Clinical trial NCT05184452
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2021-11-15; Completion date: 2023-07-19
Enrollment: 95 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Part A:

The purpose of this part of the study is to understand how the body's immune system responds to a new lab-made antibody against HIV. The study is looking to see if the way the antibody is given affects the immune response. The study will also look at whether the antibody is safe to give to people and does not make them too uncomfortable.

Part B:

The purpose of this part of the study is to understand how the body's immune system responds to lab-made antibodies against HIV when they are given in combination at different doses. The study also wants to see if the way the antibodies are given affects the immune response.

Detailed description:
The HIV Vaccine Trials Network (HVTN) and the HIV Prevention Trials Network (HPTN) are conducting this study to test a combination of different antibodies against HIV. HIV is the virus that causes AIDS. Antibodies are made by the body as one way to respond to or fight infection. Researchers can also make antibodies in laboratories and give them to people by infusions into a vein or under the skin.

There are 2 parts of this study, Part A and Part B. About 15 people will take part in Part A of this study to test one study antibody. After early safety results from Part A are obtained, a decision will be made as to whether or not to do Part B of the study. Part B of the study would test a combination of 3 antibodies. If it is decided to move forward with Part B, 80 more people will join.

Arms: arm 1: Participants will receive PGDM1400LS 5 mg/kg by intravenous (IV) infusion at Month 0 arm 2: Participants will receive PGDM1400LS 20 mg/kg by IV infusion at Month 0 arm 3: Participants will receive PGDM1400LS 20 mg/kg by subcutaneous (SC) infusion at Month 0 arm 4: Participants will receive PGDM1400LS 40 mg/kg by IV infusion at Month 0 arm 5: Participants will receive PGDM1400LS 40 mg/kg by SC infusion at Month 0 arm 6: Participants will receive PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg by IV infusion sequentially in this order at Month 0 and Month 4 arm 7: Participants will receive PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 20 mg/kg by SC infusion sequentially in this order at Month 0 and Month 4 arm 8: Participants will receive PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram by IV infusion sequentially in this order at Month 0 and Month 4 arm 9: Participants will receive PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 1.4gram by SC infusion sequentially in this order at Month 0 and Month 4 arm 10: Participants will receive PGDM1400LS 40mg/kg + VRC07-523LS 40mg/kg + PGT121.414.LS 40 mg/kg by IV infusion sequentially in this order at Month 0 and Month 4
Interventions: intervention 1: PGDM1400LS (5mg/kg, IV) intervention 2: PGDM1400LS (20mg/kg, IV) intervention 3: PGDM1400LS (20mg/kg, SC) intervention 4: PGDM1400LS (40mg/kg, IV) intervention 5: PGDM1400LS (40mg/kg, SC) intervention 6: PGDM1400LS (1.4g, IV) intervention 7: PGDM1400LS (1.4g, SC) intervention 8: VRC07-523LS (20mg/kg, IV) intervention 9: VRC07-523LS (20mg/kg, SC) intervention 10: VRC07-523LS (1.4g, IV) intervention 11: VRC07-523LS (1.4g, SC) intervention 12: VRC07-523LS (40mg/kg, IV) intervention 13: PGT121.414.LS (20mg/kg, IV) intervention 14: PGT121.414.LS (20mg/kg, SC) intervention 15: PGT121.414.LS (1.4g, IV) intervention 16: PGT121.414.LS (1.4g, SC) intervention 17: PGT121.414.LS (40mg/kg, IV)
Intervention descriptions: intervention 1: 5 mg/kg to be administered via IV infusion intervention 2: 20 mg/kg to be administered via IV infusion intervention 3: 20 mg/kg to be administered via SC infusion intervention 4: 40 mg/kg to be administered via IV infusion intervention 5: 40 mg/kg to be administered via SC infusion intervention 6: 1.4gram to be administered via IV infusion intervention 7: 1.4gram to be administered via SC infusion intervention 8: VRC07-523LS 20mg/kg administered via IV infusion intervention 9: VRC07-523LS 20mg/kg administered via SC infusion intervention 10: VRC07-523LS 1.4g administered via IV infusion intervention 11: VRC07-523LS 1.4g administered via SC infusion intervention 12: VRC07-523LS 40mg/kg administered via IV infusion intervention 13: PGT121.414.LS 20mg/kg administered via IV infusion intervention 14: PGT121.414.LS 20mg/kg administered via SC infusion intervention 15: PGT121.414.LS 1.4g administered via IV infusion intervention 16: PGT121.414.LS 1.4g administered via SC infusion intervention 17: PGT121.414.LS 40mg/kg administered via IV infusion

Protocol documents:
Prot_ICF_000.pdf: 
PROTOCOL 
HVTN 140/HPTN 101 
A phase 1 dose-escalation clinical trial to evaluate the 
safety, tolerability, and pharmacokinetics of 
PGDM1400LS alone and in combination with VRC07-
523LS and PGT121.414.LS in healthy, HIV-uninfected 
adult participants 
DAIDS DOCUMENT ID 38723 
IND 154188 HELD BY DAIDS 
CLINICAL TRIAL SPONSORED BY 
Division of AIDS (DAIDS) 
National Institute of Allergy and Infectious Diseases (NIAID) 
National Institutes of Health (NIH) 
Department of Health and Human Services (DHHS) 
Bethesda, Maryland, USA 
STUDY PRODUCT(S) PROVIDED BY 
DAIDS, NIAID, NIH, DHHS 
(Bethesda, Maryland, USA) 
Dale and Betty Bumpers Vaccine Research Center (VRC), NIAID, NIH, DHHS 
(Bethesda, Maryland, USA) 
June 23, 2021  
Final 
HVTN 140/HPTN 101 
Version 1.0 


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Contents 
1 Overview ........................................................................................................................5 
1.1 
Protocol Team ................................................................................................9 
2 Ethical considerations ..................................................................................................11 
3 IRB/EC review considerations .....................................................................................13 
3.1 
Minimized risks to participants ....................................................................13 
3.2 
Reasonable risk/benefit balance ...................................................................13 
3.3 
Equitable participant selection .....................................................................14 
3.4 
Appropriate informed consent ......................................................................14 
3.5 
Adequate safety monitoring .........................................................................14 
3.6 
Protect privacy/confidentiality .....................................................................15 
4 Background ..................................................................................................................16 
4.1 
Rationale for trial concept ............................................................................16 
4.2 
PGDM1400LS ..............................................................................................18 
4.3 
PGT121.414.LS ............................................................................................19 
4.4 
VRC07-523LS (VRC-HIVMAB075-00-AB) ..............................................20 
4.5 
Trial design rationale ....................................................................................20 
4.6 
Plans for future product development and testing ........................................26 
4.7 
Preclinical studies .........................................................................................26 
4.8 
Clinical trials of PGT121, PGT121.141LS, PGDM1400, VRC07-523LS 
alone and in combinations ............................................................................36 
4.9 
Potential risks of study products and administration ...................................48 
5 Objectives and endpoints .............................................................................................51 
5.1 
Primary objectives and endpoints ................................................................51 
5.2 
Secondary objectives and endpoints ............................................................52 
5.3 
Exploratory objectives ..................................................................................53 
6 Statistical considerations ..............................................................................................54 
6.1 
Accrual and sample size calculations ...........................................................54 
6.2 
Randomization .............................................................................................59 
6.3 
Blinding ........................................................................................................60 
6.4 
Statistical analyses ........................................................................................60 
7 Selection and withdrawal of participants .....................................................................66 
7.1 
Inclusion criteria ...........................................................................................66 
7.2 
Exclusion criteria ..........................................................................................69 
7.3 
Participant departure from study product administration schedule or 
withdrawal (Part B) ......................................................................................72 
8 Study product ...............................................................................................................75 
8.1 
Study product regimen .................................................................................75 
8.2 
Study product formulation ...........................................................................76 
8.3 
Preparation of study products .......................................................................76 
8.4 
Administration ..............................................................................................85 
8.5 
Acquisition of study products ......................................................................87 
8.6 
Pharmacy records .........................................................................................87 
8.7 
Final disposition of study products ..............................................................88 


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9 Clinical procedures ......................................................................................................89 
9.1 
Informed consent ..........................................................................................89 
9.2 
Pre-enrollment procedures ...........................................................................91 
9.3 
Enrollment and study product administration visits .....................................93 
9.4 
Follow-up visits ............................................................................................95 
9.5 
HIV counseling and testing ..........................................................................96 
9.6 
Contraception status .....................................................................................97 
9.7 
Urine testing .................................................................................................98 
9.8 
Assessments of Solicited AEs ......................................................................98 
9.9 
Visit windows and missed visits ................................................................100 
9.10 Early termination visit ................................................................................100 
9.11 Pregnancy ...................................................................................................100 
9.12 HIV infection during the study ...................................................................101 
10 Laboratory ..................................................................................................................102 
10.1 CRS laboratory procedures ........................................................................102 
10.2 Total blood volume ....................................................................................102 
10.3 PGDM1400LS, VRC07-523LS, and PGT121.414.LS concentrations ......102 
10.4 Neutralizing antibody assay .......................................................................103 
10.5 ADA detection assays ................................................................................103 
10.6 ADA functional assay ................................................................................103 
10.7 Antibody reaction assays ............................................................................103 
10.8 HVTN Laboratory Center assay portfolio ..................................................103 
10.9 Exploratory studies .....................................................................................104 
10.10 Specimen storage and other use of specimens ...........................................104 
10.11 Biohazard containment ...............................................................................104 
11 Safety monitoring and safety review .........................................................................106 
11.1 Safety monitoring and oversight ................................................................106 
11.2 Safety reporting ..........................................................................................107 
11.3 Safety reviews ............................................................................................110 
11.4 Safety pause and prompt PSRT AE review................................................113 
11.5 Review of cumulative safety data ..............................................................115 
11.6 Study termination .......................................................................................115 
12 Protocol conduct ........................................................................................................117 
12.1 Social impacts ............................................................................................118 
12.2 Emergency communication with study participants ..................................118 
13 Version history ...........................................................................................................119 
14 Document references (other than literature citations) ................................................120 
15 Acronyms and abbreviations......................................................................................123 
16 Literature cited ...........................................................................................................126 
Appendix A Sample informed consent form for Part A .................................................132 
Appendix B Sample informed consent form for Part B .................................................152 
Appendix C Approved birth control methods for persons assigned female sex at birth 
(for sample informed consent form) ...........................................................173 


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Appendix D Sample consent form for use of samples and information in other studies 175 
Appendix E Table of procedures (for sample informed consent form) ..........................180 
Appendix F Laboratory procedures for Part A ...............................................................182 
Appendix G Laboratory procedures for Part B ...............................................................184 
Appendix H Procedures at HVTN CRS for Part A .........................................................186 
Appendix I Procedures at HVTN CRS for Part B .........................................................188 
Appendix J HVTN low risk guidelines for the US ........................................................190 
Appendix K HVTN low risk guidelines for Southern Africa .........................................193 
Appendix L Visit windows .............................................................................................194 
Appendix M Protocol Signature Page .............................................................................195 


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1 
 Overview 
Title  
A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, and 
pharmacokinetics of PGDM1400LS alone and in combination with VRC07-
523LS and PGT121.414.LS in healthy, HIV-uninfected adult participants 
Primary objective(s) 
• To evaluate the safety and tolerability of PGDM1400LS when administered 
via intravenous (IV) or subcutaneous (SC) routes (Part A) and of 
PGDM1400LS + VRC07-523LS + PGT121.414.LS when administered in 
sequence IV or SC (Part B) 
• To evaluate the serum concentrations and pharmacokinetics of PGDM1400LS 
after a single administration (Part A) and of PGDM1400LS + VRC07-523LS 
+ PGT121.414.LS after each three-mAb administration (Part B) 
• To evaluate the individual mAb-specific serum neutralizing activity after 
single product administration of PGDM1400LS (Part A) and after each three-
mAb administration of PGDM1400LS, VRC07-523LS and PGT121.414.LS 
(Part B) 
Study products  
• PGDM1400LS: a human mAb that targets the HIV-1 V2 glycan, centered on 
N160. It is a derivative of PGDM1400 that was engineered to improve in vivo 
elimination half-life. It has been developed by the Vaccine Research Program 
(VRP) of the National Institute of Allergy and Infectious Diseases (NIAID). 
PGDM1400LS was manufactured under current Good Manufacturing Practice 
(cGMP) standards at Just-Evotec (Seattle, Washington) under contract to 
DAIDS’s Vaccine Translational Research Branch (VTRB). The drug product 
was filled and released at the VRC Pilot Plant, operated under contract by 
Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, 
Inc., Frederick, MD. The drug product is provided at 100 mg/mL as 10 mL 
glass vials with a 4.75 mL fill volume. 
• PGT121. 414.LS is a human mAb that targets the HIV-1 V3 glycan, centered 
on N332. It is a derivative of PGT121 that was engineered for improved 
manufacturing, stability and in vivo elimination half-life by Just 
Biotherapeutics in collaboration with Dan Barouch and Collaboration for 
AIDS Vaccine Discovery (CAVD) investigators. The drug substance was 
manufactured under cGMP standards at Just Biotherapeutics under contract to 
DAIDS’s VTRB. The drug product was filled and released by the VRC and 
VCMP, Leidos Biomedical Research, Inc., Frederick, MD. Product is 
provided at 100 mg/mL as 10 mL glass vials with a 4.75 mL fill volume. 


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• VRC-HIVMAB075-00-AB (VRC07-523LS) is a human mAb that targets the 
HIV-1 CD4 binding site. It was developed by the VRC/NIAID/NIH and 
manufactured under cGMP standards at the VRC Pilot Plant operated under 
contract by the VCMP, Leidos Biomedical Research, Inc., Frederick, MD. 
Product is provided at 100 ± 10 mg/mL as 10 mL glass vials with a 6.25 ± 0.1 
mL fill volume and 3 mL glass vials with a 2.25 mL ± 0.1 mL fill volume. 
Table 1-1 Schema 
Study 
arm 
N* 
Dose 
Route 
Month 0 
Month 4 
Part A 
 
 
 
 
 
Group 1 
3 
5 mg/kg 
IV 
PGDM1400LS 
- 
 
 
 
 
 
 
Group 21 
3 
20 mg/kg 
IV 
PGDM1400LS 
- 
 
 
 
 
 
 
Group 31 
3 
20 mg/kg 
SC 
PGDM1400LS 
- 
 
 
 
 
 
 
Group 42 
3 
40 mg/kg 
IV 
PGDM1400LS 
- 
 
 
 
 
 
 
Group 52 
3 
40 mg/kg 
SC 
PGDM1400LS 
- 
Part B** 
 
 
 
 
 
Group 63 
16 
20 mg/kg +  
20 mg/kg + 
20 mg/kg 
IV 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
 
 
 
 
 
Group 73 
16 
20 mg/kg +  
20 mg/kg +  
20 mg/kg 
SC 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
 
 
 
 
 
Group 83 
16 
1.4 g +  
1.4 g + 
1.4 g 
IV 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
 
 
 
 
 
Group 93 
16 
1.4 g +  
1.4 g + 
1.4 g 
SC 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
 
 
 
 
 
Group 104 
16 
40 mg/kg +  
40 mg/kg + 
40 mg/kg 
IV 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
Total 
95 
 
 
 
 
IV = intravenous infusion; SC = subcutaneous infusion; *additional participants may be enrolled to 
ensure the availability of safety data from at least 3 participants in each group;** 
antibodies will be administered sequentially as 3 separate infusions; + sign = “and”. 
1Opening enrollment in Groups 2 & 3 follows review of safety data for participants in Group 1. 
Details are described in Section 11.3.1. 
2Opening enrollment in Group 4 & 5 follows review of safety data for participants in Groups 1- 3. 
3Opening enrollment in Groups 6, 7, 8, and 9 follows review of safety data for participants in Part 
A. 
4Opening enrollment in Group 10 follows review of safety data for participants from Groups 1-9. 


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Participants 
About 95 healthy, HIV-1–uninfected volunteers aged 18 through 50 years 
Design 
Multicenter, randomized, open-label study 
Duration per participant 
6 months per participant in Part A and 10 months per participant in Part B of 
scheduled clinic visits  
Estimated total study duration 
14 months (includes enrollment, planned safety holds, and follow-up)  
Investigational New Drug (IND) sponsor 
DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
Study product providers 
• PGDM1400LS: DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA)  
• PGT121.414.LS: DAIDS, NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
• VRC07-523LS: Dale and Betty Bumpers Vaccine Research Center (VRC), 
NIAID, NIH, DHHS (Bethesda, Maryland, USA) 
HVTN Leadership and Operations Center (LOC)  
HIV Vaccine Trials Network (HVTN) Leadership Group/Core Operations Center, 
Fred Hutchinson Cancer Research Center (Fred Hutch) (Seattle, Washington, 
USA) 
HVTN Statistical and data management center (SDMC) 
Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutch 
(Seattle, Washington, USA) 
HVTN Laboratory Center (LC) 
HIV diagnostic laboratory 
University of Washington Virology Specialty Laboratory (UW-VSL) (Seattle, 
Washington, USA) 


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Endpoint assay laboratories 
• Duke University Medical Center (Durham, North Carolina, USA) 
• South Africa Immunology Laboratory and National Institute for 
Communicable Diseases (Johannesburg, South Africa) 
Study sites 
HVTN and HPTN Clinical Research Sites (CRSs) in the US and sub-Saharan 
Africa to be specified in the Site Announcement Memo 
Safety monitoring 
HVTN 140/HPTN 101 Protocol Safety Review Team (PSRT); HVTN Safety 
Monitoring Board (SMB) 


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1.1 
Protocol Team 
Protocol leadership 
HVTN Chairs 
Colleen Kelley 
Emory University 
404-712-1435 
colleen.kelley@emory.edu 
Sharana Mahomed 
Centre for the AIDS 
Programme of Research in 
South Africa (CAPRISA) 
+27 31 655 0610 
Sharana.Mahomed@caprisa.
org 
HPTN Chairs 
Marc Siegel 
George Washington 
Medical Faculty 
Associates 
202-741-2165 
msiegel@mfa.gwu.edu 
 
HVTN Protocol Team 
leaders 
Shelly Karuna 
HVTN LOC, Fred Hutch 
206-667-4355 
mkaruna@fredhutch.org 
Simba Takuva 
HVTN LOC, Fred Hutch 
+27 11 989 9968 
stakuva@hcrisa.org.za 
HPTN Protocol Team 
leader 
Theresa Gamble 
HPTN LOC, FHI 360 
919-544-7040 x11350 
tgamble@fhi360.org 
 
HVTN Laboratory lead 
David Montefiori 
HVTN Laboratory Center 
919-684-5278 
david.montefiori@duke.edu 
HPTN Laboratory lead 
Estelle Piwowar-
Manning 
HPTN Laboratory 
Center, Johns Hopkins 
University 
410-614-6736 
epiwowa@jhmi.edu 
DAIDS Medical officer 
Peggy Yacovone 
DAIDS, NIAID 
240-292-0826 
margaret.yacovone@nih.gov 
DAIDS Medical officer 
Wairimu Chege 
DAIDS, NIAID 
240-292-4786 
wairimu.chege@nih.gov 
HVTN Statistician 
Chenchen Yu 
HVTN SDMC, Fred Hutch 
206-667-5658 
cyu@scharp.org 
HPTN Statistician 
Fei Gao 
HPTN, LOC, FHI 360 
fgao@fredhutch.org 
 
 
 
 
 
 
 
 


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Other contributors to the original protocol 
HVTN Medical monitor 
Shelly Karuna 
HVTN LOC, Fred Hutch 
DAIDS protocol 
pharmacist 
Shawn Chiambah 
Lynette Purdue 
DAIDS, NIAID 
HVTN Regional medical 
liaison 
Simba Takuva 
HVTN LOC, Fred Hutch 
VRC Consultant 
Lucio Gama  
Dale and Betty Bumpers 
Vaccine Research Center 
HVTN Clinical safety 
specialist 
Maija Anderson 
HVTN LOC, Fred Hutch 
HPTN 
Pharmacologist 
Julie Dumond 
UNC Chapel Hill 
HVTN Clinical trials 
manager 
India Tindale 
HVTN LOC, Fred Hutch 
HPTN Senior 
Clinical research 
manager 
Bonnie Dye 
HPTN LOC, FHI360 
HVTN Laboratory 
Center representative 
Jen Hanke 
HVTN Laboratory Center, 
Fred Hutch 
HPTN Laboratory 
Program 
representative  
Amber Moser 
HPTN Laboratory Center  
HVTN Statistician 
consultant 
Yunda Huang 
HVTN SDMC, Fred Hutch 
Statistical research 
associate 
Chenchen Yu 
HVTN SDMC, Fred Hutch 
SDMC Associate director 
of lab science 
April Randhawa 
SCHARP, Fred Hutch 
Lead clinical data 
manager 
Nate Holm 
SCHARP, Fred Hutch 
HVTN Regulatory affairs 
associate 
Laurie Rinn 
HVTN LOC, Fred Hutch 
DAIDS product lead 
Michael Pensiero 
DAIDS, NIAID 
Community Advisory 
Board (CAB) members  
Lenka Tswenyana 
PHRU Soweto/Kliptown 
CAB 
Melissa Turner 
George Washington 
University CAB 
Clinic coordinators 
Geoffrey Kamau 
The Hope Clinic 
Emory Vaccine Center 
Hannah Yellin 
George Washington 
University 
HVTN Community 
engagement unit 
representative 
Gail Broder 
HVTN LOC, Fred Hutch 
 
HPTN Community 
program manager  
Jonathan Lucas 
HPTN LOC, FHI 360  
HVTN Community 
educator/recruiter 
Chelsea Greer 
Emory Vaccine Center 
CRS 
HPTN Community 
educator/recruiter  
Ntando Yola 
Groote Schuur HIV CRS  
HVTN Protocol 
development manager 
Meg Trahey 
HVTN LOC, Fred Hutch 
HPTN Prevention 
research specialist 
Zoe Jones 
Nicholas Hastings 
HPTN LOC, FHI360 
HVTN Project 
coordinator  
Anders McConachie 
Haven Wilvich  
HVTN LOC, Fred Hutch 
HPTN Ethics 
Working Group 
representative 
Robert Klitzman 
Columbia University 


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2 
Ethical considerations 
It is critical that universally accepted ethical guidelines are followed at all sites 
involved in the conduct of clinical trials. The HIV Vaccine Trials Network 
(HVTN) and HIV Prevention Trials Network (HPTN) [hereafter referred to as the 
“Networks”] have addressed ethical concerns in the following ways: 
• Network trials are designed and conducted to enhance the knowledge base 
necessary to find new methods for the prevention of HIV infection, using 
methods that are scientifically rigorous and valid, and in accordance with 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) and/or other Good Clinical Practice 
(GCP) guidelines. 
• Network scientists and operational staff incorporate the philosophies 
underlying major codes (1-3), declarations, and other guidance documents 
relevant to human subjects research into the design and conduct of HIV 
vaccine and prevention clinical trials. 
• Network scientists and operational staff are committed to substantive 
community input—into the planning, conduct, and follow-up of its research—
to help ensure that locally appropriate cultural and linguistic needs of study 
populations are met. Community Advisory Boards (CAB) are required by 
DAIDS and supported at all Network research sites to ensure community 
input, in accordance with Good Participatory Practices (GPP) and all local and 
national guidelines.”  
• Network clinical trial staff counsel study participants routinely on how to 
reduce HIV risk. Participants who become HIV-infected during the trial are 
provided counseling on notifying their partners and about HIV infection 
according to local guidelines. Staff members will also counsel them about 
reducing their risk of transmitting HIV to others. 
• The Networks require that all sites develop plans for the care and treatment of 
participants who acquire HIV infection during a trial. Each plan may be 
developed in consultation with representatives of host countries, communities 
from which potential trial participants will be drawn, sponsors, and the 
Networks. Participants who become HIV-infected during the trial 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 CRS and ART is needed, a 
privately established fund will be used to pay for access to treatment to the 
fullest extent possible. 
• The Networks provide training so that all participating sites similarly ensure 
fair participant selection, protect the privacy of research participants, and 
obtain meaningful informed consent. During the study, participants will have 


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their wellbeing monitored, and to the fullest extent possible, their privacy 
protected. Participants may withdraw from the study at any time. 
• Prior to implementation, Network trials are rigorously reviewed by scientists 
who are not involved in the conduct of the trials under consideration.  
• Network trials are reviewed by local and national regulatory bodies and are 
conducted in compliance with all applicable national and local regulations. 
• The Networks design their research to minimize risk and maximize benefit to 
both study participants and their local communities. For example, Network 
protocols provide enhancement of participants’ knowledge of HIV and HIV 
prevention, as well as counseling, guidance, and assistance with any social 
impacts that may result from research participation. Network protocols also 
include careful medical review of each research participant’s health conditions 
and reactions to study products while in the study.  
• Network research aims to benefit local communities by directly addressing the 
health and HIV prevention needs of those communities and by strengthening 
the capacity of the communities through training, support, shared knowledge, 
and equipment. Researchers involved in Network trials are able to conduct 
other critical research in their local research settings. 
• The Networks value the role of in-country Institutional Review Boards 
(IRBs), Ethics Committees (ECs), and other Regulatory Entities (REs) as 
custodians responsible for ensuring the ethical conduct of research in each 
setting. 


