A Phase 1 Double-blind, Randomized, Controlled Clinical Trial in Healthy, HIV-1-Uninfected Adult Participants to Compare the Safety, Tolerability and Immunogenicity of CH505TF gp120 Produced From Stably Transfected Cells to CH505TF gp120 Produced From Transiently Transfected Cells
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

PROTOCOL 
HVTN 123 
A phase 1 double-blind, randomized, controlled clinical 
trial in healthy, HIV-1–uninfected adult participants to 
compare the safety, tolerability and immunogenicity of 
CH505TF gp120 produced from stably transfected cells 
to CH505TF gp120 produced from transiently 
transfected cells 
DAIDS DOCUMENT ID 34569 
IND 017488 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 PRODUCTS PROVIDED BY 
DAIDS, NIAID, NIH, DHHS 
Bethesda, Maryland, USA 
December 12, 2018 
Final 
HVTN 123, Version 1.0 

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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 
Stable CH505TF gp120 ................................................................................15 
4.3 
Transient CH505TF gp120 ...........................................................................15 
4.4 
Biochemical and biophysical equivalency of Stable and Transient CH505TF 
gp120 ............................................................................................................16 
4.5 
Trial design rationale ....................................................................................20 
4.6 
Plans for future product development and testing ........................................21 
4.7 
Preclinical safety study .................................................................................22 
4.8 
Preclinical immunogenicity studies .............................................................23 
4.9 
Clinical studies .............................................................................................31 
4.10 Potential risks of study products and administration ...................................36 
5 Objectives and endpoints .............................................................................................37 
5.1 
Primary objectives and endpoints ................................................................37 
5.2 
Secondary objectives and endpoints ............................................................37 
5.3 
Exploratory objectives ..................................................................................39 
6 Statistical considerations ..............................................................................................40 
6.1 
Accrual and sample size calculations ...........................................................40 
6.2 
Randomization .............................................................................................42 
6.3 
Blinding ........................................................................................................42 
6.4 
Statistical analyses ........................................................................................42 
7 Selection and withdrawal of participants .....................................................................47 
7.1 
Inclusion criteria ...........................................................................................47 
7.2 
Exclusion criteria ..........................................................................................50 
7.3 
Participant departure from vaccination schedule or withdrawal ..................53 
8 Study product preparation and administration .............................................................56 
8.1 
Vaccine regimen ...........................................................................................56 
8.2 
Study product formulation ...........................................................................56 
8.3 
Preparation of study products .......................................................................57 
8.4 
Administration ..............................................................................................58 
8.5 
Acquisition of study products ......................................................................59 
8.6 
Pharmacy records .........................................................................................59 
8.7 
Final disposition of study products ..............................................................59 

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9 Clinical procedures ......................................................................................................61 
9.1 
Informed consent ..........................................................................................61 
9.2 
Pre-enrollment procedures ...........................................................................63 
9.3 
Enrollment and vaccination visits ................................................................64 
9.4 
Follow-up visits ............................................................................................66 
9.5 
AESI health contact ......................................................................................67 
9.6 
HIV counseling and testing ..........................................................................68 
9.7 
Contraception status .....................................................................................70 
9.8 
Urinalysis .....................................................................................................70 
9.9 
Assessments of reactogenicity .....................................................................70 
9.10 Visit windows and missed visits ..................................................................72 
9.11 Early termination visit ..................................................................................72 
9.12 Pregnancy .....................................................................................................72 
9.13 HIV infection during the study .....................................................................72 
10 Laboratory ....................................................................................................................74 
10.1 HVTN CRS laboratory procedures ..............................................................74 
10.2 Total blood volume ......................................................................................74 
10.3 Immunogenicity timepoints ..........................................................................74 
10.4 Endpoint assays: cellular ..............................................................................75 
10.5 Endpoint assays: humoral .............................................................................75 
10.6 Genotyping ...................................................................................................76 
10.7 Lab assay algorithm .....................................................................................76 
10.8 Exploratory studies .......................................................................................76 
10.9 Specimen storage and other use of specimens .............................................76 
10.10 Biohazard containment .................................................................................77 
11 Safety monitoring and safety review ...........................................................................78 
11.1 Safety monitoring and oversight ..................................................................78 
11.2 Safety reporting ............................................................................................79 
11.3 Safety pause and prompt PSRT AE review..................................................82 
11.4 Review of cumulative safety data ................................................................83 
11.5 Study termination .........................................................................................83 
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 .............................................................................................................93 
Appendix A Sample informed consent form ....................................................................98 
Appendix B Approved birth control methods (for sample informed consent form) ......117 
Appendix C Sample consent form for use of samples and information in other studies 118 
Appendix D Table of procedures (for sample informed consent form) ..........................122 

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Appendix E Laboratory procedures (1of 2) ....................................................................123 
Appendix F Procedures at HVTN CRS ..........................................................................125 
Appendix G Procedures at CRS for health contact .........................................................127 
Appendix H Adverse events of special interest ..............................................................128 
Appendix I HVTN low risk guidelines for the US ........................................................129 
Appendix J Protocol Signature Page .............................................................................131 
 

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1 
Ethical considerations 
Multiple candidate HIV vaccines will need to be studied simultaneously in 
different populations around the world before a successful HIV preventive 
vaccine is found. It is critical that universally accepted ethical guidelines are 
followed at all sites involved in the conduct of these 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 a preventive vaccine, 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 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 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.  

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• HVTN trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
• 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. 

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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 postvaccination and 
collecting information regarding side effects for several days postvaccination; (d) 
having staff properly trained in administering study procedures that may cause 
physical harm or psychological distress, such as blood draws, vaccinations, HIV 
testing and counseling and HIV risk reduction counseling; (e) providing HIV risk 
reduction counseling and checking on contraception use (for persons assigned 
female at birth); and (f) providing safety monitoring. 
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.  

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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 11). Safety is 
monitored daily by HVTN Core and routinely by the HVTN 123 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 

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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 National Institutes of Health (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. 

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3 
Overview 
Title  
A phase 1 double-blind, randomized, controlled clinical trial in healthy, HIV-1–
uninfected adult participants to compare the safety, tolerability and 
immunogenicity of CH505TF gp120 produced from stably transfected cells to 
CH505TF gp120 produced from transiently transfected cells 
Primary objective(s) 
• To evaluate and compare the safety and tolerability of the CH505TF gp120 
proteins produced by transient and stable transfection in HIV-1–uninfected, 
healthy adults 
• To evaluate and compare the magnitude of binding antibody responses elicited 
by the CH505 TF gp120 proteins produced via transient and stable 
transfection methods 
Study products and routes of administration 
• Stable: CH505TF gp120 developed via upstream stable transfection of CHO-
DG44 cell line, mixed with GLA-SE (glucopyranosyl lipid A in a stable 
emulsion [oil-in-water emulsion containing squalene]) 
• Transient: CH505TF gp120 developed via upstream transient transfection of 
CHO-S cell line, mixed with GLA-SE 
Table 3-1 Schema 
Notes 
GLA-SE will be admixed with all proteins. The total dose of GLA-SE will be 10 
mcg at all timepoints. The total volume for protein plus adjuvant for injection is 1 
mL, mixed 1:1 by volume. All injections will be administered intramuscularly 
(IM) by needle and syringe. 
Study arm 
n 
 
Month 0 
Month 2 
Month 6 
Group 1 
15 
 
100 mcg 
CH505TF gp120 
Stable 
 
100 mcg 
CH505TF gp120 
Stable 
100 mcg 
CH505TF gp120 
Stable 
Group 2 
15 
 
100 mcg 
CH505TF gp120 
Transient 
100 mcg 
CH505TF gp120 
Transient 
100 mcg 
CH505TF gp120 
Transient 
Total 
30 
 
 
 
 

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Participants 
30 healthy, HIV-1–uninfected volunteers aged 18 to 50 years 
Design 
Multicenter, randomized, controlled, double-blind trial 
Duration per participant 
12 months of scheduled clinic visits (main study) followed by an Adverse Events 
of Special Interest (AESI) health contact at month 18 
Estimated total study duration 
21 months (includes enrollment, follow-up, and AESI health contact) 
Investigational New Drug (IND) sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
Study product providers 
• Stable CH505TF gp120: DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, 
USA) 
• Transient CH505TF gp120: DAIDS, NIAID, NIH, DHHS (Bethesda, 
Maryland, USA) 
• GLA-SE adjuvant: DAIDS, 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) 

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• Fred Hutch/University of Washington (Seattle, Washington, USA) 
Study sites 
HVTN Clinical Research Sites (HVTN CRSs) to be specified in the Site 
Announcement Memo 
Safety monitoring 
HVTN 123 PSRT; HVTN SMB 

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3.1 
Protocol Team 
Protocol leadership 
Chair 
Greg Wilson 
Vanderbilt Medical Center 
615-343-5731 
greg.wilson@vumc.org 
Statistician 
Youyi Fong 
SCHARP, Fred Hutch 
206-667-1093 
yfong@fredhutch.org 
Co-chair 
Colleen Kelley 
Emory University 
404-712-1435 
colleen.kelley@emory.edu 
Medical 
officer 
Maggie Brewinski Isaacs 
DAIDS, NIAID 
301-761-7009 
maggie.brewinskiisaacs 
@nih.gov 
Protocol Team 
leader 
Cecilia Morgan 
HVTN Core, Fred Hutch 
206-667-5875 
cmorgan@fredhutch.org 
Laboratory 
lead 
David Montefiori 
HVTN Laboratory Program 
919-684-5278 
monte@duke.edu 
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 
Tony Moody 
Duke University 
Clinical trials 
manager 
Julie Hunt 
HVTN Core, Fred 
Hutch 
 
Zachary Sagawa 
IDRI 
Statistical research 
associate 
Yiwen Lu 
SCHARP, Fred Hutch 
DAIDS protocol 
pharmacist 
Katherine Shin 
DAIDS, NIAID 
240-627-3047 
SDMC Associate 
director of lab science 
April Randhawa 
SCHARP, Fred Hutch 
Laboratory protocol 
operations manager 
On Ho 
HVTN Laboratory 
Program, Fred Hutch 
Clinical data manager 
Kris Donaty 
SCHARP, Fred Hutch 
Regulatory affairs 
associate 
Meg Brandon 
HVTN Core, Fred Hutch 
Senior clinical data 
manager 
Gina Escamilla 
SCHARP, Fred Hutch 
Clinic coordinator 
Shonda Sumner 
Vanderbilt CRS 
DAIDS Project 
Officers 
Chris Butler 
DAIDS, NIAID 
Community Advisory 
Board (CAB) members 
David Long 
Vanderbilt CRS 
 
Nandini Sane 
DAIDS, NIAID 
 
Jemal Shelton-Thompson 
Atlanta Hope Clinic CRS 
Protocol development 
manager 
Meg Trahey 
HVTN Core, Fred 
Hutch 
Community engagement 
unit representative 
Stephaun Wallace 
HVTN Core, Fred Hutch 
Technical editor 
Richa Chaturvedi 
HVTN Core, Fred 
Hutch 
Community 
educator/recruiter 
Vic Sorrell 
Vanderbilt CRS 
 
 
 

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4 
Background 
4.1 
Rationale for trial concept 
An effective vaccine against HIV-1 infection remains an elusive goal (4) and will 
likely need to induce robust humoral and cellular immune responses in order to 
both reduce acquisition and control postinfection viremia (5, 6). To date, only 
four vaccine concepts have been tested in field trials (7-12) and only one vaccine 
regimen has shown efficacy in preventing HIV-1 infection (12). In RV144, an 
ALVAC env/gag/PR prime at 0, 1, 3, 6 months with an AIDSVAX B/E gp120 
Env boost at 3 and 6 months was found to have modest overall vaccine efficacy of 
31% in the modified intention-to-treat cohort (12). Subsequent detailed analyses 
of potential correlates of protection and risk found that Env-specific binding IgG 
antibodies directed against the V1V2 region were found to positively correlate 
with protection (13), although protection peaked soon after vaccination and then 
waned over several years (14). 
The successful use of a protein boost following a heterologous priming vaccine in 
RV144 has renewed interest in development of Env proteins as a component of 
future HIV-1 vaccine regimens. However, the field has been hampered by 
difficulties in manufacturing Env proteins, as well as uncertainty in the choice of 
immunogens (15). It is, therefore, quite likely that multiple different Env proteins 
will need to be tested in an iterative fashion, potentially both alone and as part of 
prime-boost combinations (16). 
Furthermore, designing a vaccine regimen which can lead to induction of broadly 
neutralizing antibodies (bnAbs) has been a significant challenge for the field (17-
19). Results thus far have mostly been limited to activity against easily-
neutralized Tier 1 viruses (for example, HVTN 073E (20) and HVTN 083(21)) 
although some activity against more representative Tier 2 viruses was seen in 
HVTN 205 (22). Amongst the reasons why eliciting bnAbs has proven such a 
challenge include the trimeric conformational structure of Env, molecular 
mimicry of host antigens by conserved viral epitopes, as well as the atypical B 
cell maturation pathways and complex somatic mutations in immunoglobulin 
variable domains which may be required (23-26). If frequent and sequential 
immunization with serial Env proteins is necessary to direct B cell somatic 
mutation toward bnAb production in a step-wise fashion (27, 28), a hypothesis 
being tested in HVTN 115, then a very large number of Env proteins will need to 
be synthesized and tested in phase 1 studies in the near future. 
One approach to shortening the product development timeline could be the use of 
transiently transfected cell lines (29) to produce Env proteins (30). In contrast 
with the current practice of developing stably transfected cell lines in order to 
produce sufficient quantities of clinical-grade product (31), use of transiently 
transfected cell lines could reduce the time required by at least several months 
(32). This would allow novel immunogens to enter phase 1 testing more quickly, 
thereby enabling faster iterative testing of more prime-boost regimens in order to 

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choose candidate regimens for efficacy trials (16). First, however, we propose that 
Env proteins produced by transiently transfected cell lines be tested in vivo to 
demonstrate that they have comparable safety and immunogenicity to Env 
proteins produced by stably transfected cell lines.  
This study will use a clade C HIV-1 gp120 envelope protein (CH505TF gp120) 
adjuvanted with GLA-SE as the immunogen. This protein, produced via stably 
transfected cells, with GLA-SE, is also being tested in HVTN 115 (see Section 
4.9.1). CH505TF gp120 produced by transient transfection has not yet been tested 
in a clinical trial, and therefore, this will serve as the first-in-human study for the 
protein produced by this method. The use of a gp120 Env has several potential 
advantages: 1) immunogenicity is related to binding affinity to B-cell receptors 
(BCRs) on the responding B cells (33, 34); 2) gp120 Env binds with high affinity 
to the germline unmutated common ancestor (UCA) antibody of the CH103-like 
bnAb lineage and binds with high affinities to other bnAb lineage intermediates; 
and 3) the exclusion of gp41 avoids stimulating non-neutralizing antibody 
responses to gp41 epitopes. This trial will allow direct comparison of an Env 
protein produced by two different methodologies and has the potential to greatly 
accelerate HIV-1 vaccine development. 
4.2 
Stable CH505TF gp120 
The Duke Human Vaccine Institute (DHVI) developed the transmitted/founder 
CH505 Env (CH505TF gp120) vaccine in collaboration with NIAID as part of the 
B cell lineage approach to develop bnAbs (27, 28). CH505TF gp120 is a 
recombinant HIV-1 gp120 clade C Env protein with an N-terminal deletion that 
facilitates production by decreasing protein dimer formation and increasing 
production yield (35). This envelope sequence was derived from an African clade 
C transmitted founder virus CH505-infected individual (36). The Stable 
CH505TF gp120 was produced via stable transfection of a CHO-DG44 cell line 
and is also being tested in HVTN 115 (see Section 4.9.1). The Stable CH505TF 
gp120 will be mixed with GLA-SE (glucopyranosyl lipid A in a stable emulsion 
[oil-in-water emulsion containing squalene]) manufactured by the Infectious 
Disease Research Institute (IDRI). 
4.3 
Transient CH505TF gp120 
The Transient CH505TF gp120 amino acid (aa) sequence is identical to the Stable 
CH505TF gp120. Transient transfection was achieved by electroporation with 
post-transfection scale up of suspension cultures to a bioreactor. CHO-DG44 cells 
did not recover from the transient transfection procedure as well as CHO-S cells; 
therefore, CHO-S cells were chosen to produce the Transient gp120. The 
purification process was similar to the stably expressed protein. As with the 
Stable CH505TF, the Transient CH505TF gp120 will be mixed with GLA-SE 
manufactured by IDRI. 

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4.4 
Biochemical and biophysical equivalency of Stable and Transient 
CH505TF gp120 
Bulk drug substance (BDS) batches of both Stable and Transient CH505TF gp120 
proteins produced from CHO cells were purified by KBI Biopharma using 
multimodal and ion-exchange chromatography. The two products were compared 
by a series of biochemical and biophysical assays. Both forms (stable and 
transient) of CH505TF gp120 were monomeric by size exclusion chromatography 
(SEC) analysis (Figure 4-1) and showed similar migration on SDS-PAGE that 
was consistent with that of a 120kDa protein band (Figure 4-2). Neither form of 
CH505TF gp120 showed any detectable proteolytically cleaved fragment by 
SDS-PAGE under reducing or non-reducing conditions, and no clearly distinct 
fragment was detected by Western Blot analysis.  
 
Figure 4-1 Size exclusion chromatography (SEC) analysis on a Superdex S200 increase (GE 
Healthcare) column confirms monomeric gp120 proteins with elution volumes (Ve) of 12.01 
and 12.07 mL for transient and stable respectively. Both forms of gp120 proteins were about 
99% monomeric. 

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Figure 4-2 SDS-PAGE analysis of CH505TF gp120 produced by transient transfection and 
stable transfection. Western blots were developed using the gp120 monoclonal antibody 
16H3.Lane 1 = MW markers, Lane 2 = Purified BDS of CH505TF from transiently expressed CHO-
S cells, Lane 3 = Purified BDS of CH505TF from stable CHO-DG44 cell line. 
The monodispersity of the two protein forms was also assessed by dynamic light 
scattering (Figure 4-3), which showed a complete absence of dimer or higher 
order oligomers. Not unlike the stable line produced CH505TF gp120, the 
transiently produced CH505TF gp120 gave a differential scanning calorimetry 
(DSC) thermal melting profile (Figure 4-4) with two resolved transition Tm 
(melting temperature) peaks (Tm1/Tm2 = 57.2/64.0 and 57.4/64.8oC for transient 
and stable respectively), indicating that both forms of the proteins adopted a 
similar folded state.  
 
Figure 4-3 Dynamic light scattering analysis shows the absence of dimer or higher-order 
oligomers 
0
10
20
30
40
50
60
70
80
90
100
0.01
0.10
1.00
10.00
% Intensity
Radius(nm)
0
10
20
30
40
50
60
0.01
0.10
1.00
10.00
% Intensity
Radius(nm)
Radius(nm): 5.02
%Pd: 2.8
Mw-R(kDa): 147
Radius(nm): 4.72
%Pd: 4.6
Mw-R(kDa): 127
Transient
Stable

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Figure 4-4 Differential Scanning Calorimetry (DSC) shows a similar unfolding profile with 
similar on-set and Tm values for stable and transient CH505TF gp120. 
The antigenic signature of the transient gp120 was identical to its stable protein 
counterpart, with both gp120 proteins binding to each UCA, the intermediate IA3 
as well as to the mature CH106 monoclonal antibody (mAb) of the CD4 binding 
site (CD4-BS) bnAb lineage (data not shown). No difference was observed in the 
affinities of either UCA (Kd = 489.5 and 491.4 nM for transient and stable 
respectively) or CH106 (Kd = 9.7 and 9.7 nM for transient and stable respectively) 
binding to the two protein forms (Table 4-1). The relative proportion of bnAb 
CH106-reactive fraction present in both stable and transient preparations when 
measured by isothermal titration calorimetry (ITC) analysis (stoichiometry n 
values) was similar (~ 60% active) (Figure 4-5). The closeness in values of 
CH106 affinities and enthalpy changes (∆H) indicated that the binding of both the 
stable line produced and the transiently produced CH505TF gp120 follows a 
similar thermodynamic mechanism when binding to the CD4-BS bnAb. Thus, 
CH505TF gp120 produced by transient transfection was comparable to the 
CH505TF gp120 protein produced by stably transfected cells with respect to its 
biochemical/biophysical properties as well as its antigenicity for binding to 
CH013 lineage antibodies. 
Stable
Tonset
Tm1 = 57.4 ± 0.1 C
Tm2 = 64.8 ± 0.5 C
Transient
Tonset
Tm1 = 57.2 ± 0.1 C
Tm2 = 64.0 ± 1.2 C

HVTN 123, Version 1.0 / December 12, 2018 
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Table 4-1 Surface Plasmon Resonance (SPR) kinetic rates and dissociation constants (Kd) 
for binding of UCA and CH106 mAbs to CH505TF gp120 
CH505 gp120 
Unit 
CH103 UCA 
CH106 
Reference gp120*: 
CH505TF_D8gp120/293F 
Lot: 160226PPF 26Feb2016 
ka (M-1s-1) 
kd (s-1) 
Kd (nM) 
2.06±0.07 
102.02±5.18 
496.2±17.8 
0.87±0.07 
0.55±0.06 
6.3±0.2 
Transient gp120:16-144-0515 
Purified BDS of CH505TF 
from transiently expressed 
CHO-S cells 
Batch# 144D16-01 Lot: 162340 
ka (M-1s-1) 
kd (s-1) 
Kd (nM) 
2.08±0.05 
101.76±8.18 
489.5±28.0 
0.75±0.05 
0.75±0.06 
9.7±0.2 
Stable gp120:15-144-0406 
Purified BDS of CH505TF 
from stable cell line 
Batch# 144A15-02 Lot: 
150769 
ka (M-1s-1) 
kd (s-1) 
Kd (nM) 
2.06±0.17 
101.71±12.98 
491.4±31.8 
0.86±0.06 
0.83±0.07 
9.7±0.3 
*Reference CH505TF gp120 was produced in 293T cells and purified by lectin (GLN) affinity  
chromatography. 

