of 132 
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 
25. 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 has 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. 
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  
26. 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]. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 117 of 132 
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 this section if using a separate consent for use of samples and 
information in other studies 
27. In Section 16 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 keep track of your decision 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, 
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.  
 
28. 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. 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 118 of 132 
 
 
 
 
 
 
 
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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 119 of 132 
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 can remove the box around the text. 
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 21 days prior to enrollment through 
the last required protocol 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 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(s) assigned female sex at birth; 
• You only have oral sex; or, 
• You are sexually abstinent (no sex at all). 
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 product infusion. 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 120 of 132 
Appendix C 
Sample consent form for use of samples and 
information in other studies 
A phase 1 clinical trial to evaluate the safety and pharmacokinetics of VRC-
HIVMAB075-00-AB (VRC07-523LS) in the sera and mucosae of healthy, HIV-
1–uninfected adult participants 
Protocol number: HVTN 128 
Site: [Insert site name] 
When samples are no longer needed for this study, the study sponsors want to use 
them in other studies and share them with other researchers. These samples are 
called “extra samples”. The HVTN will only allow your extra samples to be used 
in other studies if you agree to this. You will mark your decision at the end of this 
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. [Site: 
choose one of the following two sentences. African sites should choose the 
sentence referencing the repository in South Africa. All other sites should choose 
the sentence referencing the repository in the United States.] Your samples will 
be stored in the HVTN repository in South Africa. 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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 121 of 132 
6. Will the HVTN sell my samples and information?  
No, but the HVTN 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. 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 HVTN or 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, vaccines, 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. 
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 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 122 of 132 
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.  
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]. 
If you have questions about your rights as a research participant, contact 
[name or title and telephone number of person on IRB/EC . 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 123 of 132 
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 keeps 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, 
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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 124 of 132 
Appendix D 
Table of procedures (for sample informed 
consent form) 
 
 
 
Time after first IV visit 
Procedure 
Screenin
g 
visit 
Enrollme
nt visit 
14 days 
First  
infusio
n visit 
2 
weeks 
4 
months 
4.5 
months 
8 
months 
8.5 
months 
48 
weeks 
50 
weeks 
Infusion 
 
 
√ 
 
√ 
 
√ 
 
 
 
Cervical fluid, rectal 
fluid, and semen 
samples  
 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
 
Cervical, vaginal, and 
rectal tissue samples1 
 
√ 
 
√ 
 
 
 
√ 
√ 
 
Genital and rectal  
infection testing 
√ 
 
 
√ 
 
 
 
√ 
√ 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
√ 
 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
Urine test 
√ 
 
 
√ 
 
√ 
 
√ 
 
 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Pregnancy test 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
HIV testing and  
pretest counseling 
√ 
 
 
 
√ 
 
√ 
 
√ 
 
Risk reduction 
counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Interview/questionnai
re 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Pap smear (if needed) 
√ 
 
 
 
 
 
 
 
 
 
Safety contact 
 
 
 
 
 
 
 
 
 
√ 
1At each tissue sample visit, 2 samples will be taken from each location. 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 125 of 132 
Appendix E 
Laboratory procedures 
 
 
 
 
 
 
Visit:
1
2
3
4
5
6
7
8
9
1020
Day:
D-14
D0
D14
D112
D126 D224
D238 D336 D350
Week:
W-2
W0
W2
W16
W18
W32
W34
W48
W50
Procedure
Ship to1, 2
Assay location1, 2
Tube 
Type4
Tube size
(vol. 
capacity)4
Inf #1
Inf #2
Inf #3
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
5
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
5
HIV diagnostics 7
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
10
—
10
—
20
—
40
Safety Labs
CBC/ Diff / Platelets 19
Local lab
Local lab
EDTA
5mL
5
—
—
5
—
5
—
5
—
—
20
Chemistry panel5, 19
Local lab
Local lab
SST
5mL
5
—
—
5
—
5
—
5
—
—
20
Hormone Levels
Hormone panel15
Local lab
Local lab
SST
8.5mL
—
8.5
—
8.5
8.5
8.5
8.5
8.5
8.5
—
59.5
STI Serology
Syphilis8
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
5
Drug Levels/Detection
VRC07-523LS Ab levels
CSR
HVTN Labs / VITL
SST
8.5mL
—
y
—
y
y
y
y
y
y
—
0
Anti-Drug Antibody (ADA)
ADA detection assays
CSR
HVTN Labs / VITL
SST
8.5mL
—
y
—
—
y
—
y
—
y
—
0
ADA functional 
neutralization 
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
y
—
y
—
y
—
0
mAb Reaction Labs
Tryptase / C3 and C4 
complement / Cytokines
CSR
ARUP
SST
8.5mL
—
—
—
0
ADA detection assays
CSR
HVTN Labs / VITL
SST
8.5mL
—
—
—
0
ADA functional 
neutralization 
CSR
HVTN Labs
SST
8.5mL
—
—
—
0
STORAGE
Serum storage
CSR
—
SST
8.5mL
—
76.5
17
51
51
51
51
51
51
—
399.5
Visit total
25
95
17
79.5
69.5
69.5
69.5
79.5
89.5
0
594
56-Day total18
 