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3 
IRB/EC review considerations 
US Food and Drug Administration (FDA) and other US federal regulations 
require IRBs/ECs/REs to ensure that certain requirements are satisfied on initial 
and continuing review of research (Title 45, Code of Federal Regulations (CFR), 
Part 46.111(a) 1-7; 21 CFR 56.111(a) 1-7). The following section highlights how 
this protocol addresses each of these research requirements. Each Network 
Investigator welcomes IRB/EC/RE questions or concerns regarding these research 
requirements. 
This trial is being conducted in countries outside of the United States, with 
funding from the US NIH among others. Due to this, the trial is subject to both 
US and local regulations and guidelines on the protection of human research 
subjects and ethical research conduct. Where there is a conflict in regulations or 
guidelines, the regulation or guideline providing the maximum protection of 
human research subjects will be followed. 
In compliance with international and local (as appropriate) ICH and/or other GCP 
guidelines, each research location has a locally-based Principal Investigator (PI) 
who is qualified to conduct (and supervise the conduct of) the research; and the 
research addresses an important local health need for an HIV prevention method. 
In addition, the investigators take responsibility for the conduct of the study and 
the control of the study products, including obtaining all appropriate regulatory 
and ethical reviews of the research. 
3.1 
Minimized risks to participants 
45 CFR 46.111 (a) 1 and 21 CFR 56.111 (a) 1: Risks to subjects are 
minimized. 
This protocol minimizes risks to participants by (a) correctly and promptly 
informing participants about risks so that they can join in partnership with the 
researcher in recognizing and reporting harms; (b) respecting local/national blood 
draw limits; (c) performing direct observation of participants post study product 
administration and collecting information regarding side effects for several days 
post study product administration; (d) having staff properly trained in 
administering study procedures that may cause physical harm or psychological 
distress, such as blood draws, study product administrations, HIV testing and 
counseling and HIV risk reduction counseling; (e) providing HIV risk reduction 
counseling and checking on contraception use (for persons assigned female at 
birth); and (f) providing safety monitoring. 
3.2 
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 


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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.  
3.3 
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. 
3.4 
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 
CRS is provided training in informed consent by the and is required to have a 
Standard Operating Procedure (SOP) on the informed consent process. The 
Networks require a signed consent document for documentation, in addition to 
chart notes or a consent checklist. 
3.5 
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 clinical staff and routinely by the HVTN 140/HPTN 


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101 Protocol Safety Review Team (PSRT). In addition, the HVTN Safety 
Monitoring Board (SMB) periodically reviews study data. 
3.6 
Protect privacy/confidentiality 
45 CFR 46.111 (a) 7 and 21 CFR 56.111 (a) 7: There are adequate 
provisions to protect the privacy of subjects and maintain the 
confidentiality of data. 
Privacy refers to an individual’s right to be free from unauthorized or 
unreasonable intrusion into his/her private life and the right to control access to 
individually identifiable information about him/her. The term “privacy” concerns 
research participants or potential research participants as individuals whereas the 
term “confidentiality” is used to refer to the treatment of information about those 
individuals. This protocol respects the privacy of participants by informing them 
about who will have access to their personal information and study data (see 
Appendix A and Appendix B). The privacy of participants is protected by 
assigning unique identifiers in place of the participant’s name on study data and 
specimens. In the United States, research participants in Network protocols are 
protected by a Certificate of Confidentiality from the US NIH, which can prevent 
disclosure of study participation even when that information is requested by 
subpoena. Participants are told of the use and limits of the certificate in the study 
consent form. In addition, each staff member at each study CRS in this protocol 
signs an Agreement on Confidentiality and Use of Data and Specimens with the 
Networks. In some cases, a comparable confidentiality agreement process may be 
acceptable. Each study CRS 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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4 
Background 
4.1 
Rationale for trial concept 
In 2017, more than 35 million people were living with HIV, and 1.8 million 
people were newly infected with the virus (4). There were 940,000 deaths 
attributable to HIV infection. One reason that such high rates of HIV-related 
deaths continue to occur globally – despite the advent of drugs that are highly 
effective at suppressing HIV replication – is that only about half of people living 
with HIV have access to antiretroviral therapy (ART). Another reason for 
continued HIV-related mortality is that ART does not cure HIV infection and 
must be maintained for a lifetime. Even in the United States (US), only 49% of 
the 1.1 million people living with HIV have suppressed virus to undetectable 
levels, despite the fact that most HIV-infected people in the US have access to 
ART (5). It is clear that antiretroviral therapy is necessary but not sufficient to end 
the AIDS epidemic, both in the US and globally, and that novel efforts to prevent 
HIV are critically needed. 
The recent discovery of multiple potent and broadly neutralizing antibodies 
(bnAbs) against HIV has led to the re-emergence of the concept that passive 
administration of antibodies may be useful for prevention (6). HIV-specific 
antibodies that target the HIV envelope protein (Env) can prevent simian-human 
immunodeficiency virus (SHIV) infection in rhesus monkeys and have been 
shown to reduce HIV RNA levels in humans (7-22). Until recently, however, 
these antibodies were few in number, targeted a narrow spectrum of HIV strains 
and Env epitopes, and were not potent enough for practical use. In the last decade, 
the field has changed dramatically: new developments in high throughput single-
cell PCR-amplification and novel soluble Env baits have led to the isolation of 
new monoclonal antibodies with extraordinary potency and breadth (6, 23, 24). 
These bnAbs may be effective for prevention of HIV infection when administered 
passively (6, 25, 26). 
One of the bnAbs currently under investigation is PGDM1400, a broadly 
neutralizing mAb that was identified from African donor 84 of the IAVI Protocol 
G cohort. PGDM1400 is a human mAb that interacts with glycans in the region of 
N160 on the V2 loop of gp120 Env (27). The PGDM1400 antibody is 
exceptionally broad and potent, with 60% global coverage at a median IC80 of < 
1 mcg/mL, and is, therefore, 10 to 100-fold more potent than the previous best in 
class CD4bs antibodies VRC01 and VRC07 as shown in Figure 4-1, top panel 
(23, 27-29). PGDM1400 has been demonstrated to be safe and well-tolerated in 
phase 1 trials, and to have a median half-life of about 20 days (Yunda Huang/Dan 
Barouch, personal communication). In vitro models suggest that administering 
these mAbs in combination will produce more potent and broader neutralization 
than administering any one mAb by itself (compare solid and dotted lines in 
Figure 4-1, bottom panel). Comparison of the solid lines suggests that 
administering all 3 mAbs in combination may produce neutralization superior to 
any of 2 of the mAbs in combination.  


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Figure 4-1 Neutralization Sensitivity (IC80) to the 208-virus VRC Multi-Clade panel for 
PGDM1400, PGT1221, VRC07-523LS and VRC01 (top panel) and predicted breadth and 
potency curves for PGT121, PGDM1400, VRC07-523LS and combinations of these mAbs 
against a panel of multiclade HIV isolates (bottom panel). 
This half-life of about 20 days limits the use of PGDM1400 in settings where 
frequent dosing may be a challenge. As a result, PGDM1400 was modified in the 
laboratory through rational engineering to produce a new bnAb, PGDM1400LS. 
This modified bnAb is designed to have a longer half-life, while maintaining the 
potency and breadth of parental PGDM1400. There is no clinical experience with 
this bnAb alone or in combination with a second or third bnAb, such as a CD4 
binding site mAb like VRC07-523LS and/or a V3 binding mAb like 
PGT121.414.LS. 
This first study of the PGDM1400LS mAb is a phase 1, dose-escalation, open-
label clinical trial to examine the safety, tolerability, dose, and pharmacokinetics 
of PGDM1400LS alone and in combination with VRC07-523LS and 
PGT121.414.LS. The hypothesis is that these regimens will be safe for 


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administration to healthy adults and will have a favorable PK profile by the IV 
and SC routes. Healthy adults 18-50 years of age will be enrolled. In Part A of the 
study, PGDM1400LS will be administered alone as a single IV infusion at 5, 20, 
or 40 mg/kg (Groups 1, 2, and 4) and as a single SC infusion at 20 or 40 mg/kg 
(Groups 3 and 5). In Part B of the study, participants will receive two doses 4 
months apart of PGDM1400LS + VRC07-523LS + PGT121.414.LS administered 
in two dosing approaches: (1) weight-based dosing at 20 or 40 mg/kg each IV or 
at 20 mg/kg each SC (Groups 6, 7 and 10); or (2) a fixed dose of 1.4 g each, 
administered IV or SC (Groups 8 and 9). Participants will be followed for 24 
weeks after the last study product administration. 
4.1.1 
Cross-network implementation 
DAIDS has requested that its two major prevention trial Networks—the HVTN 
and the HPTN—work together in the rapid development of HIV-directed bnAbs 
for both the advancement of vaccine research and HIV prevention purposes. This 
priority program leverages the historical partnership between the HVTN and the 
VRC (a major developer of anti-HIV bnAbs) and other commercial developers, 
the strong portfolio of biomedical-based HIV prevention trials that the HVTN and 
HPTN have developed over the past 2 decades, the multidisciplinary expertise of 
investigators in each Network, and the Networks’ complementary laboratory and 
statistical expertise. In addition, the two Networks have complementary CRSs that 
allow for rapid enrollment of participants, worldwide. The engagement of CRSs 
from both Networks, particularly in early phase trials, accelerates recruitment, 
diversifies the trial cohort, and builds capacity for the conduct of future bnAb 
efficacy trials. 
4.2 
PGDM1400LS 
PGDM1400 is a broadly neutralizing mAb identified from African donor 84 of 
the IAVI Protocol G cohort that targets a V2 apex epitope region of the human 
immunodeficiency virus-1 (HIV-1) envelope protein. PGDM1400LS is an 
engineered variant of PGDM1400 designed to increase its binding affinity for the 
neonatal Fc receptor (FcRn). The LS designation specifies methionine to leucine 
(L) and asparagine to serine (S) (M428L/N434S, referred to as LS) changes 
within the C-terminus of the heavy chain constant region far outside of the 
antigen-combining site (30). As a result of enhanced FcRn function, 
PGDM1400LS is anticipated to have an extended half-life in both serum and 
mucosal tissue compared to PGDM1400. Other than the two amino acid 
difference, PGDM1400LS is identical to PGDM1400. PGDM1400LS drug 
substance was manufactured under cGMP standards for NIAID by Just–Evotec, 
under contract to DAIDS’s VTRB. The drug product was filled and released at the 
VRC Pilot Plant, operated under contract by VCMP. 


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4.3 
PGT121.414.LS 
PGT121.414.LS was produced by Just Biotherapeutics in collaboration with Dan 
Barouch (Beth Israel Deaconess Medical Center), and collaborative engagement 
of CAVD investigators. The drug substance was manufactured under cGMP 
standards at Just Biotherapeutics under contract to DAIDS’s VTRB. The drug 
product was filled and released for the VRC by the VCMP, Leidos Biomedical 
Research, Inc., Frederick, MD. The PGT121.414.LS mAb is an engineered 
variant of PGT121. It contains a total of 8 residue modifications to improve 
various aspects of manufacturing, stability and in vivo elimination half-life. Six of 
the modifications are in the Fragment crystallizable (Fc) region, providing 
increased conformational stability leading to improved manufacturing 
characteristics including low pH stability and an improved storage stability 
profile. The 2 modifications in the Fc region of each heavy chain are the Xencor 
Xtend LS modifications helping provide a significantly reduced elimination half-
life in vivo (30, 31). The magnitude and breadth of neutralizing activity of 
PGT121.414.LS and its parent PGT121 in vitro were shown to be nearly 
equivalent against a multiclade panel of Env-pseudotyped viruses (Figure 4-2).  
 
Figure 4-2 Comparison of in vitro neutralizing activity of PGT121 and PGT121.414.LS against 
a multiclade pseudovirus panel (n=208). 50 mcg/mL was the highest concentration tested and is 
used as the cut-off for negative neutralization. Dotted line shows median IC50 and IC80 of all 
viruses (including those not neutralized). Solid line shows median IC50 and IC80 of viruses 
sensitive to neutralization (excluding those not neutralized). Data courtesy of the Vaccine Research 
Center, NIH. 
The bnAb, PGT121, was identified from African donor 17 of the International 
AIDS Vaccine Initiative (IAVI) Protocol G cohort. It targets the V3 glycan-
dependent epitope region of the HIV-1 virus. This epitope on the gp120 outer 
domain includes both protein and glycans and is centered on the conserved 
residue N332 (32-34). Using a 162-pseudovirus panel, representative of all major 
HIV-1 circulating clades, the PGT121 had a 10-fold higher median neutralizing 
potency than mAbs PG9, VRC01, or PGV04 and a 100-fold higher potency than 
2G12, b12, or 4E10 (23). While PGT121 neutralized a smaller percentage of the 
panel of pseudoviruses than VRC01 at an IC50 < 50 mcg/mL (63% for PGT121 
vs. 93% for VRC01), it exhibited high potency against the sensitive strains, with 
neutralization of 44% of the 162-virus panel at an IC50 < 0.1 mcg/mL. This 
percentage is almost twice the neutralization under the same conditions as PG9, 


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VRC01, PGV04 and 20–40 times more neutralizing than 2G12, b12, and 4E10- 
all of which have been investigated previously in passive protection studies (23, 
27, 29). 
4.4 
VRC07-523LS (VRC-HIVMAB075-00-AB) 
VRC07-523LS is a human mAb targeting the HIV-1 CD4 binding site, developed 
by NIAID-NIH at the VRC. A similar antibody, VRC01, also targeting the CD4 
binding site, is currently in clinical trials for both HIV-1 prevention (IND 113,611 
and IND 125,494) and therapeutic (IND 126,001, IND 126,664, and IND 
133,017) indications. VRC01 was originally isolated from a subject infected with 
HIV-1 for more than 15 years whose immune system controlled the virus without 
ART (35, 36). Through advances in B-cell immunology, cloning, and structure-
guided optimization techniques, numerous HIV-1 neutralizing mAbs, including 
VRC07 (“07” denotes sequential numbering when discovered), were isolated and 
subsequently engineered to have potency and breadth greater than those of earlier 
antibodies (11). This protocol will use VRC07-523LS (“523” denotes sequential 
numbering when the engineered variant was generated; “LS” denotes 2 amino 
acid mutations). 
The VRC07 (wild-type) heavy chain was identified by 454 deep sequencing based 
on its similarity to VRC01 and was then engineered to pair it with the VRC01 
(wild-type) light chain. The mutations that together define the 523 designation are 
a glycine-to-histidine mutation at residue 54 of the heavy chain, a deletion of the 
first 2 amino acids, glutamate and isoleucine, from the light chain, and a valine-
to-serine mutation at the third amino acid residue of the light chain (11). The LS 
designation in VRC07-523LS specifies methionine to leucine (L) and asparagine 
to serine (S) (M428L/N434S, referred to as LS) changes within the C-terminus of 
the heavy chain constant region. The LS mutation was introduced by site-directed 
mutagenesis to increase the binding affinity for the neonatal Fc-receptor (FcRn); 
this mutation increases the recirculation of functional immunoglobulin G (IgG) 
(14, 30), thus, increasing plasma half-life. VRC07-523LS was found to be 5- to 8-
fold more potent than VRC01, with an IC50 < 50 mcg/mL against 96% of HIV-1 
pseudoviruses representing the major circulating HIV-1 clades, and an IC50 < 1 
mcg/mL against 92% of HIV-1 viruses tested (11). 
4.5 
Trial design rationale 
4.5.1 
Dose (amount and number) 
The doses chosen for this trial are based upon observations of the neutralization 
potency required to achieve protective efficacy in an NHP meta-analysis (37) and 
in the AMP studies (38) (see Figure 4-3) as well as models of neutralization 
potency and coverage of bnAb combinations with IV or SC administration (see 
Figure 4-4). Both the AMP studies and the NHP meta-analysis suggested that 
achieving over 80% prevention efficacy may require an ID80 of between 200-400 


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(Figure 4-3). Achieving those ID80 titers may require mAb doses of at least 60 
mg/kg, combined (eg, 20 mg/kg each of 3 bnAbs) and quite possibly higher, 
particularly for subcutaneous administration (Figure 4-4). Subcutaneous 
bioavailability has ranged from about 35% of IV bioavailability for PGT121 (Y 
Huang, personal communication) to about 75% for VRC01 (39).  
The highest dose of bnAbs that will be administered in this study, 120 mg/kg, is 
considerably less than the approved dosages for a variety of intravenous 
immunoglobulin (IVIG) products currently licensed for use in the US (eg, 200-
800 mg/kg Privigen every 2-4 weeks for primary immune deficiency). 
This trial is designed to evaluate both SC and IV routes, as SC administration may 
be more feasible than IV in some settings, and the comparison of these routes will 
elucidate the bioavailability of PGDM1400LS SC vs. IV and, thus, inform future 
decisions regarding dose, frequency and route of PGDM1400LS administration. 
Toward informing future dosing decisions, the trial is also designed to evaluate 
both weight-based and fixed dosing. The fixed dose of 4.2 g of total mAb (1.4 g 
of each mAb) would be equivalent to a weight-based dose of 60 mg/kg of total 
mAb (20 mg/kg each) for a 70 kg participant; 70 kg is the approximate median of 
participants’ baseline weights in the AMP studies (38). A PK model of 
administration of a 4.2 g fixed dose underscores the comparability of this dose to 
a 60 mg/kg dose in terms of coverage at an ID80 >200 (see Figure 4-5).  
The effect of body weight on drug biodistribution has been observed for some 
monoclonal antibodies (39-43), but body-weight-based dosing is not clearly 
necessary in human adults, who have a body size range of generally only 2- to 3-
fold (44, 45). When body weight has a significantly less than proportional effect 
on PK parameters, body-weight-based dosing may over-adjust for the body size 
effect. Fixed dosing simplifies administration, potentially enhancing safety by 
reducing dosing errors, and it can be more cost-effective and convenient to 
manufacture and administer. Of note, the anti-SARS-CoV-2 mAbs in late-stage 
clinical trials or post-EUA are administered in fixed doses (evaluated at up to 8 g 
total per administration), as are many mAbs used for oncologic and anti-
inflammatory indications. Whether fixed dosing is equivalent to body-weight-
based dosing for a given mAb is unknown until studied in the target population 
(eg, adult humans) and there is a growing call to assess it early in clinical 
development programs. (44-46). 


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Figure 4-3 Relationship between neutralization titers and level of prevention efficacy. (A) In 
humans in the AMP studies. predicted ID80 serum neutralizing titer is calculated as the median 
VRC01 concentration at mid-infusion visits (35.0 µg/ml) divided by IC80 (concentration from BAMA) 
of the acquired virus (n=162 infected cases) from the AMP trials. The median concentration was 
computed based on the n=82 non-case VRC01 recipients from both dose arms sampled for PK 
modeling (Y. Huang, unpublished data). (B) In a meta-analysis of NHP receiving a single bnAb 
(37). 
Ideally, this study will demonstrate that PGDM1400LS alone and in combination 
with VRC07-523LS and PGT121.414.LS is safe and well-tolerated when given 
IV and SC, and that the half-life of PGDM1400LS is significantly extended 
compared to parental PGDM1400, as well as unchanged by co-administration 
with VRC07-523LS and PGT121.414.LS. The study also aims to discern whether 
sera from infused participants retain the same neutralizing breadth in vitro as 
parental PGDM1400 alone and in combination with VRC07-523LS and 
PGT121.414.LS. 
This study will be part of a series of studies that aim to evaluate safety and 
tolerability of mAbs and whether combining mAbs that target different sites on 
the virus is additive or synergistic with respect to neutralization breath and 
potency. These data will be critical for designing future mAb studies. 


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A Average coverage in the first week IV, total dose amount 60 mg/kg 
 
B Average coverage in the first week: SC (bioavailability = 35%), total dose amount 60 mg/kg 
 
C Average coverage in the first week: SC (bioavailability = 75%), total dose amount 60 mg/kg 
 
Figure 4-4 Average coverage in the first week for IV bnAb combinations with a total dose of 60 
mg/kg (A); average coverage in the first week for SC bnAb combinations [bioavailability = 35% 
(B) or 75% (C)] with a total dose amount 60 mg/kg. 1-Active, 2-Active, and 3-Active refer to the 
number of bnAbs in the combination that provide coverage over the viruses in the specified panel at 
ID80 >200 min-max % coverage across all dose combinations. m= number of viruses in the panel. 
 


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A Average coverage in the first week: IV, total fixed dose 4.2 g
 
B Average coverage in the first week: SC (bioavailability = 35%), total fixed dose 4.2 g 
 
C Average coverage in the first week: SC (bioavailability = 75%), total fixed dose 4.2 g 
 
Figure 4-5 Average coverage in the first week for IV (A) or SC [bioavailability = 35% (B) or 
75% (C)] bnAb combinations with a total fixed dose of 4.2 g. 1-Active, 2-Active, and 3-Active 
refer to the number of bnAbs in the combination that provide coverage over the viruses in the 
specified panel at ID80 >200. m= number of viruses in the panel. 
4.5.2 
Schedule 
There is currently no human PK data on PGDM1400LS and PGT121.414.LS. 
Therefore, the dosing schedule in Part B was selected based on the PK modeling 
of PGDM1400, PGT121, and VRC07-523LS in combination, assuming no drug-
drug PK interactions. Specifically, the PK modeling shown in Figure 4-6 is based 
on human data from n=120 HIV-uninfected participants for VRC07-523LS in 
HVTN 127/HPTN 087, n = 16 HIV-uninfected participants for PGT121 in 
Barouch 628 (T001), and n= 18 HIV-uninfected participants for PGDM1400 in 
Barouch 693 (T002). Initiation of testing in Part B at the interval proposed will be 
supported by PGDM1400LS preclinical PK data, including in FcRn mouse and 
non-human primate (NHP) models, and PGT121.414.LS PK data from Part A of 
the ongoing HVTN 136/HPTN 092 clinical trial. The half-lives of the LS variants 
of PGDM1400 and PGT121 are predicted to be 2-3 fold longer. Predicted serum 
concentrations following multiple IV infusions at 20 mg/kg every 8 to 20 weeks 
were generated through Monte Carlo simulations of 1000 hypothetical trial 
participants based on population PK models of PK data for PGT121, IV 
PGDM1400, and VRC07-523LS as of June 2018.  


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Figure 4-6 Predicted PGDM1400, PGT121 and VRC07-523LS concentration with multiple 8- to 
20-weekly IV infusions at 20mg/kg. Shown are median (solid lines), 5th and 95th percentiles 
(shaded areas) of predicted drug levels with values truncated at half of the lower limit of 
quantification – 0.12 mcg/mL (PGDM1400), 0.25 mcg/mL (PGT121) or 1.1/2 mcg/mL (VRC07-
523LS).  
In these simulations, the body weights of the hypothetical trial participants were 
randomly drawn with replacement from the sample of body weights collected in 
the HVTN 104 study of VRC01 in US sites, some of which will be used in this 
study (39, 47). In addition, linear PK was assumed for the mAbs so that PK 
parameters estimated based on single-dose settings carried forward to multiple-
dose settings. The PK parameters used in the simulations were estimated based on 
observed serum concentration data for PGDM1400 at 3 and 10 mg/kg following a 
single IV infusion, for PGT121 at 3, 10, and 30 mg/kg following a single IV 
infusion and at 3 mg/ kg following a single SC injection, and for VRC07-523LS 
at 5, 20, and 40 mg/kg following a single IV infusion, at 20 mg/ kg following 
three 12-weekly IV infusions, at 5mg/ kg following a single and at 5 mg/kg 
following three 12-weekly SC injections. The mean and variance of log-
transformed serum concentrations were computed after each IV infusion. 
Specifically, at 16 weeks after the second IV infusion at a dose level of 20 mg/kg, 
the serum concentrations (mean ± standard deviation [SD]) were predicted to be 
1.6 ± 0.5 for PGDM1400, 1.8 ± 0.5 for PGT121, and 3.4 ± 0.6 for VRC07-523LS. 
The chance of having a VRC07-523LS serum concentration > 1 mcg/mL at 48 
weeks post the second IV infusion at 20 mg/kg is predicted to be about 24%. 


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Given the IC50 and IC80 data of the mAbs, these PK simulation results suggest that 
the proposed study design should be able to attain desirable serum concentration 
levels over time that confer sufficient neutralization against diverse panels of 
viruses (see Section 4.1). Thus, based on currently available data, in Part B, a 
dosing interval of every 16 weeks was selected to have high probability of 
achieving a trough above 1 mcg/mL for all study mAbs. This threshold of 1 
mcg/mL is the limit of detection of the currently used anti-idiotypic enzyme-
linked immunosorbent assay (ELISA) for mAb serum concentrations. 
4.6 
Plans for future product development and testing 
This trial aims to establish an initial safety, PK and neutralization profile for a 
triple-bnAb combination that is thought likely to advance to efficacy testing on 
the basis of early preclinical and clinical data, and informed by results from the 
first efficacy trials of a bnAb for HIV prevention, the AMP Studies. The approach 
of combining three bnAbs that bind and neutralize three independent epitopes on 
the HIV envelope protein is akin to triple-combination ART and appears to have 
the potential to make a comparable impact on the persistent HIV pandemic.  
4.7 
Preclinical studies 
4.7.1 
 Preclinical studies of PGDM1400  
4.7.1.1 
GLP repeat dose toxicity study in rats.  
In the repeat dose toxicity study, administration of PGDM1400 alone or in 
combination with PGT121 by once weekly subcutaneous or intravenous injection 
for one month (total of 5 injections) at 30 mg/kg/dose, and alone by once weekly 
intravenous injection at 300 mg/kg/dose, resulted in slightly higher plasma 
proteins in males, and a higher incidence of hemorrhage at the subcutaneous 
injection sites that had received PGDM1400. Neither of these findings was 
considered adverse, and they were not observed after a one-month recovery 
(treatment-free) period. No clinical signs or local reactions were noted at the 
injection sites that were considered to be related to the administration of 
PGDM1400 alone or in combination with PGT121. Body weight, food 
consumption, hematology, coagulation and urine volume and composition were 
unaffected by treatment with PGDM1400 alone or in combination. The NOAEL 
for intravenous administration was 300 mg/kg and for subcutaneous injection was 
30 mg/kg, which were the highest dose levels administered. 
4.7.1.2 
Preclinical challenge study of PGDM1400 
PGDM1400 was evaluated against a novel challenge stock, SHIV-325c, 
developed specifically for NHP challenge studies of PGDM1400, CAP256, and 
related variants and PGDM1400 demonstrated protection at low doses. As shown 
in Figure 4-7 below, rhesus macaques received a single IV infusion of 
PGDM1400 (n = 5 at 2 mg/kg; n = 5 at 0.4 mg/kg; n = 4 at 0.08 mg/kg) 24 hours 


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before high dose intrarectal challenge with SHIV-325c. All animals in the control 
group were infected between days 7 and 28. In the 2 mg/kg group, one of five 
animals receiving PGDM1400 became infected on Day 28; in the 0.4 mg/kg 
group, no animals became infected; in the 0.08 mg/kg group, three of four animals 
receiving PGDM1400 were infected. The average serum antibody concentrations 
in animals administered PGDM1400 at doses of 2, 0.4, and 0.08 mg/kg were 6.9, 
2.5, and 0.22 mcg/mL, respectively, at the time of challenge. The half-life of 
PGDM1400 was calculated for the 2, 0.4, and 0.08 mg/kg groups to be 7.7 days, 
6.7 days, and 6.3 days, respectively (28).  
 