HVTN 123, Version 1.0 / December 12, 2018 
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Figure 4-5 Isothermal titration calorimetry (ITC) analysis of CH106 binding to CH505TF 
gp120 show similar stoichiometry (n) and thermodynamic profile for stable versus 
transiently produced proteins. 
4.5 
Trial design rationale 
This is a double-blind, randomized clinical trial, which will compare the safety 
and immunogenicity of a CH505TF gp120 produced via stably transfected cell 
lines compared with production via transiently transfected cell line. Fifteen 
healthy, HIV-1–uninfected adults will be enrolled into each group, vaccinated at 
months 0, 2, and 6, and followed for a total of 12 months. The design of this 
comparative study is intended to allow rapid assessment of the comparability of 
the Env proteins in terms of safety, tolerability, and immunogenicity. It is likely 
that antibody responses to the Env proteins will peak after the 3rd injection given 
at month 6. Assessments of humoral immune responses are planned at early, peak, 
plateau, and late timepoints by analyzing binding to a panel of Env antigens using 
the binding antibody multiplex assay (BAMA). From an immunogenicity 
perspective, this study design will allow us to assess both magnitude and breadth 
of humoral immune responses as well as understand in detail the kinetics of the 
antibody responses. 

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The overarching goal of this study is to demonstrate whether immunization with 
Env protein produced by transiently transfected cells is as safe and immunogenic 
as immunization with Env produced by stably transfected cells. While past 
vaccine trials of Env proteins (Envs) have used Envs made by stable transfection, 
much of the early animal research is performed using Envs produced by transient 
transfection. Envs made by both approaches have been safe and immunogenic in 
animal studies, and are analytically similar (Section 4.4), but HIV Envs made by 
transient transfection have not yet been tested in clinical trials. By directly 
comparing CH505TF gp120 produced by transiently transfected cells with 
CH505TF gp120 produced by stably transfected cells this study has the potential 
to enable future clinical trials with novel Env immunogens to launch much faster. 
4.5.1 
Dose (amount and number) 
Both the CH505TF gp120 produced by transiently transfected cells and the 
CH505TF gp120 produced by stably transfected cells will be given at a fixed dose 
of 100 mcg per injection. In HVTN 115 Part A, the Stable CH505TF gp120 will 
be tested at 20 mcg, 100 mcg, and 400 mcg to determine the optimal dose for Part 
B. The 100 mcg dose of CH505TF gp120 was chosen for this study as it is likely 
to be in the linear range in terms of antibody responses. The TLR4 agonist GLA-
SE adjuvant will be admixed with all proteins. The total dose of GLA-SE will be 
10 mcg (lipid A) at all timepoints. The 10 mcg dose of GLA-SE was selected 
based upon preclinical studies demonstrating safety (rabbits) and immunogenicity 
(guinea pigs and rhesus macaques) of the Stable CH505TF gp120 + GLA-SE 
vaccine (see Sections 4.7 and 4.8) and the established safety profile of the GLA-
SE adjuvant in human clinical trials (see Section 4.9.2). Furthermore, the 10 mcg 
dose of GLA-SE is being used in HVTN 115 (see Section 4.9.1). All injections 
will be administered IM by needle and syringe. 
4.5.2 
Schedule 
Vaccinations will occur at months 0, 2, and 6. These immunization intervals were 
chosen based on prior studies with different Env proteins and are likely to lead to 
high peak antibody titers and high humoral response rates after the third 
vaccination. In previous trials with adjuvanted protein vaccines, peak 
immunogenicity has been observed after 3 doses of the protein, while a prolonged 
rest period between the 2nd and 3rd vaccinations is thought to enhance antibody 
maturation. 
4.6 
Plans for future product development and testing 
The Stable CH505TF gp120 vaccine is a component of the regimen being tested 
in HVTN 115, which represents the first clinical trial of administration of 
sequential Env proteins in an attempt to elicit CD4-binding site (CD4-BS) bnAbs. 
HVTN 115 is likely to be the first of a series of iterative clinical trials to optimize 
induction of bnAbs. The overarching goal of this study is to demonstrate whether 
Env protein production by transiently transfected cells is as safe and 

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HVTN123_v1-0_FINAL / Page 22 of 131 
immunogenic as production by stably transfected cells to enable future clinical 
trials with novel Env immunogens to launch much faster. 
4.7 
Preclinical safety study 
Table 4-2 Summary of preclinical safety study 
Study 
number 
Product 
Type of 
study 
Animal 
N/group 
Dose groups 
Route 
Schedule 
1726-
031 
Stable 
CH505TF 
Toxicity 
New 
Zealand 
White 
Rabbits 
10 M, 
10 F  
Group 1: saline 
control 
Group 2: CH505TF 
+ GLA-SE 
Group 3: DNA + 
CH505TF + GLA-
SE 
Group 4: GLA-SE 
IM 
Days 1, 
15, 29, 
43, 57, 
71, 85 
 
4.7.1 
Preclinical toxicology study of Stable CH505TF gp120 in rabbits  
A toxicity study with Stable CH505TF gp120 in New Zealand White (NZW) 
rabbits was conducted in compliance with Good Laboratory Practices (GLP). 
Seven biweekly IM injections of 400 mcg CH505TF gp120 with 20 mcg GLA-SE 
adjuvant coadministered with or without a 4 mg DNA, or 20 mcg GLA-SE alone, 
to NZW rabbits for 13 weeks were well tolerated. Test article-related changes in 
dermal scores, clinical pathology parameters, and microscopic injection site 
findings were resolved/partially resolved and/or trending toward recovery by the 
recovery necropsy, and none of the test article-related changes were deemed 
adverse. A more detailed description of the toxicity study can be found in the 
Investigator’s Brochure (IB). 
4.7.2 
Preclinical toxicology study of Transient CH505TF gp120  
Toxicity studies with Transient CH505TF gp120 Env have not been done. As the 
amino acid sequence is identical between the Transient and Stable CH505TF 
gp120 Env proteins, a significant difference in toxicity is not expected. 
In July 2017, a Briefing Package was sent to the FDA, in which results from 
release testing, biophysical and biochemical characterization, and antigenicity 
studies of Stable CH505TF and Transient CH505TF gp120 proteins were 
summarized. Results from these preclinical tests indicated that the two proteins 
were similar with respect to release testing and physicochemical characterization. 
Both proteins demonstrated the expected binding to CH103 lineage antibodies 
that target the CD4 binding site; showing weak affinity binding to UCA and 
higher affinity binding to both an intermediate lineage antibody (IA3.2) and the 
mature CH106 bnAb. In addition, a subset of preclinical safety and 
immunogenicity studies conducted with the Stable CH505TF variant were 
presented in support of the clinical safety experience with this gp120 protein. 
DAIDS proposed that the combination of the physicochemical data and clinical 

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safety data presented are sufficient and an additional GLP toxicology study of the 
Transient CH505TF would not provide additional useful information on the safety 
of the Transient CH505TF gp120 protein, and was not being planned. In addition, 
clinical safety data from the ongoing study of the stably produced CH505TF 
protein will be available prior to the initiation of the comparative study described 
here. The FDA concurred that no additional toxicology studies or pre-IND were 
required. 
4.8 
Preclinical immunogenicity studies  
Table 4-3 Summary of preclinical immunogenicity studies 
Study 
number 
Product 
Animal 
N 
Regimen groups 
Route 
Schedule 
(weeks) 
Assay 
501 
CH505TF 
gp120 Env 
with GLA-
SE 
Guinea pigs 
4 per 
group 
1 mcg CH505TF only 
1 mcg CH505TF, 5 mcg GLA-SE 
1 mcg CH505TF, 10 mcg GLA-SE 
1 mcg CH505TF, 25 mcg GLA-SE 
5 mcg CH505TF only 
5 mcg CH505TF, 5 mcg GLA-SE 
5 mcg CH505TF, 10 mcg GLA-SE 
5 mcg CH505TF, 25 mcg GLA-SE 
50 mcg CH505TF only 
50 mcg CH505TF, 5 mcg GLA-SE 
50 mcg CH505TF, 10 mcg GLA-SE 
50 mcg CH505TF, 25 mcg GLA-SE 
IM 
0, 3, 6, 9, 
12 
Ab binding 
NHP 79 
EnvSeq-1 
gp120 Env 
with GLA-
SE 
Rhesus 
Macaques 
4 per 
group 
100 mcg CH505TF only 
100 mcg CH505 sequential Envs 
100 mcg CH505 additive Envs 
IM 
0, 6, 12, 
19, 24, 57 
NAb, 
binding Ab, 
blocking Ab 
NHP 
106 
CH505TF 
gp120 Env 
with GLA-
SE 
Rhesus 
Macaques 
4 per 
group 
 
5 mcg CH505TF Env 
20 mcg CH505TF Env 
100 mcg CH505TF Env 
300 mcg CH505TF Env 
600 mcg CH505TF Env 
 
IM 
0, 4, 12, 
29, 37 
NAb, 
binding Ab, 
blocking Ab 
04 
Stable 
CH505TF 
gp120 with 
GLA-SE 
 
Transient 
CH505TF 
gp120 with 
GLA-SE 
 
Balb/C mice 
7 per 
group  
1 mcg Stable CH505TF, 5 mcg GLA-SE  
10 mcg Stable CH505TF, 5 mcg GLA-SE  
25 mcg Stable CH505TF, 5 mcg GLA-SE  
 
1 mcg Transient CH505TF, 5 mcg GLA-SE  
10 mcg Transient CH505TF, 5 mcg GLA-SE  
25 mcg Transient CH505TF, 5 mcg GLA-SE 
IM 
0, 2, 4, 
Ab binding, 
blocking Ab 
The CH505TF gp120 used in the initial animal studies (guinea pig 501 and NHP 
79) was generated in transiently-transfected 293 cells. The 293-produced 
CH505TF gp120 has a different glycosylation profile than that of the CHO-
produced protein used for the rabbit toxicology study, mouse immunogenicity, 
and for the nonhuman primate (NHP) dose response study (NHP 106).  

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4.8.1 
Immunogenicity of CH505-derived gp120 envelopes with GLA-SE in 
guinea pigs 
In a guinea pig study, the GLA-SE adjuvant was necessary for optimal immune 
responses to gp120 at all doses (Figure 4-6).  
 
Figure 4-6 GLA-SE enhanced immunogenicity of CH505TF gp120 protein in guinea pigs. 
Binding antibodies from guinea pigs immunized with varying doses of CH505TF gp120 and varying 
amounts of GLA-SE were measured by enzyme-linked immunosorbent assay (ELISA). The data 
were used to calculate the log-transformed area under the curve (AUC) as shown on the y-axis. 
CH505TF gp120 was immunogenic at all doses. Groups 1, 5 and 9 received no GLA-SE and had 
significantly less anti-gp120 antibodies than the groups with 5 mcg (Groups 2, 6 and 10), 10 mcg 
(Groups 3, 7, and 11) or 25 mcg (Groups 4, 8, and 12) of GLA-SE. Moreover, there was no 
difference between the three GLA-SE doses (statistical analysis not shown). 
4.8.2 
Immunogenicity of CH505-derived gp120 Envelopes, study NHP 79 
The EnvSeq-1 immunogens consist of four gp120 proteins derived from CH505: 
CH505TF, CH505w53, CH505w78, and CH505w100. These proteins were 
administered to 3 groups of four rhesus macaques (NHP 79) with the GLA-SE 
adjuvant: 1) CH505TF Env gp120 alone; 2) the Envs given in a sequential 
regimen (CH505TF, CH505w53, CH505w78, and CH505w100); and 3) an 
additive-immunization regimen consisting of CH505TF gp120 in combination 
with the evolved Env variants (CH505TF, then CH505TF + CH505w53, then 
CH505TF + CH505w53 + CH505w78, then CH505TF + CH505w53 + 
CH505w78 + CH505w100). These Envs were research grade products made by 
transient transfection of 293 cells and have different glycosylation profiles than 
the CHO-produced CH505TF gp120s to be used in this clinical trial. This study 
demonstrates the proof of concept of using sequential Env variants in NHPs. 
The CH505 gp120 Env derivatives (including CH505TF) were found to be 
immunogenic (Table 4-4). An important readout in this study was differential 
binding to the CD4-BS of the envelope protein. This assay detects antibodies 
which bind to wild type CH505 Env gp120 but not to CH505 with a deletion of 
isoleucine at aa position 371 (CH505 Env IΔ371 gp120), indicating CD4-BS 
L o g  A U C
0
5
1 0
1 5
2 0
Group #:
CH505TF (mcg):
GLA-SE (mcg):
1
1
0
6
5
5
7
5
10
8
5
25
9
50
0
10
50
5
11
50
10
12
50
25
2
1
5
3
1
10
4
1
25
5
5
0

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recognition which is a key trait of the CH103-like bnAbs. The data from the NHP 
79 study suggest that triggering of UCAs of lineages capable of binding HIV 
Envs with wild type sequences without further evolution into bnAbs can occur. In 
this study of 12 monkeys, 11/12 monkeys had differential binding antibodies 
isolated but overall the Env differential binding antibodies were subdominant and 
comprised only about 15% of the total activity of the antibody response, which is 
consistent with development of bnAbs in HIV-infected individuals. 
Table 4-4 CH505 Env gp120 derivatives are immunogenic in rhesus macaques. Plasma was 
screened for neutralization of HIV-1 isolates via the TZM-bl assay. ID50 positivity cutoff was ≥20 or 
3x > background neutralization of MuLV. *40-49% virus neutralization; less than 50% required to 
generate an ID50 value. 
 
4.8.3 
Immunogenicity of Stable CH505TF gp120, study NHP 106 
A dose ranging study was performed in rhesus macaques using 5 to 600 mcg of 
Env CH505TF gp120 (produced by stably transfected CHO-DG44 cells) along 
with 25 mcg GLA-SE with each dose administered 5 times. Immunogenicity was 
demonstrated at all dose levels and no adverse reactions were observed. Env 
binding antibody (Figure 4-7) and CD4-BS antibody (Figure 4-8) levels were 
determined and the CH505 TF gp120 was found to be immunogenic after 2 
immunizations. All dose levels gave similar binding responses. When we assessed 
the frequency of memory B cells that bind antigen probes in a CD4-BS 
differential manner (called differential binding memory B cells), all animals in the 
20, 100, 300, and 600 mcg protein dose groups demonstrated differential binding 
after 3 injections (Figure 4-9). 

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Figure 4-7 Binding of Immunized NHP 106 Plasma to CH505TF gp120. Each data point 
represents a single animal. Animals were immunized with the indicated dose at weeks 0, 4 and 12. 
Note that the x-axis shows bleed time. Bleed 0 was performed before immunization and 
subsequent bleeds were performed 2 weeks after each respective immunization. No animals had 
binding antibodies prior to immunization; binding was detected in all animals after the second 
immunization. After the third immunization, binding antibodies were similar among all groups. While 
all doses gave a similar binding response, the higher doses of 300 and 600 mcg gave earlier 
responses and trended to higher responses compared to the lower doses. No additional rise in 
antibody levels was observed after the fourth or fifth immunizations (data not shown) 
 
 
 
Figure 4-8 Inhibition of CD4 binding by NHP 106 plasma after immunization with 5 different 
doses of CH505TF gp120. Each data point represents a single animal. Animals were immunized 
with the indicated dose at weeks 0, 4 and 12. Note that the x-axis shows bleed time. Bleed 0 was 
performed before immunization and subsequent bleeds were performed 2 weeks after each 
respective immunization. The ability of plasma antibody to block the binding of CD4bs mAb CH106 
to heterologous B.63521 gp120 was quantified by ELISA. Blocking antibodies were detectable in 
the high dose groups after the second immunization and increased in Group 3 after the third 
immunization. 

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Figure 4-9 Percentage of differential binding memory B cells. Peripheral blood mononuclear 
cells (PBMC) from immunized macaques were assayed to determine the frequency of memory B 
cells that bind to CH505TF gp120 but not to CH505TF gp120 ΔI371 that disrupts the CD4 BS. 
Each data point represents a single animal. Animals were immunized at the indicated dose at 
weeks 0, 4 and 12. Note that the x-axis shows bleed time. Bleed 0 was performed before 
immunization and subsequent bleeds were performed 2 weeks after each respective immunization. 
Data show a pattern of increased differential binding memory B cell induction with increasing dose 
starting after two immunizations and increasing after a third immunization. 
4.8.4 
Immunogenicity of Stable CH505TF gp120 and Transient CH505TF 
gp120 in Balb/C mice, study 04  
Immune responses from the Transient and Stable CH505TF gp120 vaccines were 
evaluated in a preclinical immunogenicity study conducted by the Barton Haynes 
Laboratory at the Duke Human Vaccine Institute (DHVI). The immunogenicity of 
each vaccine was evaluated in female BALB/c mice after 2 or 3 IM 
immunizations with the respective protein adjuvanted with 5 mcg of GLA-SE per 
mouse dose. Six groups of 7 female BALB/c mice were immunized every 2 
weeks for a total of 3 immunizations with each respective vaccine. Pre-bleeds/sera 
were taken 2 weeks prior to and on the day of immunization 1 (day 0). Post bleeds 
were collected 1 week after each immunization. 
The immunogenicity of each form of recombinant gp120 was evaluated by 
ELISA for the ability of vaccine to induce serum antibodies to bind recombinant 
Env gp120 (Figure 4-10 and Figure 4-11) (36). The vaccine-induced antibodies’ 
ability to block the binding of the CD4 binding site neutralizing antibody to 
recombinant gp120 was also evaluated by ELISA using methods described in 
reference (35). Groups were compared by Exact Wilcoxon test (also called 
Wilcoxon-Mann-Whitney) with the Benjamini-Hochberg (1995) correction for 
multiple testing (see Figure 4-12 and Figure 4-13). 

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Figure 4-10 The binding of serum antibody to coating antigen CH505 gp120 reference 
produced in 293F cells 
Figure 4-10A shows the binding of serum antibodies induced by the Stable 
CH505TF (blue circles) and the Transient CH505TF (red squares) to a reference 
coating antigen CH505 gp120, produced in 293F cells. The data show equivalent 
binding of antibodies induced by either vaccine to the reference gp120, with a 
slight trend of better binding with 10 and 25 mcg doses after the second 
immunization by serum antibodies induced by the Transient CH505TF Env. 
However, this difference was not statistically significant. Figure 4-10B shows the 
same analysis after the third immunization and again showed no difference in the 
binding of the antibodies induced by the two proteins. 
Figure 4-11 shows the time course of serum antibody binding to the indicated 
coating Env protein listed over each graph of antibodies induced by the highest 
dose (25 mcg) of Stable CH505TF gp120 Env (blue dots) or Transient CH505TF 
gp120 Env (red squares). Binding of immune serum to Stable CH505TF is shown 
in Panel A and binding to Transient CH505TF is shown in Panel B. The 
engineered resurfaced core 3 (RSC3) protein was used to detect antibodies 
antigenically related to CD4-binding site binding, and results are shown in Panel 
C (37). Panel D shows binding to the heterologous gp120 YU2. YU2 gp120 is 
CD4-binding site knock-out mutant lacking variable regions V1, V2, and V3 and 
truncated at the N- and C-terminal regions; binding to YU2 gp120 indicates serum 
antibodies directed to the gp120 scaffold (37). Panel E displays binding to the 
CH505TF V2 peptide 
(GMKNCSFNITTELRDKREKKNALFYKLDIVQLDGNSSQYRLIN). Lastly, 
Panel F demonstrates binding to CH505 V3 peptide 
(TRPNNKTRTSIRIGPGQAFYATGQVIGDIREAY). These data show that the 
binding profile of antibodies induced by either the stable cell line gp120 or the 
transiently transfected-produced gp120 was near identical. With the data in Panels 
A, B, D and F, there was a slight but statistically non-significant trend to the 
transiently transfected-produced material to be better as an immunogen. 