25
120
137
216.5
69.5
139
69.5
149
89.5
89.5
URINE COLLECTION
Urine dipstick14
Local lab
Local lab
X
—
—
X
—
X
—
X
—
—
Pregnancy Test6
Local lab
Local lab
X
X
X
X
X
X
X
X
X
—
Chlamydia/Gonorrhea9
Local lab
Local lab
X
—
—
X
—
—
—
X
X
—
RECTAL SWAB COLLECTION
Chlamydia/Gonorrhea9
Local lab
Local lab
X
—
—
X
—
—
—
X
X
—
CERVICAL/VAGINAL SWAB COLLECTION
Chlamydia/Gonorrhea9
Local lab
Local lab
X
—
—
X
—
—
—
X
X
—
Trichomonas vaginalis 10
Local lab
Local lab
X
—
—
—
—
—
—
—
—
—
Bacterial vaginosis 11
Local lab
Local lab
X
—
—
X
—
—
—
X
X
—
Yeast12
Local lab
Local lab
—
—
—
—
—
—
—
—
—
—
MUCOSAL BIOPSY COLLECTION13
Colorectal
Total Biopsies
VRC07-523LS Ab levels
CSR
HVTN Labs / VITL
—
2
—
2
—
—
—
2
2
—
0
2
0
2
0
0
0
2
2
0
8
Cervical
VRC07-523LS Ab levels
CSR
HVTN Labs / VITL
—
2
—
2
—
—
—
2
2
—
0
2
0
2
0
0
0
2
2
0
8
Vaginal
VRC07-523LS Ab levels
CSR
HVTN Labs / VITL
—
2
—
2
—
—
—
2
2
—
0
2
0
2
0
0
0
2
2
0
8
MUCOSAL SECRETION COLLECTION13
Semen
CSR
HVTN Labs / VITL
—
X
—
X
X
X
X
X
X
—
Cervicovaginal Secretions
CSR
HVTN Labs / VITL
—
X
—
X
X
X
X
X
X
—
Rectal Secretions
CSR
HVTN Labs / VITL
—
X
—
X
X
X
X
X
X
—
Visit total vaginal biopsies16
Screening 
visit3
Total
Visit total colorectal biopsies16
Visit total cervical biopsies16
See footnote 17
See footnote y
See footnote y

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 126 of 132 
Footnotes 
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), Dartmouth College (Hanover, New Hampshire, USA). 
Non-HVTN laboratories: VITL = Vaccine Research Center - Immunology Testing Laboratory (Gaithersburg, Maryland, USA), ARUP 
Laboratories (Salt Lake City, Utah, USA). 
3 Screening may occur over the course of several contacts/visits up to and including day 14 prior to biopsy collection.  
4 Local labs may assign appropriate alternative tube types for locally performed tests. 
5 Chemistry panels are defined in Section 9.2 (pre-enrollment). 
6 For a participant who was born female (ie, assigned female sex at birth), pregnancy test must be performed on urine or blood 
specimens on the day of study product infusion with negative results received prior to infusion.  
 A pregnancy test must be performed and confirmed negative prior to biopsy sampling and rectal secretion sampling. For 
cervicovaginal secretion sampling, a pregnancy test must be done on the same day but can be performed prior to or after sampling. 
7 At an early termination visit for a withdrawn or terminated participant (see Section 7.3.4), blood should be drawn for HIV diagnostic 
testing, as shown for visit 9 above. If the terminated participant is HIV-infected, do not collect blood for HIV diagnostic testing. 
8 Syphilis testing will be done by serology.  
9 In males, chlamydia/gonorrhea testing will be done with both rectal swabs and urine. In females, chlamydia/gonorrhea testing will 
be done with rectal swabs, and with urine or vaginal swabs. Testing will occur at indicated visits and when clinically indicated. 
10 Trichomonas testing will be done with cervical/vaginal swabs or urine; testing will occur at screening and when clinically 
indicated.  
11 Bacterial vaginosis testing will be done with cervical/vaginal swabs; testing will occur at the indicated visits and when clinically 
indicated.  
12 Cervical/vaginal swabs will be collected from females for yeast only when clinically indicated. 
13 Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria 
specified in the HVTN 128 SSP. 
14 And microscopy if needed. 
15 Hormone panel is defined in Sections 9.3 (enrollment visits) and 9.5 (follow-up visits). 
16 The visit total indicates the total number of colorectal, cervical, or vaginal biopsies collected per visit. 
17 SST blood will be collected at specific timepoints after the onset of any mAb reaction. Refer to the HVTN 128 SSP for more 
information. 
18 The 56-day total blood volume includes 10mL maximum blood loss per biopsy collection visit. It does not include up to 51mL SST 
blood collected for any mAb reaction; however, the 56-day limit is not exceeded at any visit by the possible collection of SST blood 
for a mAb reaction. 
19 For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, 
urinalysis, and pregnancy tests (ie, CBC/Diff/Platelets and Chemistry Panel) will be collected. 
20 For information concerning the visit 10 safety contact, see Section 11.2.2.  
y = SST blood collected for serum storage will also cover specimen needs for VRC07-523LS drug levels/detection, and ADA 
detection and functional neutralization assays (including for any mAb reactions); no separate blood draw is needed. 
 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 127 of 132 
Appendix F 
Procedures at HVTN CRS 
 