Figure 4-7 Protective efficacy of PGDM1400 against SHIV-325c in rhesus macaques. Plasma 
viral RNA (as log vRNA copies/mL) is shown for animals that received: (A) saline control; (B) 
PGDM1400 (2mg/kg); (C) PGDM1400 (0.4 mg/kg); (D) PGDM1400 (0.08 mg/kg). The assay 
sensitivity limit was >50 RNA copies/mL 
4.7.2 
Preclinical studies of PGDM1400LS 
4.7.2.1 
Preclinical study in rhesus macaques (Sanofi, VRC, BIDMC, Ragon 
Institute, Scripps, NIAID) 
In 2017, L. Xu et al reported in Science (48) on the development of broadly 
neutralizing trispecific antibodies to HIV-1. Trispecific antibodies combine the 
specificities against 3 distinct epitopes on the HIV-1 envelope protein into a 
single molecule; one of these epitopes is the V2 binding site of PGDM1400. LS 
mutations were engineered into the Trispecific molecules as well as the parental 
antibodies, including PGDM1400. As shown in Figure 4-8B, plasma antibody 
levels in rhesus macaques administered 5 mg/kg IV of PGDM1400LS are 
comparable to that of VRC01LS which has a published half-life in humans of 71± 
18 days (49). And as depicted in Figure 4-8C, three antibody specificities were 
required to prevent viremia in 100% of rhesus macaques challenged with a 
mixture of SHIV BaLP4 and SHIV 325c.  


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Figure 4-8 Trispecific and broad neutralizing antibody sensitivity of SHIVs, plasma 
antibody levels and viremia in rhesus macaques. All antibodies in the figure are LS 
variants. (A) The IC50 neutralizing titers (mcg/ml) of VRC01, PGDM1400, and 
VRC01/10E8v4-PGDM1400 against replication competent SHIV BaLP4 or SHIV 325c. 
(B) Plasma levels of VRC01, PGDM1400 and VRC01/PGDM1400-10E8v4 in rhesus 
macaques (n=8 on each arm, done in two separate experiments with 4 animals each). All 
animals were administered 5 mg/kg of the indicated antibody intravenously. Each data 
point represents the mean +/− SEM of the values from all 8 animals per group. (C) 
Plasma viral loads in rhesus macaques (n=8 per group) challenged with a mixture of 
SHIV BaLP4 and SHIV 325c, 5 days after intravenous administration of either VRC01, 
PGDM1400 or VRC01/PGDM1400-10E8v4. (Figure from Xu et al., (48)). 
4.7.2.2 
Pharmacokinetic study of PGDM1400LS in human neonatal Fc receptor 
(FcRn) transgenic mice 
The VRC, NIAID, NIH evaluated the in vivo pharmacokinetic parameters of 
PGDM1400LS in human FcRn transgenic mice at a dose of 5 mg/kg via the IV 
route. The levels of antibody in the sera of these animals at various time points 
after administration were then quantified by using a HIV-1 trimer based ELISA 
(see Figure 4-9).  


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Figure 4-9 Sera levels of PGDM1400LS antibody in five human FcRn transgenic mice 
administered at 5 mg/kg via the IV route. 
The pharmacokinetic parameters were calculated using a non-compartment model 
in WinNonLin software package and are summarized in Table 4-1. 
PGDM1400LS displayed a PK profile similar to other anti-HIV-1 antibodies in 
this animal model and the data provide support for the development of 
PGDM1400LS for clinical studies.  
Table 4-1 In vivo pharmacokinetic parameters for PGDM1400LS in human FcRn transgenic 
mice administered at 5 mg/kg via the IV route. 
 
4.7.2.3 
Binding affinity study of PGDM1400LS compared to parental PGDM1400  
The VRC, NIAID, NIH compared the binding affinity of PGDM1400LS and 
PGDM1400. HIV Env Trimer 4571 binding to PGDM1400LS and the parental 
antibody PGDM1400 was measured by bio layer interferometry on a ForteBio 
OctetRED384. The binding affinity was measured and the equilibrium 
dissociation constant values were comparable (see Table 4-2) 


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Table 4-2 Binding Affinity of PGDM1400LS and PGDM1400 to HIV Env Trimer 4571 
Antibody 
KD (nM) ± standard error of the mean 
PGDM1400LS 4.6 ± 0.9 
PGDM1400 
4.6 ± 0.8, 5.2 ± 0.6 
 
4.7.2.4 
In vitro neutralization study comparing PGDM1400LS with parental 
PGDM1400 
The VRC, NIAID, NIH compared the in vitro neutralization activities of 
PGDM1400LS and PGDM1400 against a multiclade virus panel (n=3). The 80% 
inhibitory concentration (IC80) for PGDM1400LS and PGDM1400 were 
comparable (see Table 4-3). For additional in vitro neutralization data for 
PGDM1400 LS, please see the Investigator’s Brochure (IB). 
Table 4-3 Neutralization potency of PGDM1400LS and parental PGDM1400 in a 3-
pseudovirus panel assay 
Virus 
Clade 
IC80 (mcg/mL) 
PGDM1400 LS 
(production run 
5537) 
PGDM1400 LS 
(production run 
5515) 
PGDM1400 
MI369.A5 
A 
27.25 
25.46 
25.00 
DU156.12 
C 
17.37 
16.54 
16.00 
A03349MI.vrc4a D 
428.47 
238.65 
320.00 
4.7.2.5 
Autoreactivity evaluation of PGDM1400LS 
The VRC, NIAID, NIH assessed potential reactivity to human epithelial type 2 
(HEp-2) cells and to phospholipid cardiolipin. The reactivity to HEp-2 cells was 
assessed by immunofluorescence staining (see Figure 4-10) and potential binding to 
cardiolipin by ELISA (see Figure 4-11). 4E10 and VRC01LS bnAbs were used as 
positive and negative controls, respectively. The results showed that PGDM1400LS 
did not display detectable binding to either HEp-2 cells or cardiolipin, suggesting that 
PGDM1400LS does not exhibit detectable polyspecific autoreactivity. 


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Figure 4-10 Representative images for the reactivity of 4E10, VRC01-LS and PGDM1400LS to 
HEp-2 cells by immunofluorescence staining using 25 or 50 mcg/mL of antibody. The tests 
on two separate days showed same results, thus only one was shown. Reactivity scores are shown 
as red inset numbers.  
 
 
Figure 4-11 Antibody binding to cardiolipin by ELISA. 4E10, VRC01LS and PGDM1400LS 
were tested at 100, 33.3, 11.1 and 3.7 μg/mL and plotted with red squares, black diamonds and 
green dots, respectively. 
4.7.3 
 Preclinical studies of PGT121.414.LS  
Preclinical studies of PGT121.414.LS include: humanized FcRn mouse PK, NHP 
PK, repeat dose toxicity and Tissue Cross Reactivity as detailed below. 


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4.7.3.1 
Pharmacokinetic study of PGT121.414.LS in human neonatal Fc receptor 
(FcRn) transgenic mice 
The VRC, NIAID, NIH evaluated the in vivo pharmacokinetic profile of 
PGT121.414.LS in three human FcRn transgenic mice (50-52). In this study, we 
tested PGT121.414.LS (lot #S-20190121-1) produced from a stably transfected 
CHO cell line. The antibody was given at a single bolus dose of 10 mg/kg via the 
intravenous route. The levels of antibody in the sera of these animals at various 
time points up to 28 days after administration were then quantitated by an anti-
PGT121 idiotype based ELISA method. Figure 4-12 shows the sera levels of 
PGT121.414.LS in each animal, with levels maintained above 10 mcg/mL up to 
day 9 post infusion in all animals. After day 9, the sera levels of PGT121.414.LS 
steeply dropped to below the detection limit in 2 out of the 3 animals indicative of 
an anti-drug antibody (ADA) response against PGT121.414.LS in those animals. 
The third animal showed a longer persistence of the antibody in the sera with 
levels dropping below the detection limit at day 28 post infusion. 
 
Figure 4-12 Sera levels of PGT121.414.LS antibody in three human FcRn transgenic mice 
administered 10 mg/kg of the antibody via the intravenous route. 
The pharmacokinetic parameters were calculated using a non-compartment model 
in the WinNonLin software package and are presented in Table 4-4. The average 
half-life was calculated to be 3.61 days with a range of 2.53 to 4.59 days. The 
average AUC (Area Under the Curve) was calculated to be 332 Day mcg/mL with 
a range of 312 to 368 Day mcg/mL. The average clearance was calculated to be 
15.13 mL/Day/kg with a range of 13.58 to 15.99 mL/Day/kg. 


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Table 4-4 In vivo pharmacokinetic parameters for PGT121.414.LS in human FcRn 
transgenic mice 
Antibody 
Animal ID 
Half-life 
AUC 
Clearance 
Day 
Day*mcg/mL 
mL/Day/kg 
PGT121.414LS 
2283 
4.59 
368 
13.58 
2284 
3.70 
315 
15.82 
2285 
2.53 
312 
15.99 
Average 
3.61 
332 
15.13 
Standard error 
0.46 
14 
0.60 
 
4.7.3.2 
Pharmacokinetic study of PGT121.414.LS in rhesus macaques 
The VRC evaluated the in vivo pharmacokinetic profile of PGT121.414.LS in 
four male and two female rhesus macaques. In this study, we tested 
PGT121.414.LS (lot #S-20190121-1) produced from a stably transfected CHO 
cell line. The antibody was given at a single bolus dose of 10 mg/kg via either the 
subcutaneous (n=3) or intravenous route (n=3). The levels of antibody in the sera 
of these animals at various time points up to 105 days after administration were 
then quantitated by an anti-PGT121 idiotype based ELISA method. Figure 4-13 
shows the sera levels of PGT121.414.LS in each animal. The initial sera antibody 
levels were higher when the antibody was given IV compared to SC, but by day 2 
the sera antibody levels were similar in all animals irrespective of route and 
followed similar distribution over time Also, sera antibody levels were maintained 
above 5mcg/mL for up to 105 days after dosing in all animals irrespective of 
route. In addition, none of the animals developed anti-drug antibody responses 
against PGT121.414.LS in this study. 
 
Figure 4-13 Sera levels of PGT121.414.LS antibody in six rhesus macaques administered at 
10 mg/kg of the antibody via either the subcutaneous (SC) or intravenous (IV) route. 
The pharmacokinetic parameters were calculated using a non-compartment model 
in the WinNonLin software package and are presented in Table 4-5. The average 


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half-life for PGT121.414.LS was 28.4 days for the IV route and 27.8 days for the 
SC route, which were very similar to each other, with a range of 26.6 days to 
31.9 days. The AUC was slightly higher for the IV route (4710 day*mcg/mL) 
than for the SC route (3617 day*mcg/mL) due to the higher initial peak observed 
in the serum levels for the IV route compared to the SC route. The clearance was 
similar between the 2 routes (2.24 mL/day/kg for IV versus 2.61 mL/day/kg for 
SC). 
Table 4-5 In vivo pharmacokinetic parameters for PGT121.414.LS in rhesus macaques 
Route 
Animal ID 
Half-life 
AUC 
Clearance 
(days) 
(day*mcg/mL) 
(mL/day/kg) 
IV 
0DG 
26.80 
4221 
2.22 
IV 
DGFH 
26.65 
3702 
2.54 
IV 
DGKX 
31.91 
4586 
1.96 
Average 
28.45 
4170 
2.24 
Standard error 
1.73 
257 
0.17 
SC 
09Z 
30.13 
4223 
2.15 
SC 
DGDW 
27.73 
3353 
2.78 
SC 
DGFK 
25.53 
3274 
2.90 
Average 
27.80 
3617 
2.61 
Standard error 
1.33 
304 
0.23 
Abbreviations: AUC, area under the curve; IV, intravenous; SC, subcutaneous.  
4.7.3.3 
GLP repeat dose IV or SC of PGT121.414.LS in rats 
PGT121.414.LS was tested in a GLP-compliant study to determine the potential 
toxicity and toxicokinetics of the mAb in Sprague Dawley rats after three IV or 
SC dose administrations at 10-day intervals (on Days 1, 11, and 21) followed by a 
recovery period. No clinically significant findings were noted in the toxicology 
study. The study details and results are included in the IB. 
4.7.3.4 
PGT121.414.LS Tissue Cross Reactivity (TCR) study 
PGT121.414.LS was tested in a GLP-compliant study to determine the potential 
cross reactivity of the mAb in human tissue cryosections. The TCR study was 
conducted using a panel of normal human tissue cryosections from 3 separate 
donors, according to recommendations in the Points to Consider in the 
Manufacture and Testing of Monoclonal Antibody Products for Human Use 
(CBER 1997) and consistent with ICH guidance S6(R1). No clinically significant 
findings were noted in the tissue cross reactivity study. The study details and 
results are included in the IB. 


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4.7.3.5 
4.5.2.5 PGT121.414.LS preclinical functional studies 
PGT121.414.LS was recently assayed against a multiclade panel of 208 Env-
pseudoviruses at the VRC (Table 4-6 below). As expected, it had less breadth 
than VRC07-523LS and VRC01 but was approximately 4-times more potent than 
VRC07-523LS and 10-times more potent than VRC01 against the viruses that 
were neutralized. 
Table 4-6. Neutralization data of mAbs assayed against VITL/VRC Multiclade Panel 
 
See IB for further details. 
4.7.4 
Preclinical studies of VRC07-523LS 
VRC07-523LS has been assessed in several preclinical safety studies evaluating 
potential off-target binding, TCR, toxicity, and local tolerance.  
VRC07-523LS was found to be 5- to 8-fold more potent than VRC01, with an 
IC50 < 50 mcg/mL against 96% of HIV-1 pseudoviruses representing the major 
circulating HIV-1 clades, and an IC50 < 1 mcg/mL against 92% of HIV-1 viruses 
tested. In addition, it displayed minimal levels of autoreactivity.  
VITL/VRC Multiclade Panel
IC50
PGT121 
.414 LS
PGT121
VRC01
VRC01.23
VRC07-
523-LS
N6-LS
10-1074
PGDM 
1400
10E8v4
# Viruses
208
208
208
208
208
208
208
208
208
% VS Neutralized
IC50 <50ug/ml
58
65
90
96
96
98
63
80
98
IC50 <10ug/ml
55
64
89
96
96
97
63
79
98
IC50 <1.0ug/ml
50
56
72
94
92
95
60
75
71
IC50 <0.1ug/ml
44
44
17
73
53
63
42
60
15
For Sensitive Viruses Only:
Median IC50
0.022
0.040
0.328
0.041
0.081
0.069
0.054
0.014
0.463
Geometric Mean
0.044
0.072
0.339
0.042
0.088
0.072
0.060
0.024
0.419
For All Viruses:
Median IC50
0.904
0.352
0.392
0.042
0.086
0.071
0.204
0.043
0.468
Geometric Mean
0.868
0.691
0.548
0.055
0.116
0.081
0.724
0.107
0.470
IC80
PGT121 
.414 LS
PGT121
VRC01
VRC01.23
VRC07-
523-LS
N6-LS
10-1074
PGDM 
1400
10E8v4
# Viruses
208
208
208
208
208
208
208
208
208
% VS Neutralized
IC80 <50ug/ml
50
59
89
96
96
97
60
74
98
IC80 <10ug/ml
50
56
83
96
94
96
59
72
89
IC80 <1.0ug/ml
45
49
46
90
83
88
52
63
26
IC80 <0.1ug/ml
36
29
2
45
23
23
26
44
3
For Sensitive Viruses Only:
Median IC80
0.051
0.099
0.959
0.107
0.238
0.221
0.126
0.047
2.31
Geometric Mean
0.076
0.154
1.06
0.120
0.257
0.231
0.157
0.069
1.91
For All Viruses:
Median IC80
33.3
1.50
1.24
0.117
0.257
0.235
0.884
0.201
2.36
Geometric Mean
1.89
1.68
1.63
0.151
0.323
0.270
1.57
0.394
2.06


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In vivo proof-of-concept studies showed that VRC07-523LS is about 5-fold more 
potent than VRC01LS in Rhesus macaques and displays a longer half-life (9.8 
days) than VRC07 (4.9 days) after a single dose of mAb at 10 mg/kg administered 
intravenously (11). 
See the IB for further details. 
4.8 
Clinical trials of PGT121, PGT121.141LS, PGDM1400, VRC07-523LS 
alone and in combinations 
Table 4-7 Summary of clinical studies  
Study number/ status  
Antibodies  
Population(s)  
Routes  ClinicalTrials.gov 
#  
Protocol 
section  
IAVI T001  
completed  
PGT121 FIH  
HIV-  
HIV+ on ART 
HIV+ off ART  
IV, SC  NCT02960581 
4.8.1 
IAVI T002  
completed  
PGDM1400 FIH, 
PGDM1400+PGT121,  
PGDM1400 + PGT121 + 
VRC07-523LS HIV+ off ART   
HIV-  
HIV+ off ART  
IV  
NCT03205917 
4.8.2 
IAVI T003  
ongoing  
PGT121 + VRC07-
523LS, PGT121 + VRC07-
523LS + PGDM1400,   
PGT121 + VRC07-523LS + 
PGDM1400 in HIV+ on ART  
HIV-  
HIV+ on ART  
IV 
NCT03721510 
4.8.3 
VRC605  
Completed (53)  
VRC07-523LS, FIH  
HIV-  
IV, SC  NCT03015181 
4.8.4 
HVTN 127/HPTN 087  
ongoing  
VRC07-523LS  
HIV-  
IV, SC  NCT03387150 
4.8.5 
HVTN 128 
ongoing 
VRC07-523LS  
HIV-  
IV 
NCT03735849 
4.8.6 
HVTN 130/HPTN 089  
ongoing  
PGT121 + VRC07-523LS, 
PGDM1400 + VRC07-523LS,  
10-1074 + VRC07-523LS,  
PGDM1400 + PGT121 + 
VRC07-523LS  
HIV-  
IV  
NCT03928821 
4.8.7 
HVTN 136/HPTN 092  
ongoing  
PGT121.414LS FIH,  
PGT121.414LS + VRC07-
523LS  
HIV-  
IV, SC  NCT04212091 
4.8.8 
FIH: first-in-human trial, IV:intravenous, SC: subcutaneous. 
4.8.1 
IAVI T001 
IAVI T001 is a phase 1 randomized placebo-controlled clinical trial of the safety, 
pharmacokinetics, and antiviral activity of PGT121 in HIV-uninfected and HIV-
infected adults. The study design is shown below in Table 4-8. 


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Table 4-8: IAVI T001 study schema 
 
The trial evaluated a single IV administration of PGT121 in healthy adults and in 
HIV-infected adults. Up to three escalating doses were tested, 3 mg/kg, 10 mg/kg 
and 30 mg/kg. Additionally, a single SC administration of PGT121 in healthy 
adults was tested at 3 mg/kg. A total of 48 volunteers were enrolled into the 
following dose subgroups: 
• 1A (HIV-uninfected, 3 mg/kg IV, n=5), 
• 1B (HIV-uninfected, 10 mg/kg IV, n=5), 
• 1C (HIV-uninfected, 30 mg/kg IV, n=5), 
• 1D (HIV-uninfected, 3 mg/kg SC, n=5); 
• 2A (HIV-infected on ART, 3 mg/kg IV, n=5), 
• 2B (HIV-infected on ART, 10 mg/kg IV, n=5), 
• 2C (HIV-infected on ART, 30 mg/kg IV, n=5); 
• 3A (HIV-infected not on ART, plasma HIV-RNA between 2,000 and 
100,000 copies/mL,30 mg/kg IV, n=9), and 
• 3B (HIV-infected not on ART, plasma HIV-RNA between 100 and 2,000 
copies/mL, 30 mg/kg IV, n=4).  
The most common systemic reactogenicity events reported based on the 
percentage of participants exhibiting the event across all groups were: headache 
10/48 (20.8%), malaise 5/48 (10.4%), chills 4/48 (8.3%), nausea 1/48 (2%), 
arthralgia 1/48 (2%), and fever 1/48 (2%). The majority were mild (Grade 1); 
moderate (Grade 2) systemic reactions were reported for headache 4/48 (8.3%), 


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malaise 2/48 (4.1%), nausea 1/48 (2%), and fever 1/48 (2%). No severe (Grade 3) 
events were reported during the study. 
The most common local reactogenicity events reported based on the percentage of 
participants exhibiting the event across all groups were: tenderness 14/48 
(29.1%), pain 7/48 (14.5%), erythema/skin discoloration 2/48 (4.1%) and 
swelling/hardening 2/48 (4.1%). Most were mild (Grade 1) l moderate (Grade 2) 
local reactions were reported for pain 1/48 (2%), tenderness 1/48 (2%) and 
erythema/skin discoloration 1/48 (2%). No severe (Grade 3) events were reported 
during the study. 
Unsolicited adverse events (AEs) were adverse events reported in addition to the 
solicited reactogenicity events. A total of 39 unsolicited AEs were reported by the 
participants during the study, 34 non-serious adverse events in 21/48 (43.7%) 
participants who received investigational product and 5 non-serious adverse 
events in participants who had received placebo. The most common AEs reported 
based on percentage of participants exhibiting the event across all groups were: 
fatigue 4/48 (8.3%), headache 2/48 (4.1%), nasal congestion 2/48 (4.1%), upper 
respiratory tract infection 2/48 (4.1%), vessel puncture site bruising 2/48 (4.1%) 
and viral infection 2/48 (4.1%). 
The majority were Grade 1 or 2 (mild or moderate), with one Grade 3 tonsillitis 
that was judged unrelated to study product. No adverse events were assessed as 
probably or definitely related to the study product. Two Grade 1 adverse events 
(headache and fatigue) and two Grade 2 adverse events (fatigue and 
gastroenteritis) were assessed as possibly related to study product. 
One serious adverse event (SAE), a case of pre-patellar bursitis occurring 2 
months after administration of study product, was assessed as not related. No 
deaths, potential immune mediating disease, or HIV infections were reported 
during the study. One pregnancy occurred during the study in an HIV-infected 
participant. The pregnancy was considered unremarkable and a healthy infant was 
delivered vis caesarian section at 36-weeks gestation.  
The PGT121 elimination half-life in HIV-uninfected groups was 15.5 to 28.8 days 
and in HIV-infected groups was 8.2 to 28.9 days. The median AUC estimates 
from the HIV-uninfected groups were larger than the median AUC estimates from 
comparable HIV-infected groups (ie, 3 mg/kg HIV-uninfected vs. 3 mg/kg HIV-
infected, etc.). In general, the median Cmax estimates from HIV-uninfected 
groups were similar to the median Cmax estimates from comparable HIV-infected 
groups. 
4.8.2 
IAVI T002 
T002 is a phase 1, randomized, placebo-controlled clinical trial of the safety, 
pharmacokinetics, and antiviral activity of PGDM1400 alone or in combination 
with PGT121 in HIV-uninfected adults, and in combination with PGT121 and 
VRC07-523LS in HIV-infected adults. The study design is shown in Table 4-9. 


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Table 4-9: IAVI T002 study schema 
 
As of January 2021, the study is completed and closed. A total of 29 individuals 
were enrolled, including 12 participants in group 1, 12 participants in group 2 and 
4 participants in group 3. In groups 1 and 2 the MTD of 30 mg/kg for both 
products was confirmed. Overall, study product administration was safe and well-
tolerated. Only grade 1 local reactogenicity was reported. Grade 1 and 2 systemic 
reactogenicity events included headache, myalgia, malaise and arthralgia. No 
Grade 3 or Grade 4 systemic symptoms were reported during the study. No AEs 
were assessed as probably or definitely related to the study product. No deaths, 
SAEs or potential immune-mediated disease adverse events were reported during 
the conduct of the study.  
PGDM1400 concentrations have been measured in Groups 1A, 1B, and 1C (HIV-
uninfected, 3, 10, and 30 mg/kg IV, respectively) and in Groups 2A, 2B and 2C 
(HIV-uninfected, 3, 10, and 30 mg/kg IV of each antibody, PGDM1400 and 
PGT121, respectively) by validated anti-idiotype BAMA-based PK assays 
through day 168 postinfusion (Figure 4-14). Among HIV-uninfected participants, 
the median (min, max) PGDM1400 elimination half-life estimate was 19.4 (15.3, 
24.7) days, the population-level estimate of clearance (CL) was 0.191 (95% CI: 
0.177, 0.206) L/day, the median (min, max) volume of distribution (Vd) was 5.67 
(3.42, 8.04) L, and the median (min, max) dose- and weight-adjusted AUC was 
371.74 (263.76, 507.73) day/L/Kg. There were no statistically significant 
differences in these parameters by PGDM1400 administration alone vs. co-
administration with PGT121 (Group 1 vs. Group 2). 


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Figure 4-14 PGDM1400 binding antibody concentrations in Group 1A, 1B and 1C (HIV 
uninfected; 3, 10 and 30 mg/kg of PGDM1400), and in Group 2A, 2B and 2C (HIV uninfected; 
3, 10 and 30 mg/kg of PGDM1400 and PGT121 each).  
4.8.3 
IAVI T003 
IAVI T003 is a phase 1/2a, open-label clinical trial of the safety, tolerability, 
pharmacokinetics, and antiviral activity of PGT121, VRC07-523LS and 
PGDM1400 in HIV-uninfected and HIV-infected adults. The study design is 
shown below in Table 4-10. 


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Table 4-10: IAVI T003 study schema 
 
Notes: ART: Antiretroviral Therapy; ATI: Analytical Treatment Interruption (starting on Day 2 after 
participants complete their full course of ART for Day1 an after first IV infusion on Day 0); IV: intravenous; 
N/A: not applicable. 
As of January 2021, Group 1A (PGT121 and VRC07-523LS, 30 mg/kg each, IV) 
and 1B (PGT121, VRC07-523LS and PGDM1400, 20 mg/kg each, IV) have been 
fully enrolled. Furthermore, PGT121, VRC07-523LS and PGDM1400, 20 mg/kg 
each, IV have been administered to 10 participants in Group 2, of which 1 
participant has received 6 monthly infusions, 3 participants have received 3 
monthly infusions and 6 participants have received between 1 and 3 monthly 
infusions, so far. There are still 2 open slots for enrollment. Study product 
administrations have been well tolerated overall, with no reported SAEs or 
potential immune-mediated disease. 
4.8.4 
VRC 605 
VRC 605 is a phase 1, open-label, dose-escalation study of VRC07-523LS 
(NCT03015181) in healthy, HIV-uninfected adults to evaluate the safety and 
pharmacokinetics of 1 to 3 administrations of the antibody. The study is complete 
and results have been published (53) . The doses evaluated were a single 
administration of 1 mg/kg and 5 mg/kg IV and SC, 20 mg/kg and 40 mg/kg IV, 
and 3 administrations (q 12 weeks) of 5 mg/kg SC and 20 mg/kg IV VRC07-
523LS (Table 4-11).  
Study objectives included evaluating the safety and tolerability of the study 
regimen and the pharmacokinetics of each dose level, determining the presence or 
absence of detectable ADA to VRC07-523LS, and evaluating for evidence of 
functional activity of VRC07-523LS. 