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Figure 4-11 Time course of serum antibodies to the indicated coating Env protein induced 
by 25 mcg dose of immunogen 
 
Figure 4-12 Vaccine induced serum antibodies to block soluble (s) CD4 or CH106 bnAb 
binding to the reference CH505 gp120 

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Figure 4-12 and Figure 4-13 show the results of the vaccine-induced antibodies to 
block either sCD4 or CH106 neutralizing antibody binding to reference CH505 
Env gp120. Figure 4-12A shows the dose response of induced serum antibodies 
generated by vaccination with either Stable CH505 (blue dots) or Transient 
CH5050 gp120 (red squares). Data show that after the second immunization 
(Figure 4-12A), there was a significant improvement in blocking of sCD4 binding 
to gp120 with transiently transfected Env-immunized serum compared to stable 
cell line-produced gp120-immunized serum. A similar difference was seen after 
the second immunization for ability of serum to block the binding of the broadly 
neutralizing antibody (bnAb) CH106 to Env gp120 (Figure 4-12B). 
Figure 4-13 shows the time course of blocking in the sCD4 blocking assay (Panel 
A) and the CH106 blocking assay (Panel B) and shows slight (not statistically 
significant) trend of increased blocking by the transient gp120-induced antibodies 
after the second immunization but no difference in blocking after the 3rd 
immunization. 
The immunogenicity of each form of the recombinant gp120 was near identical in 
all performed assays. The Transient CH505TF gp120 induced slightly better CD4 
binding site antibodies than the Stable CH505TF. Thus, the two proteins were 
highly comparable in their immunogenicity in BALB/c mice, as measured by 
Env-reactive antibodies, with a trend toward higher induction of CD4 binding site 
targeted antibodies by Transient produced gp120. 
 
Figure 4-13 Time course of serum antibodies to block sCD4 and CH106 to the reference 
CH505 gp120 

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4.9 
Clinical studies 
4.9.1 
Clinical studies of Stable CH505TF gp120 vaccine  
The Stable CH505TF gp120 is being evaluated in HVTN 115. In the dose ranging 
portion of that clinical trial (HVTN 115 Part A) safety and immunogenicity data 
will be collected to inform the protein dose for the second part of that study. 
HVTN 115 Part A reached full enrollment with 42 participants in May 2018. As 
of June 25, 2018, there has been one case of grade 3 erythema/induration with 
grade 2 cellulitis after the second vaccination. All other reactogenicity events 
have been mild-moderate and vaccinations have been well tolerated.  
There is extensive clinical trial experience with other gp120 Env proteins 
evaluated either alone or in combination with various prime or boost regimens. 
The AIDS Vaccine Evaluation Group (AVEG) conducted an analysis of safety 
data from over 15 clinical trials of gp120 and gp160 proteins administered to over 
500 individuals demonstrating that overall, HIV Env proteins at doses up to 640 
mcg were well tolerated. The majority of the local and systemic reactions were 
deemed associated with the adjuvant components of the vaccine rather than the 
Env proteins themselves (38). 
A monovalent subtype B and bivalent subtype B/E (CRF01_AE) recombinant 
gp120 HIV-1 vaccine (AIDSVAX B/E) was evaluated in an efficacy study 
conducted in over 2500 injection drug users in Thailand. A total of 600 mcg of 
AIDSVAX B/E was administered with alum as an adjuvant. The most commonly 
reported adverse event (AE) was tenderness at the injection site (71% of vaccine 
recipients versus 66% of placebo recipients), which did not increase with 
subsequent injections. There were no differences between vaccine and placebo 
recipients with respect to the number of serious AEs (SAEs) (39). 
The RV144 study evaluated the same gp120 vaccine in a heterologous prime-
boost vaccination regimen consisting of a recombinant canarypox vector 
expressing gag, PR, and env (ALVAC-HIV; vCP1521) followed by the gp120 
protein boost. Over 8000 participants received multiple combined doses of 600 
mcg of gp120 in combination with ALVAC-HIV (12). Local and systemic 
reactogenicity noted after the gp120 protein (AIDSVAX B/E) was mostly mild 
with very few SAEs reported (40). 
Prior clinical experience comparing various doses of gp120 and gp160 Env 
proteins has not identified significant differences in the safety profile when the 
protein dose was altered and adjuvant dose remained constant. For example, in a 
study evaluating AIDSVAX B/E gp120 at 100 mcg (N=31), 300 mcg (N=31) and 
600 mcg (N=30) of the protein adjuvanted with alum, the majority (80%) of 
participants reported at least one reactogenicity event, most commonly injection 
site pain/tenderness, but all of the reactogenicity symptoms were mild to moderate 
and self-limited. Furthermore, although there were fewer reactogenicity events at 
the 100 mcg dose, the safety profile in the 300 mcg and 600 mcg groups was 
similar (41). A study of recombinant gp160 VaxSyn formulated with an alum 

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adjuvant compared two doses of 160 mcg (N=20) and 640 mcg (N=21) of the 
protein administered as 4 injections over a 12 month period. Local reactogenicity 
(injection site erythema/induration) was frequent but self-limited, lasted less than 
48 hours, and the frequency of local reactogenicity was similar between the two 
dose groups. There were no significant differences in severe local or systemic 
reactions between the dose groups. Importantly, there were no significant 
differences in laboratory abnormalities (hepatic, hematologic and renal function) 
between the two different protein doses (42). 
Taken together, the combined data from the large numbers of trial participants in 
these studies demonstrate that gp120 recombinant protein vaccines administered 
in combined doses of up to 600 mcg are immunogenic and well tolerated. There 
has been one recent case of anaphylaxis deemed related to the vaccine. There 
were no other unusual or serious vaccine-associated AEs reported. 
4.9.2 
Clinical studies of the GLA-SE adjuvant and protein combinations  
GLA-SE is a synthetic TLR4 agonist formulated in a stable nano-emulsion of 
squalene oil and promotes a strong Th1-type immune response to vaccine 
antigens (43, 44). Although the Transient CH505TF gp120 protein in combination 
with GLA-SE has not been evaluated in humans to date, as summarized in Section 
4.9.1, the Stable CH505TF gp120 is under evaluation in HVTN 115. In addition, 
there is considerable clinical trial experience with the GLA-SE adjuvant in 
combination with other antigens. These data are summarized below and in Table 
4-5 and Table 4-6. Over 1100 individuals have received at least one dose of the 
GLA-SE adjuvant at doses ranging from 0.5 to 20 mcg with no significant safety 
concerns identified to date. Please see the IB for additional details of the clinical 
trials performed with GLA-SE.  
Five studies have included the 10 mcg dose of the GLA-SE adjuvant proposed for 
this study. The first was an open-label phase 1 clinical trial conducted in Brazil 
with a Schistosoma mansoni antigen (Sm14) (45). Twenty healthy males received 
3 IM doses of 50 mcg Sm14 + 10 mcg GLA-SE at one-month intervals. The 
vaccine was safe and generally well tolerated with no SAEs or Grade 4 AEs (45). 
Injection site pain was commonly reported (80%, 50%, and 41% after the first, 
second, and third dose, respectively), but generally mild and self-limited. There 
were no abnormalities in physical exams, serum chemistries, and hematology 
values that were considered related to study vaccine. Humoral and CD4+ T cell 
responses to Sm14 were reported (45). 
The second clinical trial using the 10 mcg dose of GLA-SE is a recently 
completed phase 1, open-label evaluation of the safety, tolerability, and 
immunogenicity of a Leishmania vaccine (LEISH-F3) in combination with SLA-
SE (second generation glucopyranosyl lipid A in stable oil-in-water emulsion) 
adjuvant compared to LEISH-F3 with GLA-SE in healthy adults (NCT02071758; 
Protocol IDRI-LVVPX-117). The SLA-SE adjuvant is a next generation TLR4 
adjuvant formulation. Thirty-nine participants were randomized to 4 arms: high 
dose LEISH-F3 (20 mcg) and low dose SLA-SE (5 mcg); high dose LEISH-F3 

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and high dose GLA-SE adjuvant (10 mcg); low dose LEISH-F3 (5 mcg) and high 
dose GLA-SE adjuvant (10 mcg); and high dose LEISH-F3 and high dose SLA-
SE adjuvant (10 mcg). Participants received 3 injections at one-month intervals. 
This study is complete. The LEISH-F3 + GLA-SE and LEISH-F3 + SLA-SE 
vaccines were safe and well tolerated in adult subjects. No deaths, no dose-
limiting toxicities (DLTs), no Grade 3 or 4 AEs, no SAEs, and no AESIs occurred 
during the study. All study injection reactions were Grade 1 or Grade 2. The most 
frequently reported reactions were injection site tenderness/pain and fatigue. 
Three other clinical trials are evaluating GLA-SE in oncology. Two ongoing trials 
are investigating GLA-SE alone as an immunotherapy and one trial tested GLA-
SE in combination with a prostate cancer antigen. No data are currently available 
from these trials. 
Clinical experience with GLA-SE as an adjuvant for other vaccines at doses 
ranging from 1 mcg to 5 mcg suggests that it is safe and well-tolerated. Treanor et 
al. tested an avian influenza hemagglutinin (H5) subunit vaccine at a range of 
doses with and without a fixed dose of GLA-SE (1 mcg) and reported mild to 
moderate injection site pain and/or tenderness in 50–70% of H5 + GLA-SE 
recipients, with myalgias and headaches reported by a minority (25-27%) of 
vaccinees. No other safety findings were noted and the GLA-SE adjuvant 
substantially increased the immunogenicity of the vaccine (46). 
A recent phase 1 clinical trial of a respiratory syncytial virus (RSV) vaccine in 
older adults (≥ 60 years of age) found that a combination of the RSV fusion (F) 
protein at three different doses with 2.5 mcg of GLA-SE was safe, well-tolerated, 
and immunogenic. Compared with unadjuvanted vaccine, GLA-SE increased 
local reactogenicity, with 40-65% of subjects reporting mild-to-moderate, self-
limited injection site pain and/or tenderness (47). No other safety concerns were 
reported. Immune responses were F protein dose-dependent, and the adjuvant 
enhanced both humoral and cellular immune responses (47). A follow-up study 
using a higher dose of F protein and three doses of GLA-SE has been completed 
(NCT02289820). The vaccine was safe, tolerable, and immunogenic and the data 
supported the selection of 120 mcg F protein /5 mcg of GLA-SE for further 
evaluation (48). 
GLA-SE was also found to be safe and well-tolerated at doses of 2 mcg and 5 
mcg in a phase 1 trial of LEISH-F3 given three times at one month intervals (49). 
Injection site pain and/or tenderness was quite common (90-100%) with fatigue 
noted by 40-60% of vaccinees receiving the adjuvanted product versus 33% of 
subjects who received unadjuvanted vaccine (49). The unadjuvanted LEISH-F3 
was essentially non-immunogenic while antibody and cytokine responses were 
noted in vaccinees in both dose groups of GLA-SE (49). 
GLA-SE at a 5 mcg dose has also been tested together with protein antigens in 
several other clinical trials which are included in Table 4-5 and Table 4-6. 

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Table 4-5 Completed clinical trials using IDRI GLA-SE adjuvant formulations in combination 
with other vaccines (as of March 20, 2018) 
Sponsor/Partner 
Disease Area/Antigen 
GLA-SE 
Dose 
# Receiving 
GLA-SE 
# 
Total 
in 
Study 
Oswaldo Cruz Foundation / IDRI 
NCT01154049  
Schistosomiasis (Sm14)  
10 mcg  
20 
20 
IDRI / Rockefeller University 
NCT01397604 and NCT01864876  
Adjuvant only 
2 mcg  
5 mcg  
10 
7 
49 
IDRI  
NCT01484548  
Leishmaniasis (LEISH-F3)  
2 mcg  
5 mcg  
12 
12 
36 
NIAID / IDRI  
NCT01751048  
Leishmaniasis (LEISH-F3)  
5 mcg  
16 
 
48 
IDRI 
NCT02071758  
Leishmaniasis (LEISH-F3)  
10 mcg 
18 
39 
WRAIR / IDRI 
NCT01540474  
Malaria (CelTOS)  
2 mcg  
5 mcg  
10 
20 
30 
European Vaccine Initiative / IDRI 
NCT01949909  
Malaria (p27A)  
2.5 mcg 
5 mcg  
24 
8 
56 
European Vaccine Initiative / IDRI 
NCT02014727  
Malaria (AMA-1 DiCo)  
2.5 mcg  
33 
66 
IDRI / Aeras 
NCT01599897  
TB (ID93)  
2 mcg  
5 mcg  
24 
24 
60 
IDRI / Aeras 
NCT01927159 
TB (ID93) 
2 mcg 
5 mcg 
39 
15 
66 
IDRI  
NCT02465216 
TB (ID93) 
2 mcg 
5 mcg 
20 
28 
60 
CONFIDENTIAL  
Seasonal influenza  
0.5 mcg  
1 mcg  
2.5 mcg  
5 mcg  
6 
12 
36 
4 
96 
Protein Sciences / Immune Design  
NCT01147068  
Pandemic influenza 
(recombinant protein)  
1 mcg  
220 
392 
Novavax / Immune Design 
NCT01596725  
Pandemic influenza (H5-VLP)  
2.5 mcg  
169 
333 
Medicago / Immune Design 
NCT01991561  
Pandemic influenza (H5-VLP)  
5 mcg  
130 
390 
Immune Design 
NCT02015416 
Cancer (NY-ESO-1) 
2 mcg 
5 mcg 
10 mcg 
3 
3 
6 
12 

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Medimmune / Immune Design 
NCT02115815  
Respiratory syncytial virus (sF) 
2.5 mcg 
60 
144 
Medimmune / Immune Design 
NCT02289820  
Respiratory syncytial virus (sF) 
1 mcg 
2.5 mcg 
5 mcg 
39 
99 
79 
261 
Medimmune / Immune Design 
NCT02508194 
Respiratory syncytial virus (sF) 
5 mcg 
946 
1894 
 
Table 4-6 Ongoing clinical trials using IDRI GLA-SE adjuvant formulations in combination 
with other vaccines (as of March 20, 2018) 
Sponsor/Partner 
Disease Area/Antigen 
GLA-SE 
Dose 
# Receiving 
GLA-SE 
# Total in 
Study  
IDRI  
NCT03302897 
Leprosy (LEP-F1)  
5 mcg  
24 
24 
NIH/NIAID/DMID 
NCT02508376 
TB (ID93) 
5 mcg 
 
20 
 
70 
University Hospital Tuebingen 
NCT02647489 
Malaria (PAMVAC) 
5 mcg 
 
21 
 
63 
Institut National de la Santé Et de la 
Recherche Médicale 
NCT02658253 
Malaria (PRIMVAC) 
2.5 mcg 
29 
68 
Immune Design 
NCT02035657 
Merkel cell carcinoma 
5 mcg 
9 
9 
Immune Design  
NCT02501473 
Non-Hodgkins lymphoma  
5 mcg 
10 mcg 
20 mcg 
3 
3 
4 
10 
Immune Design  
NCT02180698 
Sarcoma  
5 mcg 
10 mcg 
20 mcg 
4 
4 
4 
12 
Immune Design  
NCT02387125 
Cancer (CMB305, G305) 
Not 
Available 
 
 
Immune Design  
NCT02609984 
Cancer (CMB305) 
Not 
Available 
 
 
Immune Design  
NCT02320305 
Melanoma (MART1) 
Not 
Available 
 
 
HVTN 115 
HIV Vaccine 
10 mcg 
116 
132 
 

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4.10 
Potential risks of study products and administration 
Table 4-7 Summary of potential risks of study products and administration 
Common 
• 
Mild to moderate injection site pain, tenderness, erythema, or 
swelling/induration/edema 
• 
Malaise/fatigue, myalgia, or headache in the first few days following 
injection 
• 
A vaccine-induced positive HIV antibody test result 
Less common 
• 
Severe injection site pain or tenderness 
• 
Fever, chills, flu-like syndrome, arthralgia, rash, decreased appetite, nausea, 
or dizziness in the first few days following injection  
• 
Vasovagal reaction/lightheadedness/dizziness related to the injection 
procedure 
• 
Transient changes in clinical laboratory values 
• 
Injection site hematoma, bruising/ecchymosis, other transient lesions, itching, 
or bleeding related to the injection procedure 
Uncommon or rare 
• 
Severe localized injection site reaction, such as sterile abscess or secondary 
bacterial infection  
• 
Allergic reaction, including rash, urticaria, angioedema, bronchospasm, or 
anaphylaxis 
• 
Muscle damage at the injection site 
Theoretical risks 
• 
Autoimmune disease  
• 
Effects on a participant’s response to an approved HIV vaccine administered 
in the future 
• 
Effects on susceptibility to HIV, if the participant is exposed to HIV  
• 
Effects on the course of HIV infection/disease, if the participant is infected 
with HIV 
• 
Effects on the fetus and on pregnancy 
 

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5 
Objectives and endpoints 
5.1 
Primary objectives and endpoints 
Primary objective 1:  
To evaluate and compare the safety and tolerability of the CH505TF gp120 
proteins produced by transient and stable transfection in HIV-1–uninfected, 
healthy adults 
Primary endpoint 1:  
Local and systemic reactogenicity signs and symptoms, laboratory measures of 
safety, and AEs and SAEs 
Primary objective 2:  
To evaluate and compare the magnitude of binding antibody responses elicited by 
the CH505TF gp120 proteins produced via transient and stable transfection 
methods 
Primary endpoint 2:  
HIV-specific total IgG binding antibody responses against the homologous 
proteins, as assessed by BAMA at peak timepoint (2 weeks after 3rd vaccination) 
5.2 
Secondary objectives and endpoints 
Secondary objective 1: 
To evaluate and compare the breadth and kinetics of binding antibody responses 
elicited by the CH505TF gp120 proteins produced via transient and stable 
transfection methods 
Secondary endpoint 1: 
HIV-specific total IgG binding antibody responses against the homologous 
proteins and magnitude-breadth (M-B) measures against panels of cross-clade 
Env proteins and of cross-clade V2 proteins, as assessed by BAMA at peak 
timepoints (2 weeks after the 2nd and 3rd vaccinations) and late timepoints (3 and 
6 months after the 3rd vaccination) 

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Secondary objective 2: 
To evaluate and compare the IgG subclass and IgA binding antibody responses 
elicited by the CH505TF gp120 proteins produced via transient and stable 
transfection methods 
Secondary endpoint 2: 
HIV-specific IgG subclass and IgA binding antibody response rates and 
magnitudes against homologous Env and V2 proteins, as assessed by BAMA at 2 
weeks after the 2nd vaccination, 2 weeks after the 3rd vaccinations, and 3 and 6 
months after the 3rd vaccination 
Secondary objective 3: 
To evaluate the ability of the two CH505TF gp120 proteins to elicit HIV-specific 
neutralizing antibodies (nAbs) 
Secondary endpoint 3: 
Magnitude and breadth of nAb responses against a panel of viral isolates as 
assessed by area under the M-B curves 2 weeks after the 2nd and 3rd vaccinations 
Secondary objective 4: 
To evaluate the avidity of antibody responses elicited by the CH505TF gp120 
proteins 
Secondary endpoint 4 
Avidity of Env-specific IgG antibodies at baseline and 2 weeks after the 3rd 
vaccination 
Secondary objective 5: 
To evaluate HIV-specific T-cell responses induced by the two CH505TF gp120 
proteins 
Secondary endpoint 5: 
Response rate, magnitude, and polyfunctionality of CD4+ T-cell responses as 
assessed by intracellular cytokine staining (ICS) assays 2 weeks after the 2nd and 
3rd vaccinations 

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5.3 
Exploratory objectives 
Exploratory objective 1: 
To evaluate the ability of the two CH505TF gp120 proteins to elicit memory B 
cells that differentially bind wildtype CH505 gp120Env vs mutant CH505 Env 
IΔ371 gp120 
Exploratory objective 3: 
To characterize the BCR repertoire of HIV-specific B cells 
Exploratory objective 4: 
To further evaluate vaccine immunogenicity, additional immunogenicity assays 
may be performed, including on samples from other timepoints, based on the 
HVTN Laboratory Assay Algorithm 
Exploratory objective 5: 
To conduct analyses related to furthering the understanding of HIV, immunology, 
vaccines, and clinical trial conduct 

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6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target enrolling 30 healthy, HIV-uninfected adult participants 
aged 18 to 50 years. 
6.1.1 
Sample size calculations for safety 
The goal of the safety evaluation for this study is to identify safety concerns 
associated with product administration. The ability of the study to detect SAEs 
(Table 6-1) 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 vaccine arm of the study (n =15), there 
is a 90% chance of observing at least 1 event if the true rate of such an event is 
15% or more; and there is a 90% chance of observing no events if the true rate is 
0.5% 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.  
Probabilities of observing 0, 1 or more, and 2 or more events among arms of size 
15 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 the vaccine. 
Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
arms of size 15, for different true event rates 
True event rate (%) 
Pr(0/15) 
Pr(1+/15) 
Pr(2+/15) 
0.5 
0.928 
0.072 
0.003 
1 
0.860 
0.140 
0.010 
4 
0.542 
0.458 
0.119 
10 
0.206 
0.794 
0.451 
15 
0.087 
0.913 
0.681 
20 
0.035 
0.965 
0.833 
30 
0.005 
0.995 
0.965 
40 
0.000 
1.000 
0.995 
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 (50). If none of the 30 participants receiving a vaccine regimen 
experience a safety event, the 95% 2-sided upper confidence bound for the true 
rate of such events in the total vaccinated population (n = 30) is 11.4%. For each 
individual vaccine arm (n = 15), the 2-sided upper confidence bound for this rate 
is 20.4%. 