 
011 
02 
03 
04 
05 
06 
07 
08 
09 
10 
Day: 
 
D 14 
D0 
D14 
D112 
D126 
D224 
D238 
D336 
D350 
Week: 
 
W 2 
W0 
W2 
W16 
W18 
W32 
W34 
W48 
W50 
Procedure 
Scr 
Enr 
Inf 1 
 
Inf 2 
 
Inf 3 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
X 
 
Confirm eligibility and obtain demographics 
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Randomize  
— 
X 
— 
— 
— 
— 
— 
— 
— 
 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
X 
— 
 
Risk reduction counseling16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pregnancy prevention assessment2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Behavioral risk assessment questionnaire18 
X 
— 
— 
— 
X 
— 
X 
— 
X 
 
Social impact assessment 
— 
X 
X 
X 
X 
X 
X 
X 
X 
 
Social impact assessment questionnaire 
— 
— 
— 
— 
X 
— 
X 
— 
X 
 
Mucosal sampling acceptability questionnaire 
— 
— 
X 
— 
— 
X 
— 
— 
X 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Intercurrent illness/Unsolicited AEs 
— 
X 
X 
X 
X 
X 
X 
X 
X 
 
AESI 
— 
— 
— 
X 
— 
X 
— 
X 
— 
 
HIV infection assessment3, 18 
X 
— 
— 
— 
X 
— 
X 
— 
X 
 
Confirm HIV test results provided to participant18 
— 
X 
— 
— 
— 
X 
— 
X 
— 
X 
Safety contact15 
 
 
 
 
 
 
 
 
 
X 
Study product administration18 
 
 
 
 
 
 
 
 
 
 
Infusion4 
— 
— 
X 
— 
X 
— 
X 
— 
— 
 
Solicited AE assessment5 
— 
— 
X 
— 
X 
— 
X 
— 
— 
 
Local lab assessments17, 18 
 
 
 
 
 
 
 
 
 
 
Screening HIV test 
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Hepatitis B, Hepatitis C 
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Syphilis 
X 
 
 
 
 
 
 
 
 
 
Hormone panel 
— 
X 
— 
X 
X 
X 
X 
X 
X 
 
Pap smear6 
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Safety labs 
 
 
 
 
 
 
 
 
 
 
CBC, differential 
X 
— 
— 
X 
— 
X 
— 
X 
— 
 
Chemistry panel7 
X 
— 
— 
X 
— 
X 
— 
X 
— 
 
Urine collection 
 
 
 
 
 
 
 
 
 
 
Urine dipstick8 
X 
— 
— 
X 
— 
X 
— 
X 
— 
 
Pregnancy (urine or serum HCG)9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Chlamydia/Gonorrhea10, 18,  
X 
— 
— 
X 
— 
— 
— 
X 
X 
 
Rectal swab collection 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Gonorrhea10, 18,  
X 
— 
— 
X 
— 
— 
— 
X 
X 
 
Cervical/vaginal swab collection 18 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Gonorrhea10,  
X 
— 
— 
X 
— 
— 
— 
X 
X 
 