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Table 4-11 VRC 605 study schema 
Group 
Participants 
Administration Schedule 
Day 0 
Week 12 
Week 24 
1 
3 
1 mg/kg IV 
 
 
2 
3 
5 mg/kg IV 
 
 
3 
3 
5 mg/kg SC 
 
 
4 
3 
20 mg/kg IV 
 
 
5 
3 
40 mg/kg IV 
 
 
6 
5 
5 mg/kg SC 
5 mg/kg SC 
5 mg/kg SC 
7 
5 
20 mg/kg IV 
20 mg/kg IV 
20 mg/kg IV 
Total 
25 
 
 
IV = intravenous infusion 
SC = subcutaneous injection 
In VRC 605, a total of 41 administrations of VRC07-523LS occurred during the 
study. VRC07-523LS was safe and well tolerated, with no SAEs or dose-limiting 
toxicities. No anti-drug antibodies (ADA) were detected following IV or SC 
routes of administration (53). 
PK analysis showed an elimination half-life of 38 days for IV groups and 33 days 
for subcutaneous groups (see Figure 4-15). VRC07-523LS containing sera 
showed equivalent or greater neutralization activity than sera from participants in 
previous trials receiving VRC01 or VRC01LS (53).  


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Figure 4-15 Serum concentrations of VRC07-523LS (A) Serum concentrations by individual 
participants, (B) Group geometric mean serum concentrations with error bars indicating the 
SD after a single administration, or (C) by individual participant after repeat administrations 
at weeks 0, 12, and 24. The upward pointing arrows indicate the time of VRC07-523LS 
administration. The participant in group 7 who only received a single dose of antibody was 
analyzed with group 4 participants. SC=subcutaneous. IV=intravenous. Figure from (53). 


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4.8.5 
HVTN 127/HPTN 087 
HVTN 127/HPTN 087 (NCT03387150) is a randomized phase 1 clinical trial 
evaluating the safety and serum concentrations of VRC07-523LS administered in 
multiple doses via different routes to healthy, HIV-uninfected adults (Table 4-12).  
Table 4-12 HVTN 127/HPTN 087 (Version 2.0) study schema 
Group 
N 
Route 
Dose 
VRC07-523LS administration schedule 
W0 
W16 
W32 
W48 
W64 
1 
20 
IV 
2.5 mg/kg 
X 
X 
X 
X 
X 
2 
20 
IV 
5 mg/kg 
X 
X 
X 
X 
X 
3 
20 
IV 
20 mg/kg 
X 
X 
X 
X 
X 
4 
20 
SC 
2.5 mg/kg 
X 
X 
X 
X 
X 
5 
20 
SC 
5 mg/kg 
X 
X 
X 
X 
X 
6 
20 
IM 
2.5 mg/kg 
X 
X 
X 
X 
X 
4 
Placebo 
X 
X 
X 
X 
X 
Total 
124 
 
IV = intravenous infusion 
SC = subcutaneous injection 
IM = intramuscular injection 
HVTN 127/HPTN 087 enrolled 124 healthy, HIV-uninfected adult participants to 
receive five administrations of VRC07-523LS via IV, SC, or IM routes (4 IM 
participants receive placebo). A total of 440 administrations of VRC07-523LS via 
IV or SC occurred during the study; the IM group remains blinded and a total of 
110 IM injections were administered.  
The primary objectives of the study are to assess safety and tolerability of 
repeated IV, SC, or IM administrations of VRC07-523LS and to characterize 
serum concentration over time for different doses, schedules, and routes of 
administration. Additional objectives include building a population PK model of 
VRC07-523LS and determining whether ADAs emerge in response to repeated 
administrations of the antibody. 
As of December 2020, three participants in Group 4 (2.5 mg/kg SC) experienced 
grade 3 SC injection site erythema or induration after their fifth administration 
including: (1) left arm erythema with a maximum erythema of 15x7 cm beginning 
two days after SC administration in the bilateral arms; (2) abdominal erythema 
and induration with a maximum erythema of 15x9.5 cm and a maximum 
induration of 14x8.5 cm beginning on the day of administration; and (3) 
abdominal erythema with a maximum measurement of 11x9 cm beginning one 
day after administration. One Grade 3 elevated alanine aminotransferase (ALT) 
deemed related to VRC07-523LS has been reported; the remaining AEs deemed 


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related have been grade 1 (mild) or grade 2 (moderate). No related SAEs have 
been reported. Six mAb reactions have been reported in five participants, 
including: (1) grade 1 generalized pruritus in a participant in Group 2 (5 mg/kg 
IV) after her first infusion; (2) grade 1 generalized pruritus in a participant in 
Group 5 (5 mg/kg SC) after the second series of SC injections; (3) two infusion 
related reactions in a participant in Group 3 (20 mg/kg IV)- the first occurred after 
his first infusion and was grade 2 and characterized by chills, myalgia, arthralgia, 
malaise/fatigue, nausea and headache and the second occurred after his second 
infusion and was grade 1 and characterized by malaise/fatigue, chills and myalgia; 
(4) grade 1 infusion related reaction in a participant in Group 3 (20 mg/kg IV) and 
characterized by facial flushing, diaphoresis, myalgia, and arthralgia; and (5) 
grade 2 infusion related reaction in a participant in Group 3 (20 mg/kg IV) and 
characterized by facial flushing, asthenia, headache, pyrexia, pre-syncope, 
anxiety, fatigue/malaise, and warm sensation/sensation of feeling hot. 
4.8.6 
HVTN 128 
HVTN 128 is a randomized, phase 1 clinical trial that evaluates the safety, 
tolerability and pharmacokinetics of VRC07-523LS in the sera and mucosae of 
healthy, HIV-uninfected adults (Table 4-13).  
Table 4-13 HVTN 128 (Version 1.0) study schema 
Group 
N* 
Route 
VRC07-
523LS Dose 
Product administration  
schedule 
D0 
D112 
D224 
W0 
W16 
W32 
1 
12 
IV 
10 mg/kg 
X 
X 
X 
2 
12 
IV 
30 mg/kg 
X 
X 
X 
Total 
24 
 
 
 
 
 
IV = intravenous infusion 
N* = number of participants receiving at least one product infusion 
HVTN 128 enrolled 24 participants to receive three IV infusions. A total of 66 
administrations of VRC07-523LS occurred during the study. As of December 
2020, no grade 3 or higher infusion site erythema or induration was reported; the 
only AEs deemed related to VRC07-523LS were mAb reactions detailed below. 
No related SAEs have been reported. Twelve mAb reactions have been reported 
in ten participants, including: (1) grade 1 facial flushing in a participant who 
enrolled into Group 2 (30 mg/kg); (2) grade 2 generalized pruritus in a participant 
in Group 2 (30 mg/kg); (3) grade 1 oropharyngeal itching in a participant who 
was randomized to Group 1 (10 mg/kg); (4) two grade 1 mAb reactions in a 
Group 1 (10 mg/kg) participant in whom the first was characterized by 
tachycardia, nausea, chills and headache after the first infusion and the second 
was characterized by nausea, vomiting, chills, muscle stiffness in her legs, arms 


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and back after the third infusion; (5) grade 1 infusion related reaction 
characterized by non-exertional dyspnea and tachycardia in a participant in Group 
2 (30 mg/kg); (6) grade 1 infusion related reaction characterized by headache, 
fatigue/malaise, and chills in a participant in Group 2 (30 mg/kg); (7) grade 1 
infusion related reaction characterized by pyrexia, chills, fatigue/malaise, 
arthralgia, and myalgia in a participant in Group 2 (30 mg/kg); (8) two grade 1 
mAb reactions in a in a participant in Group 1 (10 mg/kg), in whom the first was 
an infusion related reaction characterized by nausea, fatigue/malaise, chills, and 
myalgia that occurred after the first infusion, and the second reaction was chills 
after the third infusion; (9) grade 2 infusion related reaction characterized by 
hypotension, chills, nausea, fatigue/malaise, tachycardia and pyrexia in a 
participant in Group 2 (30 mg/kg); and (10) grade 1 infusion related reaction 
characterized by feeling cold, headache, mild rigors, headache, and generalized 
myalgia in a participant in Group 2 (30 mg/kg). 
4.8.7 
HVTN 130/HPTN 089 
HVTN 130/HPTN 089 is a randomized, phase 1 clinical trial that will evaluate the 
safety, tolerability and serum concentrations of PGT121, PGDM1400, 10-1074 
and VRC07-523LS when given sequentially in single and multiple doses via IV 
administration to healthy, HIV-uninfected adults (Table 4-14).  
Table 4-14 HVTN 130/HPTN 089 (Version 1.0) study schema 
Study 
arm 
N 
Dose 
Route 
M0 
M4 
Group 
1 
6 
20+20 mg/kg 
IV 
PGT121  
VRC07-523LS  
— 
 
 
 
 
 
 
Group 
2 
6 
20+20 mg/kg 
IV 
PGDM1400  
VRC07-523LS  
— 
 
 
 
 
 
 
Group 
3 
6 
20+20 mg/kg 
IV 
10-1074 
VRC07-523LS  
— 
 
 
 
 
 
 
Group 
4* 
9 
20+20+20 mg/kg 
IV 
PGDM1400 PGT121 
VRC07-523LS 
PGDM1400 PGT121  
VRC07-523LS 
 
 
 
 
 
 
Total 
27 
 
 
 
 
IV = intravenous infusion. The mAbs are infused sequentially in the order shown. 
* Opening enrollment in Group 4 follows review of safety data for all participants in Groups 
1-3.  
A total of 33 administrations of PGT121, VRC07-523LS, 10-1074 and 
PGDM1400 occurred during the study. As of December 2020, no grade 3 or 
higher infusion site erythema or induration was reported; no grade 3 AEs deemed 
related to PGT121, PGDM1400, 10-1074 or VRC07 523LS were reported; no 
related SAEs have been reported. One mAb reaction was reported: a grade 1 
infusion related reaction in a participant in Group 2 (20+20 mg/kg) characterized 
by chills, muscle pain in his upper back, joint pain in his wrists and headache.  


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4.8.8 
HVTN 136/HPTN 092 
HVTN 136/HPTN 092 is the first clinical study of the PGT121.414.LS mAb. This 
phase 1, dose-escalation, open-label clinical trial is aiming to examine the safety, 
tolerability, dose, and pharmacokinetics of PGT121.414.LS with and without 
VRC07-523LS, a CD4 binding site mAb (see Table 4-15). The hypothesis is that 
PGT121.414.LS alone and paired with VRC07-523LS will be safe for 
administration to healthy adults by both the IV and SC routes. 
In Part A of the study, PGT121.414.LS will be administered via IV infusion at 3, 
10, or 30 mg/kg (Groups 1-3) or via SC infusion at 5 mg/kg (Group 4). Each 
group in Part A will have 3 participants. At each of 3 visits in Part B of the study, 
participants will receive consecutive administration of PGT121.414.LS followed 
by VRC07-523LS, at 20 mg/kg IV each per dose (Group 5) or 5 mg/kg SC each 
per dose (Group 6). Each group in Part B will have 10 participants, yielding a 
total sample size for Parts A and B of 32. Participants will be followed for 32 
weeks after the last study product administration via IV infusion and 24 weeks 
after the last study product administration via SC infusion. 
Table 4-15 HVTN 136/HPTN 092 schema 
Study 
arm 
Number 
Dose 
Route 
Month 0  
(Day 0) 
Month 4  
(Day 112) 
Month 8  
(Day 224) 
Part A 
 
 
 
 
 
 
Group 
1* 
3 
3 mg/kg 
IV 
PGT121.414.LS 
— 
— 
Group 
2a* 
3 
10 
mg/kg 
IV 
PGT121.414.LS 
— 
— 
Group 
3b* 
3 
30 
mg/kg 
IV 
PGT121.414.LS 
— 
— 
Group 
4b* 
3 
5 mg/kg 
SC 
PGT121.414.LS 
— 
— 
Part B 
 
 
 
 
 
 
Group 
5c 
10 
20 
mg/kg +  
20 
mg/kg 
IV 
PGT121.414.LS + 
VRC07-523LS 
PGT121.414.LS + 
VRC07-523LS 
PGT121.414.LS + 
VRC07-523LS 
Group 
6c 
10 
5 mg/kg 
+ 
5 mg/kg 
SC 
PGT121.414.LS + 
VRC07-523LS 
PGT121.414.LS + 
VRC07-523LS 
PGT121.414.LS + 
VRC07-523LS 
Total 
32 
 
 
 
 
 
 
IV = intravenous infusion; SC = subcutaneous infusion. 
A total of 9 administrations of PGT121.414.LS in Part A and no administrations 
of PGT121.414.LS with VRC07-523LS in Part B occurred during the study. As of 
May 2021, no Grade 3 or higher infusion site erythema or induration was 
reported; no AEs deemed related to PGT121.414.LS or VRC07-523LS were 


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reported. No related SAEs have been reported. No mAb reactions have been 
reported. As this study is ongoing and directly relevant to this study, the protocol 
team will be informed of any additional, relevant HVTN 136/HPTN 092 data as it 
becomes available.  
4.9 
Potential risks of study products and administration 
General Risks of Monoclonal Antibodies (mAbs): Overall, the side effects of 
mAbs are generally mild and can include fever, flushing, chills, rigors, nausea, 
vomiting, diarrhea, pain, pruritus, rash, urticaria, angioedema, headache, 
dizziness, shortness of breath, bronchospasm, tachycardia, hypotension, 
hypertension, and chest pain. There can also be a risk of infection from mAbs 
targeting human cytokines or human cell antigens, but this is not expected with a 
mAb targeting a viral antigen (54). Other uncommon potential side effects of 
mAbs include thrombocytopenia, autoimmune diseases, cancer, dermatitis, and 
cardiotoxicity (54). 
Additional reactions such as tumor lysis syndrome and cytokine release syndrome 
have been previously described with chimeric and humanized Abs, usually with 
mAbs targeting human antigens. Cytokine release syndrome has been described 
with human mAbs targeting lymphocyte cell-surface antigens. Serious allergic 
reactions such as anaphylaxis, angioedema, bronchospasm, hypotension, and 
hypoxia are rare and often associated with mAbs targeting human proteins or with 
non-human mAbs. These mAb-related events typically occur within the first 24 
hours of administration, though have not been observed with anti-HIV mAbs to 
date. Cytokine release syndrome typically occurs within the first few hours of 
administration, and usually with the first administration when the largest number 
of target cells expressing antigen are present. Reactions related to the rate of 
infusion have been described for several FDA-licensed mAbs. Cytokine release 
syndrome can be effectively managed by temporarily holding the administration, 
administering anti-histamines, and restarting the IV infusion at a slower rate (55). 
More delayed allergic reactions may occur approximately 24 hours after 
administration, though can occur several days to a few weeks after administration, 
and can include serum sickness, which is characterized by urticaria, fever, 
lymphadenopathy, and arthralgia. This reaction is more likely to occur with 
chimeric Abs, and has not been observed with fully human mAbs. 
Other potential side effects of mAbs include thrombocytopenia, autoimmune 
diseases, cancer, dermatitis, and cardiotoxicity (54). 
Risk of Monoclonal Antibody-Associated Reactivity: There is a possibility that 
receipt of the study products will cause a reactive result on some currently 
available HIV test kits, especially if testing occurs close to study product 
administration timepoints (see Section 9.5.1).  


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Risks of Blood Drawing: Blood drawing may cause pain and bruising and may, 
infrequently, cause a feeling of lightheadedness or fainting. Rarely, it may cause 
infection at the site where the blood is taken. Problems from use of an IV for 
blood drawing are generally mild and may include pain, bruising, minor swelling 
or bleeding at the IV site and, rarely, infection, vein inflammation (phlebitis), or 
blood clots. Blood drawing may also cause anemia.  
Risks of IV Infusion: The placement of an IV catheter can allow for the 
development of bacteremia because of the contact between the catheter and 
unsterile skin during insertion. Risk of infection from IV infusion will be 
minimized through careful decontamination of skin prior to catheter placement 
and through the use of infection control practices during infusion. The risk of 
product contamination will be minimized through the use of aseptic technique 
during product preparation and administration. 
Risks of SC Administration: SC administration can result in pain, nodule 
formation, and possible infection. The risk of infection from SC administration 
will be minimized through skin decontamination of the skin prior to needle 
insertion. The risk of product contamination will be the same as for IV 
administration and will be minimized through the use of aseptic technique during 
product preparation and administration. 
Risks of study products: 
Experience is accruing with PGT121.414.LS and its parental PGT121 mAb, 
PGDM1400 (the parental mAb for PGDM 1400LS) and VRC07523-LS mAbs 
alone and in the combinations mentioned above (Section 4.8). This study 
evaluating PGDM1400LS alone and in combination with PGT121.414.LS and 
VRC07-523LS will be a first-in-human for the LS-modified form of PGDM1400. 
Human experience with PGDM1400 is limited to the IAVI T002 and T003 and 
HVTN 130/HPTN 089 clinical trials.  
As of January 2021, the IAVI T003 and HVTN 130/HPTN 089 clinical trials’ 
accrual is ongoing, and there have been no related SAEs. To date, there have been 
no study safety pauses for AEs and product administrations have been generally 
well tolerated. 
To date, the clinical trial safety experience with VRC01-class mAbs has been 
reassuring. In HVTN 104, IV administration of VRC01 was generally well-
tolerated with mild pain and/or tenderness commonly reported at the site of the IV 
infusion. Mild-to-moderate systemic reactogenicity symptoms were reported by 
VRC01 recipients following at least 1 of the infusions, but there was no clear 
relationship with frequency or severity to the dose of VRC01 (39). SC 
administration of VRC01 was generally well-tolerated and associated with mild to 
moderate local pain and/or tenderness, but there was no difference in the 
frequency or severity between VRC01 recipients and placebo recipients. 
Erythema and/or induration at the SC injection sites were generally less than 25 


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cm2 whether VRC01 or placebo was injected (39). No hypersensitivity reactions 
or cytokine release syndrome symptoms were reported in HVTN 104 (39).  
The efficacy trials HVTN 704/HPTN 085 and HVTN 703/HPTN 081 have 
accumulated significant additional VRC01 clinical experience. More than 40,000 
infusions of 10 mg/kg and 30 mg/kg VRC01 have been given to more than 4,500 
HIV-uninfected adults across both trials. While final safety analysis is ongoing, 
the safety profile is reassuring, thus far. In the combined trials, 40,642 IV 
infusions were administered and 209 AEs deemed related to study product were 
reported. The mean and median onset of these AEs was Day 0, the day of 
infusion. Of these AEs deemed related to study product, all ≥ grade 3 AEs and 
95% of AEs of any grade were reported within three days post infusion. VRC01 
was well-tolerated, with low rates of infusion-related reactions (IRRs): 1.7% of 
participants in HVTN 704/HPTN 085 and 4.8% of participants in HVTN 
703/HPTN 081 experienced IRRs to VRC01/placebo. In the combined trials, 132 
out of 160 IRRs developed in VRC01 recipients. IRR were typically mild or 
moderate (96.2% were deemed mild or moderate and 3.8% were deemed severe), 
successfully managed at the clinical research site, and resolved without sequelae.  
Early-phase human experience with administration of VRC07-523LS has been 
reassuring in the VRC605 and HVTN 127/HPTN 087 trials (see Sections 4.8.4 
and 4.8.5). The majority of participants have reported no local or systemic 
Solicited AEs and no Unsolicited AEs. Severe reactions associated with mAb 
administration, such as acute anaphylaxis, serum sickness, anti-drug antibodies, 
and increased risk of infections have not been observed to date in trials of 
VRC01-class mAbs, nor in trials of PGT121 or PGDM1400.  
Risks of interference with common HIV tests: 
An anti-HIV mAb is not likely to directly reduce or inhibit the assays used to 
detect HIV-1 infection. 


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5 
Objectives and endpoints 
5.1 
Primary objectives and endpoints 
Primary objective 1:  
To evaluate the safety and tolerability of PGDM1400LS when administered via 
intravenous (IV) or subcutaneous (SC) routes (Part A) and of PGDM1400LS, 
VRC07-523LS and PGT121.414.LS when administered in sequence IV or SC 
(Part B) 
Primary endpoints 1: 
• Local and systemic Solicited AEs, laboratory measures of safety, Unsolicited 
AEs, and SAEs 
• Early discontinuation of administration and reason(s) for discontinuation and 
early study termination 
Primary objective 2:  
To evaluate the serum concentrations and pharmacokinetics of PGDM1400LS 
after a single administration (Part A) and of PGDM1400LS, VRC07-523LS, and 
PGT121.414.LS after each three-mAb administration (Part B) 
Primary endpoint 2:  
Serum concentrations of PGDM1400LS, VRC07-523LS and PGT121.414.LS at 
prespecified timepoints among participants who received all scheduled product 
administrations  
Primary objective 3:  
To evaluate the individual mAb-specific serum neutralizing activity after single 
product administration of PGDM1400LS (Part A) and after each three-mAb 
administration of PGDM1400LS, VRC07-523LS and PGT121.414.LS (Part B) 
Primary endpoint 3:  
Magnitude and breadth of neutralizing activity measured with Env pseudotyped 
viruses specific for either PGDM1400LS, VRC07-523LS or PGT121.414LS in 
TZM-bl cells at prespecified timepoints among participants who received all 
scheduled product administrations 


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5.2 
Secondary objectives and endpoints 
Secondary objective 1: 
To correlate serum concentrations of PGDM1400LS, VRC07-523LS and 
PGT121.414.LS with corresponding virus neutralization titers in serum 
Secondary endpoints 1: 
• Serum concentrations of PGDM1400LS, VRC07-523LS and PGT121.414.LS 
at prespecified timepoints for all participants in all groups regardless of how 
many product administrations and how much product they received  
• Magnitude of serum neutralizing activity measured with mAb-specific Env-
pseudotyped viruses in TZM-bl cells at prespecified timepoints for all 
participants in all groups regardless of how many product administrations and 
how much product they received 
Secondary objective 2: 
To determine whether the mAbs maintain their expected combined magnitude and 
breadth of serum neutralizing activity after each PGDM1400LS, VRC07-523LS 
and PGT121.414.LS three-mAb administration (Part B) as predicted by the 
known magnitude and breadth of neutralization of the corresponding mAb 
combinations as non-infused clinical products 
Secondary endpoint 2: 
Magnitude of neutralizing activity against a panel of Env-pseudotyped reference 
viruses that are sensitive to all three bnAbs in TZM-bl cells at selected timepoints 
for all participants in all groups regardless of how many product administrations 
and how much product they received 
Secondary objective 3: 
To determine whether anti-drug antibodies (ADA) are present  
Secondary endpoint 3: 
ADA titers in each group measured at prespecified timepoints for all participants 
in all groups regardless of how many product administrations and how much 
product they received 
Secondary objective 4: 
To evaluate the impact of body weight and other baseline covariates on the 
pharmacokinetics of PGDM1400LS, VRC07-523LS and PGT121.414.LS in both 
the weight-based and fixed-dose groups. 


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Secondary endpoint 4: 
Serum concentrations of PGDM1400LS, VRC07-523LS and PGT121.414.LS at 
prespecified timepoints  
5.3 
Exploratory objectives 
Exploratory objective 1: 
To determine whether any confirmed positive ADA samples have functional 
activity that impacts the neutralizing activity of PGDM1400LS, VRC07-523LS 
and PGT121.414.LS 
Exploratory objective 2: 
To further evaluate non-neutralizing anti-viral activities, additional assays (eg, 
ADCC, ADCP, virion capture) may be performed for activities that the 
PGDM1400LS, VRC07-523LS and PGT121.414.LS are shown to exhibit in vitro 
Exploratory objective 3: 
To conduct analyses related to predicting serum neutralization over time against a 
set of potentially exposing viruses in a future efficacy trial for ranking and down-
selecting bnAb regimens 
Exploratory objective 4: 
To conduct analyses related to furthering the understanding of HIV, passive 
immunity, immunology, vaccines, and clinical trial conduct. 