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Table 6-2 Two-sided 95% CIs based on observing a particular rate of safety endpoints for 
sample sizes 15 and 30 
Observed event rate 
95% CI (%) 
0/15 
[0.0, 20.4] 
1/15 
[0.3, 29.8] 
2/15 
[3.7, 37.9] 
 
 
0/30 
[0.0, 11.4] 
1/30 
[0.2, 16.7] 
2/30 
[1.8, 21.3] 
 
6.1.2 
Sample size calculations for immunogenicity 
Binding antibodies will be measured by geometric mean fluorescence intensity 
(FI) for homologous proteins. We will test the null hypothesis that the geometric 
mean FI in the transient arm is less than 1/4 of the geometric mean FI in the stable 
arm. The power to reject this null hypothesis depends on the variability of the 
binding antibodies measurements and sample sizes. Based on HVTN 505 data, the 
standard deviation of the natural log of geometric mean FI at the dilutions 
optimized for immune correlates analyses, which maximize the proportion of 
samples within the linear range of the dilution-response curve, is around 1.4. 
Table 6-3 lists the power under a range of standard deviations, non-inferiority 
margins, and sample sizes. 
The power study assumes that loge(geometric mean FI for a panel of Envs) is 
normally distributed and has the same spread in both arms. We will form a 95% 
confidence interval for the difference in loge(FI)s between the transient arm and 
the stable arm and compare the lower confidence interval to loge(1/4). Under the 
parameters of the proposed study, the estimated power to reject the null 
hypothesis ranges from 0.86 to 0.63 for standard deviation ranging from 1.2 to 
1.6. 
Table 6-3 Power to reject the null hypothesis that the geometric mean FI in the transient arm 
is less than non-inferiority margin of the geometric mean FI in the stable arm. Standard 
deviation: spread of loge (FI); n: sample size for each arm. The alpha level is set at 0.05 for a two-
sided test. 
 

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6.2 
Randomization  
A participant’s randomization assignment will be computer-generated and 
provided to the HVTN CRS pharmacist through a Web-based randomization 
system. At each institution, the pharmacist with primary responsibility for 
dispensing study products is charged with maintaining security of the treatment 
assignments (except in emergency situations as specified in the HVTN MOP). 
6.3 
Blinding 
Participants and site staff (except for site pharmacists) will be blinded as to 
participant treatment arm assignments. Study product assignments are accessible 
to those HVTN CRS pharmacists, DAIDS protocol pharmacists and contract 
monitors, and SDMC staff who are required to know this information in order to 
ensure proper trial conduct. Any discussion of study product assignment between 
pharmacy staff and any other HVTN CRS staff is prohibited. The HVTN SMB 
members also are unblinded to treatment assignment in order to conduct review of 
trial safety.  
When a participant leaves the trial prior to study completion, the participant will 
be told he or she must wait until all participants are unblinded to learn his or her 
treatment assignment.  
In some cases, the CRS, PSRT, or study sponsor may believe unblinding of the 
site PI and participant would be appropriate to facilitate the clinical management 
of an AE or SAE. The HVTN Unblinding MOP specifies procedures for 
emergency unblinding, and for early unblinding for medical reasons.  
6.4 
Statistical analyses 
This section describes the final study analyses, unblinded as to treatment arm 
assignment. All safety data from enrolled participants will be analyzed according 
to the initial randomization assignment regardless of how many vaccinations they 
received. In the rare instance that a participant receives the wrong treatment at a 
specific vaccination time, the Statistical Analysis Plan (SAP) will address how to 
analyze the participant’s safety data. Analyses are modified intent-to-treat in that 
individuals who are randomized but not enrolled do not contribute data and hence 
are excluded. Because of blinding and the brief length of time between 
randomization and enrollment—typically no more than 4 working days—very 
few such individuals are expected. The primary and secondary analyses of 
immunogenicity data are per-protocol in that only individuals who receive the 
expected vaccinations within the expected visit window contribute data. 
Analyses for primary endpoints will be performed using SAS and R. All other 
descriptive and inferential statistical analyses will be performed using SAS, 
StatXact, or R statistical software. 

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6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, and 
immunogenicity for primary- and secondary-objective analyses. 
6.4.2 
Baseline comparability 
Treatment arms will be compared for baseline participant characteristics using 
descriptive statistics. 
6.4.3 
Safety/tolerability analysis 
Since enrollment is concurrent with receiving the first vaccination, all participants 
will have received at least 1 vaccination and therefore will provide some safety 
data. 
6.4.3.1 
Reactogenicity 
The number and percentage of participants experiencing each type of 
reactogenicity sign or symptom will be tabulated by severity and treatment arm 
and the percentages displayed graphically by arm. For a given sign or symptom, 
each participant’s reactogenicity will be counted once under the maximum 
severity for all injection visits. In addition, to the individual types of events, the 
maximum severity of local pain or tenderness, induration or erythema, and of 
systemic symptoms will be calculated. Wilcoxon tests will be used to test for 
differences in severity between arms. 
6.4.3.2 
AEs and SAEs 
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 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 AEs within a category will be counted 
once under the maximum severity or the strongest recorded causal relationship to 
study product. Formal statistical testing comparing arms is not planned since 
interpretation of differences must rely heavily upon clinical judgment. 
A listing of SAEs reported to the DAIDS Regulatory Support Center (RSC) 
Safety Office will provide details of the events including severity, relationship to 
study product, time between onset and last vaccination, and number of 
vaccinations received.  
6.4.3.3 
Reasons for vaccination discontinuation and early study termination 
The number and percentage of participants who discontinue vaccination and who 
terminate the study early will be tabulated by reason and treatment arm. 

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6.4.4 
Immunogenicity analysis 
6.4.4.1 
General approach 
For the statistical analysis of immunogenicity endpoints analyses will be limited 
to participants who received all scheduled injections per protocol. Assay results 
that are unreliable, from specimens collected outside of the visit window, or from 
HIV-infected participants postinfection are excluded. Since the exact date of HIV 
infection is unknown, any assay data from blood draws 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 may be excluded from the analysis. 
Discrete categorical assay endpoints (eg, response rates) will be analyzed by 
tabulating the frequency of positive response for each assay by antigen and 
treatment arm at each timepoint for which an assessment is performed. Crude 
response rates and difference between treatment arms will be presented with their 
corresponding 95% CI estimates calculated using the score test method (50). 
For quantitative assay data, graphical and tabular summaries of the distributions 
by antigen, treatment arm, and timepoint will be made. For all primary and 
secondary immunogenicity endpoints, box plots and plots of estimated reverse 
cumulative distribution curves will be used for graphical display of all of the 
study arms.  
Mean or median (if normality assumption severely violated) assay readouts will 
be compared between arms and bootstrap CIs will be estimated.  
More sophisticated analyses employing repeated measures methodology (for 
example, linear mixed models or marginal mean models fit by generalized 
estimating equations) may be utilized to incorporate immune responses over 
several timepoints and to test for differences over time. 
6.4.4.2 
Multivariate display of immunogenicity endpoints 
Data visualization techniques may be used to explore the relationship among 
immunogenicity readouts. The set of readouts may be based on the set of primary 
endpoints, or on immunogenicity endpoints that also include secondary or 
exploratory endpoints. To understand the relationship between pairs of readouts, 
scatter plots may be used when the number of readouts is small or for a larger 
number of readouts, a heatmap showing the degree of correlation between any 
two pairs. Principal component analysis (PCA) and associated ‘biplots’ of the 
scores and loadings are particularly useful to understand associations between 
readouts, especially when readouts are correlated (51). PCA is a method to reduce 
the dimensionality of the number of readouts to a smaller set of values (principal 
components) that are normalized linear combinations of the readouts in such a 
way that the first principal component accounts for the most variability in the data 
and subsequent components, while maximizing variability, are uncorrelated with 

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each other. A ‘biplot’ displays the first and second principal component scores 
and principal component loadings. The x-axis is the value from the first principal 
component and the y-axis is the second principal component, where each axis 
label includes the percentage of variation in the total set of readouts captured by 
the principal component. The top axis is the first principal component loadings 
and the right axis is the second principal component loadings. An arrow is drawn 
for each immunogenicity readout (eg, Env-specific CD4+ T cell polyfunctionality 
score, Env-specific CD8+ T cell total magnitude) from the origin to the point 
defined by its first two principal component loadings. The length of the arrow 
represents the amount of total variation of the set of readouts captured by the 
given readout. The direction of an arrow conveys the extent to which the variation 
of a readout is in the direction of the first or second principal component. The 
angle between two arrows conveys information about the correlation of the two 
readouts, with a zero degree angle denoting perfect correlation and a 90 degree 
angle denoting no correlation. Each arrow on the biplot is labeled by the 
immunogenicity readout it represents. A biplot is annotated with key meta-
information such as the treatment arm (most common application) or a 
demographic category. Depending on the application, K-means clustering and 
hierarchical clustering may also be applied for multivariate graphical display of 
immunogenicity readouts. 
6.4.4.3 
Analysis of multiplexed immunoassay data 
Two approaches will be considered to evaluate the magnitude and breadth of 
these responses. First, M-B curves maybe employed to display individual- and 
group-level response breadth as a function of magnitude. Two choices are to 
compare the M-B curves among vaccine arms, as follows: a non-parametric 
Wilcoxon rank sum test on the subject-specific area-under-the M-B curve (AUC-
MB) or a Kolmogorov-Smirnov type test on the 2 group-average M-B curves. 
Simulations can be used to obtain 2-sided p-values for the latter test. Second, a 
weighted-average score-like variable may be constructed to account for the 
correlations between analytes as an integrate magnitude of responses to multiple 
analytes. Similar group comparison methods described in the first approach may 
be adopted. Details of either approach will be described in the SAP.  
6.4.4.4 
Analysis of neutralization magnitude-breadth curves 
The area-under-the-magnitude-breadth curve (AUC-MB) to the panel of isolates 
will be computed for each participant with evaluable neutralization data, as 
described in Huang et al. (52). Methods for comparing AUC-MB are similar to 
those described in Section 6.4.4.3. 
6.4.4.5 
Analysis of CD4+ and CD8+ T-cell response as measured by the ICS 
assay 
The analysis of CD4+ and CD8+ T-cell response rates as measured by the ICS 
assay will be evaluated and compared as described under the general approach. 
For each T-cell subset, the positivity call for each peptide pool will include a 
multiple comparison adjustment for the number of peptide pools used in the 

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assay. In general, the Mixture Models for Single-cell Assays (MIMOSA) 
statistical framework (53) and/or the Fisher’s exact test-based positivity criteria 
will be used. Details of the positivity criteria will be discussed in the SAP. The 
magnitude of marginal response will be analyzed as described for quantitative 
data in the general approach section. For each T-cell subset, graphs will be used to 
display the background-subtracted magnitudes for each participant by protein, 
treatment arm and timepoint. When 3 or more cytokines are being measured by 
the ICS assay, the polyfunctionality of ICS responses may also be analyzed as an 
exploratory endpoint. Besides descriptive plots of the magnitude of polyfunctional 
responses, the COMPASS (Combinatorial Polyfunctionality analysis of Antigen-
Specific T-cell Subsets) statistical framework (54) may also be used to perform 
joint modelling of multiple T-cell subsets of different cytokine combinations. For 
example, the functionality score (FS) and the polyfunctionality score (PFS) may 
be used to summarize the multi-parameter ICS responses.  
6.4.5 
Analyses and data sharing prior to end of scheduled follow-up visits 
Any analyses conducted prior to the end of the scheduled follow-up visits should 
not compromise the integrity of the trial in terms of participant retention or safety 
or immunogenicity endpoint assessments. In particular, early unblinded analyses 
by treatment assignment require careful consideration and should be made 
available on a need to know basis in accordance with Section 6.4.5.1. Interim 
blinded safety and immunogenicity data should not be shared outside of the SMB, 
HVTN 123 PSRT, the protocol team leadership, the HVTN Executive 
Management Team, the study product developer, and the study sponsor and/or its 
designee(s) for their regulatory reporting unless approved by the protocol 
leadership and the HVTN leadership. 
6.4.5.1 
Safety analyses 
During the course of the trial, unblinded analyses of safety data will be prepared 
approximately every 4 months for review by the SMB. Ad hoc safety reports may 
also be prepared for SMB review at the request of the HVTN 123 PSRT. Refer to 
the process described in the HVTN Unblinding MOP for any requests for 
unblinded safety data prior to the end of the scheduled follow-up visits. 

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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; completes a questionnaire prior to first vaccination with verbal 
demonstration of understanding of all questionnaire items answered incorrectly 
5. Willing to be contacted in person or by phone, text message, or e-mail 6 
months after completion of the scheduled clinic visits 
6. Agrees not to enroll in another study of an investigational research agent before 
the last required protocol clinic visit 
7. Good general health as shown by medical history, physical exam, and screening 
laboratory tests 

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HIV-Related Criteria 
8. Willingness to receive HIV test results 
9. Willingness to discuss HIV infection risks and amenable to HIV risk reduction 
counseling 
10. 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 I). 
Laboratory Inclusion Values 
Hemogram/Complete blood count (CBC) 
11. Hemoglobin ≥ 11.0 g/dL for volunteers who were assigned female sex at birth, ≥ 
13.0 g/dL for volunteers who were assigned male sex at birth. For transgender 
participants who have been on hormone therapy for more than 6 consecutive 
months, determine hemoglobin eligibility based on the gender with which they 
identify (ie, a transgender female who has been on hormone therapy for more than 
6 consecutive months should be assessed for eligibility using the hemoglobin 
parameters for persons assigned female sex at birth). 
12. White blood cell count = 3,300 to 12,000 cells/mm3 
13. Total lymphocyte count ≥ 800 cells/mm3 
14. Remaining differential either within institutional normal range or with site 
physician approval 
15. Platelets = 125,000 to 550,000/mm3 
Chemistry 
16. Chemistry panel: alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), and alkaline phosphatase < 1.25 times the 
institutional upper limit of normal; creatinine ≤ institutional upper limit of 
normal. 
Virology 
17. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-
approved enzyme immunoassay (EIA).  
18. Negative Hepatitis B surface antigen (HBsAg)  
19. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV 
polymerase chain reaction (PCR) if the anti-HCV is positive 

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Urine 
20. Normal urine: 
• Negative urine glucose, and 
• Negative or trace urine protein, and 
• Negative or trace urine hemoglobin (if trace hemoglobin is present on 
dipstick, a microscopic urinalysis with red blood cells levels within 
institutional normal range). 
Reproductive Status 
21. Volunteers who were assigned female sex at birth: negative serum or urine beta 
human chorionic gonadotropin (β-HCG) pregnancy test performed prior to 
vaccination on the day of initial vaccination. Persons who are NOT of 
reproductive potential due to having undergone total hysterectomy or bilateral 
oophorectomy (verified by medical records), are not required to undergo 
pregnancy testing. 
22. 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 until 3 months after the 
final study vaccination. 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 123 PSRT 
▪ Successful vasectomy in any partner assigned male sex at birth 
(considered successful if a volunteer reports that a male partner has [1] 
documentation of azoospermia by microscopy, or [2] a vasectomy more 
than 2 years ago with no resultant pregnancy despite sexual activity 
postvasectomy); 
• Or not be of reproductive potential, such as having reached menopause (no 
menses for 1 year) or having undergone hysterectomy, bilateral 
oophorectomy, or tubal ligation; 
• Or be sexually abstinent. 

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23. Volunteers who were assigned female sex at birth must also agree not to seek 
pregnancy through alternative methods, such as artificial insemination or in 
vitro fertilization until after the last required protocol clinic visit 
7.2 
Exclusion criteria 
General 
1. Blood products received within 120 days before first vaccination  
2. Investigational research agents received within 30 days before first vaccination 
3. Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: age 
> 45, systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, 
current smoker, known hyperlipidemia  
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 HVTN 123 study  
5. Pregnant or breastfeeding 
6.  Active duty and reserve US military personnel 
Vaccines and other Injections 
7. HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have 
received control/placebo in an HIV vaccine trial, the HVTN 123 PSRT will 
determine eligibility on a case-by-case basis. 
8. Previous receipt of monoclonal antibodies (mAbs), whether licensed or 
investigational; the HVTN 123 PSRT will determine eligibility on a case-by-case 
basis. 
9. Non-HIV experimental vaccine(s) received within the last 5 years in a prior 
vaccine trial. Exceptions may be made by the HVTN 123 PSRT for vaccines that 
have subsequently undergone licensure by the FDA. For volunteers who have 
received control/placebo in an experimental vaccine trial, the HVTN 123 PSRT 
will determine eligibility on a case-by-case basis. For volunteers who have 
received an experimental vaccine(s) greater than 5 years ago, eligibility for 
enrollment will be determined by the HVTN 123 PSRT on a case-by-case basis. 
10. Live attenuated vaccines received within 30 days before first vaccination or 
scheduled within 14 days after injection (eg, measles, mumps, and rubella 
[MMR]; oral polio vaccine [OPV]; varicella; yellow fever) 

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11. Any vaccines that are not live attenuated vaccines and were received within 14 
days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B) 
12. Allergy treatment with antigen injections within 30 days before first 
vaccination or that are scheduled within 14 days after first vaccination  
Immune System  
13. Immunosuppressive medications received within 168 days before first 
vaccination (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 < 60 
mg/day and length of therapy < 11 days with completion at least 30 days prior to 
enrollment) 
14. Serious adverse reactions to vaccines including history of anaphylaxis and 
related symptoms such as hives, respiratory difficulty, angioedema, and/or 
abdominal pain. (Not excluded from participation: a volunteer who had a 
nonanaphylactic adverse reaction to pertussis vaccine as a child.)  
15. Immunoglobulin received within 60 days before first vaccination 
16. Autoimmune disease  
17. Immunodeficiency 
Clinically significant medical conditions  
18. Clinically significant medical condition, physical examination findings, 
clinically significant abnormal laboratory results, or past medical history with 
clinically significant implications for current health. A clinically significant 
condition or process includes but is not limited to: 
• A process that would affect the immune response, 
• A process that would require medication that affects the immune response, 
• Any contraindication to repeated injections or blood draws, 
• 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 for which signs or symptoms could be confused with 
reactions to vaccine, or 
• Any condition specifically listed among the exclusion criteria below. 