Trichomonas vaginalis 11 
X 
— 
— 
— 
— 
— 
— 
— 
— 
 
Bacterial vaginosis12,  
X 
— 
— 
X 
— 
— 
— 
X 
X 
 
Yeast13 
— 
— 
— 
— 
— 
— 
— 
— 
— 
 
Mucosal biopsy collection14, 18 
 
 
 
 
 
 
 
 
 
 
Colorectal biopsy 
— 
X 
— 
X 
— 
— 
— 
X 
X 
 
Cervical biopsy 
— 
X 
— 
X 
— 
— 
— 
X 
X 
 
Vaginal biopsy 
— 
X 
— 
X 
— 
— 
— 
X 
X 
 
Mucosal secretion collection14, 18 
 
 
 
 
 
 
 
 
 
 
Semen 
— 
X 
— 
X 
X 
X 
X 
X 
X 
 
Cervicovaginal secretions 
— 
X 
— 
X 
X 
X 
X 
X 
X 
 
Rectal secretions 
— 
X 
— 
X 
X 
X 
X 
X 
X 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 128 of 132 
1 Screening may occur over the course of several contacts/visits up to and including day 14 prior to enrollment biopsy 
collection. 
2 Pregnancy prevention (contraception) assessment is required only for participants who were assigned female sex 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. 
3 Includes pretest counseling and HIV testing. A subsequent follow-up contact is conducted to provide post-test counseling 
and to report results to participant. 
4 Specimen collection required at study product administration visits 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. 
5 Solicited AE assessments performed daily for at least 3 days following study product administration (see Section 9.10). 
6 Only for volunteers who were assigned female sex at birth, per Sections 7.1 and 9.6. If collection of a pap smear is 
required, this may be done at any time provided the results are available prior to the collection of cervical samples. 
7 Chemistry panels are defined in Section 9.2. 
8 And microscopy if needed. 
9 For a participant who was born female (ie, assigned female sex at birth), pregnancy test must be performed on urine or 
blood specimens on the day of study product infusion with negative results received prior to infusion. A pregnancy test 
must be performed and confirmed negative prior to biopsy sampling and rectal secretion sampling. For cervicovaginal 
secretion sampling, a pregnancy test must be done on the same day but can be performed prior to or after sampling. 
10 Chlamydia/Gonorrhea testing will be done with both rectal swabs and urine in males, and with urine and/or vaginal and 
rectal swabs in females; testing will occur at indicated visits and when clinically indicated. 
11 Trichomonas vaginalis testing will be done with cervical/vaginal swabs or urine; testing will occur at the indicated visits 
and when clinically indicated. 
12 Bacterial vaginosis testing will be done with cervical/vaginal swabs; testing will occur at the indicated visits and when 
clinically indicated. 
13 Cervical/vaginal swabs will be collected from females for yeast only when clinically indicated. 
14 Mucosal specimens will be collected once the participant has been found to have met mucosal specimen collection criteria 
specified in the HVTN 128 SSP. Mucosal biopsy collections must be at least 28 days from the previous biopsy collection.  
15 This contact can be done by email, text, or telephone call. 
16 Includes transmission risk reduction counseling for HIV-infected participants. 
17 For participants with confirmed diagnosis of HIV infection, only specimens required for scheduled “Safety labs” will be 
drawn (see Appendix E). 
18 Not applicable to HIV-infected participants. 
 
 
 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 129 of 132 
Appendix G 
HVTN low risk guidelines for the US 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 130 of 132 
 

HVTN 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 131 of 132 
Appendix H 
Adverse events of special interest (AESI) 
AEs of special interest (AESI) for this protocol include those listed below. 
•  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 128 Version 1.0 / September 18, 2018 
HVTN128_v1.0_FINAL / Page 132 of 132 
Appendix I 
Protocol Signature Page 
 
A phase 1 clinical trial to evaluate the safety and pharmacokinetics of VRC-
HIVMAB075-00-AB (VRC07-523LS) in the sera and mucosae of healthy, HIV-
1–uninfected adult participants 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (US) Health and Human Service regulations (45 
CFR 46); applicable U.S. Food and Drug Administration regulations; standards of 
the International Conference on Harmonization Guideline for Good Clinical 
Practice (E6); Institutional Review Board/Ethics Committee determinations; all 
applicable in-country, state, and local laws and regulations; and other applicable 
requirements (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 128 
DAIDS Protocol Version: Version 1.0 
Protocol Date: September 18, 2018