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6 
Statistical considerations 
6.1 
Accrual and sample size calculations 
Recruitment will target enrolling about 95 healthy, HIV-uninfected adult 
participants. 
In Part A of the study, PGDM1400LS will be administered as a single IV infusion 
at 5, 20, or 40 mg/kg (Groups 1, 2, and 4) or as a single SC dose at 20 or 40 
mg/kg (Groups 3 and 5) with n=3 participants per group. The trial will begin with 
enrollment in Group 1 only. Groups 2 and 3, and Groups 4 and 5, will be enrolled 
stepwise by two groups and randomized in a 1:1 ratio, respectively. Additional 
participants may be enrolled in each group to ensure the availability of early post-
infusion safety data from at least 3 participants in each group.   
In Part B of the study, participants will receive two doses of PGDM1400LS + 
VRC07-523LS + PGT121.414.LS at 20 or 40 mg/kg IV each per dose (Group 6 
and 10) or 20 mg/kg SC each per dose (Group 7), or a fixed dose of 4.2 g IV 
(Group 8) or SC (Group 9). Groups 6, 7, 8, and 9 will begin enrollment 
simultaneously. Additional participants may be enrolled in each group to ensure 
the availability of early post-infusion safety data from at least 8 participants in 
Groups 6 through 9 together; or at least 3 participants in Group 10. All groups 1-
10 are open-label. See also in Section 11.3. 
To ensure balance across both sexes assigned at birth, participants of each sex 
assigned at birth should constitute approximately 40-60% of those enrolled in the 
trial (Part A and Part B combined). The study team will work closely with the 
sites to monitor enrollment progress to ensure appropriate balance. Since 
enrollment is concurrent with receiving the first study product administration, all 
participants will provide some safety data. However, for mAb concentrations and 
anti-viral functional activities, it is possible that data may be missing for various 
reasons, such as participants terminating from the study early, problems in 
shipping specimens, or high assay background. For this reason, the sample size 
calculations in Section 6.1.2 account for 20% enrolled participants having missing 
data for the primary lab endpoint at a given timepoint. As a reference, 
immunogenicity data from 17 phase 1 and 2 phase 2a HVTN vaccine trials, which 
began enrolling after June 2005 (data as of September 2014), indicate that 17% is 
a reasonable estimate for the rate of missing data at a given timepoint. In HVTN 
104 (phase 1 trial of VRC01), approximately 15% of mAb concentration data 
were missing at the primary timepoints.  
6.1.1 
Sample size calculations for safety 
The goal of the safety evaluation for this study is to identify safety concerns 
associated with product administration. The ability of the study to detect serious 
adverse events (SAEs) (see Section 11) can be expressed by the true event rate 
above which at least 1 SAE would likely be observed and the true event rate 


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below which no events would likely be observed. Specifically, for each treatment 
group of size n = 3 in Part A, there is at least a 90% or more chance of observing 
at least 1 event if the true rate of such an event is 53.6% or more; and there is at 
least a 90% or more chance of observing no events if the true rate is 3.4% or less. 
For IV administration Groups 1, 2 and 4 combined n = 9 in Part A, there is at least 
a 90% or more chance of observing at least 1 event if the true rate of such an 
event is 22.6% or more; and there is at least a 90% or more chance of observing 
no events if the true rate is 1.2% or less. For SC administration Groups 3 and 5 
combined n = 6 in Part A, there is at least a 90% or more chance of observing at 
least 1 event if the true rate of such an event is 31.9% or more; and there is at least 
a 90% or more chance of observing no events if the true rate is 1.7% or less. For 
all Groups 1-5 combined n = 15 in Part A, there is at least a 90% or more chance 
of observing at least 1 event if the true rate of such an event is 14.2% or more; 
and there is at least a 90% or more chance of observing no events if the true rate is 
0.7% or less. For each group of size n=16 in Part B, there is 90% or more chance of 
observing at least 1 event if the true rate of such an event is 13.4% or more; and there 
is 90% or more chance of observing no events if the true rate is 0.7% or less. For IV 
administration Groups 6, 8 and 10 combined with n=48 in Part B, there is 90% or 
more chance of observing at least 1 event if the true rate of such an event is 4.7% or 
more; and there is 90% or more chance of observing no events if the true rate is 0.2% 
or less. For SC administration Groups 7 and 9 combined with n=32 in Part B, there is 
90% or more chance of observing at least 1 event if the true rate of such an event is 
6.9% or more; and there is 90% or more chance of observing no events if the true rate 
is 0.3% or less. For all Groups 6-10 combined n = 80 in Part B, there is at least a 
90% or more chance of observing at least 1 event if the true rate of such an event 
is 2.8% or more; and there is at least a 90% or more chance of observing no 
events if the true rate is 0.1% or less. As a reference, in HVTN vaccine trials from 
April 2008 through March 2018, about 1.7% of participants who received 
placebos experienced an SAE.  
Binomial probabilities of observing 0, 1 or more, and 2 or more events among 
arms of size 3 and 16 are presented in Table 6-1 for a range of possible true 
adverse event rates. These calculations provide a more complete picture of the 
sensitivity of the study design to identify potential safety problems with 
PGDM1400LS, VRC07-52310LS and PGT121.414.LS. 


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Table 6-1 Probability of observing 0 events, 1 or more events, and 2 or more events, among 
groups of size 3, 9, 10, 15, 20, and 30 for different true event rates 
Group 
Size 
True event  
rate (%) 
Pr(0/n1) 
Pr(1+/n1) 
Pr(2+/n1) 
3 
1 
0.97 
0.03 
<0.01 
4 
0.88 
0.12 
<0.01 
10 
0.73 
0.27 
0.03 
20 
0.51 
0.49 
0.1 
30 
0.34 
0.66 
0.22 
40 
0.22 
0.78 
0.35 
9 
1 
0.91 
0.09 
<0.01 
4 
0.69 
0.31 
0.05 
10 
0.39 
0.61 
0.23 
20 
0.13 
0.87 
0.56 
30 
0.04 
0.96 
0.8 
40 
0.01 
0.99 
0.93 
15 
1 
0.86 
0.14 
<0.01 
4 
0.54 
0.46 
0.12 
10 
0.21 
0.79 
0.45 
20 
0.04 
0.96 
0.83 
30 
<0.01 
>0.99 
0.96 
40 
<0.01 
>0.99 
>0.99 
16 
1 
0.85 
0.15 
0.01 
4 
0.52 
0.48 
0.13 
10 
0.19 
0.81 
0.49 
20 
0.03 
0.97 
0.86 
30 
<0.01 
>0.99 
0.97 
40 
<0.01 
>0.99 
>0.99 
48 
1 
0.62 
0.38 
0.08 
4 
0.14 
0.86 
0.58 
10 
<0.01 
>0.99 
0.96 
20 
<0.01 
>0.99 
>0.99 
30 
<0.01 
>0.99 
>0.99 
40 
<0.01 
>0.99 
>0.99 
80 
1 
0.45 
0.55 
0.19 
4 
0.04 
0.96 
0.83 
10 
<0.01 
>0.99 
>0.99 
20 
<0.01 
>0.99 
>0.99 
30 
<0.01 
>0.99 
>0.99 
40 
<0.01 
>0.99 
>0.99 
95 
1 
0.38 
0.62 
0.25 
4 
0.02 
0.98 
0.9 
10 
<0.01 
>0.99 
>0.99 
20 
<0.01 
>0.99 
>0.99 
30 
<0.01 
>0.99 
>0.99 
40 
<0.01 
>0.99 
>0.99 
 


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An alternative way of describing the statistical properties of the study design is in 
terms of the 95% confidence interval for the true rate of an adverse event based 
on the observed data. Table 6-2 shows the 2-sided 95% confidence intervals for 
the probability of an event based on a particular observed rate. Calculations are 
done using the score test method (56). If none of the 15 or 80 participants 
receiving an antibody treatment regimen in Part A or Part B experience a safety 
event, the 95% 2-sided upper confidence bound for the true rate of such events in 
the total treated population is 20.4% or 4.6%. For each individual antibody 
treatment arm n = 3 or 16 in Part A or Part B, the 2-sided upper confidence bound 
for this rate is 56.1% and 19.4%, respectively. 
Table 6-2 Two-sided 95% confidence intervals for the probability of observing a safety event 
based on observing a particular rate of safety endpoints for arms of size 3, 15, 16, 80 and 95. 
Observed event rate 
95% Confidence interval (%) 
0/3 
(0.0, 56.1) 
1/3 
(6.2, 79.2) 
2/3 
(20.8, 93.8) 
 
 
0/15 
(0.0, 20.4) 
1/15 
(1.2, 29.8) 
2/15 
(3.7, 37.9) 
 
 
0/16 
(0.0, 19.4) 
1/16 
(1.1, 28.3) 
2/16 
(3.5, 36.0) 
 
 
0/80 
(0.0, 4.6) 
1/80 
(0.2, 6.8) 
2/80 
(0.7, 8.7) 
 
 
0/95 
(0.0, 3.9) 
1/95 
(0.2, 5.7) 
2/95 
(0.6, 7.3) 
 
 
6.1.2 
Sample size calculations for serum mAb concentrations  
Primary Objective 2 of this study is to evaluate serum concentrations of 
PGDM1400LS, VRC07-523LS and PGT121.414.LS at several timepoints (ie, 
pharmacokinetics) following single or multiple IV or SC administrations. This 
objective is descriptive in nature, and will be accomplished by estimating the 
mean serum concentration of each mAb within each active arm at specific 
timepoints following product administration. The precision with which a true 
mean concentration can be estimated from observed data depends on the standard 


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deviation (SD) of the measurements and the sample size. Table 6-3 displays two-
sided 95% confidence intervals for the mean drug concentration for several values 
of the observed average drug concentration. The construction of these confidence 
intervals assumed sample sizes of n = 12 per arm, reflecting an attrition rate of 
20% compared to a planned treatment group size of 16 participants. The 
calculations assumed that log-transformed serum concentrations are 
approximately normally distributed. To account for the small sample sizes, a t-
distribution was used to construct CIs. For instance, with an observed mean loge 
serum level of loge(10 mcg/mL) and assuming a standard deviation of 0.5 for their 
log-transformed values, a two-sided 95% confidence interval for the true mean 
drug concentration level is (7.3, 13.7) (in mcg/mL) with an effective sample size 
of 12 participants. Of note, in the HVTN104 trial of VRC01, SD smaller than 1.0 
for the loge -transformed serum concentrations of VRC01 were repeatedly 
observed over time following either IV infusions or SC injections of the study 
product (39, 47). 
Table 6-3 Two-sided 95% confidence intervals based on observing a particular average loge 
mAb concentration in participants in any of the active arms, taking 20% attrition into 
consideration (n= 12) 
Observed 
average loge- 
concentration 
(loge mcg/mL) 
SD of loge-
concentration 
(loge 
mcg/mL) 
95% confidence interval (mcg/mL) 
n = 12 
loge(0.5) 
0.5 
(0.4, 0.7) 
loge(1) 
(0.7, 1.4) 
loge(5) 
(3.6, 6.9) 
loge(10) 
(7.3, 13.7) 
loge(50) 
(36.4, 68.7) 
loge(100) 
(72.8, 137.4) 
loge(250) 
(182.0, 343.5) 
loge(500) 
(363.9, 687.0) 
loge(1000) 
(727.8, 1373.9) 
loge(0.5) 
1 
(0.3, 0.9) 
loge(1) 
(0.5, 1.9) 
loge(5) 
(2.6, 9.4) 
loge(10) 
(5.3, 18.9) 
loge(50) 
(26.5, 94.4) 
loge(100) 
(53.0, 188.8) 
loge(250) 
(132.4, 471.9) 
loge(500) 
(264.9, 943.9) 
loge(1000) 
(529.7, 1887.7) 
 
6.1.3 
Sample size calculations for serum neutralization activity 
Primary Objective 3 of this study is to evaluate serum neutralization titers of 
PGDM1400LS, VRC07-523LS and PGT121.414.LS against a panel of Env-
pseudotyped viruses (57) at several timepoints following IV or SC 


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administrations. This objective is also descriptive in nature, and will be 
accomplished by estimating, within each mAb treatment group, the mean area-
under-the-magnitude-breadth-curve (AUC-MB) (58) of serum neutralization titers 
of each mAB against the panel of viruses. The precision with which a true mean 
AUC-MB of neutralization titers can be estimated from observed data depends on 
the SD of the measurements and the sample size. Table 6-4 displays two-sided 
95% confidence intervals for the mean AUC-MB of neutralization titer for several 
values of the observed average AUC-MB of ID50 or ID80 neutralization titer. 
The construction of these confidence intervals assumed sample sizes of n = 12 per 
group, reflecting an attrition rate of 20% compared to the planned treatment group 
size of 16 participants, respectively. The calculations assumed that loge-
transformed neutralization titers are approximately normally distributed. To 
account for the small sample sizes, a t-distribution was used to construct CIs. For 
instance, with an observed mean loge AUC-MB titer of loge(50) and assuming a 
standard deviation of 0.5 for their log-transformed values, a two-sided 95% 
confidence interval for the true mean drug concentration level is (36.4, 68.7) with 
effective sample sizes of 12 participants, respectively. Of note, based on 
neutralization data against a global panel of 11 pseudoviruses in six participants in 
HVTN104, an SD of less than 1.0 was observed in the log-transformed AUC-MB 
of ID50 titers at various time-points post IV infusions of VRC01 (47). 
Table 6-4 Two-sided 95% confidence intervals based on observing a particular average loge- 
AUC-MB neutralization titer in participants in any of the active arms, taking 20% attrition into 
consideration (n = 12) 
Observed average loge- 
AUC-MB 
neutralization titer 
SD of loge-AUC-MB 
neutralization titer 
95% confidence interval 
n = 12 
loge(5) 
0.5 
(3.6, 6.9) 
loge(20) 
(14.6, 27.5) 
loge(50) 
(36.4, 68.7) 
loge(100) 
(72.8, 137.4) 
loge(250) 
(182.0, 343.5) 
loge(500) 
(363.9, 687.0) 
loge(1000) 
(727.8, 1373.9) 
loge(5) 
1.0 
(2.6, 9.4) 
loge(20) 
(10.6, 37.8) 
loge(50) 
(26.5, 94.4) 
loge(100) 
(53.0, 188.8) 
loge(250) 
(132.4, 471.9) 
loge(500) 
(264.9, 943.9) 
loge(1000) 
(529.7, 1887.7) 
6.2 
Randomization 
There will be no randomization for Group 1 as they will be enrolled first. 
Contingent on safety data from Group 1, Groups 2 and 3 will be randomized and 


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enrolled simultaneously. Contingent on safety data from Groups 2 and 3, Groups 
4 and 5 will be randomized and enrolled simultaneously. Contingent on data from 
Part A, Groups 6, 7, 8, and 9 will be randomized in blocks to ensure balance 
across groups for simultaneous enrollment. There will be no randomization for 
Group 10. A participant’s randomization assignment will be computer generated 
and provided to the CRS pharmacist through a web-based randomization system.   
6.3 
Blinding 
Participants and CRS staff will be unblinded to participant treatment arm 
assignments. Laboratory Center staff will be unblinded to whether a sample is 
from Part A or Part B, but will remain blinded to treatment assignment within Part 
A or Part B during sample analysis.  
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 study product 
administrations and how much study product they received. In the rare instance 
that a participant receives the wrong treatment at a specific study product 
administration time, the Statistical Analysis Plan (SAP) will address how to 
analyze the participant’s safety data. Analyses of safety data are modified intent-
to-treat (MITT) in that individuals who are randomized but not enrolled do not 
contribute data and hence are excluded. Because of the brief length of time 
between randomization and enrollment—typically no more than 4 working 
days—very few such individuals are expected. The primary analysis of mAb 
concentration and anti-viral functional activity data are per-protocol (PP) in that 
only individuals who receive the expected mAb at the expected dose level within 
the expected visit window contribute data. Secondary analysis will also involve 
the MITT cohort, and when necessary account for the actual specimen collection 
time, and the actual time and dose amount of each product administration.  
Analyses for primary endpoints will be performed using SAS and R. Additional 
software may be used to perform non-compartmental PK and population PK 
analyses (eg, Monolix). All other descriptive and inferential statistical analyses 
will be performed using SAS, StatXact, or R statistical software. 
No formal multiple comparison adjustments will be employed for multiple 
primary or secondary endpoints. However, multiplicity adjustments will be made 
for certain primary or secondary endpoint assays, as discussed below, when the 
assay endpoint is viewed as a collection of hypotheses (eg, testing multiple 
pseudo-viruses to determine a positive antiviral functional activity response). 
Unless otherwise noted, all statistical tests will be 2-sided and will be considered 
statistically significant if p < 0.05. 


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6.4.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, mAb 
concentration, mAb functionality, and ADA 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 study product 
administration, all participants will have received at least 1 product administration 
and therefore will provide some safety data. 
6.4.3.1 
Solicited AEs 
The number and percentage of participants experiencing each type of Solicited 
AE sign or symptom (see Section 11.2.2) will be tabulated by severity and 
treatment arm and the percentages displayed graphically by arm. For a given sign 
or symptom, each participant’s Solicited AEs will be counted once under the 
maximum severity for all 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. Kruskal-Wallis tests will be used to 
test for differences in severity between arms. 
6.4.3.2 
SAEs and Unsolicited AEs 
Unsolicited AEs (see Section 11.2.2) will be summarized using MedDRA System 
Organ Class and preferred terms. Tables will show by treatment arm the number 
and percentage of participants experiencing an Unsolicited AE within a System 
Organ Class or within preferred term category by severity or by relationship to 
study product. For the calculations in these tables, a participant with multiple 
Unsolicited AEs within a category will be counted once under the maximum 
severity or the strongest recorded causal relationship to study product. Formal 
statistical testing comparing arms is not planned since interpretation of differences 
must rely heavily upon clinical judgment. 
A listing of SAEs reported to the DAIDS Regulatory Support Center (RSC) 
Safety Office will provide details of the events including severity, relationship to 
study product, time between onset and last study product administration, and 
number of study product administrations received.  
6.4.3.3 
Local laboratory values  
Box plots of local laboratory values will be generated for baseline values and for 
values measured during the course of the study by treatment arm and visit. Each 


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box plot will show the first quartile, the median, and the third quartile. Outliers 
(values outside the box plot) will also be plotted. If appropriate, horizontal lines 
representing boundaries for abnormal values will be plotted. 
For each local laboratory measure, summary statistics will be presented by 
treatment arm and timepoint, as well as changes from baseline for postenrollment 
values. In addition, the number (percentage) of participants with local laboratory 
values recorded as meeting Grade 1 AE criteria or above as specified in the 
Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (see Section 9.8) will be tabulated by treatment arm for each poststudy 
product administration timepoint. Reportable clinical laboratory abnormalities 
without an associated clinical diagnosis will also be included in the tabulation of 
AEs described above. 
6.4.3.4 
Reasons for study product administration discontinuation and early study 
termination 
The number and percentage of participants who discontinue study product 
administration and who terminate the study early will be tabulated by reason and 
treatment arm. 
6.4.4 
mAb concentration and PK analysis  
6.4.4.1 
Primary analyses of mAb concentrations 
The primary analysis of serum concentration and PK of PGDM1400LS, VRC07-
523LS and PGT121.414.LS (Primary Objective 2) will be restricted to 
participants who received all scheduled administrations per-protocol. Serum 
concentrations that fail the quality control of the assay, or from specimens 
collected outside of the visit window, or from HIV-infected participants 
postinfection may be excluded. The primary analysis of serum concentration will 
be descriptive and performed separately for each mAb.  
A non-compartmental PK analysis will be performed on the concentration data. 
PK parameters may include, but are not limited to: area-under-the-curve (AUC), 
maximum concentration (Cmax), time to Cmax (Tmax), clearance (CL), volume of 
distribution (Vd), terminal elimination rate constant (λz) and the terminal half-life 
(T1/2). For SC Groups, the PK parameters will include AUC, Cmax, Tmax, clearance 
(CL/F, where F is the bioavailability via SC relative to IV), volume of distribution 
(Vd/F), λz and T1/2. Data will be summarized by each dose group and overall for 
CL, Vd and T1/2. The potential for non-linear PK among IV or SC recipients will 
be determined by comparing the dose-adjusted ratios for Cmax and AUC within IV 
or SC dosing groups. Graphical displays of the data (eg, boxplots, scatterplots, 
histograms, spaghetti plots) will be generated to visually explore distributional 
properties of the data. These summary statistics and graphical displays may be 
produced for each treatment arm and each time point separately. 


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6.4.5 
Analysis of neutralization activity and correlation with serum 
concentrations  
6.4.5.1 
Primary analyses of neutralization magnitude-breadth curves  
To address Primary objective 3, at each specified timepoint, the area-under-the-
magnitude-breadth curve (AUC-MB) to a global panel of pseudoviruses (57) will 
be computed for each participant in the PP cohort with evaluable neutralization 
ID50 or ID80 data, as described in (58). Magnitude–Breadth (M-B) curves maybe 
employed to display individual- and group-level response breadth as a function of 
magnitude. Response breadth is defined as the percentage of viruses in the panel 
with neutralization titer above certain thresholds. Two choices are to compare the 
M-B curves among arms, as follows: a non-parametric Wilcoxon rank sum test on 
the subject-specific area-under-the M-B curve (AUC M-B) 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 virus isolates 
as an integrated magnitude of responses to multiple isolates. Similar group 
comparison methods described in the first approach may be adopted. Details of 
either approach will be described in the SAP. 
6.4.5.2 
Secondary analyses of correlations between serum concentrations and 
serum neutralization levels 
To address Secondary objective 1, pharmacodynamics (PD) models based on 
either linear or non-linear mixed effects models will be performed to characterize 
the correlation between serum concentration (observed or popPK model-
predicted) and serum neutralization against each virus or the AUC-MB of serum 
neutralization against the panel. Data from all enrolled participants will be 
analyzed regardless of how many administrations and how much mAb dose they 
received (MITT analysis). Similar to the popPK analysis, data from specimens 
collected outside of the visit window may be included in the PK/PD analyses that 
account for the actual specimen collection time, and the actual time and dose 
amount of each product administration. Since the exact date of HIV infection is 
unknown, any serum level data from blood draws 4 weeks prior to an infected 
participant’s last seronegative sample and thereafter may be excluded. All data 
from HIV-infected participants who have no seronegative samples postenrollment 
may be excluded from the analysis. 
6.4.5.3 
Secondary analyses of neutralization magnitude-breadth curves 
To address Secondary objective 2, at each specified timepoint, the area-under-the-
magnitude-breadth curve (AUC-MB) to a panel of Env-pseudotyped reference 
viruses that are sensitive to all three bnAbs will be computed for all participants 
with evaluable neutralization ID50 or ID80 data, as described in (58). Magnitude–
Breadth (M-B) curves may be employed to display individual- and group-level 
response breadth as a function of magnitude.  


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6.4.6 
Analysis of ADA and other non-neutralizing functional activities 
For the analysis of ADA (Secondary objective 3), data from enrolled participants 
will be used regardless of how many administrations they received (MITT). For 
Exploratory objectives regarding mAb functionality, data from enrolled 
participants who received all scheduled administrations PP will be used. Assay 
results that are unreliable or from HIV-infected participants postinfection will be 
excluded. Additional exploratory analyses examining the impact of confirmed 
positive ADA on PK will be described in the SAP.  
6.4.7 
General approach 
Univariate and bivariate descriptive analyses of continuous assay data (eg, 
Luminex-based serum concentrations) will be performed using mean, median, 
standard deviation, range, skewness, Spearman’s and Pearson’s correlation 
coefficients, for example. Graphical displays of the data based on appropriate 
techniques (eg, boxplots, histograms, kernel density estimates, probability plots, 
two- or three-dimensional scatterplots, spaghetti plots) will be generated to 
visually explore distributional properties of the data as well as potential pairwise 
associations. Statistics and graphical displays will be produced for each treatment 
arm across timepoints. 
Comparisons of continuous assay data between treatment groups or timepoints 
will be primarily performed using nonparametric rank-based tests, the Wilcoxon 
rank-sum test, or Friedman nonparametric two-way analysis of variance 
(ANOVA). In the event the data appear normally distributed, the comparisons 
may be performed using appropriate parametric tests (eg, two-sample t-tests with 
unequal variances). Appropriate data transformations (eg, square-root, 
logarithmic) may be applied prior to testing hypotheses in order for key 
distributional assumptions [eg, normality, homoscedasticity (ie, constancy of 
variance) to be satisfied. 
Analyses of categorical variables (eg, binary) will be conducted by constructing 
frequency tables. One such table will be produced for each treatment group and 
each timepoint. Crude response rates will be presented with their corresponding 
95% confidence interval estimates calculated using the score test method (59). 
Associations between categorical variables will be assessed using Barnard’s (2x2 
tables), Fisher’s exact or Chi-squared tests. 
Analysis of longitudinal data may be performed using mixed effects models or 
generalized estimating equations (GEE). These approaches allow describing 
outcome responses over several timepoints while accounting for potential inter-
subject heterogeneity. To achieve unbiased statistical estimation and inferences 
with nonparametric tests and generalized linear models fit by GEE methods, 
missing data need to be missing completely at random (MCAR). MCAR assumes 
that missingness does not depend on any observed or unobserved data (ie, the 
observed data is just a random sample of all the potential data). When missingness 
is negligible (eg, less than 20%), statistical methods (eg, nonparametric tests and 


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GEE methods) based on the MCAR assumption can be used with limited impact 
on the analysis. When the frequency of missing data is more substantial, methods 
that require the MCAR assumption may give misleading results. In this situation, 
statistical analyses will be performed based on appropriate modeling assumptions 
and adjusted using weighting methods, or combined with imputation, under the 
assumption that the missing data are missing at random (MAR). MAR assumes 
that the probability of an observation being missing only depends on the observed 
responses or covariates. Thus, this assumption is less stringent than the MCAR 
assumption. Weighting adjustments (eg, weighted GEE) and imputation methods 
are valid under MAR. We will consider including any of the available baseline 
predictors of the missing outcomes as covariates in statistical models. Please see 
Little and Rubin (59), Chapters 1, 3, and 6] for elaborate definitions and examples 
of missing data mechanisms and Ibrahim et al (60) for a review of missing data 
methods in clinical studies. 
Generalized linear models for response rates will use a binomial error distribution 
and for quantitative endpoints, a normal error distribution. We will assess 
repeated functional measurement using linear mixed effects models. If functional 
activity outcomes are left- and/or right- censored, we will use Hughes’ (73) linear 
mixed effects models to accommodate censoring. In addition, exploratory 
analyses of repeated functional measurements may be done using weighted GEE 
(74) methods, which are valid under MAR. We will again consider including any 
of the available baseline predictors of the missing outcomes as covariates in 
statistical models.  
6.4.8 
Analyses prior to end of scheduled follow-up visits 
Any analyses conducted prior to the end of the scheduled follow-up visits should 
not compromise the integrity of the trial in terms of participant retention or other 
study endpoint assessments.  
6.4.8.1 
Safety 
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 140/HPTN 101 
PSRT.  