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19. Any medical, psychiatric, occupational, or other condition that, in the 
judgment of the investigator, would interfere with, or serve as a contraindication 
to, protocol adherence, assessment of safety or reactogenicity, or a volunteer’s 
ability to give informed consent 
20. 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. 
21. Current anti-tuberculosis (TB) prophylaxis or therapy 
22. Asthma exclusion criteria: 
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. 
23. Diabetes mellitus type 1 or type 2 (Not excluded: type 2 cases controlled with 
diet alone or a history of isolated gestational diabetes.) 
24. Thyroidectomy, or thyroid disease requiring medication during the last 12 
months 
25. 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 

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pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg 
at enrollment. 
26. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or 
platelet disorder requiring special precautions) 
27. 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) 
28. 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. 
29. Asplenia: any condition resulting in the absence of a functional spleen 
30. History of hereditary angioedema, acquired angioedema, or idiopathic 
angioedema. 
7.3 
Participant departure from vaccination schedule or withdrawal 
This section concerns an individual participant’s departure from the study product 
administration schedule. Pause rules for the trial are described in Section 11.3. 
7.3.1 
Delaying vaccinations for a participant 
Under certain circumstances, a participant’s scheduled vaccination will be 
delayed. The factors to be considered in such a decision include but are not 
limited to the following: 
• Within 45 days prior to any study injection  
▪ Receipt of blood products or immunoglobulin 
• Within 30 days prior to any study injection 
▪ Receipt of live attenuated vaccines  
▪ Receipt of allergy treatment with antigen injections 
• Within 14 days prior to any study injection 
▪ Receipt of any vaccines that are not live attenuated vaccines (eg, 
pneumococcal)  
• Prevaccination abnormal vital signs or clinical symptoms that may mask 
assessment of vaccine reaction. 

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Vaccinations should not be administered outside the visit window period specified 
in the HVTN 123 Study Specific Procedures. 
In order to avoid vaccination delays and missed vaccinations, participants who 
plan to receive licensed vaccines or allergy treatments should be counseled to 
schedule receipt of these substances, when possible, outside the intervals 
indicated above. The effects of these substances on safety and immunogenicity 
assessments and their interactions with study vaccines are unknown. Therefore, if 
circumstances allow, these substances should also be avoided in the 2 week 
interval between a study vaccination and completion of the 2 week 
postvaccination follow-up visit. 
7.3.2 
Participant departure from vaccination schedule 
Every effort should be made to follow the vaccination schedule per the protocol. 
If a participant misses a vaccination and the visit window period for the 
vaccination has passed, that vaccination cannot be given. The participant should 
be asked to continue study visits. The participant should resume the vaccination 
schedule with the next vaccination unless there are circumstances that require 
further delay or permanent discontinuation of vaccination (see Sections 7.3.1 and 
7.3.3).  
7.3.3 
Discontinuing vaccination for a participant 
Under certain circumstances, an individual participant’s vaccinations will be 
permanently discontinued. Specific events that will result in stopping a 
participant’s vaccination schedule include: 
• Co-enrollment in a study with an investigational research agent (rare 
exceptions allowing for the continuation of vaccinations may be granted with 
the unanimous consent of the HVTN 123 PSRT) 
• Clinically significant condition (ie, a condition that affects the immune system 
or for which continued vaccinations and/or blood draws may pose additional 
risk), including but not limited to the following: 
▪ Pregnancy (regardless of outcome) 
▪ HIV infection 
▪ Any grade 4 local or systemic reactogenicity symptom, lab abnormality, or 
AE that is subsequently considered to be related to vaccination 
▪ Any grade 3 lab abnormality that is subsequently considered to be related 
to vaccination 
▪ Other grade 3 clinical AE that is subsequently considered to be related to 
vaccination with the exception of fever, vomiting, and subjective local and 
systemic symptoms. For grade 3 injection site erythema and/or induration, 
upon review, the PSRT may allow continuation of vaccination 

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▪ SAE that is subsequently considered to be related to vaccination 
▪ Clinically significant type 1 hypersensitivity reaction associated with 
study vaccination. Consultation with the HVTN 123 PSRT is required 
prior to subsequent vaccinations following any type 1 hypersensitivity 
reaction associated with study vaccination 
• Investigator determination in consultation with Protocol Team leadership (eg, 
for repeated nonadherence to study staff instructions) 
Participants discontinuing study product for reasons other than 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 123 SSP). 
Participants diagnosed with HIV infection during the study should be encouraged 
to participate in follow-up visits as indicated in Section 9.13 
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, or 
• Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff). 
• Any condition where termination from the study is required by applicable 
regulations. 

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8 
Study product preparation and administration 
The 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 IBs for further information about 
study products. 
8.1 
Vaccine regimen 
The schedule of vaccination is shown in Section 3 and additional information is 
given below.  
Group 1 
Treatment 1 (T1): 100 mcg of Stable CH505TF gp120 admixed with 10 mcg of 
GLA-SE, to be administered as a 1mL IM injection in the deltoid of the non-
dominant arm at Months 0, 2, and 6. 
Group 2 
Treatment 2 (T2): 100 mcg of Transient CH505TF gp120 admixed with 10 mcg 
of GLA-SE, to be administered as a 1mL IM injection in the deltoid of the non-
dominant arm at Months 0, 2, and 6. 
8.2 
Study product formulation  
8.2.1 
Stable CH505TF gp120 
The Stable CH505TF gp120 will be provided at a concentration of 0.8 mg/mL of 
protein in phosphate-buffered saline per vial. Each sterile, single use vial contains 
0.75 mL of study product. The study product must be stored frozen at ≤ -65°C. 
When thawed, the Stable CH505TF gp120 will be clear, and colorless to slightly 
yellow, liquid. The study product is described in further detail in the IB. 
8.2.2 
Transient CH505TF gp120 
The Transient CH505TF gp120 will be provided at a concentration of 0.8 mg/mL 
of protein in phosphate-buffered saline per a vial. Each sterile, single use vial 
contains 0.7 mL of study product. The study product must be stored frozen at       
≤ -65°C. When thawed, the Transient CH505TF gp120 will be clear, and colorless 
to slightly yellow, liquid. The study product is described in further detail in the 
IB. 

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8.2.3 
GLA-SE (Glucopyranosyl Lipid Adjuvant-Stable Emulsion) 
The GLA-SE adjuvant will be provided at a concentration of 20 mcg/mL GLA in 
a 4% oil-in-water emulsion in a vial. Each sterile, single use vial contains 0.4 mL 
of this mixture, which appears as a milky-white liquid. GLA-SE must be stored at 
2-8°C and must not be frozen. The study product is described in further detail in 
the IB. 
8.3 
Preparation of study products 
8.3.1 
Group 1 (T1): 100 mcg of Stable CH505TF gp120 + 10mcg of GLA-SE 
One vial of Stable CH505TF gp120 (0.8 mg/mL) and two vials of GLA-SE (20 
mcg/mL) will be needed to prepare the dose. 
Prior to admixture, the pharmacist will remove a vial of Stable CH505TF gp120 
from the freezer and allow to thaw completely at room temperature. Once thawed 
completely, invert the vial 10 times to ensure a homogeneous product. Remove 
two vials of GLA-SE from the refrigerator and allow to equilibrate to room 
temperature. 
Using aseptic technique, the pharmacist will add 0.5 mL of Stable CH505TF 
gp120 and 1.5 mL of Sodium Chloride for injection, 0.9% USP to an empty 
sterile vial. Mix the contents of this vial thoroughly using a vortex machine at 
high speed for 3 seconds. The final concentration of Stable CH505TF gp120 is 
200 mcg/mL. 
Next, using aseptic technique, withdraw 0.6 mL of the diluted 200 mcg/mL Stable 
CH505TF gp120 admixture and 0.6 mL of GLA-SE (20 mcg/mL) and inject it 
into an empty sterile vial. Mix thoroughly by gently inverting 10 times, yielding a 
concentration of 100 mcg/mL Stable CH505TF gp120 and 10 mcg/mL GLA-SE.  
Finally, using aseptic technique, withdraw 1 mL from the vial containing 100 
mcg/mL Stable CH505TF gp120 and 10 mcg/mL GLA-SE, using a 3 or 5 mL size 
syringe. Remove the needle and cap syringe.  
The prepared syringe for administration must be covered with an overlay and then 
labeled as “Stable CH505TF/GLA-SE or Transient CH505TF/GLA-SE”. The 
syringe must also be labeled for IM administration into the deltoid of the non-
dominant arm, with an expiration date and time of 8 hours following the last 
mixing procedure.  
Any unused portion of vials or expired prefilled syringes should be disposed of in 
accordance with institutional or pharmacy policy. 

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8.3.2 
Group 2 (T2): 100 mcg of Transient CH505TF gp120 + 10 mcg of GLA-
SE 
One vial of Transient CH505TF gp120 (0.8 mg/mL) and two vials of GLA-SE (20 
mcg/mL) will be needed to prepare the dose. 
Prior to admixture, the pharmacist will remove a vial of Transient CH505TF 
gp120 from the freezer and allow to thaw completely at room temperature. Once 
thawed completely, invert the vial 10 times to ensure a homogeneous product. 
Remove two vials of GLA-SE from the refrigerator and allow to equilibrate to 
room temperature. 
Using aseptic technique, the pharmacist will add 0.5 mL of Transient CH505TF 
gp120 and 1.5 mL of Sodium Chloride for injection, 0.9% USP to an empty 
sterile vial. Mix the contents of this vial thoroughly using a vortex machine at 
high speed for 3 seconds. The final concentration of Transient CH505TF gp120 is 
200 mcg/mL. 
Next, using aseptic technique, withdraw 0.6 mL of the diluted 200 mcg/mL 
Transient CH505TF gp120 admixture and 0.6 mL of GLA-SE (20 mcg/mL) and 
inject it into an empty sterile vial. Mix thoroughly by gently inverting 10 times, 
yielding a concentration of 100 mcg/mL Transient CH505TF gp120 and 10 
mcg/mL GLA-SE.  
Finally, using aseptic technique, withdraw 1 mL from the vial containing 100 
mcg/mL Transient CH505TF gp120 and 10 mcg/mL GLA-SE, using a 3 or 5 mL 
size syringe. Remove the needle and cap syringe.  
The prepared syringe for administration must be covered with an overlay and then 
labeled as “Stable CH505TF/GLA-SE or Transient CH505TF/GLA-SE”. The 
syringe must also be labeled for IM administration into the deltoid of the non-
dominant arm, with an expiration date and time of 8 hours following the last 
mixing procedure.  
Any unused portion of vials or expired prefilled syringes should be disposed of in 
accordance with institutional or pharmacy policy. 
8.4 
Administration 
All injections should be administered in the deltoid of the non-dominant arm.  
The prepared study product in the syringe should be rolled gently prior to 
administration. 
The prepared study product in the syringe must be administered as soon as 
possible and before the 8-hour expiration. 

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Any administrator of study product will be blinded to the individual participant's 
treatment assignment.  
When preparing a dose in a syringe and administering the dose, consideration 
should be given to the volume of solution in the needle before and after the dose 
is administered. Particularly, if the needle used to withdraw the product is 
replaced prior to vaccine administration, consideration should be given to 
conserving the full dose of product. The pharmacy and clinic staff members are 
encouraged to work together to administer the dose specified in the protocol. 
Group 1 (T1): 
100 mcg of Stable CH505TF gp120 admixed with 10 mcg of GLA-SE, to be 
administered as a 1mL IM injection in the deltoid of the non-dominant arm at 
Months 0, 2, and 6. 
Group 2 (T2): 
100 mcg of Transient CH505TF gp120 admixed with 10 mcg of GLA-SE, to be 
administered as a 1mL IM injection in the deltoid of the non-dominant arm at 
Months 0, 2, and 6. 
8.5 
Acquisition of study products 
Stable CH505TF gp120, Transient CH505TF gp120, and GLA-SE will be 
provided by DAIDS. Sodium Chloride for injection, 0.9% USP will not be 
provided through the protocol and must be obtained by the site. 
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 Pharmacy Guidelines 
and Instructions for DAIDS Clinical Trials Networks. 
8.6 
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. 
8.7 
Final disposition of study products 
For US clinical research sites, all unused study products must be returned to the 
CRPMC after the study is completed or terminated unless otherwise instructed by 

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the study sponsor. The procedures are included in the Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks.  

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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 informed consent forms prior to 
implementation at a site.” CRSs are responsible for knowing the requirements of 
their applicable REs. 
9.1.1 
Screening consent form 
Without a general screening consent, screening for a specific study cannot take 
place until the site receives protocol registration from the DAIDS RSC Protocol 
Registration Office. 
Some 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 
vaccine trial. In this way, HVTN CRS staff can continually screen potential 
participants and, when needed, proceed quickly to obtain protocol-specific 

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enrollment consent. Sites conducting general screening or prescreening approved 
by their IRB/EC and any applicable RE may use the results from this screening to 
determine eligibility for this protocol, provided the tests are conducted within the 
time periods specified in the eligibility criteria.  
9.1.2 
Protocol-specific consent forms 
The protocol-specific consent forms describe the study products to be used and all 
aspects of protocol participation, including screening and enrollment procedures. 
A sample protocol-specific consent form for the main study is located in 
Appendix A. A separate sample consent form for other uses of specimens is 
located in Appendix C. 
Each 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 C. The consent form(s) must be developed in 
accordance with requirements of the following: 
• CRS’s IRB/EC and any applicable REs, 
• CRS’s institution, and 
• Elements of informed consent as described in Title 45, CFR Part 46 and Title 
21 CFR, Part 50, and in the ICH E6, Good Clinical Practice: Consolidated 
Guidance 4.8.  
Study sites are strongly encouraged to have their local CABs review their sites-
specific consent forms. This review should include, but should not be limited to, 
issues of cultural competence, local language considerations, and the level of 
understandability. 
The sample informed consent forms include instructions throughout the 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 HIV vaccine 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. 

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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 vaccination on day 0. All inclusion and exclusion criteria must 
be assessed within 56 days before enrollment, unless otherwise specified in the 
eligibility criteria (or below in this section). 
After the appropriate informed consent has been obtained and before enrollment, 
the following procedures are performed: 
• Medical history, documented in the case history record 
• Assessment of whether the volunteer is at low risk for HIV infection 
• Complete physical examination, including height, weight, vital signs, and 
clinical assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; 
heart; chest; abdomen; extremities; neurological function; and skin 
• Assessment of concomitant medications the volunteer is taking, including 
prescription and nonprescription drugs, vitamins, topical products, 
alternative/complementary medicines (eg, herbal and health food 
supplements), recreational drugs, vaccinations, and allergy shots  
• Laboratory tests including: 
▪ Screening HIV test, 
▪ HBsAg, 
▪ Anti-HCV antibodies, 
▪ CBC with differential and platelets, 
▪ Chemistry panel (ALT, AST, alkaline phosphatase, and creatinine), 
▪ Urine dipstick (as described in Section 9.8), and 
▪ Urine or serum pregnancy test (participants who were assigned female sex 
at birth)  

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• Syphilis test 
• 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) 
• Behavioral risk assessment 
• 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 9.6 
• 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). 
9.3 
Enrollment and vaccination visits 
Enrollment is simultaneous with first vaccination. The HVTN CRS requests the 
randomization assignment via a Web-based randomization system. In general, the 
time interval between randomization and enrollment should not exceed 4 working 
days. However, circumstances may require a participant’s enrollment visit to be 
changed. This may exceed the 4-day randomization time limit. 
At all vaccination visits, the following procedures are performed before 
vaccination: 
• 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; 

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• Assessment of baseline reactogenicity parameters; 
• Assessment of concomitant medications (as described in Section 9.2); 
• Assessment of any new or unresolved AEs/intercurrent illnesses; and 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Persons who are NOT of reproductive potential due to having 
undergone total hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. 
Following completion of all procedures in the preceding list, and if results 
indicate that vaccination may proceed, vaccination is prepared and administered 
(see Sections 8.3 and 8.4). 
Immediately following vaccination, the participant remains in the clinic for 
observation. An initial reactogenicity assessment is made at a target of 30 minutes 
after injection, with an acceptable range of 25-60 minutes. Before leaving the 
clinic, the participant is given the Participant Diary and is instructed on how to 
complete it. The site will make arrangements to be in contact with the participant 
during the reactogenicity period (as described in Section 9.9). 
The following procedures will be performed at all vaccination visits. These 
procedures may be performed prior to or following vaccination:  
• Risk reduction counseling (as described in Section 9.6);  
• Pregnancy prevention assessment (as described in Section 9.2 and 9.7); and 
• 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). 
Additional procedures will be performed at scheduled visits as specified in 
Appendix E and Appendix F:  
• HIV infection assessment including pretest counseling and HIV testing. A 
subsequent follow-up contact is conducted to provide post-test counseling and 
to report results to participant; 
• Confirm that participants received HIV test results from previous visit. If not, 
provide test results and post-test counseling as appropriate;  
• Administration of a questionnaire that asks the participant about any HIV 
testing he or she may have received outside of the study. Participants will also 
be asked whether they believe they received the active vaccine or the control; 

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• 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); 
• Behavioral risk assessment; and 
• Specimen collection (must be performed prior to vaccination). 
9.4 
Follow-up visits 
The following procedures are performed at all scheduled follow-up visits: 
• Risk reduction counseling (as described in Section 9.6);  
• Assessment of new or unresolved social impacts (site staff will ask participant 
about the status of any unresolved social impacts and if s/he has experienced 
any new social impacts as a result of the trial participation); 
• Assessment of new or continuing concomitant medications (as described in 
Section 9.2);  
• Assessment of new or unresolved AEs/intercurrent illnesses; and 
• Specimen collection. 
Additional procedures will be performed at scheduled follow-up visits as 
specified in Appendix E and Appendix F:  
• 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); 
• Administration of a questionnaire that asks the participant about any HIV 
testing he or she may have received outside of the study. Participants will also 
be asked whether they believe they received the active vaccine or the control; 
• Pregnancy prevention assessment (as described in Section 9.2 and 9.7); 
• Behavioral risk assessment; 
• HIV infection assessment including pretest counseling and HIV testing. A 
subsequent follow-up contact is conducted to provide post-test counseling and 
to report results to participant; 

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• Confirm that participants received HIV test results from previous visit. If not, 
provide test results and post-test counseling as appropriate; 
• Abbreviated physical examination including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
• Complete physical examination, including weight, vital signs, and clinical 
assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; heart; 
chest; abdomen; extremities; neurological function; and skin; 
• Clinical laboratory tests including: 
▪ CBC with differential and platelets, 
▪ Chemistry panel (see Section 9.2), and 
▪ Urine dipstick (urinalysis if appropriate; see Section 9.8); and 
• Urine or serum pregnancy test (for participants who were assigned female sex 
at birth). Persons who are NOT of reproductive potential due to having 
undergone total hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. 
9.5 
AESI health contact 
CRS staff will contact study participants 18 months after enrollment to collect the 
information listed below. Clinic visits will only be required if HIV confirmatory 
testing is necessary (see Section 9.6.1); however, a clinic visit may be arranged 
for other reasons. 
• Confirmation of vital status; if deceased, attempt to learn cause and date of 
death; 
• If participant is alive, record the following events: 
▪ New AEs related to study product(s) 
▪ AEs of special interest (AESI, see Section 11.2.2). A sample list of AESI 
is provided in Appendix H. AESI are reported regardless of relationship to 
study product(s); 
▪ New diagnosis of HIV infection; and 
▪ Pregnancies and outcomes, including congenital anomalies/birth defects. 
All such events will be recorded, and AEs will be assessed for relationship to 
study product(s).  

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9.5.1 
Interim contacts 
CRSs may report safety information obtained at a contact other than the annual 
contact. These contacts are reported as interim visits. 
9.6 
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 and on the potential negative social impacts of testing antibody positive 
due to the vaccine. They will also be counseled on the risks of HIV antibody 
testing outside of the HVTN CRSs and will be discouraged from doing so during 
study participation and/or during any period of vaccine-induced positive serology. 
Study staff will take particular care to 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. Such testing has become more 
likely due to the CDC’s revised guidelines for HIV counseling and testing, as well 
as policy changes in many countries to make HIV testing more frequent and 
routine. CRS staff should 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 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 also inform participants of the need to 
maintain study blinding by getting HIV testing only at the study CRS. CRS staff 
should provide participants with CRS contact information and should encourage 
participants to ask medical providers to contact the CRS. The CRS can verify that 
the participant is in an HIV vaccine clinical trial and should only be tested at the 
study CRS. 
Potential participants identified as being HIV-infected during screening are not 
enrolled. Potential and enrolled participants identified as being HIV-infected will 
be referred for medical treatment, counseling, and management of the HIV 
infection. Participants who are found to be HIV-infected after enrollment will not 
receive any additional study product but will continue to be followed in the study 
for safety assessments. These individuals may also be referred to appropriate 
ongoing clinical trials or observational studies. 