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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 other endpoints 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 through 50 years 
2. Access to a participating CRS and willingness to be followed for the planned 
duration of the study 
3. Ability and willingness to provide informed consent 
4. Assessment of understanding: volunteer demonstrates understanding of this 
study and completes a questionnaire prior to first study product administration 
with verbal demonstration of understanding of all questionnaire items answered 
incorrectly 
5. Agrees not to enroll in another study of an investigational research agent until 
completion of the last required protocol clinic visit. 
6. Good general health as shown by medical history, physical exam, and screening 
laboratory tests 
HIV-Related Criteria: 
7. Willingness to receive HIV test results 


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8. Willingness to discuss HIV infection risks and amenable to HIV risk reduction 
counseling.  
9. Assessed by the clinic staff as being at “low risk” for HIV infection and 
committed to maintaining behavior consistent with low risk of HIV exposure 
through the last required protocol clinic visit (see Appendix J and Appendix K).  
Laboratory Inclusion Values 
Hemogram/Complete blood count (CBC) 
10. Hemoglobin  
• ≥ 11.0 g/dL for volunteers who were assigned female sex at birth 
• ≥ 13.0 g/dL for volunteers who were assigned male sex at birth and 
transgender males who have been on hormone therapy for more than 6 
consecutive months 
• ≥ 12.0 g/dL for transgender females who have been on hormone therapy for 
more than 6 consecutive months 
• For transgender volunteers who have been on hormone therapy for less than 6 
consecutive months, determine hemoglobin eligibility based on the sex 
assigned at birth  
11. White blood cell count = 2,500 to 12,000 cells/mm3 
12. WBC differential either within institutional normal range or with site clinician 
approval 
13. Platelets = 125,000 to 550,000 cells/mm3 
Chemistry 
14. Chemistry panel: alanine aminotransferase (ALT) < 1.25 times the 
institutional upper limit of normal (ie, < 1.25 times the reference range upper 
limit) and creatinine < 1.1 times the institutional upper limit of normal (ie, <1.1 
times the reference range upper limit) 
Virology 
15. Negative HIV-1 and -2 blood test: US volunteers must have a negative FDA-
approved enzyme immunoassay (EIA) or chemiluminescent microparticle 
immunoassay (CMIA). Non-US sites may use locally available assays that have 
been approved by HVTN and HPTN Laboratory Operations 
16. Negative Hepatitis B surface antigen (HBsAg)  


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17. Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV 
polymerase chain reaction (PCR) if the anti-HCV is positive 
Urine 
18. Negative or trace urine protein 
Reproductive Status 
19. Volunteers who were assigned female sex at birth: negative serum or urine beta 
human chorionic gonadotropin (β-HCG) pregnancy test(s) performed within 48 
hours prior to initial study product administration. Persons who are NOT of 
reproductive potential due to having undergone total hysterectomy or bilateral 
oophorectomy (verified by medical records), are not required to undergo 
pregnancy testing. 
20. Reproductive status 
A volunteer who was assigned female sex at birth must: 
• Agree to use effective contraception for sexual activity that could lead to 
pregnancy from at least 21 days prior to enrollment through the last required 
protocol visit. Effective contraception is defined as using one of the following 
methods: 
▪ Condoms (internal and external) with or without a spermicide, 
▪ Diaphragm or cervical cap with spermicide, 
▪ Intrauterine device (IUD), 
▪ Hormonal contraception,  
▪ Tubal ligation, or 
▪ Any other contraceptive method approved by the HVTN 140/HPTN 101 
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 or bilateral 
oophorectomy; or, 
• Be sexually abstinent. 


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21. Volunteers who were assigned female sex at birth must also agree not to seek 
pregnancy through alternative methods, such as artificial insemination or in 
vitro fertilization until after the last required protocol clinic visit 
7.2 
Exclusion criteria 
General 
1. Weight < 35kg or > 115 kg  
2. Blood products received within 120 days before first study product 
administration, unless eligibility for earlier enrollment is determined by the 
HVTN 140/HPTN 101 PSRT 
3. Investigational research agents received within 30 days before first study 
product administration 
4. Intent to participate in another study of an investigational research agent or 
any other study that requires non-Network HIV antibody testing during the 
planned duration of the HVTN 140/HPTN 101 study  
5. Pregnant or breastfeeding 
Vaccines, Antibodies, and other Injections or Infusions 
6. HIV vaccine(s) received in a prior HIV vaccine trial. Volunteers who have 
received control/placebo in an HIV vaccine trial are not excludedHVTN 
140/HPTN 101. 
7. SARS-CoV-2 vaccine(s) received within 7 days prior to HVTN 140/HPTN 101 
enrollment or planned within 7 days after enrollment. 
8. Receipt of humanized or human mAbs, whether licensed or investigational.  
9. Previous receipt of mAbs VRC01, VRC01LS, VRC07-523LS, PGDM1400, 
PGT121, PGT121.414.LS.  
Immune System  
10. Immunosuppressive medications received within 30 days before first study 
product administration (Not exclusionary: [1] corticosteroid nasal spray; [2] 
inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated 
dermatological condition; or [4] a single course of oral/parenteral prednisone or 
equivalent at doses < 20 mg/day and length of therapy < 14 days) 
11. Serious adverse reactions to PGDM1400LS, VRC07-523LS, or PGT121.414.LS 
formulation components (see Section 8.2) including history of anaphylaxis and 


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related symptoms such as hives, respiratory difficulty, angioedema, and/or 
abdominal pain.  
12. Immunoglobulin received within 60 days before first study product 
administration (for mAb see criterion 8 above) 
13. Autoimmune disease (Not excluded from participation: Volunteer with mild, 
stable and uncomplicated autoimmune disease that does not require 
immunosuppressive medication and that, in the judgment of the CRS investigator, 
is likely not subject to exacerbation and likely not to complicate Solicited and 
Unsolicited AE assessments.) 
14. Immunodeficiency 
Clinically significant medical conditions  
15. 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: 
• Symptoms consistent with COVID-19 or known SARS-CoV-2 infection, 
• A process that would affect the immune response, 
• A process that would require medication that affects the immune response, 
• Any contraindication to repeated infusions, or blood draws, including inability 
to establish venous or subcutaneous access, 
• A condition that requires active medical intervention or monitoring to avert 
grave danger to the volunteer’s health or well-being during the study period, 
• A condition or process (eg, chronic urticaria or recent injection or infusion 
with evidence of residual inflammation) for which signs or symptoms could 
be confused with reactions to the study product, or 
• Any condition specifically listed among the exclusion criteria. 
16. Any medical, psychiatric, or skin condition (eg, tattoos), or occupational 
responsibility that, in the judgment of the investigator, would interfere with or 
serve as a contraindication to protocol adherence, assessment of safety or 
Solicited AEs, or a participant’s ability to give informed consent.  
17. 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. 


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18. Current anti-tuberculosis (TB) therapy 
19. 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 had either of the following: 
▪ Greater than 1 exacerbation of symptoms treated with oral/parenteral 
corticosteroids; 
▪ Emergency care, urgent care, hospitalization, or intubation for asthma. 
20. Diabetes mellitus type 1 or type 2 (Not excluded: type 2 cases controlled with 
diet alone or a history of isolated gestational diabetes.) 
21. 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 in this protocol as 
consistently ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic, with or without 
medication, with only isolated, brief instances of higher readings, which must 
be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, 
blood pressure must be ≤ 140 mm Hg systolic and ≤ 90 mm Hg diastolic at 
enrollment. 
• If a person has NOT been found to have elevated blood pressure or 
hypertension during screening or previously, exclude for systolic blood 
pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg 
at enrollment. 
22. Bleeding disorder diagnosed by a clinician (eg, factor deficiency, coagulopathy, 
or platelet disorder requiring special precautions) 
23. 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) 
24. Seizure disorder: History of seizure(s) within past 3 years. Also exclude if 
volunteer has used medications in order to prevent or treat seizure(s) at any time 
within the past 3 years. 


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25. Asplenia: any condition resulting in the absence of a functional spleen 
26. History of generalized urticaria, angioedema, or anaphylaxis (Not 
exclusionary: angioedema or anaphylaxis to a known trigger with at least 5 years 
since last reaction to demonstrate satisfactory avoidance of trigger). 
7.3 
Participant departure from study product administration schedule or 
withdrawal (Part B) 
This section concerns an individual participant’s departure from the study-product 
administration schedule. Pause rules for the trial are described in Section 11.4. 
7.3.1 
Delaying study product administrations for a participant (Part B only) 
Under certain circumstances, a participant’s scheduled study product 
administration will be delayed. Refer to the SSP for further guidance regarding 
which procedures to conduct in these instances. The factors to be considered in 
such a decision include but are not limited to the following: 
• Within 7 days prior to study product administration 
▪ Receipt of systemic glucocorticoids (eg, prednisone or other 
glucocorticoids) or other immunomodulators (other than nonsteroidal anti-
inflammatory drugs [NSAIDs]) 
• Within 7 days of study product administration (ie, within 7 days prior to study 
product administration, or planned within 7 days after study product 
administration)  
▪ Receipt of SARS CoV-2 vaccine 
• Preinfusion abnormal vital signs or clinical symptoms that may mask 
assessment of study product reaction. 
• Intercurrent illness that is assessed by CRS principal investigator (or designee) 
to require delaying study product administration. The investigator may consult 
the HVTN 140/HPTN 101 PSRT. 
• Pregnancy: study product administration will be stopped while a participant is 
pregnant. If the participant is no longer pregnant (as defined by two 
consecutive negative tests) or breast-feeding and study product administration 
can be performed within an appropriate visit window, study product 
administration may resume with unanimous consent of the HVTN 140/HPTN 
101 PSRT. 


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7.3.2 
Participant departure from study product administration schedule 
Every effort should be made to follow the study product-administration schedule 
per the protocol. If a participant misses a study product administration and the 
visit window period for the study product administration has passed, that study 
product cannot be given. The participant should be asked to continue study visits. 
(see Sections 7.3.1 and 7.3.3).  
7.3.3 
Discontinuing study product administration for a participant 
Under certain circumstances, an individual participant’s study product 
administrations will be permanently discontinued. Specific events that will result 
in stopping a participant’s study product-administration schedule include: 
• Co-enrollment in a study with an investigational research agent (rare 
exceptions allowing for the continuation of study product administrations may 
be granted with the unanimous consent of the HVTN 140/HPTN 101 PSRT) 
• Clinically significant condition (ie, a condition that affects the immune system 
or for which continued study product administrations and/or blood draws may 
pose additional risk), including but not limited to the following: 
▪ HIV infection 
▪ Any grade 4 local or systemic Solicited or Unsolicited adverse event (AE) 
that is subsequently considered to be related to study product 
administration 
▪ Grade 3 clinical AE that is subsequently considered to be related to study 
product administration with the exception of fever, vomiting, and 
subjective local and systemic symptoms. For grade 3 infusion site 
erythema and/or induration, upon review, the HVTN 140/HPTN 101 
PSRT may allow continuation of study product administration 
▪ Any grade 3 or 4 lab abnormality confirmed by a repeated value that is 
subsequently considered to be related to study product; 
▪ SAE that is subsequently considered to be related to study product 
administration 
▪ Clinically significant hypersensitivity or mAb reaction including, but not 
limited to, type 1 hypersensitivity reaction, urticaria, or serum sickness 
associated with study product administration. Consultation with the 
HVTN 140/HPTN 101 PSRT is required prior to subsequent study product 
administrations following any hypersensitivity reaction associated with 
study product administration 
• Investigator determination in consultation with Protocol Team leadership (eg, 
for repeated nonadherence to study staff instructions) 


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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 140/HPTN 101 SSP). 
Participants diagnosed with HIV infection during the study should be encouraged 
to participate in follow-up visits as indicated in Section 9.12. 
7.3.4 
Participant termination from the study 
Under certain circumstances, an individual participant may be terminated from 
participation in this study. Specific events that will result in early termination 
include: 
• Participant refuses further participation, 
• Participant relocates and remote follow-up or transfer to another CRS is not 
possible, 
• CRS determines that the participant is lost to follow-up, 
• Investigator decides, in consultation with Protocol Team leadership, to 
terminate participation (eg, if participant exhibits inappropriate behavior 
toward clinic staff), or 
• Any condition where termination from the study is required by applicable 
regulations. 


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8 
Study product  
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 1-1. See the IBs for further information about study 
products. 
8.1 
Study product regimen 
The schedule of study product administration is shown in Section 1 and additional 
information is given below.   
Part A 
Group 1: PGDM1400LS 5 mg/kg to be administered via IV infusion at Month 0 
Group 2: PGDM1400LS 20 mg/kg to be administered via IV infusion at Month 0 
Group 3: PGDM1400LS 20 mg/kg to be administered via SC infusion at Month 0 
Group 4: PGDM1400LS 40 mg/kg to be administered via IV infusion at Month 0 
Group 5: PGDM1400LS 40 mg/kg to be administered via SC infusion at Month 0 
Part B 
Group 6: PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 
20 mg/kg to be administered via IV infusion sequentially in this order at Month 0 
and Month 4 
Group 7: PGDM1400LS 20mg/kg + VRC07-523LS 20mg/kg + PGT121.414.LS 
20 mg/kg to be administered via SC infusion sequentially in this order at Month 0 
and Month 4 
Group 8: PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 
1.4gram to be administered via IV infusion sequentially in this order at Month 0 
and Month 4 
Group 9: PGDM1400LS 1.4gram + VRC07-523LS 1.4gram + PGT121.414.LS 
1.4gram to be administered via SC infusion sequentially in this order at Month 0 
and Month 4 
Group 10: PGDM1400LS 40mg/kg + VRC07-523LS 40mg/kg + PGT121.414.LS 
40 mg/kg to be administered via IV infusion sequentially in this order at Month 0 
and Month 4 
 


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8.2 
Study product formulation  
8.2.1 
PGDM1400LS  
PGDM1400LS will be supplied as 10 mL single-use glass vials with a 4.75± 0.1 
mL fill volume, at a concentration of 100 mg/mL. Upon thaw, each vial contains a 
clear, colorless to yellow solution for injection, which is essentially free from 
foreign particles, but some opaque or translucent particles may be present. The 
formulation buffer is composed of 10 mM Acetate, 9% w/v Sucrose, 0.01% w/v 
Polysorbate 80 at pH 5.2. It does not contain a preservative.  
The product is stored frozen at -35°C to -15°C in a qualified, continuously 
monitored, temperature-controlled freezer until use. The study product is 
described in further detail in the IB. 
8.2.2 
VRC07-523LS  
VRC07-523LS will be supplied as 10 mL single-use glass vials with a 6.25 ± 
0.1mL fill volume and 3 mL single-use glass vials with a 2.25 mL ± 0.1 mL fill 
volume, at a concentration of 100 ± 10 mg/mL. Each vial contains a clear, 
colorless to yellow liquid, essentially free of visible particles; some opaque or 
translucent particles may be present. The formulation buffer is composed of 
50mM histidine, 50 mM sodium chloride, 5% sucrose, and 2.5% sorbitol at pH 
6.8. Vials do not contain a preservative. 
VRC07-523LS product label designates the long-term storage as -35ºC to -15 ºC 
(-31 ºF to 5 ºF). The study product is described in further detail in the IB. 
8.2.3 
PGT121.414.LS 
PGT121.414.LS will be supplied as 10 mL single-use glass vials with a 4.75 mL 
fill volume, at a concentration of 100 mg/mL. Each vial contains a clear, colorless 
to yellow, preservative free, sterile solution for injection. The formulation buffer 
is composed of acetate, sucrose, polysorbate 80 at pH of 5.2. PGT121.414.LS 
product label designates the long-term storage as -35°C to -15°C (-31°F to 5°F). 
8.3 
Preparation of study products 
Prior to preparation of the first infusion (enrollment visit), a new prescription will 
be sent to the pharmacy. For participants randomized to a weight-based (mg/kg) 
dosing group, the prescription MUST contain the participant’s weight based upon 
the participant’s weight at the most recent visit where weight was measured (this 
includes screening). If this information is NOT on the prescription, the 
prescription will be returned to the clinic from the pharmacy to be completed 
appropriately prior to the pharmacist beginning preparation of study product. 
Subsequent visit weights (based upon the participant’s weight at the most recent 
visit where weight was measured) must be communicated to the pharmacy in 


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writing prior to the day of the visit. Any changes in weight of more than 10% 
(between the prior weight and the weight on the day of the infusion visit) will 
require an updated visit weight communication to the pharmacy in writing so that 
product can be prepared based on that weight change. 
For Groups 8 and 9, the prescription will be written as the fixed dose per the 
randomized dose assignment. 
For Groups 3, 5, 7 and 9, the prescription must also contain the number of 
infusion sites that will be used for each study product. The prescription may also 
need to contain additional information (eg, amount of overfill the syringe must 
contain to account for residual volume in the tubing), depending on the tubing and 
pump to be used for study product administration. See HVTN 140/HPTN 101 
SSP for more details. 
Pharmacists must follow appropriate aseptic technique and sterile preparation 
procedures as outlined in United States Pharmacopeia (USP) <797> 
Pharmaceutical Compounding – Sterile Preparations, utilizing a pharmacy 
biosafety cabinet/isolator or better. Local regulations and site institutional policies 
and procedures for use of personal protective equipment such as gloves, gowns, 
masks, and safety glasses, must be followed. Pharmacists should follow the 
requirements of their country, their institution, and their pharmacy regulatory 
authority regarding these procedures. 
Any unused portion of study product will not be used for another participant. Any 
empty vials, unused portion of entered vials, or unused solution which contains 
study product should be discarded in a biohazard containment bag and incinerated 
or autoclaved in accordance with institutional or pharmacy policy. 
8.3.1 
PGDM1400LS 
8.3.1.1 
Thawing instructions 
1. Remove PGDM1400LS vials from the freezer and thaw at controlled room 
temperature (maximum 27°C). 
2. After thawing, the PGDM1400LS vials may be stored at 2°C to 8°C for up 
to 48 hours and/or at 15°C to 27°C for up to 24 hours. Product may not be 
stored in direct sunlight. If stored at 2°C to 8°C, vials must be equilibrated 
at controlled room temperature (15°C - 27°C) for a minimum of 30 
minutes and may be held at room temperature for up to 8 hours prior to 
product preparation. PGDM1400LS vials should not be refrozen after 
thaw. 
8.3.1.2 
PGDM1400LS weight-based dose intravenous infusion preparation  
1. Calculate the total dose (mg) of PGDM1400LS required based on the 
participant’s weight (in kg). Obtain the minimum number of thawed 


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PGDM1400LS vials, as well as an appropriately sized IV container 
(bag/glass bottle) containing 100 mL of 0.9% Sodium Chloride for 
Injection, USP, that will also permit the addition of the required calculated 
volume of PGDM1400LS.  
2. Using an 18G needle, withdraw the calculated volume of PGDM1400LS 
into a sterile syringe.  
3. Using aseptic technique, remove the air from the IV container and then 
add the withdrawn volume of PGDM1400LS to the IV container with 100 
mL of 0.9% Sodium Chloride for Injection, USP. Record this as the study 
product preparation time. 
4. Gently mix the prepared IV container. Ensure there are no visible 
particulates in the IV container. 
5. After product preparation in IV bags, the prepared PGDM1400LS product 
may be stored at 2°C to 8°C up to 24 hours and/or at controlled room 
temperature (15°C - 27°C) for a maximum of 4 hours total including the 
infusion time. Product may not be stored in direct sunlight. If stored at 2°C 
to 8°C, prepared product must be equilibrated at controlled room 
temperature (15°C - 27°C) for a minimum of 30 minutes prior to product 
administration. 
8.3.1.3 
PGDM1400LS fixed-dose intravenous infusion 
1. Obtain 4 vials of thawed PGDM1400LS vials, as well as an appropriately 
sized IV container (bag/glass bottle) containing 100 mL of 0.9% Sodium 
Chloride for Injection, USP, that will also permit the addition of the 
required calculated volume of PGDM1400LS.  
2. Using an 18G needle, withdraw a total of 14 mL of PGDM1400LS into a 
sterile syringe.  
3. Using aseptic technique, remove the air from the IV container and then 
add the withdrawn 14 mL of PGDM1400LS to the IV container with 100 
mL of 0.9% Sodium Chloride for Injection, USP. Record this as the study 
product preparation time. 
4. Gently mix the prepared IV container. Ensure there are no visible 
particulates in the IV container. 
5. After product preparation in IV bags, the prepared PGDM1400LS product 
may be stored at 2°C to 8°C up to 24 hours and/or at controlled room 
temperature (15°C - 27°C) for a maximum of 4 hours total including the 
infusion time. Product may not be stored in direct sunlight. If stored at 2°C 
to 8°C, prepared product must be equilibrated at controlled room 


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temperature (15°C - 27°C) for a minimum of 30 minutes prior to product 
administration. 
8.3.1.4 
PGDM1400LS weight-based dose subcutaneous infusion preparation 
1. Calculate the total dose (mg) of PGDM1400LS required based on the 
participant’s weight (in kg). Remove the minimum number of thawed 
PGDM1400LS vials from storage.   
2. Using aseptic technique, withdraw the calculated volume of 
PGDM1400LS from the vial(s) into a syringe using a 5-micron filter 
needle (see HVTN 140/HPTN 101 SSP for needle/filter specifications and 
details). A new filter needle must be used for each vial. Add the additional 
volume of PGDM1400LS needed to accommodate for the residual volume 
left in the tubing after infusion. Discard the filter needle(s) prior to 
dispensing. Record this as the study product preparation time. 
3. After preparation in syringes for SC administration, the prepared 
PGDM1400LS product may be stored at 2°C to 8°C up to 24 hours or at 
controlled room temperature (15°C - 27°C) up to 4 hours including 
administration time. Product may not be stored in direct sunlight. If stored 
at 2°C to 8°C, prepared product must be equilibrated at controlled room 
temperature (15°C - 27°C) for a minimum of 30 minutes prior to product 
administration. 
8.3.1.5 
PGDM1400LS fixed-dose subcutaneous infusion preparation 
1. Remove 4 vials of thawed PGDM1400LS vials from storage.   
2. Using aseptic technique, withdraw 14 mL of PGDM1400LS from the 
vial(s) into a syringe using a 5-micron filter needle (see HVTN 140/HPTN 
101 SSP for needle/filter specifications and details). A new filter needle 
must be used for each container. Add the additional volume of 
PGDM1400LS needed to accommodate for the residual volume left in the 
tubing after infusion. Discard the filter needle prior to dispensing. Record 
this as the study product preparation time. 
3. After preparation in syringes for SC administration, the prepared 
PGDM1400LS product may be stored at 2°C to 8°C up to 24 hours or at 
controlled room temperature (15°C - 27°C) up to 4 hours including 
administration time. Product may not be stored in direct sunlight. If stored 
at 2°C to 8°C, prepared product must be equilibrated at controlled room 
temperature (15°C - 27°C) for a minimum of 30 minutes prior to product 
administration.  


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8.3.2 
VRC07-523LS 
VRC07-523LS is a highly concentrated protein solution and may develop white, 
opaque to translucent particles after thawing. 
8.3.2.1 
Thawing instructions 
1. Thaw vial(s) for a minimum of 1 hour at controlled room temperature 
(maximum 27°C) after removing from the freezer. 
2. Keep the material at room temperature during the entire preparation period 
until use, up to the maximum storage times described in # 4 below. 
3. Prior to preparation for administration, swirl vials for 30 seconds to 
resuspend any visible particles, avoid foaming. DO NOT SHAKE THE 
VIALS. If particles are observed, return the vials to 2°C to 8°C storage. If 
the particles re-dissolve within the maximum storage times described in # 
4 below, they may be used for product preparation. If particles continue to 
be observed, do not use the vials. 
4. Thawed vials may be stored for up to 24 hours at controlled room 
temperature (maximum 27°C) and/or up to 2 weeks (14 days) at 2°C to 
8°C. Product may not be stored in direct sunlight. If stored at 2 ºC to 8 ºC, 
vials must be equilibrated at controlled room temperature (maximum 27 
ºC) for a minimum of 30 minutes and may be held at room temperature for 
up to 8 hours prior to product preparation. 
8.3.2.2 
VRC07-523LS weight-based dose intravenous infusion preparation 
1. Calculate the total dose (mg) of VRC07-523LS required based on 
participant’s weight (in kg). Remove the minimum number of thawed 
particle free VRC07-523LS vials from storage, as well as an appropriately 
sized IV container (bag/glass bottle) containing 100 mL of 0.9% Sodium 
Chloride for Injection, USP, that will also permit the addition of the 
required calculated volume of VRC07-523LS. 
2. Gently swirl thawed vials for 30 seconds, avoiding foaming. DO NOT 
SHAKE VIALS. Keep the vials upright at all times until ready to 
withdraw the contents. Do not invert the vials during inspection. 
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.2.1. 
4. Using aseptic technique, add the calculated volume of VRC07-523 LS to 
the IV container with 100 mL of Sodium Chloride for Injection, 0.9 USP. 
Record this as the study product preparation time.  
5. The prepared VRC07-523LS IV container may be stored at 2°C to 8°C up 
to 48 hours or at controlled room temperature (maximum 27°C) for a 


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maximum of 4 hours total including the infusion time. Product may not be 
stored in direct sunlight. If stored at 2°C to 8°C, prepared product must be 
equilibrated at controlled room temperature (maximum 27°C) for a 
minimum of 30 minutes prior to product administration. 
8.3.2.3 
VRC07-523LS fixed-dose intravenous infusion preparation 
1. Remove either three 10 mL vial sizes or eight 3 mL vial sizes of thawed 
particle free VRC07-523LS from storage, as well as an appropriately sized 
IV container (bag/glass bottle) containing 100 mL of 0.9% Sodium 
Chloride for Injection, USP, that will also permit the addition of the 
required calculated volume of VRC07-523LS. 
2. Gently swirl thawed vials for 30 seconds, avoiding foaming. DO NOT 
SHAKE VIALS. Keep the vials upright at all times until ready to 
withdraw the contents. Do not invert the vials during inspection. 
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.2.1. 
4. Using aseptic technique, add 14 mL of VRC07-523 LS to the IV container 
with 100 mL of 0.9% Sodium Chloride for Injection, USP. Record this as 
the study product preparation time.  
5. The prepared VRC07-523LS IV container may be stored at 2°C to 8°C up 
to 48 hours or at controlled room temperature (maximum 27°C) for a 
maximum of 4 hours total including the infusion time. Product may not be 
stored in direct sunlight. If stored at 2°C to 8°C, prepared product must be 
equilibrated at controlled room temperature (maximum 27°C) for a 
minimum of 30 minutes prior to product administration.  
8.3.2.4 
VRC07-523LS weight-based dose subcutaneous infusion preparation 
1. Calculate the total (mg) of VRC07-523LS required based on the 
participant’s weight (in kg). Remove the minimum number of thawed 
particle-free VRC07-523LS vials from storage. 
2. Gently swirl thawed vials for 30 seconds to avoid foaming. DO NOT 
SHAKE VIALS. Keep the vials upright until ready to withdraw the 
contents. Do not invert the vial during inspection. 
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.2.1. 
4. Using aseptic technique, withdraw the calculated volume of VRC07-
523LS from the vial(s) into a syringe using a 5 micron filter needle (see 
HVTN 140/HPTN 101 SSP for needle/filter specifications and details). A 


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new filter needle must be used for each vial. Discard the filter needle prior 
to dispensing. Record this as the study product preparation time. 
5. The prepared VRC07-523LS syringe(s) may be stored at 2°C to 8°C for 
up to 24 hours or at controlled room temperature (maximum 27°C) for a 
maximum of 4 hours, including the administration time. Product may not 
be stored in direct sunlight. If stored at 2°C to 8°C, prepared product must 
be equilibrated at controlled room temperature (maximum 27°C) for a 
minimum of 30 minutes prior to product administration. 
8.3.2.5 
VRC07-523LS fixed-dose subcutaneous infusion preparation 
1. Remove either three 10 mL vial sizes or eight 3 mL vial sizes of thawed 
particle free VRC07-523LS from storage. 
2. Gently swirl thawed vials for 30 seconds, avoiding foaming. DO NOT 
SHAKE VIALS. Keep the vials upright at all times until ready to 
withdraw the contents. Do not invert the vials during inspection. 
3. Observe vials for particles. If particles are observed, refer to the thawing 
instructions described above in Section 8.3.2.1. 
4. Using aseptic technique, withdraw 14 mL of VRC07-523 LS into a 
syringe using a 5 micron filter needle (see HVTN 140/HPTN 101 SSP for 
needle/filter specifications and details). A new filter needle must be used 
for each vial. Add the additional volume of VRC07-523LS needed to 
accommodate for the residual volume left in the tubing after infusion. 
Discard the filter needle prior to dispensing. Record this as the study 
product preparation time.  
5. The prepared VRC07-523LS syringe(s) may be stored at 2°C to 8°C for 
up to 24 hours or at controlled room temperature (maximum 27°C) for a 
maximum of 4 hours, including the administration time. Product may not 
be stored in direct sunlight. If stored at 2°C to 8°C, prepared product must 
be equilibrated at controlled room temperature (maximum 27°C) for a 
minimum of 30 minutes prior to product administration.   
8.3.3 
PGT121.414.LS 
8.3.3.1 
Thawing instructions 
1. Thaw vial(s) at room temperature and hold for at least 30 minutes post-
thaw (no ice crystals present). Vials must not be moved directly from the 
freezer to storage at 2°C to 8°C. 
2. Keep the material at room temperature during the entire preparation period 
until use, up to the maximum storage times described in #4 below. 