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9.6.1 
Distinguishing intercurrent HIV infection from vaccine-induced 
positive serology 
The study product may elicit an antibody response to HIV proteins. Therefore, 
vaccine-induced positive serology may occur in this study. Several precautionary 
measures will be taken to distinguish intercurrent HIV infection from vaccine-
induced positive serology. These precautionary measures include: 
• Participants will have physical examinations at visits specified in Appendix F. 
Signs or symptoms of an acute HIV infection syndrome, an intercurrent illness 
consistent with HIV-1 infection, or probable HIV exposure would prompt a 
diagnostic workup per the HVTN algorithm for Recent Exposure/Acute 
Infection Testing to determine HIV infection. 
• HIV testing will be performed at multiple timepoints throughout the study 
(see Appendix F). The Laboratory Program (or approved diagnostic 
laboratory) will follow the HVTN HIV testing algorithm (see Study Specific 
Procedures (SSP)), which is able to distinguish vaccine-induced antibody 
responses from actual HIV infections.  
• All participants can receive HIV-1 diagnostic testing from the site following 
their last scheduled visit until they are told that they did not receive an HIV 
vaccine or that they do not have vaccine-induced seropositivity. 
• All participants who received vaccine product and who have vaccine-induced 
positive or indeterminate HIV-1 serology (as measured by the standard anti-
HIV antibody screening tests) at or after the study is unblinded will be offered 
poststudy HIV-1 diagnostic testing (per the HVTN poststudy HIV-1 testing 
algorithm) periodically and free of charge as medically/socially indicated 
(approximately every 6 months) unless or until HIV Ab testing is no longer 
the standard test in clinical settings.  
9.6.2 
VISP registry  
Experimental HIV vaccines may induce antibody production to HIV antigens, 
producing reactive results on commercially available HIV test kits. This is called 
“vaccine-induced seropositivity” (VISP) (see Section 9.6.1). In order to provide 
poststudy HIV testing to distinguish between VISP and HIV infection, and to 
mitigate potential social harms resulting from VISP in HIV vaccine recipients 
who are not infected with HIV, the HVTN has created a VISP registry. Following 
study unblinding, the registry will allow trained staff to verify that an individual 
has received an HIV vaccine, and therefore has the potential for VISP. 
Information in the VISP registry will not be used for research. Rather, the registry 
exists to support provision of poststudy testing and counseling services to HIV 
vaccine recipients. The registry contains the names of all study participants, 
unless they request that their names be removed. 

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9.7 
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. 
Self-reported infertility—including having reached menopause (no menses for 1 
year) or having undergone hysterectomy, bilateral oophorectomy, or tubal 
ligation—must be documented in the participant’s study record. 
9.8 
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 and, if within the eligibility limits specified in the protocol, the 
participant may be enrolled. 
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. 
9.9 
Assessments of reactogenicity 
For all participants, baseline assessments are performed before and reactogenicity 
assessments are performed after each vaccination. All reactogenicity symptoms 
are followed until resolution and 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, except as noted in Section 11.2.2. 
The reactogenicity assessment period is 7 full days following each vaccination per 
the assessment schedule shown in Table 9-1. Participants are instructed to record 
symptoms using a Participant Diary. Contacts between the participant and the site 

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staff should take place at least once between 1-3 days postvaccination. In general, 
a participant who self-reports any postvaccination 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 
reactogenicity symptoms present at day 7 to resolution. 
Reactogenicity events are reported using CRFs that correspond to the time of 
assessment in Table 9-1. Reactogenicity assessments include assessments of 
systemic and local symptoms, and vaccine-related lesions. Events not listed on a 
CRF, or with an onset after the reactogenicity assessment period (day of 
vaccination and 7 full days after), or those meeting SAE/AEs requiring expedited 
reporting to DAIDS criteria, are recorded on an adverse experience log form.  
Table 9-1 Schedule of reactogenicity assessments 
Day 
Time 
Performed by 
0a 
Baseline: before vaccination 
HVTN CRS clinician 
 
Early: 25-60 minutes after vaccination 
HVTN CRS clinician 
 
Between early assessment and 11:59pm 
day 0 
HVTN CRS clinician or 
participant 
1-7b 
Between 12:00am and 11:59pm on the 
respective day 
HVTN CRS clinician or 
participant 
a Day of vaccination 
b New or unresolved reactogenicity symptoms present on day 7 are followed until resolution 
9.9.1 
Assessment of systemic and local symptoms 
Systemic symptoms include increased body temperature, malaise and/or fatigue, 
myalgia, headache, chills, arthralgia, and nausea. Local symptoms include pain 
and/or tenderness at the injection site. The daily maximum severity reached for 
each symptom during the assessment period is reported.  
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 
reactogenicity period. 
Temperature is reported in degrees Celsius. If temperature is measured in 
Fahrenheit, the conversion to Celsius should be documented in the participant’s 
chart note. A measurement is taken once daily during the assessment period and 
should be repeated if participant is feeling feverish. 
9.9.2 
Assessment of injection site 
Typical injection site reactions are erythema/redness and induration/swelling. The 
maximum diameter for all injection site reactions are recorded. 
All injection site reactions are monitored until resolution. Reactions with 
diameters greater than 5 cm are followed daily; otherwise, the frequency of 
follow-up is based on clinician judgment. 

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9.10 
Visit windows and missed visits 
Visit windows are defined in HVTN 123 SSP. For a visit not performed within 
the window period, a Missed Visit form is completed. If the missed visit is one 
that required safety assessments or local safety labs, HVTN CRS staff should 
attempt to bring the participant in for an interim visit as soon as possible. 
Procedures performed at an interim visit are usually toxicity/safety assessments 
(including local safety labs) and HIV testing. With the exception of HIV testing, 
these procedures are performed only if they were required at the missed visit or if 
clinically indicated. HIV testing may be performed as deemed appropriate by the 
study staff. Blood samples for immunogenicity assays are not typically collected 
at interim visits. 
If a missed visit required vaccination, please refer to Section 7.3.2 and Section 
7.3.3 for resolution. 
9.11 
Early termination visit 
In the event of early participant termination, site staff should consider if the 
following assessments are appropriate: a final physical examination, clinical 
laboratory tests (including urine dipstick, CBC with differential and platelets, and 
chemistry panel), pregnancy testing, social impact assessment, and HIV test. For 
participants who have a confirmed diagnosis of HIV infection, see Section 9.13 
9.12 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more 
injections of study product will be given, but remaining visits and study 
procedures should be completed unless medically contraindicated or applicable 
regulations require termination from the study. If the participant terminates from 
the study prior to the pregnancy outcome, the site should make every effort to 
keep in touch with the participant in order to ascertain the pregnancy outcome. 
Pregnancies and pregnancy outcomes will be reported. 
9.13 
HIV infection during the study 
If a participant becomes HIV-infected during the course of the study, no 
additional study product will be administered. Participants will be encouraged to 
continue scheduled study visits for up to 6 months 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 123 PSRT (eg, to avoid interference with participant initiation of HIV 
treatment). At post-infection follow-up visits, only specimens required for 
protocol-specified safety laboratory tests, urinalysis and pregnancy tests will be 

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collected; in addition, some clinic procedures may be modified or discontinued 
(see Appendix E and Appendix F). 

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10 
Laboratory 
10.1 
HVTN CRS laboratory procedures 
The HVTN 123 Site Lab Instructions and SSP provide further guidelines for 
operational issues concerning the clinical and processing laboratories. These 
documents include guidelines for general specimen collection, special 
considerations for phlebotomy, specimen labeling, whole blood processing, HIV 
screening/diagnostic testing, and general screening and safety testing. 
Tube types for blood collection are specified in Appendix E. For tests performed 
locally, the local lab may assign appropriate tube types. 
In specific situations, the blood collection tubes may be redirected to another 
laboratory or may require study-specific processing techniques. In these cases, 
laboratory special instructions will be posted on the protocol-specific section of 
the HVTN website. 
Of note, all assays described below are performed as research assays to evaluate 
the ability of the vaccine to induce immune responses in the context of the 
participants’ genetic background, 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 E. 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 
Immunogenicity timepoints 
The immunogenicity timepoints in this study occur: 2 weeks after the 2nd 
vaccination visit, 2 weeks after the 3rd vaccination visit, 3 months after the 3rd 
vaccination visit, and 6 months after the 3rd vaccination visit. Endpoint assays for 
humoral and cellular responses are performed on samples collected from 
participants at the immunogenicity timepoints and may be performed on samples 
collected at baseline. Depending on the initial results, assays for humoral and 
cellular responses may be performed on samples collected from participants at 
other timepoints; the schedule is shown in Appendix E. 

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10.4 
Endpoint assays: cellular 
10.4.1 
Flow cytometry: ICS 
Flow cytometry will be used to examine vaccine-specific CD4+ T-cell responses 
following stimulation of peripheral blood mononuclear cells (PBMCs) with 
synthetic HIV peptides that span the proteins encoded by the vaccine. ICS 
parameters will include cytokines such as interferon (IFN)-γ, interleukin (IL)-2, 
and tumor necrosis factor (TNF)-α, and may include other cytokines (such as 
cytokines relevant to Th2 and Th17 responses) to identify T cells of specific 
functionality. Data will be reported as percentages of CD4+ T cells responding to 
a specific peptide pool. Additional cell surface markers, cytokines, or functional 
markers may also be analyzed. 
10.4.2 
Flow cytometry: antigen-specific B cell phenotyping assay 
Antigen-specific B cells induced by vaccination will be identified and 
characterized using fluorescently-labeled recombinant proteins in combination 
with a flow cytometry phenotyping panel. In particular, HIV Env-reactive B cells 
will be enumerated and may be further characterized for expression of memory, 
activation, inhibitory or other markers of interest. B cells may also be sorted for 
further analysis by BCR sequencing or gene expression analysis. B cells may 
instead be cultured for detection of and functional testing of secreted antibodies 
by ELISA or microneutralization assays, and/or BCR sequencing. 
10.4.3 
BCR repertoire analysis 
Single or bulk populations of naïve or memory B cells, or plasmablasts, may be 
sorted for any combination of BCR sequencing, gene expression analysis, or 
functional antibody testing by microneutralization or binding assays. 
10.5 
Endpoint assays: humoral 
10.5.1 
Binding antibody multiplex assay (BAMA) 
HIV-1–specific total binding IgG antibodies to CH505TF gp120 and a panel of 
heterologous gp120s will be assessed on serum samples from study participants 
taken at the primary immunogenicity timepoints and baseline. In addition, HIV-1–
specific total binding IgA antibodies and binding to IgG subclasses (IgG1, IgG2, 
IgG3, and IgG4) may also be assessed. Specimens from other timepoints may also 
be assayed based on the results of the initial assay.  
10.5.2 
Neutralizing antibody (nAb) assay 
HIV-1–specific nAb assays will be performed on serum samples from study 
participants taken at the primary immunogenicity timepoints. Specimens from the 
baseline and other timepoints may also be analyzed at the discretion of the HVTN 

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Laboratory Program, which may be contingent on the results of the primary 
immunogenicity timepoints. The TZM-bl assay will test neutralization of the 
vaccine strains (CH505TF, CH505.w4.3) and a single highly neutralization-
sensitive Tier 1 virus as a positive control. The global panel and/or clade-specific 
panels may be used to assess Tier 2 neutralization (55, 56). 
10.5.3 
Antibody avidity 
Antibody avidity will be measured using BAMA with the addition of a 
dissociation step to calculate the avidity index or by surface plasmon resonance 
assay.  
10.6 
Genotyping 
Molecular human leukocyte antigen (HLA) typing may be performed on enrolled 
participants using cryopreserved PBMC collected at baseline, initially on 
specimens from participants who demonstrate vaccine-induced T-cell responses at 
postvaccination timepoints. Other participants (including control recipients) may 
be HLA-typed to support future studies of immunological interest at the discretion 
of the HVTN Laboratory Program. Other genes, including those associated with 
immune responses (eg, immunoglobulin or T-cell receptor genes) or HIV-1 
disease progression may also be assessed.  
10.7 
Lab assay algorithm 
The Lab Assay Algorithm lists assays to characterize cellular, humoral, and innate 
immune responses as well as host genetics that may be conducted to determine 
endpoints in HVTN vaccine trials. The type of assay(s) employed will be 
dependent on the response obtained by the primary immunogenicity assays at 
relevant timepoints. Please note that the Lab Assay Algorithm will be updated 
periodically to include new assays. 
10.8 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of HIV immunology or vaccines. In addition, cryopreserved 
samples may be used to perform additional assays to support standardization and 
validation of existing or newly developed methods.  
10.9 
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. 

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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, 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 (“other use”) will occur only after review and approval by the HVTN, 
the IRB/EC of the researcher requesting the specimens, and the CRS’s 
IRBs/ECs/REs if required.  
As part of consenting for the study, participants document their initial decision to 
allow or not allow their specimens to be used in other research, and they may 
change their decision at any time. The participant’s initial decision about other 
use of their specimens, and any later change to that decision, is recorded by their 
CRS in a Web-based tool that documents their current decisions for other use of 
their specimens. The HVTN will only allow other research to be done on 
specimens from participants who allow such use.  
CRSs must notify HVTN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on specimen storage or 
other use of specimens. 
10.10 
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. 

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11 
Safety monitoring and safety review 
11.1 
Safety monitoring and oversight 
11.1.1 
HVTN 123 PSRT 
The HVTN 123 PSRT is composed of the following members: 
• DAIDS medical officer representative 
• Protocol chair and cochair 
• Protocol Team leader 
• Core medical monitor 
• Clinical safety specialist 
The clinician members of HVTN 123 PSRT are responsible for decisions related 
to participant safety. 
The Protocol Team clinic coordinator, clinical data manager, vaccine developer 
representative, clinical trial manager, and others may also be included in HVTN 
123 PSRT meetings. 
11.1.2 
HVTN SMB 
The SMB is a multidisciplinary group consisting of biostatisticians, clinicians, 
and experts in HIV vaccine research that, collectively, has experience in the 
conduct and monitoring of vaccine 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 during the main study, as defined in Section 3. The reviews 
consist of evaluation of cumulative reactogenicity events, AE, laboratory safety 
data, and individual reports of adverse events requiring expedited reporting to 
DAIDS. The SMB conducts additional special reviews at the request of the 
HVTN 123 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: 

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• Maintaining a central database management system for HVTN clinical data; 
• Providing reports of clinical data to appropriate groups such as the HVTN 123 
PSRT and HVTN SMB (see Section 11.1.2); 
11.1.4 
HVTN Core roles and responsibilities in safety monitoring 
• Daily monitoring of clinical data for events that meet the safety pause and 
HVTN 123 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 123 PSRT. 
11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC 
Site staff must submit all safety forms (eg, reactogenicity, adverse experience, 
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 
product/procedure(s). All AEs are graded according to the Division of AIDS 

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(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, 
Corrected Version 2.1, July 2017, available on the RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-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 
123 Study Specific Procedures); 
• Injection Site Erythema or Redness and Injection Site Induration or Swelling 
will not consider interference with usual social and functional activities such 
that: 
• Grade 1 is: 2.5 to < 5 cm in diameter OR 6.25 to < 25 cm2 surface area; 
• Grade 2 is: ≥ 5 to < 10 cm in diameter OR ≥ 25 to < 100 cm2 surface area; 
• Grade 3 is: ≥ 10 cm in diameter OR ≥ 100 cm2 surface area OR Ulceration OR 
Secondary infection OR Phlebitis OR Sterile abscess OR Drainage; 
• Grade 4 is: Potentially life-threatening consequences (eg, abscess, exfoliative 
dermatitis, necrosis involving dermis or deeper tissue); 
During the main study period (see Section 3) 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) if the AE meets the criteria for a prompt AE review (see Section 
11.3). 
After the main study period, report the subset of AEs bulleted in Section 9.5 until 
the AESI health contact (see Section 3) is complete. 
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/hvtn123). 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 (local time) to confirm that the email has been received and reviewed. If 
email service is not available, the CRS should notify clinical safety staff of the 
event by telephone, then submit CRFs. 
In addition, site investigators are required to submit AE information in accordance 
with IRB/EC and any applicable RE requirements. 

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11.2.3 
Expedited reporting of adverse events 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 https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-
reporting-adverse-events-daids. 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, EAE reports may be submitted via the DAIDS 
EAE Form. This form is available on the DAIDS RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/paper-eae-reporting. 
For questions about DAERS, please contact CRMSsupport@niaid.nih.gov or 
from within the DAERS application itself. 
For questions about EAE reporting, please contact the DAIDS RSC Safety Office 
at (DAIDSRSCSafetyOffice@tech-res.com). 
The study products for which expedited reporting are required are:  
• Stable CH505TF HIV gp120 with GLA-SE 
• Transient CH505TF HIV gp120 with GLA-SE 
While the participant is in the main study reporting period (see Section 3), the 
SAE Reporting Category will be used.  
After completion of the main study period through completion of the AESI health 
contact (see Section 3) the SUSAR Reporting Category will be used. 
After the participant has completed the AESI health contact and is off study, sites 
must report SUSARS if the study site staff becomes aware of the events on a 
passive basis (eg, from publicly available information). 
The NIAID/DAIDS will report all unexpected SAEs related to the study products 
observed in this clinical trial to the FDA in accordance with 21 CFR 312.32 (IND 
Safety Reports). However, because safety is a primary study endpoint, the study 
sponsor Medical Officer will not routinely be unblinded to study treatment 
assignment when there is an assessment of relatedness of the SAE with the study 
product(s); and the safety report will be sent to the FDA based on the blinded 
attribution assessment. 
In some cases, the PSRT or CRS may believe unblinding of the site PI and 
participant would be appropriate to facilitate the clinical management of an AE or 

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SAE. The HVTN MOP specifies procedures for emergency unblinding, and for 
early unblinding for medical reasons.  
11.3 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all enrollment and vaccination 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 123 PSRT AE 
review are summarized in Table 11-1. Vaccinations 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 123 PSRT, participant safety may be threatened. 
Criteria for an individual participant’s departure from the schedule of vaccinations 
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 action 
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 
AEb, 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/hvtn123). 
b Does not include the following Grade 3 subjective reactogenicity symptoms:injection site pain, tenderness, 
fatigue/malaise, myalgia, arthralgia, chills, headache, nausea (unless IV rehydration required). 
For all safety pauses, HVTN Core notifies the HVTN 123 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 123 PSRT reviews safety data and decides 
whether the pause can be lifted or permanent discontinuation of vaccination 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 vaccinations. Based on the HVTN 123 PSRT assessment, DAIDS RAB 
notifies the FDA as needed. 

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If an immediate HVTN 123 PSRT notification or prompt HVTN 123 PSRT AE 
review is triggered, HVTN Core notifies the HVTN 123 PSRT as soon as possible 
during working hours (local time)—or, if the information was received during off 
hours, by the morning of the next workday. If a prompt HVTN 123 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 CRS submit to its IRB/EC and any applicable RE 
protocol-related safety information (such as IND safety reports, notification of 
vaccine holds due to the pause rules, unanticipated problems involving risks to 
participants or others, and notification of other unplanned safety pauses). CRSs 
must also follow all applicable RE reporting requirements. 
In addition, all other AEs are reviewed routinely by the HVTN 123 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 
Blinded daily safety reviews are routinely conducted by HVTN Core for events 
requiring expedited reporting to DAIDS, and events that meet safety pause criteria 
or prompt HVTN 123 PSRT AE review criteria. 
11.4.2 
Weekly review 
During the injection phase of the trial, the HVTN 123 PSRT reviews clinical 
safety reports on a weekly basis and conducts calls to review the data as 
appropriate. After the injections and the final 2-week safety visits are completed, 
less frequent reporting and safety reviews may be conducted at the discretion of 
the HVTN 123 PSRT. HVTN Core 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 123 PSRT, 
a pertinent national regulatory authority, NIH, Office for Human Research 

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Protections (OHRP), FDA, 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. 

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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; 
• Unblinding of staff and participants; 
• Quality control; 
• Protocol monitoring and compliance; 
• Advocacy and assistance to participants regarding negative social impacts 
associated with the vaccine 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 and HVTN standards or require 
additional instructions (eg, instructions for randomization specific to this study) 
will be described in the HVTN 123 Study Specific Procedures.  

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12.1 
Social impacts 
Participants in this study risk experiencing discrimination or other personal 
problems, resulting from the study participation itself or from the development of 
VISP. The HVTN CRS is obliged to provide advocacy for and assistance to 
participants regarding these negative social impacts associated with the vaccine 
trial. If HVTN CRS staff have questions regarding ways to assist a participant 
dealing with a social impact, a designated NIAID or HVTN Core representative 
can be contacted.  
Social harms are tabulated by the SDMC and are subjected to descriptive analysis. 
The goal is to reduce their incidence and enhance the ability of study staff to 
mitigate them when possible. 
Summary tables of social impact events will be generated weekly, and made 
available for review by the protocol chairs, protocol team leader, and the 
designated NIAID representative. 
12.2 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare.  
When such communication is needed, the CRS will request that its IRB/EC and 
any applicable RE expedite review of the message. If this review cannot be 
completed in a timeframe consistent with the urgency of the required 
communication, the site can contact the participant without IRB/EC approval if 
such communication is necessary to avoid imminent harm to the study participant. 
The CRS must notify the IRB/EC and any applicable RE of the matter as soon as 
possible. 

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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 123 are described 
below. 
Protocol history and modifications 
Date: December 12, 2018 
Protocol version: 1.0 
Protocol modification: 
 
Original Protocol 
 
 

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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 (DAIDS) Table for Grading the Severity of Adult and 
Pediatric Adverse Events. Corrected Version 2.1, July 2017. Available at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-
tables  
• The Manual for Expedited Reporting of Adverse Events to DAIDS. Version 
2.0, January 2010. Available https://rsc.niaid.nih.gov/clinical-research-
sites/manual-expedited-reporting-adverse-events-daids  
• HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
• HVTN 123 Special Instructions. Accessible through the HVTN protocol-
specific website. 
• HVTN 123 Study Specific Procedures. Accessible through the HVTN 
protocol-specific website. 
• HVTN 123 Site Lab Instructions. Accessible through the HVTN protocol-
specific website. 
• HVTN Manual of Operations. Accessible through the HVTN website. 

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• 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 (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 
https://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. 
 

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15 
Acronyms and abbreviations 
aa 
amino acid 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUC-MB area under the magnitude-breadth curve 
AVEG 
AIDS Vaccine Evaluation Group 
BAMA 
binding antibody multiplex assay 
BCR 
B-cell receptor 
BDS 
bulk drug substance 
β-HCG 
beta human chorionic gonadotropin 
BMI 
body mass index 
bnAb 
broadly neutralizing antibody 
CAB 
Community Advisory Board 
CBC 
complete blood count 
CD4-BS 
CD4 binding site 
CDC 
US Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CI 
confidence interval 
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 
DHVI 
Duke Human Vaccine Institute 
DSC 
differential scanning calorimetry 
DSMB 
NIAID Data and Safety Monitoring Board 
EAE 
adverse events requiring expedited reporting to DAIDS 
EC 
Ethics Committee 
EIA 
enzyme immunoassay 
ELISA 
enzyme-linked immunosorbent assay 
Envs 
envelope proteins 
FDA 
US Food and Drug Administration 
FI 
fluorescence intensity 

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Fred Hutch Fred Hutchinson Cancer Research Center 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GLA-SE glucopyranosyl lipid adjuvant-stable emulsion 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
HVTN 
HIV Vaccine Trials Network 
IB 
Investigator’s Brochure 
IBC 
Institutional Biosafety Committee 
ICH 
International Council on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ICS 
intracellular cytokine staining 
IDRI 
Infectious Disease Research Institute 
IFN 
interferon  
IM 
intramuscular 
IND 
Investigational New Drug 
IL 
interleukin 
IRB 
Institutional Review Board 
ITC 
Isothermal titration calorimetry 
IUD 
intrauterine device 
LTFU 
loss to follow-up 
mAb 
monoclonal antibody 
M-B 
magnitude-breadth 
MMR 
measles, mumps, and rubella 
nAb 
neutralizing antibody 
NHP 
nonhuman primate 
NIAID 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
US National Institutes of Health 
NZW 
New Zealand White 
OHRP 
US Office for Human Research Protections 
OPV 
oral polio vaccine 
PAB 
DAIDS Pharmaceutical Affairs Branch 
PBMC 
peripheral blood mononuclear cell 
PBS 
phosphate-buffered saline 
PCR 
polymerase chain reaction 
PI 
Principal Investigator 

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PCA 
principal component analysis 
PSRT 
Protocol Safety Review Team 
RAB 
DAIDS Regulatory Affairs Branch 
RE 
regulatory entity 
RSC 
DAIDS Regulatory Support Center 
RSV 
respiratory syncytial virus 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SCHARP Statistical Center for HIV/AIDS Research and Prevention 
SDMC 
statistical and data management center 
SEC 
size exclusion chromatography 
SMB 
Safety Monitoring Board 
SPT 
DAIDS Safety and Pharmacovigilance Team 
SUSAR 
suspected unexpected serious adverse reaction 
TB 
tuberculosis 
Tm 
melting temperature 
TNF 
tumor necrosis factor 
UCA 
unmutated common ancestor 
UW-VSL University of Washington Virology Specialty Laboratory 
Ve 
elution volume 
VISP 
Vaccine-induced seropositivity 
 

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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. 
Gray GE, Laher F, Lazarus E, Ensoli B, Corey L. Approaches to preventative and 
therapeutic HIV vaccines. Curr Opin Virol. 2016;17:104-9. 
5. 
Cohen YZ, Dolin R. Novel HIV vaccine strategies: overview and perspective. Ther 
Adv Vaccines. 2013;1(3):99-112. 
6. 
Goepfert P, Bansal A. Human immunodeficiency virus vaccines. Infect Dis Clin 
North Am. 2014;28(4):615-31. 
7. 
Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, et al. 
Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a 
double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 
2008;372(9653):1881-93. 
8. 
Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF. Placebo-
controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 
infection. J Infect Dis. 2005;191(5):654-65. 
9. 
Gray GE, Allen M, Moodie Z, Churchyard G, Bekker LG, Nchabeleng M, et al. 
Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 
vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-
concept phase 2b study. Lancet Infect Dis. 2011;11(7):507-15. 
10. 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. 
11. Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, et 
al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent 
recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in 
Bangkok, Thailand. J Infect Dis. 2006;194(12):1661-71. 
12. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, et 
al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in 
Thailand. N Engl J Med. 2009;361(23):2209-20. 
13. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, et 
al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 
2012;366(14):1275-86. 

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14. Robb ML, Rerks-Ngarm S, Nitayaphan S, Pitisuttithum P, Kaewkungwal J, Kunasol 
P, et al. Risk behaviour and time as covariates for efficacy of the HIV vaccine 
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Appendix A 
Sample informed consent form 
Title: A phase 1 double-blind, randomized, controlled clinical trial in healthy, 
HIV-1–uninfected adult participants to compare the safety, tolerability and 
immunogenicity of CH505TF gp120 produced from stably transfected cells to 
CH505TF gp120 produced from transiently transfected cells 
HVTN protocol number: HVTN 123 
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 HIV vaccines. HIV is the virus that causes AIDS. 
About 30 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. 
• Are the study vaccines safe to give to people? 
• Are people able to take the study vaccines without becoming too 
uncomfortable? 
• How do people’s immune systems respond to the study vaccines? (Your 
immune system protects you from disease.) 
• Does a small difference in the way the 2 vaccines were made change how 
people’s immune systems respond?  
2. The study vaccines cannot give you HIV. 
The study vaccines are not made from actual HIV. It is impossible for the study 
vaccines to give you HIV. Also, they cannot cause you to give HIV to someone 
else. 

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3. We do not know if the study vaccines will decrease, increase, or not change 
your risk of becoming infected with HIV if you are exposed to the virus. 
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. 
Several studies have tested whether HIV vaccines can reduce the risk of getting 
HIV from another person. In some studies, people who got the vaccine seemed to 
have the same risk of getting HIV as people who did not get the vaccine. In one 
study, people who got the vaccine seemed to have a lower risk of getting HIV 
than people who did not get the vaccine. In studies with a different vaccine, some 
people who got the vaccine had a higher risk of getting HIV than people who did 
not get the vaccine.  
This study differs from the studies in which people who got the vaccine had a 
higher or lower risk of getting HIV. We can tell you about the differences.  
We do not know whether the vaccines in this study will affect your risk of getting 
HIV from another person. The risk could be higher, lower, or unchanged. It’s very 
important to avoid exposure to HIV during and after the study. We will tell you 
how to avoid HIV. 
4. These study vaccines are experimental. 
The study vaccines are protein vaccines called Stable CH505TF gp120 and 
Transient CH505TF gp120. From here on, we will call them gp120S and gp120T 
study vaccines. They are experimental HIV vaccines. That means we do not 
know if the vaccines will be safe to use in people, or if they will work to prevent 
HIV infection. These vaccines are used only in research studies. 
For both vaccines, first DNA is used in a lab to tell cells how to make the protein. 
The gp120S vaccine was made by having the DNA that makes the protein become 
a part of the DNA of the cell. For the gp120T vaccine, the DNA that makes the 
protein was put into the cells, but did not become a part of the cell’s DNA. In both 
cases, after the protein is made, it is separated from the cells and purified into a 
vaccine. 
The vaccines were developed by the Division of AIDS (DAIDS) at the National 
Institutes of Health (NIH). The vaccines have man-made pieces of protein that 
look like part of the protein found in HIV. Your body’s immune system might 
learn to recognize these proteins and prepare itself to fight HIV. This is called an 
immune response. 
The vaccines are mixed with an adjuvant. An adjuvant is a substance added to the 
vaccine to help the immune system respond better. The adjuvant in this study is 
called GLA-SE. GLA-SE was made by Infectious Disease Research Institute 
(Seattle, Washington, USA). 

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The gp120S and gp120T vaccines are very similar protein vaccines made in the 
laboratory in two slightly different ways.  
The gp120S study vaccine has been tested in animals and it did not cause any 
health concerns. Animal testing may not always tell us what will happen with 
humans. It has been given to about 42 people in another study that is ongoing and 
has not caused serious health problems. If we learn anything from that study that 
might affect your participation in this study, we will tell you. 
The gp120T study vaccine has not been given to people before. Similar vaccines 
to those being used in this study have been given to thousands of people and have 
not caused serious health problems.  
General risks of vaccines: 
All vaccines can cause fever, chills, rash, aches and pains, nausea, headache, 
dizziness, and feeling tired. Vaccines can also cause pain, redness, swelling, or 
itching where you got the injection. Most people can still do their planned 
activities after getting a vaccine. Rarely, people have side effects that limit their 
normal activities or make them go to the doctor. 
Rarely, a vaccine can cause an allergic reaction, including a rash, hives, or trouble 
breathing. Allergic reactions can be life-threatening. You should tell us if you 
have ever had a bad reaction to any injection or vaccine. 
Very rarely, a vaccine causes an autoimmune disease in a person, or makes an 
autoimmune disease worse. An autoimmune disease happens when your immune 
system attacks your own body, instead of attacking an infection. 
Risks of the study vaccines: 
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 gp120S vaccine with the GLA-SE adjuvant has been given to a small number 
of people in a study that is still going on. The most common complaints have been 
pain or tenderness where they got the injection. One person had a skin infection 
where they got the injection. It did not affect that person’s daily routine. That 
person took some medicine and it got better within 5 days. 
The gp120T study vaccine has not been given to people before. 
The adjuvant, GLA-SE, has also been tested in over 900 people with vaccines for 
other diseases. The most common complaints were pain and tenderness where 
they got the injection and feeling tired. 

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Joining the study 
5. 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 other HIV vaccine or 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. Being in more than one study 
may not be safe. 
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 6 if you use a separate screening consent that covers these 
procedures. 
6. 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) 
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: Hepatitis B, Hepatitis C and syphilis. We will ask you about 
medications you are taking. We will ask you about behaviors that might put you 
at risk for getting HIV. If you were assigned female sex at birth, we will test you 
for pregnancy.  
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. 

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7. 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. 
8. 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 vaccines could affect the developing baby. You must agree to use 
effective birth control from 21 days before your first injection until 3 months after 
your last study injection. 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: 
9. You will come to the clinic for scheduled visits about [#] times over 
[Insert period of time]. 
Site: Insert number of visits and range of visit lengths. (There is site-specific variation 
in screening protocols and in the number of possible follow-up visits between 
protocol-mandated visits.) 
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). 
10. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for female participants 
who could become pregnant). 
US sites: Include the following paragraph. You can remove the box around the text. 

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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. 
11. We will give you either the gp120S study vaccine or the gp120T study 
vaccine.  
Half the people in this study will get the gp120S study vaccine and half will get 
the gp120T study vaccine. We will compare the results.  
Whether you get the gp120S or gp120T study vaccine is completely random, like 
flipping a coin.  
We have no say in whether you get the gp120S or gp120T study vaccine. We will 
not know which one you are getting, and neither will you. Only the pharmacist at 
this clinic will have this information while the study is going on.  
You will have to wait until everyone completes their final study visits to find out 
whether you got the gp120S or gp120T study vaccine. This could be several 
years. But, if you have a serious medical problem and need to know what you got 
before the end of the study, we can tell you. 
12. We will give you the study products on a schedule. 
You will be in one of 2 groups. You will get 3 injections during the study in your 
upper arm. 
 
Injection Schedule 
Group 
First 
injection 
2 month 
later 
6months 
later 
1 
gp120S 
gp120S 
gp120S 
2 
gp120T 
gp120T 
gp120T 
You will have to wait in the clinic for about a half hour after each injection to see 
if there are any problems. Then for that night and for 7 more days, you will need 
to keep track of how you are feeling and if you have any symptoms. Within 3 
days of each injection, we will also ask you how you are doing. Contact the clinic 
staff if you have any issues or concerns after getting an injection. If you have a 
problem, we will continue to check on you until it goes away. 
13. 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 

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• 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 10 mL and 275 mL (2 teaspoons to a little over 1 
cup). Your body will make new blood to replace the blood we take out.  
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 
Site: Insert Appendix D, Table of procedures (for informed consent form) in this 
section or distribute it as a separate sheet if it is helpful to your study participants. 
You are not required to do either. 
We will be looking for side effects. We will review the results of these procedures 
and tests with you at your next visit, or sooner if necessary. If any of the results 
are important to your health, we will tell you.  
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. The HVTN will test your samples to see how your immune system responds 
to the study products. 
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. 

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If you become HIV infected, the researchers may look at all of the genes of the 
virus found in your samples. The researchers will use this information to learn 
more about HIV and the study product(s).  
In some cases, researchers may take cells from your samples and grow more of 
them over time, so that they can continue to contribute to this study.  
These tests done on your samples are for research purposes, not to check your 
health. The labs will not give the results to you or this clinic because their tests 
are not approved for use in making health care decisions. These labs are only 
approved to do research tests.  
When your samples are no longer needed for this study, the HVTN will continue 
to store them. 
Site: Delete next section if using separate consent for use of samples and information 
in other studies 
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.  
The HVTN calls these samples “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. 

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Will the HVTN sell my samples and information? No, but the HVTN may share 
your samples with HVTN or 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 
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 do research with them.  
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks. 
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 

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• Any regulatory agency that reviews clinical trials, 
• The researcher’s IRB or EC 
• 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. 
US sites: Check HIPAA authorization for conflicts with this section. 
Your study records and samples will be kept in a secure location. We will label all 
of your samples and most of your records with a code number, not your name or 
other personal information. However, it is possible to identify you, if necessary. 
We will not share your name with the lab that does the tests on your samples, or 
with anyone else who does not need to know your name. 
Site: Any change to the following boxed text requires approval from HVTN 
Regulatory Affairs. You can remove the box around the text.  
We do need to share your name with the HVTN in case you need proof in the 
future that you participated in an HIV vaccine study. The HVTN will keep your 
name in a secure file with these items:  
• The name of your study  
• Your age or date of birth  
• Your study ID number  
• What study product(s) you received  
There are no HIV test results kept in this file. The HVTN will not share any 
information that could identify you without your agreement. The HVTN will 
remove your name from the file if you do not want it there. 
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 (FDA), 
• Any regulatory agency that reviews clinical trials, 

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• [Insert name of local IRB/EC] , 
• [Insert name of local and/or national regulatory authority as appropriate], 
• Infectious Disease Research Institute (IDRI) 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] 
US sites: Include the following boxed text. You can remove the box around the text. 
We have a Certificate of Confidentiality from the US government, to help protect 
your privacy. With the certificate, we do not have to release information about 
you to someone who is not connected to the study, such as the courts or police. 
Sometimes we can’t use the certificate. Since the US government funds this 
research, we cannot withhold information from it. Also, you can still release 
information about yourself and your study participation to others. 
The results of this study may be published. No publication will use your name or 
identify you personally. 
We may share information from the study with other researchers. We will not 
share your name or information that can identify you. 
A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov. This website will not include information that can 
identify you. At most, the website will include a summary of the results. You can 
search this website at any time. 

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18. We may stop your injections or take you out of the study at any time. We 
may do this even if you want to stay in the study and even if you were 
scheduled for more injections.  
This may happen if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, 
• you enroll in a different research study where you get another study product, 
or 
• the study is stopped for any reason. 
If we stop your injections, we may ask you to stay in the study to complete other 
study procedures. 
19. We will stop your injections if you become pregnant.  
We will encourage you to stay in the study if you choose. We will discuss your 
study options with you. 
If you leave the study while you are still pregnant, we will contact you after your 
due date to ask some questions about your pregnancy and delivery. 
20. If you get infected with HIV during the study, we will stop your injections, 
take fewer samples, and help you get care and support. 
We will encourage you to stay in the study for up to 6 months 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 routine medical procedures:  
In this study, we will do some routine medical procedures. These are taking blood 
and giving injections. These procedures can cause bruising, pain, fainting, 
soreness, redness, swelling, itching, a sore, bleeding, and (rarely) muscle damage 

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or infection where you got the injection. Taking blood can cause a low blood cell 
count (anemia), making you feel tired. 
Personal problems/discrimination/testing HIV antibody positive: 
About 10 to 20% of people who join HVTN studies report personal problems or 
discrimination because of joining an HIV vaccine 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.  
The body makes antibodies to fight or prevent infection. Most vaccines cause the 
body to make antibodies as a way of preventing infection. Your body may make 
antibodies to HIV because you received HIV study vaccines. The study vaccines 
may cause you to test positive on some types of HIV antibody tests, even if you 
are not infected with HIV. This is called vaccine-induced seropositivity (VISP). 
VISP means that after you get the study vaccines, a routine HIV test done outside 
this clinic may say you have HIV, even if you don’t. For this reason, you should 
plan to get HIV tests only at this clinic during the study. Our tests can tell the 
difference between true HIV infection and a positive result that is caused by the 
study vaccines. 
If you have a positive test result caused by the study vaccines at any time, we can 
arrange free HIV testing for as long as you need it. If this happens, we do not 
know how long you will test positive due to the study vaccines. If you receive a 
positive HIV test result and we determine it is because you have HIV, we will 
refer you for follow-up care. 
It is unlikely, but you could test negative at the end of the study and positive some 
time later, even though you don’t have HIV. This could happen if different HIV 
tests come into use. We will give you a phone number to call for more 
information.  
Site: Modify the following paragraph if applicable. If someone believes you are 
infected with HIV even if you are not, you could face discrimination and other 
problems. For example, in some countries, you could be denied medical or dental 
care, employment, insurance, a visa, or entry into the military. If you do have a 
positive HIV antibody test caused by the study vaccines, you will not be able to 
donate blood or organs. Your family and friends may treat you differently. We 
will give you a brochure that tells you more about testing HIV positive because of 
an HIV vaccine, and how you can avoid some of these problems. 
If you become pregnant during or after the study and have VISP, we don't know if 
the antibodies could be passed to your baby. We know that this happens with 
other vaccines, like tetanus vaccine. These antibodies from the mother are not a 
danger to the baby, and they go away over time. For most babies antibodies from 
the mother last for about six months. 

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You should always tell the delivery staff if you have VISP. However, you may 
still be tested for HIV using the antibody test when you deliver your baby. If your 
test is positive and the delivery staff believes you have an HIV infection, your 
baby may be started on antiretroviral treatment when it is not needed. If this 
happens, we can arrange for you and the baby to have a test that can tell the 
difference between true HIV infection and a VISP result. If you or the baby 
continue to have VISP, we can arrange this testing for free for as long as it is 
needed. 
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.  
US sites, include the following paragraph In the very unlikely event that your 
genetic information becomes linked to your name, a federal law called the 
Genetic Information Nondiscrimination Act (GINA) helps protect you. GINA 
keeps health insurance companies and employers from seeing results of genetic 
testing when deciding about giving you health insurance or offering you work. 
GINA does not help or protect you against discrimination by companies that sell 
life, disability or long-term care insurance. 
Unknown risks:  
We do not know if the study vaccines 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 [vaccine(s)]  might affect your HIV infection or how 
long it takes to develop AIDS. 