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3. Prior to preparation for administration, swirl vials for 30 seconds to 
resuspend any visible particles, avoid foaming. DO NOT SHAKE THE 
VIALS. If some white to translucent particles continue to be observed, 
vials may be used for the preparation of the IV or SC product. 
4. Thawed vials may be stored for up to 24 hours at room temperature 
(maximum 27°C). If vials are not used within that time, they may be 
refrigerated for up to 2 weeks (14 days) at 2°C to 8°C and should be used 
within 8 hours of any subsequent return to room temperature (maximum 
27°C). Refrigerated product must be equilibrated at room temperature 
(maximum 27°C) for a minimum of 30 minutes prior to use. 
8.3.3.2 
PGT121.414.LS weight-based dose intravenous infusion preparation 
1. Calculate the total dose (mg) of PGT121.414.LS required based on the 
participant’s weight (in kg). Remove the minimum number of thawed 
PGT121.414.LS vials from storage, as well as an appropriately sized IV 
container (bag/glass bottle) containing 100 mL of 0.9% Sodium Chloride 
for Injection, USP, that will also permit the addition of the required 
calculated volume of PGT121.414.LS. 
2. Gently swirl thawed vials for 30 seconds, avoiding foaming. DO NOT 
SHAKE VIALS. Keep the vials upright until ready to withdraw the 
contents. Do not invert the vials during inspection. 
3. Using aseptic technique, remove the air from the IV container and then 
add the calculated volume of PGT121.414.LS to the IV container with 100 
mL of Sodium Chloride for Injection, 0.9 % USP. Record this as the study 
product preparation time. 
4. The prepared PGT121.414.LS product may be stored at 2°C to 8°C up to 
24 hours or at room temperature (maximum 27°C) for a maximum of 4 
hours, including the administration time. If stored at 2°C to 8°C, prepared 
product must be equilibrated at room temperature (maximum 27°C) for a 
minimum of 30 minutes prior to product administration. 
8.3.3.3 
PGT121.414.LS fixed-dose intravenous infusion preparation 
1. Obtain 4 vials of thawed PGT121.414.LS vials, as well as an appropriately 
sized IV container (bag/glass bottle) containing 100 mL of 0.9% Sodium 
Chloride for Injection, USP, that will also permit the addition of the 
required calculated volume of PGT121.414.LS.  
2. Using an 18G needle, withdraw a total of 14mL of PGT121.414.LS into a 
sterile syringe.  
3. Using aseptic technique, remove the air from the IV container and then 
add the withdrawn 14 mL of PGT121.414.LS to the IV container with 100 


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mL of 0.9% Sodium Chloride for Injection, USP. Record this as the study 
product preparation time. Assign a 4-hour expiration from this time.  
4. Gently mix the prepared IV container. Ensure there are no visible 
particulates in the IV container. 
8.3.3.4 
PGT121.414.LS weight-based dose subcutaneous infusion preparation 
1. Calculate the total (mg) of PGT121.414.LS required based on the 
participant’s weight (in kg). Remove the minimum number of thawed 
PGT121.414.LS vials from storage. 
2. Gently swirl thawed vials for 30 seconds to avoid foaming. DO NOT 
SHAKE VIALS. Keep the vials upright until ready to withdraw the 
contents. Do not invert the vial during inspection. 
3. Using aseptic technique, withdraw the calculated volume of 
PGT121.414.LS from the vial(s) into a syringe using a 5 micron filter 
needle (see HVTN 140/HPTN 101 SSP for needle/filter specifications and 
details). A new filter needle must be used for each vial. Add the additional 
volume of PGT121.414.LS needed to accommodate for the residual 
volume left in the tubing after infusion. Discard the filter needle prior to 
dispensing. Record this as the study product preparation time. 
4. The prepared PGT121.414.LS product may be stored at 2°C to 8°C up to 
24 hours or at room temperature (maximum 27°C) for a maximum of 4 
hours, including the administration time. If stored at 2°C to 8°C, prepared 
product must be equilibrated at room temperature (maximum 27°C) for a 
minimum of 30 minutes prior to product administration. 
8.3.3.5 
PGT121.414.LS fixed-dose subcutaneous infusion preparation 
1. Remove 4 vials of thawed PGT121.414.LS from storage. 
2. Gently swirl thawed vials for 30 seconds to avoid foaming. DO NOT 
SHAKE VIALS. Keep the vials upright until ready to withdraw the 
contents. Do not invert the vial during inspection. 
3. Using aseptic technique, withdraw 14 mL of PGT121.414.LS from the 
vial(s) into a syringe using a 5 micron filter needle (see HVTN 140/HPTN 
101 SSP for needle/filter specifications and details). A new filter needle 
must be used for each vial. Add the additional volume of PGT121.414.LS 
needed to accommodate for the residual volume left in the tubing after 
infusion. Discard the filter needle prior to dispensing. Record this as the 
study product preparation time. 
4. The prepared PGT121.414.LS product may be stored at 2°C to 8°C up to 
24 hours or at room temperature (maximum 27°C) for a maximum of 4 
hours, including the administration time. If stored at 2°C to 8°C, prepared 


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product must be equilibrated at room temperature (maximum 27°C) for a 
minimum of 30 minutes prior to product administration. 
8.3.3.6 
Labeling of Study Product 
Label the study product as follows: 
• Participant identifier(s) 
• Participant weight (in kg) for weight-based dosing 
• Study product name 
• Total dose (mg) 
• Final volume (mL) 
• Route (IV or SC)  
• Beyond use date and time 
• Any additional information required by jurisdiction  
8.4 
Administration 
For weight-based dosing, the container prepared by the pharmacy will include the 
weight that was used for preparation of the study product. The clinician 
responsible for administration will check the container label and confirm that the 
participant identifier(s) is/are correct and that the weight listed on the container 
label is within 10% of the participant’s current actual weight.  
In Groups 6-10, three separate IV containers each containing one study product 
will be administered sequentially.  
8.4.1 
General considerations for subcutaneous infusion study product 
administration 
Due to factors such as dose and volume, participant weight and body habitus, and 
participant tolerability and preference, the site clinicians and participants must 
decide whether to subcutaneously infuse each study product at 1, 2, or 3 anatomic 
locations simultaneously. In Part B, three mAbs are infused sequentially; thus in 
Part B there are a minimum of 3 and a maximum of 9 infusion sites. The HVTN 
140/HPTN 101 SSP provides information about subcutaneous infusion sets, 
recommended infusion pumps and clinical considerations for study product 
administration. 


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A suitable SC infusion set (tubing and needle(s)) should be affixed to the syringe 
prior to administration. The SC infusion sets are carefully and gently primed with 
the study product just to the end of the tubing leaving the needle dry. Dry needles 
are less painful. The syringe will be prepared with overfill to accommodate for the 
residual study product left in the tubing. 
Refer to the HVTN 140/HPTN 101 SSP for further information on SC 
administration. 
8.4.2 
General considerations for intravenous infusion study product 
administration 
For all IV infusions: 
• A 1.2 micron in-line filter must be used for IV product administration. Filters 
must comply with the specifications described in the HVTN 140/ HPTN 101 
SSP. 
• Once the in-line filter is added to the tubing, prime the administration set with 
0.9% Sodium Chloride for Injection, USP.  
• Refer to the HVTN 140/HPTN 101 SSP for further information on IV 
administration. 
8.4.3 
PGDM1400LS (Intravenous Infusion) 
PGDM1400LS will be administered IV over approximately 30 to 60 minutes. 
8.4.4 
PGDM1400LS (Subcutaneous Infusion) 
PGDM1400LS will be administered via SC infusion at a rate of approximately 15 
mL/hr per infusion site for the first infusion visit. The rate may be increased up to 
approximately 20 mL/hr per infusion site as tolerated by the participant for the 
second infusion visit in Part B.  
8.4.5 
VRC07-523LS (Intravenous Infusion) 
VRC07-523LS will be administered IV over approximately 15 to 30 minutes or 
more as needed using a volumetric pump. 
8.4.6 
VR07-523LS (Subcutaneous Infusion) 
VRC07-523LS will be administered via subcutaneous infusion at a rate of 
approximately 15 mL/hr for the first infusion visit. The rate may be increased up 
to approximately 20 mL/hr per infusion site as tolerated by the participant for the 
second infusion visit in Part B.  


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8.4.7 
PGT121.414.LS (Intravenous Infusion) 
PGT121.414.LS will be administered IV over approximately 30 to 60 minutes.   
8.4.8 
PGT121.414.LS (Subcutaneous Infusion) 
PGT121.414.LS will be administered via SC infusion at a rate of approximately 
15 mL/hr for the first infusion visit. The rate may be increased up to 
approximately 20 mL/hr per infusion site as tolerated by the participant for the 
second infusion visit in Part B.  
8.5 
Acquisition of study products 
PGDM1400LS is provided by DAIDS, NIAID, NIH, DHHS (Bethesda, MD, 
USA). 
VRC07-523LS is provided by Dale and Betty Bumpers Vaccine Research Center 
(VRC), NIAID, NIH, DHHS (Bethesda, MD, USA). 
PGT121.414.LS is provided by Dale and Betty Bumpers Vaccine Research Center 
(VRC), NIAID, NIH, DHHS (Bethesda, MD, USA). 
Once a CRS is protocol registered, the pharmacist can obtain study products from 
the NIAID Clinical Research Products Management Center (CRPMC) by 
following the ordering procedures outlined in Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks. 
Filter needles, in-line filters, infusion sets, infusion pump, tubing, and 0.9% 
Sodium Chloride for Injection, USP will be locally sourced by the site. Refer to 
the study product considerations section of the HVTN 140/HPTN 101 SSP for 
product specific reference numbers. Should it be determined by the Networks or 
the HVTN 140/HPTN 101 team that specialized multiple leg subcutaneous 
infusion needle sets and specialty tubing that controls flow rate with constant 
pressure system pumps need to be supplied to the sites conducting this protocol, 
the Network LOCs will purchase the specialized infusion sets and they will be 
distributed by the CRPMC or via another distribution method. 
8.6 
Pharmacy records 
The CRS pharmacist is required to maintain complete records of all study 
products. The pharmacist of record is responsible for maintaining randomization 
codes and randomization confirmation notices for each participant in a secure 
manner. 


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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 
the study sponsor. For non-US clinical research sites, all unused study products 
must be destroyed after the study is completed or terminated unless otherwise 
instructed by the study sponsor. The procedures are included in the Pharmacy 
Guidelines and Instructions for DAIDS Clinical Trials Networks. 


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9 
Clinical procedures 
The schedule of clinical procedures is shown in Appendix H and Appendix I. 
Procedures are in place so that study visits may be conducted remotely, such as 
via phone, text message, email or other electronic means, in lieu of, or in 
combination with, in-person visits at the clinical research site. Furthermore, some 
visit procedures may be conducted outside the CRS (eg, PK sampling, see HVTN 
140/HPTN 101 SSP for additional details). Direct data entry or direct data capture 
of study data into the study database is allowed when capturing information from 
the participant. Study data may also be sourced from electronic or paper source 
documents prior to being entered into the study database (see HVTN 140/HPTN 
101 SSP). 
9.1 
Informed consent 
Informed consent is the process of working with participants so that they fully 
understand what will and may happen to them while participating in a research 
study. The informed consent form documents that a participant (1) has been 
informed about the potential risks, benefits, and alternatives to participation, and 
(2) is willing to participate in the study. Informed consent encompasses all written 
or verbal study information CRS staff provide to the participant, before and 
during the trial. CRS staff will obtain informed consent of participants according 
to HVTN and HPTN policies and procedures, as well as per the CRS’s SOP on 
the informed consent process. 
The informed consent process continues throughout the study. Key study concepts 
should be reviewed periodically with the participant and the review should be 
documented. At each study visit, CRS staff should consider reviewing the 
procedures and requirements for that visit and for the remaining visits. 
Additionally, if any new information is learned that might affect the participants’ 
decisions to stay in the trial, this information will be shared with trial participants. 
If necessary, participants will be asked to sign revised informed consent forms as 
directed by the IRB/EC. 
A CRS may employ recruitment efforts prior to the participant consenting. For 
example, some CRSs use a telephone script to prescreen people before they come 
to the clinic for a full screening visit. Participants must sign a screening or 
protocol-specific consent before any procedures are performed to determine 
eligibility. CRSs must submit recruitment and prescreening materials to their 
IRB/EC and any applicable RE for human subjects protection review and 
approval. 
Note: As defined in the DAIDS Protocol Registration Manual, an RE is “Any 
entity/body that has the power to regulate which includes authorities that review 
submitted clinical data and those that conduct inspections. These are sometimes 
referred to as competent authorities. These are entities/bodies whose 


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approval/authorization/acknowledgment of a clinical trial is required for 
conducting a clinical trial. Any organization whose approval is required prior to a 
CRS’s participation in DAIDS funded and/or Sponsored Clinical Trial. Includes 
but not limited to approvals from state/national health systems and administrative 
bodies, drug agencies etc. (DAIDS adopted from ICH E6).” CRSs are responsible 
for complying with 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 CRS receives protocol registration from the DAIDS RSC Protocol 
Registration Office. 
Some CRSs have approval from their IRB/EC and any applicable RE to use a 
general screening consent form that allows screening for an unspecified HIV 
prevention clinical trial. In this way, CRS staff can continually screen potential 
participants and, when needed, proceed quickly to obtain protocol-specific 
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 forms for the main study is located in 
Appendix A and Appendix B. A separate sample consent form for other uses of 
specimens is located in Appendix D. 
Each CRS is responsible for developing a protocol-specific consent form(s) for 
local use, based on the sample protocol-specific consent forms in Appendix A, 
Appendix B, and Appendix D. 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 ICH E6(R2) 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. 


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The sample informed consent form(s) include instructions 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 is responsible for ensuring that participants fully understand the study 
before enrolling them. This process involves reviewing the informed consent form 
with the participant, allowing time for the participant to reflect on the procedures 
and issues presented, and answering all questions completely.  
An Assessment of Understanding is used to document the participant’s 
understanding of key concepts in this clinical trial. The participant must complete 
the Assessment of Understanding before enrollment. Staff may provide assistance 
in reading and understanding the questions and responses, if necessary. 
Participants must verbalize understanding of all questions answered incorrectly. 
This process and the participant’s understanding of the key concepts should be 
recorded in source documentation at the site. 
IRB/EC and any applicable RE may require that a participant has signed either a 
screening or protocol-specific consent document prior to administering the 
Assessment of Understanding. The consent process (including the use of the 
Assessment of Understanding) should be explained thoroughly to the IRB/EC and 
any applicable RE, whose recommendations should be followed. 
9.2 
Pre-enrollment procedures 
Screening may occur over the course of several contacts/visits, up to and 
including before study product administration on day 0. All inclusion and 
exclusion criteria must be assessed within 56 days before enrollment, unless 
otherwise specified in the eligibility criteria (or below in this section). 
After the appropriate informed consent has been obtained and before enrollment, 
the following procedures are performed: 
• Medical history, documented in the case history record; 
• Assessment of whether the volunteer is at low risk for HIV infection (see 
Appendix J and Appendix K);  
• 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; 


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• 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, 
▪ Hepatitis B surface antigen (HBsAg), 
▪ Anti-HCV Abs, 
▪ Syphilis, 
▪ Complete Blood Count (CBC) with differential, 
▪ Chemistry panel (alanine aminotransferase [ALT], creatinine), 
▪ Urine dipstick (urinalyses if indicated; see Section 9.7), and 
▪ Urine or serum pregnancy test (volunteers who were assigned female sex 
at birth); persons who are not of reproductive potential due to having 
undergone total hysterectomy with bilateral oophorectomy (verified by 
medical records) are not required to undergo pregnancy testing;  
• Administration of behavioral risk assessment questionnaire; 
• Obtaining volunteer demographics in compliance with the NIH Policy on 
Reporting Race and Ethnicity Data: Subjects in Clinical Research, Aug. 8, 
2001 (available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-01-
053.html); 
• Counseling on HIV testing and risk reduction, performed in compliance with 
the US Centers for Disease Control and Prevention (CDC)’s current 
guidelines or other local guidelines for HIV counseling, testing, and referral as 
described in Section 9.5; and 
• Discussion of reproductive status and pregnancy prevention. A pregnant or 
breastfeeding person may not be enrolled in this trial. Specific criteria and 
assessment of contraception and reproductive status are described in study 
inclusion criteria. Discussion of contraception includes advising a participant 
who was assigned female sex at birth and who reports no current sexual 
activity that could lead to that participant becoming pregnant to have a plan to 
begin adequate birth control. This plan would be put to use if, during the 
study, the participant becomes sexually active in a way that could lead to that 
participant becoming pregnant. 
9.2.1 
Use of screening results from another HVTN or HPTN study 
If a participant screens for an HVTN or HPTN study at the same CRS but then 
does not join that study, screening results from that effort may be applied to the 


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screening for this protocol, as long as the screening was done under participant 
consent, the participant has signed a consent form to begin screening for this 
study, and the tests were conducted within the time periods specified in the 
eligibility criteria (see Sections 7.1 and 7.2). 
9.3 
Enrollment and study product administration visits 
Once a volunteer has consented to trial participation and is found to meet all 
eligibility criteria (see Sections 7.1 and 7.2), the CRS requests the randomization 
assignment via a Web-based randomization system. Enrollment is simultaneous 
with first study product administration. 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 study product administration visits, the following procedures are 
performed before study product administration: 
• Abbreviated physical examination, including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
• Assessment of baseline Solicited AEs; 
• Assessment of concomitant medications (as described in Section 9.2); 
• Assessment of any new or unresolved Unsolicited AEs/intercurrent illnesses; 
and 
• Clinical laboratory tests including: 
▪ CBC with differential; 
▪ Chemistry panel (alanine aminotransferase [ALT], aspartate 
aminotransferase [AST], alkaline phosphatase [Alk Phos] and creatinine); 
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 hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. For pregnant 
participants, see Section 9.11. 
Following completion of all procedures in the preceding list, and if available 
results indicate that study product administration may proceed, study product 
administration is administered (see Sections 8.3 and 8.4). 


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Administration of all infusions during a study product administration visit must be 
accomplished within 1 calendar day. 
Immediately following study product administration, the participant remains in 
the clinic for observation for about 1 hour. See the HVTN 140/HPTN 101 SSP for 
details regarding study product administration visit procedures. Before leaving the 
clinic, the participant is given the Participant Diary and is instructed on how to 
complete it. The CRS will make arrangements to be in contact with the participant 
as described in Section 9.8. 
The following procedures will be performed at all study product administration 
visits. These procedures may be performed prior to or following study product 
administration:  
• Risk reduction counseling (as described in Section 9.5);  
• For participants capable of becoming pregnant, contraception status 
assessment (as described in Sections 9.2 and 9.6). In persons who are 
confirmed pregnant, contraception status assessment is not required; and 
• Assessment of new or unresolved social impacts (CRS 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). 
The following procedures will be performed at all infusion visits following study 
product administration: 
• Acceptability questionnaire (see Appendix H and Appendix I); and 
• Drug concentrations/detection collection (see Appendix F and Appendix G). 
Additional procedures will be performed at scheduled visits as specified in 
Appendix H and Appendix I:  
• 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; and 
• Specimen collection (should be completed per Appendix F and Appendix G,). 
9.3.1 
Managing Antibody reactions 
Since PGDM1400LS, VRC07-523LS, and PGT121.414.LS are human mAbs, 
rather than murine or chimeric mAbs, that target a viral antigen, rather than 
human cell surface antigens, serious Ab reactions are expected to be rare. 


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Nevertheless, participants will be closely monitored in the clinic during study 
product administration and during a post study-product-administration 
observation period. 
CRS staff are trained to recognize suspected Ab reactions and to provide 
immediate medical care consistent with the HVTN 140/HPTN 101 SSP. 
Medications used to treat Ab reactions may include acetaminophen, 
antihistamines, and/or corticosteroids. CRSs are also equipped with additional 
emergency medical supplies to provide other immediate medical intervention, if 
indicated, and are near medical emergency services. Should the need arise, CRSs 
may transfer the participant, once stabilized, to a tertiary care center for further 
management.  
The following procedures should be performed after an Ab reaction: 
• Ab reaction clinical assessment; and 
• Ab reaction blood collection. 
For detailed management of Ab reactions see the HVTN 140/HPTN 101 SSP. 
9.4 
Follow-up visits 
The following procedures are performed at scheduled follow-up visits as 
specified in Appendix H and Appendix I: 
• Risk reduction counseling (as described in Section 9.5);  
• For participants capable of becoming pregnant, contraception status 
assessment (as described in Sections 9.2 and 9.6). In persons who are 
confirmed pregnant, contraception status assessment is not required;  
• Assessment of new or unresolved social impacts (CRS 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;  
• 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); 


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• Administration of a questionnaire that asks the participant about any HIV 
testing they may have received outside of the study; 
• 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; 
• Abbreviated physical examination including weight, vital signs, and a 
symptom-directed evaluation by history and/or appropriate physical exam 
based on participant self-reported symptoms or complaints; 
• Complete physical examination, including weight, vital signs, and clinical 
assessments of head, ears, eyes, nose, and throat; neck; lymph nodes; heart; 
chest; abdomen; extremities; neurological function; and skin; 
• Specimen collection (should be completed per Appendix F and Appendix G,); 
and 
• Clinical laboratory tests including: 
▪ CBC with differential; 
▪ Chemistry panel (alanine aminotransferase [ALT], aspartate 
aminotransferase [AST], alkaline phosphatase [Alk Phos] and creatinine);  
▪ Urine dipstick (urinalysis if appropriate; see Section 9.7); and 
▪ Urine or serum pregnancy test (for participants who were assigned female 
sex at birth). Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical 
records), are not required to undergo pregnancy testing. During follow-up 
in persons who are confirmed pregnant, contraception status assessment is 
not required, unless clinically indicated. 
9.4.1 
Interim contacts 
CRSs may report safety information obtained at a contact other than the regularly 
scheduled visits. These contacts are reported as interim visits. 
9.5 
HIV counseling and testing 
HIV counseling will be performed in compliance with the CDC’s guidelines or 
other local guidelines for HIV counseling and referral. HIV testing will be 
performed in accordance with the protocol-specific HIV testing algorithm 
following enrollment. 