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We do not know if getting these study vaccines will affect how you respond to 
any future approved HIV vaccine. Currently, no HIV vaccine has been approved 
for use.  
We do not know how the study vaccines will affect a pregnant participant or a 
developing baby.  
Benefits 
22. The study may not benefit you. 
We do not expect the study vaccines to benefit you in any way. However, being in 
the study might still help you in some ways. The counseling that you get as part of 
the study may help you avoid getting HIV. The lab tests and physical exams that 
you get while in this study might detect health problems you don’t yet know 
about.  
This study may help in the search for a vaccine to prevent HIV. However, if the 
study vaccines later become 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.  
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 

HVTN 123, Version 1.0 / December 12, 2018 
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previously approved by HVTN Regulatory Affairs) to the boxed text. You can remove 
the box around the 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 products 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 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 vaccine 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, the HVTN will ask independent experts to review the decision. You 
always have the right to use the court system if you are not satisfied. 
Health contact visit  
26. After your clinic visits end, we will contact you 18 months after your first 
injection.  
We will contact you by phone, email, or text message [Site: Modify mode of 
contact as appropriate; consult IRB/EC if necessary] 18 months after your first 
injection to ask questions about your health. If you prefer to answer these 
questions in person, you can come to the clinic to do this. 
If we have any concerns about your health, we may need to have more contact 
with you. You are also welcome to contact us at any time if you have concerns 
about your health related to being in the study.  
If we ask you to come to the clinic, we will give you 
[Site: Insert compensation amount] for each visit. This amount is to cover the 
costs of [Site: Insert text]. 

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If someone outside this study clinic told you that you are infected with HIV, we 
will ask you to come back to the clinic for another HIV test. We will draw about 
15 mL (1 tablespoon) of blood. We may ask you to come back more than once for 
this testing. 
Because we will want to contact you after the main study, please tell us if your 
contact information changes, if you are moving away, or if you do not want us to 
contact you anymore. 
You can tell us at any time that you don’t want us to contact you after the main 
study. If you do so, you will not lose any benefits or rights you would normally 
have. 
All other information that is discussed earlier in this consent also applies to the 18 
month health contact. 
Questions  
27. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact  
"[name or title and telephone number of person on IRB/EC]" , at the committee. 
If you want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
28. In Section 15 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN keeps track of your decision about how 

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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, 
vaccines, 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.  
 
29. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
• You have read this consent form, or someone has read it to you. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the signature 
block below: 

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Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 
 

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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 vaccines could affect the developing baby. 
You must agree to use effective birth control from 21 days before your first 
injection until 3 months after your last study injection.  
Effective birth control means using any of the following methods every time you 
have sex: 
• Birth control drugs that prevent pregnancy—given by pills, shots, patches, 
vaginal rings, or inserts under the skin; 
• Male or female condoms, with or without a cream or gel that kills sperm; 
• Diaphragm or cervical cap with a cream or gel that kills sperm; 
• Intrauterine device (IUD); or 
• Any other contraceptive method approved by the researchers. 
You do not have to use birth control if: 
• You are only having sex with a partner or partners who have had a vasectomy. 
(We will ask you some questions to confirm that the vasectomy was 
successful.); 
• You have reached menopause, with no menstrual periods for one year; 
• You have had a hysterectomy (your uterus removed); 
• You have had your ovaries removed; 
• You have a tubal ligation (your “tubes tied”) or confirmed successful 
placement of a product that blocks the fallopian tubes; 
• You are having sex only with a partner(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 injection. 

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Appendix C 
Sample consent form for use of samples and 
information in other studies 
Title: A phase 1 double-blind, randomized, controlled clinical trial in healthy, 
HIV-1–uninfected adult participants to compare the safety, tolerability and 
immunogenicity of CH505TF gp120 produced from stably transfected cells to 
CH505TF gp120 produced from transiently transfected cells 
HVTN protocol number: HVTN 123 
Site: [Insert site name] 
When samples are no longer needed for this study, the HVTN wants to use them 
in other studies and share them with other researchers. The HVTN calls these 
samples “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. 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. 

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6. Will the HVTN sell my samples and information?  
No, but the HVTN may share your samples with HVTN or 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. 

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10. What are the risks of genetic testing?  
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you.  
US sites, include the following paragraph 
In the very unlikely event that your genetic information becomes linked to your 
name, a federal law called the Genetic Information Nondiscrimination Act 
(GINA) helps protect you. GINA keeps health insurance companies and 
employers from seeing results of genetic testing when deciding about giving you 
health insurance or offering you work. GINA does not help or protect you against 
discrimination by companies that sell life, disability or long-term care insurance.  
11. Who will have access to my information in studies using my extra samples? 
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• Any regulatory agency that reviews clinical trials, 
• The researcher’s IRB or EC 
• 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]. 

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If you have questions about your rights as a research participant, contact 
[name or title and telephone number of person on IRB/EC . 
13. Please choose only one of the options below and write your initials or make 
your mark in the box next to it. Whatever you choose, the HVTN 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, 
vaccines, 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. 
 

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Appendix D 
Table of procedures (for sample informed consent form) 
 
 
 
 
Time after first injection visit  
Procedure 
Screening 
visit 
First 
injection 
visit 
2 weeks 
2 months 
2 months +  
2 weeks 
6 months 
6 months +  
2 weeks 
9 months 
12 months 
18 months2 
Injection 
 
√ 
 
√ 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
√ 
 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
Urine test 
√ 
 
√ 
 
 
 
√ 
 
 
 
Blood drawn 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
Pregnancy test 
(participants 
assigned female 
sex at birth)1 
√ 
√ 
 
√ 
 
√ 
 
√ 
 
 
HIV testing and 
pretest counseling 
√ 
 
 
 
√ 
√ 
 
√ 
√ 
 
Risk reduction 
counseling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Interview/ 
questionnaire 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Health contact 
 
 
 
 
 
 
 
 
 
√ 
 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
1Persons who had a total hysterectomy (removal of the uterus verified by medical records) or removal of both ovaries (verified by medical records), are not required to 
have a pregnancy test. 
2Visit at 18 months is a health contact visit. 

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 123 of 131 
Appendix E 
Laboratory procedures (1of 2) 
 
 
Visit:
1
2
3
4
5
6
7
8
9
Day:
D0
D14
D56
D70
D168
D182
D273
D364
Week:
W0
W2
W8
W10
W24
W26
W39
W52
Month:
M0
M0.5
M2
M2.5
M6
M6.5
M9
M12
VAC1
VAC2
VAC3
Procedure
Ship to1
Tube4
Tube size
(vol. capacity)4
BLOOD COLLECTION
Screening or diagnostic assays
     Screening HIV test
Local Lab
Local Lab
SST
5mL
5
—
—
—
—
—
—
—
—
5
     HBsAg/anti-HCV
Local Lab
Local Lab
SST
5mL
5
—
—
—
—
—
—
—
—
5
     Syphilis
Local Lab
Local Lab
SST
5mL
5
—
—
—
—
—
—
—
—
5
     HIV diagnostics 9
UW-VSL
UW-VSL
EDTA
10mL
—
—
—
—
10
10
—
10
209
50
Safety labs11
     CBC/ Diff/ platelets
Local lab
Local lab
EDTA
5mL
5
—
5
—
5
—
5
5
—
25
     Chemistry panel5
Local lab
Local lab
SST
5mL
5
—
5
—
5
—
5
5
—
25
Immunogenicity assays 6
     Host genetics 7
CSR
FHCRC
ACD
8.5mL
—
17
—
—
—
—
—
—
—
17
     Cellular assays
ICS
CSR
HVTN Labs
ACD
8.5mL
—
42.5
—
—
59.5
—
59.5
—
42.5
204
Ag-specific B cell phenotyping
CSR
HVTN Labs
ACD
8.5mL
—
42.5
—
—
42.5
—
42.5
—
42.5
170
B cell repertoire analysis
CSR
HVTN Labs
ACD
8.5mL
—
34
—
—
34
—
34
—
34
136
     Humoral assays
Binding Ab
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
8.5
—
8.5
8.5
8.5
42.5
Neutralizing Ab
CSR
HVTN Labs
SST
8.5mL
—
8.5
—
—
8.5
—
8.5
—
8.5
34
Ab avidity 
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
y
—
—
0
Specimen storage
     PBMC
CSR
ACD
8.5mL
—
85
—
—
85
—
85
—
85
340
     Plasma
CSR
ACD
8.5mL
—
z
—
—
z
—
z
—
z
0
     Serum
CSR
SST
8.5mL
—
17
17
—
17
—
17
17
17
102
Visit total
25
255
27
0
275
10
265
45.5
258
1160.5
56-Day total
25
280
307
307
302
10
275
45.5
258
URINE COLLECTION
      Urine dipstick10,11
Local lab
Local lab
X
—
X
—
—
—
X
—
—
      Pregnancy test8,11
Local lab
Local lab
X
X
—
X
—
X
—
X
—
Tube volume (mL)
Total
Screening 
visit3
Assay Location2

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 124 of 131 
Appendix E 
Laboratory procedures (2 of 2) 
Footnotes 
1CSR = Central Specimen Repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA). 
2HVTN Laboratories include Fred Hutchinson Cancer Research Center (Seattle, Washington, USA); Duke University Medical Center (Durham, 
North Carolina, USA). 
3Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
4Local labs may assign appropriate alternative tube types for locally performed tests. 
5Chemistry panels are defined in Section 9.2 (pre-enrollment) and section 9.4 (postenrollment).  
6Immunogenicity assays will be performed at M0, M2.5, M6.5, M9, and M12. Based on the number of responders observed at these timepoints, lab 
assays may be performed on participants for humoral and cellular responses at other timepoints. 
7Genotyping may be performed on enrolled participants using cryopreserved PBMC collected at baseline, initially in participants who demonstrate 
vaccine-induced T-cell responses at postvaccination timepoints. 
8 For a participant who was born female (ie, assigned female sex at birth), pregnancy test must be performed on urine or blood specimens within 24 
hours of vaccination with negative results received prior to vaccination. Persons who have undergone total hysterectomy or bilateral oophorectomy 
(verified by medical records), are not required to undergo pregnancy testing. 
9At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.11), blood should be drawn for HIV 
diagnostic testing, as shown for visit 9 above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood for HIV diagnostic 
testing (see Section 9.13). 
10And microscopy if needed. 
11 For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, urinalysis and 
pregnancy tests will be collected. 
y = SST blood collected for binding Ab assay, neutralizing Ab assay and serum storage will also cover specimen needs for the Ab avidity assay; no 
separate blood draw is needed.  
z = 5 x 1mL aliquots of ACD plasma will be harvested for storage during PBMC processing; no separate blood draw is needed. 

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 125 of 131 
Appendix F 
Procedures at HVTN CRS  
Visit: 
011  
0211 
03 
04 
05 
06 
07 
08 
09 
Post 
Day: 
 
D0 
D14 
D56 
D70 
D168 
D182 
D273 
D364 
 
Month: 
 
M0 
M0.5 
M2 
M2.5 
M6 
M6.5 
M9 
M12 
 
Procedure 
Scr 
VAC1 
 
VAC2 
 
VAC3 
 
 
 
 
Study procedures2 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if 
used) 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
— 
X 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Risk reduction counseling3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Pregnancy prevention 
assessment4 
X 
X 
X 
X 
X 
X 
X 
X 
— 
— 
Behavioral risk assessment 
X 
— 
— 
— 
X 
X 
— 
X 
X 
— 
Confirm eligibility, obtain 
demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Social impact assessment 
— 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Social impact assessment 
questionnaire 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
Outside testing and belief 
questionnaire 
— 
— 
— 
— 
— 
X 
— 
— 
X 
— 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
— 
Intercurrent illness/adverse 
experience 
— 
X 
X 
X 
X 
X 
X 
X 
X 
— 
HIV infection assessment5 
X 
— 
— 
— 
X 
X 
— 
X 
X 
— 
Confirm HIV test results 
provided to participant 
— 
X 
— 
— 
— 
X 
X 
— 
X 
X 
Local lab assessment6 
 
 
 
 
 
 
 
 
 
 
Urine dipstick 
X 
— 
X 
— 
— 
— 
X 
— 
— 
— 
Pregnancy (urine or serum 
HCG)7 
X 
X 
— 
X 
— 
X 
— 
X 
— 
— 
CBC, differential and platelets 
X 
— 
X 
— 
X 
— 
X 
X 
— 
— 
Chemistry panel (see Sections 
9.2, 9.4) 
X 
— 
X 
— 
X 
— 
X 
X 
— 
— 
Syphilis, Hepatitis B, Hepatitis 
C 
X 
— 
— 
— 
— 
— 
— 
— 
— 
— 
Vaccination procedures8 
 
 
 
 
 
 
 
 
 
 
Vaccination9 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
Reactogenicity assessments10 
— 
X 
— 
X 
— 
X 
— 
— 
— 
— 
Poststudy 
 
 
 
 
 
 
 
 
 
 
Unblind participant  
— 
— 
— 
— 
— 
— 
— 
— 
— 
X 
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to vaccination. 
2 For specimen collection requirements, see Appendix E. 
3 Includes transmission risk reduction counseling for HIV-infected participants. 
4 Pregnancy prevention assessment is required only for participants who were assigned female sex at birth and 
are capable of becoming pregnant. 
5 Includes pretest counseling and HIV testing. A subsequent follow-up contact is conducted to provide post-test 
counseling and to report results to participant. If a participant has a confirmed diagnosis of HIV infection, do 
not perform HIV infection assessment. 

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 126 of 131 
6 For participants with a confirmed diagnosis of HIV infection, specimens listed under “Safety labs” in 
Appendix E, urinalysis, and urine pregnancy tests will be collected per the protocol schedule. 
7 For a participant who was assigned female sex at birth, pregnancy test must be performed on urine or blood 
specimens within 24 hours of vaccination with negative results received prior to vaccination. Pregnancy test to 
determine eligibility may be performed at screening, but must also be done on Day 0 prior to vaccination. 
Persons who have undergone total hysterectomy or bilateral oophorectomy (verified by medical records), are 
not required to undergo pregnancy testing. 
8 Not applicable to HIV-infected participants. 
9 Blood draws required at vaccination visits must be performed prior to vaccination; however, it is not necessary 
to have results prior to vaccination, except for results of a urine or serum pregnancy test, if indicated. 
10 Reactogenicity assessments performed daily for at least 7 days postvaccination (see Section 9.9). 
11 Specimens indicated for Day 0 may be obtained within the 14 days prior to vaccination, except for a 
pregnancy test which must be performed on urine or blood specimens within 24 hours of vaccination with 
negative results received prior to vaccination. 
 

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 127 of 131 
Appendix G 
Procedures at CRS for health contact 
 
Contact1 day: 546 
 
Month: 18 
Procedures 
 
 
Vital status and health events2 
 
X 
1 Clinic visits are not required, except that any participant reporting a diagnosis of 
HIV infection will be asked to come to the clinic so that HIV status can be 
confirmed. 
2 See Section 9.5 

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 128 of 131 
Appendix H 
Adverse events of special interest 
AEs of special interest (AESI) for this protocol include but are not limited to potential 
immune-mediated diseases; representative examples of AESI are listed below. Updates to 
AESI will be provided as an appendix to the HVTN 123 Study Specific Procedures. 
Gastrointestinal disorders 
Liver disorders 
Metabolic diseases 
• 
Celiac disease 
• 
Crohn’s disease 
• 
Ulcerative colitis 
• 
Ulcerative proctitis 
• 
Autoimmune cholangitis 
• 
Autoimmune hepatitis 
• 
Primary biliary cirrhosis 
• 
Primary sclerosing cholangitis 
• 
Addison’s disease 
• 
Autoimmune thyroiditis 
(including Hashimoto 
thyroiditis) 
• 
Diabetes mellitus type I 
• 
Grave’s or Basedow’s 
disease 
Neuroinflammatory disorders 
Musculoskeletal disorders 
Skin disorders 
• 
Acute disseminated 
encephalomyelitis, including site 
specific variants (eg, non-infectious 
encephalitis, encephalomyelitis, 
myelitis, myeloradiculomyelitis) 
• 
Cranial nerve disorders, included 
paralyses/paresis (eg, Bell’s palsy) 
• 
Guillain-Barré syndrome, including 
Miller Fisher syndrome and other 
variants 
• 
Immune-mediated peripheral 
neuropathies and plexopathies, 
including chronic inflammatory 
demyelinating polyneuropathy, 
multifocal motor neuropathy and 
polyneuropathies associated with 
monoclonal gammopathy 
• 
Multiple sclerosis 
• 
Narcolepsy 
• 
Optic neuritis 
• 
Transverse Myelitis 
• 
Antisynthetase syndrome 
• 
Dermatomyositis 
• 
Juvenile chronic arthritis 
(including Still’s disease) 
• 
Mixed connective tissue disorder 
• 
Polymyalgia rheumatic 
• 
Polymyositis 
• 
Psoriatic arthropathy 
• 
Relapsing polychondritis 
• 
Rheumatoid arthritis 
• 
Scleroderma, including diffuse 
systemic form and CREST 
syndrome 
• 
Spondyloarthritis, including 
ankylosing spondylitis, reactive 
arthritis (Reiter’s Syndrome) and 
undifferentiated 
spondyloarthritis 
• 
Systemic lupus erythematosus 
• 
Systemic sclerosis 
• 
Alopecia areata 
• 
Autoimmune bullous skin 
diseases, including 
pemphigus, pemphigoid 
and dermatitis 
herpetiformis 
• 
Cutaneous lupus 
erythematosus 
• 
Erythema nodosum 
• 
Morphoea 
• 
Lichen planus 
• 
Psoriasis 
• 
Sweet’s syndrome 
• 
Vitiligo 
Vasculitides 
Others 
• 
Large vessels vasculitis including: 
giant cell arteritis such as 
Takayasu’s arteritis and temporal 
arteritis 
• 
Medium sized and/or small vessels 
vasculitis including: polyarteritis 
nodosa, Kawasaki’s disease, 
microscopic polyangiitis, Wegener’s 
granulomatosis, Churg-Strauss 
syndrome (allergic granulomatous 
angiitis), Buerger’s disease 
thromboangiitis obliterans, 
necrotizing vasculitis and anti-
neutrophil cytoplasmic antibody 
(ANCA) positive vasculitis (type 
unspecified), Henoch-Schonlein 
purpura, Behcet’s syndrome, 
leukocytoclastic vasculitis 
• 
Antiphospholipid syndrome 
• 
Autoimmune hemolytic anemia 
• 
Autoimmune glomerulonephritis (including IgA nephropathy, 
glomerulonephritis rapidly progressive, membranous 
glomerulonephritis, membranoproliferative glomerulonephritis, and 
mesangioproliferative glomerulonephritis) 
• 
Autoimmune myocarditis/cardiomyopathy 
• 
Autoimmune thrombocytopenia 
• 
Goodpasture syndrome 
• 
Idiopathic pulmonary fibrosis 
• 
Pernicious anemia 
• 
Raynaud’s phenomenon 
• 
Sarcoidosis 
• 
Sjögren’s syndrome 
• 
Stevens-Johnson syndrome 
• 
Uveitis 
 

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 129 of 131 
Appendix I 
HVTN low risk guidelines for the US 
 

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 130 of 131 
 
 

HVTN 123, Version 1.0 / December 12, 2018 
HVTN123_v1-0_FINAL / Page 131 of 131 
Appendix J 
Protocol Signature Page 
A phase 1 double-blind, randomized, controlled clinical trial in healthy, HIV-1–
uninfected adult participants to compare the safety, tolerability and 
immunogenicity of CH505TF gp120 produced from stably transfected cells to 
CH505TF gp120 produced from transiently transfected cells 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (U.S.) Health and Human Service regulations (45 
CFR 46); applicable US 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, U.S. National Institutes of Health, Division of AIDS) and 
institutional policies 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
Investigator of Record Signature 
Date 
 
 
DAIDS Protocol Number: HVTN 123 
DAIDS Protocol Version: HVTN 123, Version 1.0 
Protocol Date: December 12, 2018