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Participants will be counseled routinely during the trial on the avoidance of HIV 
infection.  
Potential participants identified during screening as having acquired HIV 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. With respect to enrolled participants who acquire HIV during the study, 
see Section 9.12. 
It is theoretically possible that an anti-HIV mAb may suppress viral replication, 
which can reduce the ability to detect HIV infection, even if a person has actually 
acquired HIV.  
An anti-HIV mAb is not likely to directly affect the assays used to detect HIV-1 
acquisition. 
9.5.1 
Monoclonal antibody-associated reactivity 
Tests of human plasma containing anti-HIV mAbs have been conducted using a 
variety of commercially available HIV test kits. At high plasma concentrations, 
reactive or indeterminate results have been observed on some test kits. See the 
HVTN 140/HPTN 101 SSP for further detail. Thus, there is a possibility that 
receipt of the study product will cause a reactive result on some currently 
available HIV test kits, especially if testing occurs close to study product 
administration timepoints. 
Study staff will advise study participants to confine their HIV testing while in the 
study to that provided through the CRS. Staff will also inform study participants 
of the likelihood of routine HIV testing being offered or performed outside the 
study CRS at emergency rooms, clinics, and medical offices, and will inform 
participants of their right to opt out of HIV testing outside the study site. CRS 
staff should inform study participants if local and/or state/regional policies and 
regulations permit medical providers to perform HIV testing without first 
informing patients. If this is the case, then CRS staff should advise study 
participants that they may decline testing preemptively. CRS staff should also 
inform participants if positive results must be reported to local public health 
authorities. CRS staff should provide participants with CRS contact information 
and should encourage participants to ask medical providers to contact the CRS. 
The CRS can verify that the participant is in an HIV mAb clinical trial and should 
only be tested at the study CRS.  
9.6 
Contraception status 
Contraception status is assessed and documented at clinic visits indicated in 
Appendix H and Appendix I 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 


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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, or bilateral oophorectomy—must be 
documented in the participant’s study record. 
9.7 
Urine testing 
Dipstick testing must include the following required elements: glucose, protein, 
and hemoglobin. The examination is performed on urine obtained by clean catch. 
If the screening dipstick is transiently abnormal due to non-urinary bleeding (eg, 
menstruation) or infection, document this issue in the participant’s source 
documentation. For infection, provide appropriate treatment and/or referral and 
document this in the participant’s chart. Following resolution, repeat the dipstick 
and, if within the eligibility limits specified in the protocol, the participant may be 
enrolled. 
Follow-up visit dipstick testing should be deferred if a participant is experiencing 
non-urinary bleeding (eg, menstruation) but should be performed as soon as 
possible. If a follow-up visit dipstick is abnormal due to a participant’s non-
urinary bleeding (eg, menstruation) document in the comment section of the case 
report form (CRF)’ and repeat the dipstick once the participant is no longer 
experiencing non-urinary bleeding. A micro-urinalysis is not required. If a follow-
up visit dipstick or micro-urinalysis is abnormal due to infection, provide 
appropriate treatment and/or referral and document this in the participant's source 
documentation. See the Urinalysis Sample Collection, Interpretation, 
Management, and Reporting section of the Ab Manual of Operations (MOP) for 
further details.  
9.8 
Assessments of Solicited AEs 
For all participants, baseline assessments are performed before, and Solicited AE 
assessments are performed after each study product administration. All Solicited 
AEs are graded according to the Division of AIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017, except 
as noted in Section 11.2.2. See HVTN 140/HPTN 101 SSP for further details. 
The Solicited AE assessment period is 3 full days following each study product 
administration per the assessment schedule shown in Table 9-1. Participants are 


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instructed to record symptoms using a Participant Diary. The CRS staff and the 
participant will be in contact after the 3-day Solicited AE assessment period, or 
sooner if indicated. In general, a participant who self-reports any post study 
product administration reactions greater than mild is seen by a clinician within 48 
hours after onset, unless the reaction is improving and/or has completely resolved. 
Clinic staff will follow new or unresolved Solicited AEs present at day 3 to 
resolution. 
Solicited AEs are reported using CRFs that correspond to the time of assessment 
in Table 9-1. Solicited AE assessments include assessments of systemic and local 
symptoms, and study product-related lesions. Events not listed on a CRF, or with 
an onset after the Solicited AE assessment period (day of study product 
administration and 3 full days after), or those meeting SAE/Unsolicited AEs 
requiring expedited reporting according to DAIDS criteria, are recorded on an AE 
Log CRF.  
Table 9-1 Schedule of Solicited AE assessments 
Day 
Time 
Performed by 
0a 
Baseline: before study product 
administration 
CRS clinician 
 
Early: 25-60 minutes after study product 
administration 
CRS clinician 
 
Between early assessment and 11:59pm 
day 0 
CRS clinician or participant 
1-3b 
Between 12:00am and 11:59pm on the 
respective day 
CRS clinician or participant 
a Day of study product administration 
b New or unresolved Solicited AEs present on day 3 are followed until resolution 
9.8.1 
Assessment of systemic and local symptoms 
Systemic symptoms to be assessed as Solicited AEs in this trial include increased 
body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, 
nausea, urticaria, non-exertional dyspnea, non-exertional tachycardia (assessed by 
CRS staff, not by the participant), generalized pruritus, facial flushing, and 
unexplained diaphoresis. Local symptoms include pain and/or tenderness at the 
infusion site. Additionally, in participants receiving SC injection, local pruritus 
will be assessed. The daily maximum severity reached for each symptom during 
the assessment period is reported. 
Body temperature is measured by oral or infrared thermometry. All temperatures 
must be measured by non-axillary thermometry. This includes temperatures taken 
in the clinic, as well as temperatures taken by participants during the Solicited AE 
period. 
Temperature is reported in degrees Celsius. If temperature is measured in 
Fahrenheit, the conversion to Celsius should be documented in the participant’s 
chart note. A measurement is taken once daily during the assessment period and 
should be repeated if participant is feeling feverish. 


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9.8.2 
Assessment of IV or SC infusion site 
Typical infusion site reactions are erythema/redness and induration/swelling. The 
maximum diameter measurement for all infusion site reactions is recorded. 
All infusion site reactions are monitored until resolution. Reactions with areas 
with diameters ≥ 5 cm are followed daily; otherwise, the frequency of follow-up 
is based on clinician judgment. See HVTN140/HPTN101 SSP for details. 
9.9 
Visit windows and missed visits 
Visit windows are shown in Appendix L. The procedures for documenting missed 
visits and out of window visits are described in HVTN140/HPTN101 SSP.  
If a participant misses a scheduled visit, the CRS staff should either attempt to 
bring the participant in to the CRS or conduct the visit remotely as soon as 
possible to complete the required safety assessments and other procedures. See 
the SSP for more details. 
If a missed visit required study product administration or if study product 
administration must be permanently discontinued, please refer to Section 7.3.2 
and Section 7.3.3 for resolution. 
9.10 
Early termination visit 
In the event of early participant termination, CRS staff should attempt to complete 
the following assessments, as appropriate: a final physical examination, clinical 
laboratory tests (including urine dipstick, CBC with differential, and chemistry 
panel (see Section 7.1), pregnancy testing (note: for persons who are confirmed 
pregnant, pregnancy testing is not required, unless clinically indicated), social 
impact assessment, and HIV test. For participants who have a confirmed 
diagnosis of HIV infection, see Section 9.12. 
9.11 
Pregnancy 
If a participant becomes pregnant during the course of the study, no more 
infusions 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. During follow-up in persons who 
are confirmed pregnant, pregnancy testing is not required, unless clinically 
indicated. If the participant terminates from the study prior to the pregnancy 
outcome, the CRS should make every effort to keep in touch with the participant 
in order to ascertain the pregnancy outcome. Pregnancies and pregnancy 
outcomes will be reported. If the participant is no longer pregnant, refer to Section 
7.3.1. 


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See Pregnancy Management and Reporting section of the Ab MOP for further 
details. 
9.12 
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 24 weeks following their last study 
product administration. Follow-up duration for participants diagnosed with HIV 
infection may be adjusted in consultation with the CRS investigator and the 
HVTN 140/HPTN 101 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 
collected (note: for persons who are confirmed pregnant, pregnancy testing is not 
required, unless clinically indicated); in addition, some clinic procedures may be 
modified or discontinued (see Appendix F and Appendix G). These individuals 
may also be referred to appropriate ongoing clinical trials or observational studies. 
See the HIV Infection section in the Ab MOP for further details. 


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10 
Laboratory 
10.1 
CRS laboratory procedures 
The HVTN 140/HPTN 101 Site Lab Instructions and SSP provide further 
guidelines for operational issues concerning the clinical and processing 
laboratories. These documents include guidelines for general specimen collection, 
special considerations for phlebotomy, specimen labeling, whole blood 
processing, HIV screening/diagnostic testing, and general screening and safety 
testing. 
Tube types for blood collection are specified in Appendix F and Appendix G. For 
tests performed locally, the local lab may assign appropriate tube types. 
In specific situations, the blood collection tubes may be redirected to another 
laboratory or may require study-specific processing techniques. In these cases, 
laboratory special instructions will be posted on the protocol-specific section of 
the HVTN website. 
Of note, all assays described below are performed as research assays and are not 
approved for use in medical care. Results from these assays are not made 
available to participants or medical professionals to guide treatment decisions. 
10.2 
Total blood volume 
Required blood volumes per visit are shown in Appendix F and Appendix G. 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 
PGDM1400LS, VRC07-523LS, and PGT121.414.LS concentrations 
PGDM1400LS, VRC07-523LS and PGT121.414.LS concentrations will be 
measured in serum collected at prespecified timepoints. A quantitative 
immunoassay will be used to determine the concentration of each mAb. Ultra-
sensitive bead-based analyses enable a broad dynamic range and higher sensitivity 
(eg, for the anti-idiotype mAb, 5C9, the lower limit of quantification is 
approximately 50 pg/mL). The operational sensitivity of the quantitative assays 
will be determined for the clinical grade PGDM1400LS, VRC07-523LS and 
PGT121.414.LS used for this study. For multiplexed PK measurements, 
interference testing will be included as part of the qualification/validation. The 
mAb concentrations may be normalized relative to total protein. 


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10.4 
Neutralizing antibody assay 
HIV-1–specific nAb assays will be performed on serum samples from study 
participants taken at post administration timepoint(s) and at baseline. The TZM-bl 
assay will test neutralization of mAb-specific viruses (one virus per mAb). The 
assay will also test the neutralization of a panel of viruses that exhibit a range of 
known sensitivities to PGDM1400LS, VRC07-523LS and PGT121.414.LS. The 
viruses will be selected from a global and/or clade-specific panel (57, 61) and 
may be modified by site-directed mutagenesis to be capable of measuring the 
activity of each mAb individually. 
10.5 
ADA detection assays 
A tiered testing approach will be used to identify and characterize ADAs that may 
arise (62, 63). Anti-PGDM1400LS, -VRC07-523LS, and -PGT121.414.LS 
antibody detection assays (screening, confirmatory, and/or titration) will be 
performed on serum samples from study participants at indicated timepoints. 
Samples will be evaluated with a sensitive screening assay in Tier 1. Samples 
showing positive responses in the screening assay will be evaluated in a 
confirmatory assay of specificity. Specific or Tier 2 positive responses will be 
characterized by titration (Tier 3). 
10.6 
ADA functional assay 
A functional ADA assay will be used to characterize any positive activity that is 
observed in the ADA detection assays. Functional activity will measure a 
reduction in PGDM1400LS, VRC07-523LS and/or PGT121.414.LS neutralizing 
activity against a qualified virus in the TZM-bl assay. 
10.7 
Antibody reaction assays 
To investigate Ab reactions, serum samples collected after the onset of reaction 
may be tested to measure levels of certain markers [eg, tryptase, complement 
components (C3 and C4), and cytokines]. ADA detection and functional assays, 
as described above, may be performed on serum samples taken prior to the study 
product administration associated with the reaction. Refer to the HVTN 
140/HPTN 101 SSP for more information. 
10.8 
HVTN Laboratory Center assay portfolio 
Additional assays may be performed per the HVTN Laboratory Center assay 
portfolio, which includes immune assessments such as those for cellular, humoral, 
and innate immune responses, and host genetics. The assay portfolio will be 


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updated periodically to include new assays and adjust qualification levels of 
existing assays.  
10.9 
Exploratory studies 
Samples may be used for other testing and research related to furthering the 
understanding of HIV immunology, antibody mediated prevention, or vaccines. In 
addition, samples may be used to perform additional assays to support 
standardization and validation of existing or newly developed methods.  
10.10 
Specimen storage and other use of specimens 
The Networks store specimens from all study participants indefinitely, unless a 
participant requests that specimens be destroyed or if destruction or a time limit 
for storage is required by IRB/EC, or RE.  
Other use of specimens is defined as studies not covered by the protocol or the 
informed consent forms for the main study (see Appendix A and Appendix B).  
This research may relate to HIV, vaccines, antibodies, 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 HPTN, the IRB/EC of the researcher requesting the specimens, 
and IRBs/ECs/REs of the CRS’s if required.  
As part of consenting for the study, participants document their initial decision to 
allow or not allow their specimens to be used in other research, and they may 
change their decision at any time. The participant’s initial decision about other 
use of their specimens, and any later change to that decision, is recorded by their 
CRS in a Web-based tool that documents their current decisions for other use of 
their specimens. The Networks will only allow other research to be done on 
specimens from participants who allow such use.  
CRSs must notify HVTN Regulatory Affairs if institutional or local governmental 
requirements pose a conflict with or impose restrictions on specimen storage or 
other use of specimens. 
10.11 
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 


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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 140/HPTN 101 PSRT 
The HVTN 140/HPTN 101 PSRT is composed of the following members: 
• DAIDS medical officer representatives 
• Protocol chairs 
• Protocol Team leaders 
• Core medical monitor 
• Clinical safety specialist 
• Regional medical liaison 
The clinician members of the HVTN 140/HPTN 101 PSRT are responsible for 
decisions related to participant safety. 
The Protocol Team clinic coordinator, clinical data manager, study product 
developer representative, clinical trial manager, clinical research manager, and 
others may also be included in HVTN 140/HPTN 101 PSRT meetings. 
11.1.2 
HVTN SMB 
The SMB is a multidisciplinary group consisting of biostatisticians, clinicians, 
and experts in HIV vaccine and drug research that, collectively, has experience in 
the conduct and monitoring of vaccine, mAb, and other drug trials. Members of 
the SMB are not directly affiliated with the protocols under review.  
The SMB reviews safety data approximately every 4 months. The reviews consist 
of evaluation of cumulative Solicited AEs, Unsolicited AEs, 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 140/HPTN 101 PSRT.  
Study sites will receive SMB summary minutes and are responsible for 
forwarding them to their IRB/EC and any applicable RE. 
11.1.3 
Roles and responsibilities in safety monitoring  
The roles and responsibilities of the SDMC in relation to safety monitoring 
include: 


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• Maintaining a central database management system for clinical data; and 
• Providing reports of clinical data to appropriate groups such as the HVTN 
140/HPTN 101 PSRT and HVTN SMB (see Section 11.1.2). 
The roles and responsibilities of the HVTN CSS or HVTN Core designee in 
relation to safety monitoring include: 
• Daily monitoring of clinical data for events that meet the safety pause and 
HVTN 140/HPTN 101 PSRT AE review criteria (see Section 11.4); 
• Notifying CRSs and other groups when safety pauses or planned holds are 
instituted and lifted (see Sections 11.3 and 11.4); 
• Querying CRSs for additional information regarding reported clinical data; 
and 
• Providing support to the HVTN 140/HPTN 101 PSRT. 
11.2 
Safety reporting 
11.2.1 
Submission of safety forms to SDMC. 
CRS staff must submit all safety forms (eg, Solicited AEs, Unsolicited AEs, 
urinalysis, local lab results, and concomitant medications) before the end of the 
next business day, excluding federal or bank holidays. The forms should not be 
held in anticipation of additional information at a later date. If additional 
information is received at a later date, the forms should be updated and 
resubmitted before the end of the next business day after receiving the new 
information. For the case of a longer CRS holiday closure, CRS 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 CRS becomes aware of an AE on Thursday (Day 0, the first 
day), the CRS must submit the data by the end of the next business day, on Friday 
(Day 1). If there is a longer CRS holiday closure, then this AE must be reported 
no later than the end of 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 


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product/procedure(s). AEs include both solicited AEs and unsolicited AEs. 
Solicited AEs are a subset of AEs that are defined per protocol and specifically 
asked about for 3 full days after each study infusion. Unsolicited AEs include all 
other AEs that do not fit the definition of a solicited AE. See the SSP for further 
detail regarding Solicited and Unsolicited AEs. 
The Unsolicited AE reporting period for this study comprises the entire study 
period for each individual participant (from study enrollment until study 
completion or discontinuation of the study). 
All AEs are graded according to the Division of AIDS (DAIDS) Table for 
Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 
2.1, July 2017, available on the RSC website at 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 
140/HPTN 101 SSP); 
• Infusion Site Erythema or Redness and Infusion Site Induration or Swelling 
will not consider surface area and interference with usual social and functional 
activities such that: 
▪ Grade 1 is: 2.5 to < 5 cm in diameter; 
▪ Grade 2 is: ≥ 5 to < 10 cm in diameter; 
▪ Grade 3 is: ≥ 10 cm in diameter 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); 
• Creatinine is required to be reported as an AE only if it is gradable per the 
increase from local lab ULN/reference range parameter. Do not grade elevated 
creatinine based on the change from the baseline parameter. 
• Creatinine clearance or eGFR is required to be reported based only on the 
reported value or if dialysis is needed. Do not grade Creatinine clearance or 
eGFR based on the change from the baseline parameter. 
• Ab reactions not represented in the DAIDS Table to be graded per the 
“infusion related reaction” row from the Common Terminology Criteria for 
Adverse Events (CTCAE) from the US DHHS (Version 5.0. Published 
November 27, 2017, available at 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctca
e_v5_quick_reference_5x7.pdf (see also HVTN 140/HPTN 101 SSP). 
All AEs are reported to the SDMC on the appropriate CRF. Clinic staff should 
evaluate every AE to determine if: (1) the AE meets the requirements for 


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expedited reporting to DAIDS (see Section 11.2.3); (2) if the AE meets the 
criteria for a safety pause/prompt AE review (see Section 11.4). 
Sites are expected to notify HVTN clinical safety staff of any serious safety 
concern requiring their attention (Table 11-2). Telephone numbers and email 
addresses are found on the protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn140-hptn101). Concerns requiring 
immediate attention should be communicated by calling the clinical safety phone. 
In the case of email notification, clinical safety staff will reply within one 
business day. Serious events that meet pause rule criteria will be addressed 
immediately (as outlined in Table 11-2) . If email service is not available, the 
CRS should notify clinical safety staff of the event by telephone, and then submit 
CRFs. 
In addition, CRS investigators are required to submit AE information in 
accordance with IRB/EC and any applicable RE requirements. 
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 
DAIDS RSC website at https://rsc.niaid.nih.gov/clinical-research-sites/manual-
expedited-reporting-adverse-events-daids. The SAE Reporting Category, as 
defined in Version 2.0 of DAIDS EAE Manual, will be used for this study.  
The internet-based DAIDS Adverse Experience Reporting System (DAERS) must 
be used for expedited AE (EAE) reporting to DAIDS. In the event of system 
outages or technical difficulties, expedited AE reports may be submitted via the 
DAIDS EAE form. This form is available on the DAIDS RSC website at 
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:  
• PGDM1400LS 
• PGT121.414.LS 
• VRC07-523LS 


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While the participant is in the study, from enrollment to the end of trial 
participation for that participant, the SAE Reporting Category will be used.  
After the end of trial participation for that participant, unless otherwise noted, 
only Suspected, Unexpected Serious Adverse Reactions (SUSARs) as defined in 
Version 2.0 of the DAIDS EAE Manual must be reported to DAIDS, if the study 
staff become aware of the events. 
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). In addition, the NIAID/DAIDS or designee(s) will prepare and 
file expedited reports to other appropriate regulatory authorities within the 
timelines required by pertinent national regulatory agencies.  
CRS Investigators of Record (IoRs)/designees will submit AE information and 
any other relevant safety information to their IRBs/ECs in accordance with 
IRB/EC requirements. 
In some cases, the PSRT or CRS may believe unblinding of the CRS PI and 
participant would be appropriate to facilitate the clinical management of an AE or 
SAE. The Ab MOP specifies procedures for emergency unblinding, and for early 
unblinding for medical reasons. 
11.3 
Safety reviews 
11.3.1 
Safety Considerations for Part A dose escalation 
The HVTN 140/HPTN 101 PSRT will monitor participant safety data throughout 
the study period as described in this section. The PSRT will review safety data for 
all groups to determine if enrollment may commence in subsequent groups for 
dose escalation. In addition, the HVTN 140/HPTN 101 PSRT will consider all 
available safety data on the antibodies in this study, including from ongoing and 
concurrent clinical trials (eg, HVTN 136/HPTN 092), in determining the 
appropriateness of opening HVTN 140/HPTN 101 groups to enrollment 
throughout the course of the trial.  
The trial will begin with enrollment in Part A Group 1 only. Groups 2 and 3 will 
be enrolled simultaneously; then groups 4 and 5 will be enrolled simultaneously. 
Additional participants may be enrolled in each group to ensure the availability of 
safety data from at least 3 participants in each group.   
Enrollment will start with Group 1 and will be restricted to a maximum of 1 
participant per day across all participating CRSs until a total of 3 participants 
have been enrolled. Enrollment will then be held. The HVTN 140/HPTN 101 
PSRT will review all cumulative safety data reported, including Group 1 data 
through the Day 6 visit post study product administration. Upon PSRT 


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determination that it is safe to proceed, enrollment in both Group 2 and Group 3 
will begin (see Table 11-1).  
If any ≥ Grade 3 AE(s) deemed related to study product are reported in Group 1, 
the HVTN SMB will perform an additional unblinded review of Group 1 safety 
data to make the final determination based on safety for proceeding to Groups 2 
and 3 enrollment.  
Groups 2 and 3 will be enrolled simultaneously and will be restricted to a 
maximum of 1 participant per day in either group across all participating CRSs 
until a total of 6 participants have been enrolled. Enrollment will then be held. 
The HVTN 140/HPTN 101 PSRT will review all cumulative safety data reported, 
including Groups 2 and 3 data through the Day 6 visit post study product 
administration. Upon PSRT determination that it is safe to proceed, enrollment in 
both Group 4 and Group 5 will begin (see Table 11-1).  
If any ≥ Grade 3 AE(s) deemed related to study product are reported in Group 2 
or 3, the HVTN SMB will perform an additional unblinded review of Groups 2 
and 3 safety data to make the final determination based on safety for proceeding 
to Groups 4 and 5 enrollment. 
Groups 4 and 5 will be enrolled simultaneously and will be restricted to a 
maximum of 1 participant per day in either group across all participating CRSs 
until a total of 6 participants have been enrolled. Enrollment will then be held. 
11.3.2 
Safety evaluation for moving from Part A to Part B 
In addition to monitoring participant safety throughout the study period, the 
HVTN 140/HPTN 101 PSRT will review all cumulative safety data available 
from Groups 1 through 5 reported through the Day 6 visit after study product 
administration. Based on the assessment of this safety data and all available safety 
data on the antibodies in this study, including from ongoing and concurrent 
clinical trials, the HVTN 140/HPTN 101 PSRT will make a decision regarding 
the appropriateness of moving to Part B. Additional participants may be enrolled 
in each group in Part A to ensure the availability of safety data from at least 3 
participants in each group. If any ≥ Grade 3 AE(s) deemed related to study 
product are reported in Part A, the HVTN SMB will perform an additional 
unblinded review of this safety data to make the final determination based on 
safety for proceeding to Part B. 
11.3.3 
Safety Considerations for Part B dose escalation 
Part B will begin with enrollment in Groups 6, 7, 8 and 9 simultaneously. Group 
10 will enroll last. Additional participants may be enrolled in each group to ensure 
the availability of safety data from at least 8 participants in Groups 6 through 9 
together; or at least 3 participants in Group 10. 


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Enrollment in Part B begins with simultaneous enrollment into Groups 6 through 
9 and will be restricted to a maximum of 1 participant per day in any group across 
all participating CRSs for the first 8 participants (at least 2 participants in each 
group). Enrollment will then be held. The HVTN 140/HPTN 101 PSRT will 
review all cumulative safety data available, including Groups 6 through 9 reported 
through the Day 6 visit post study product administration. Upon PSRT 
determination that it is safe to proceed, enrollment of the remaining participants in 
Groups 6 through 9 will reopen to enrollment without restrictions and enrollment 
into Group 10 will begin (see Table 11-1). If any ≥ Grade 3 AE(s) deemed related 
to study product have been reported in Groups 6 through 9, the HVTN SMB will 
perform an additional unblinded review of Groups 6 through 9 safety data to 
make the final determination based on safety for continuing enrollment and 
subsequent product administrations in Groups 6 through 9 without restrictions and 
proceeding to Group 10 enrollment. 
Group 10 will be restricted to a maximum of 1 participant per day across all 
participating CRSs for the first 3 participants. Enrollment will then be held. The 
HVTN 140/HPTN 101 PSRT will review all cumulative safety data reported, 
including Group 10 data through the Day 6 visit post study product 
administration. Upon PSRT determination that it is safe to proceed, enrollment of 
the remaining participants in Group 10 will reopen to enrollment without 
restrictions (see Table 11-1). If any ≥ Grade 3 AE(s) deemed related to study 
product have been reported in Group 10, the HVTN SMB will perform an 
additional unblinded review of Group 10 safety data to make the final 
determination based on safety for continuing enrollment and subsequent product 
administrations in Group 10 without restrictions. 
Table 11-1 Summary of planned safety holds and safety data reviews for dose escalations 
Planned Safety 
Hold # 
Group(s) 
Timepoint/Data Reviewed 
Action 
Part Aa 
1 
1 
Begins after the 3rd participant is enrolled (infused) and the 
solicited AE assessment data through the Day 6 visit is 
reported.  
Review of all cumulative safety data available for the 3 
participants in Group 1 up to and including the solicited AE 
assessment data reported at the Day 6 visit after the study 
product administration.  
The PSRT (+/- SMB) will decide 
the appropriateness of beginning 
enrollment in Groups 2 and 3 
based on these safety data. 
  
2 
2 & 3 
Begins after the 6th participant is enrolled (infused) in either 
Group 2 or 3 and the solicited AE assessment data through 
the Day 6 visit is reported (3 participants in Group 2 and 3 
participants in Group 3).  
Review of all cumulative safety data available, including 
the first 6 participants in Groups 2 and 3 up to and 
including the solicited AE assessment data reported at the 
Day 6 visit after the study product administration. 
The PSRT (+/- SMB) will decide 
the appropriateness of beginning 
enrollment in Groups 4 and 5 
based on these safety data. 
 


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Planned Safety 
Hold # 
Group(s) 
Timepoint/Data Reviewed 
Action 
3 
4 & 5 
Begins after the 6th participant is enrolled (infused) and the 
solicited AE assessment data through the Day 6 visit is 
reported (3 participants each in Groups 4 and 5). 
Review of all cumulative safety data available for all 
participants in Part A and the first 6 participants in Groups 
4 and 5 up to and including the solicited AE assessment 
data reported at the Day 6 visit after the product 
administration. 
The PSRT (+/- SMB) will decide 
the appropriateness of beginning 
enrollment in Part B based on all 
available safety data from all 
participants included in Part A. 
 
Part Ba 
4 
6, 7, 8 
and 9 
Begins after the 8th participant is enrolled (infused) and the 
solicited AE assessment data through the Day 6 visit is 
reported (at least 2 participants in Groups 6 through Group 
9). 
Review of all cumulative safety data available, including 
the first 8 participants in Groups 6 through Group 9 up to 
and including the solicited AE assessment data reported at 
the Day 6 visit after the first study product administration. 
The PSRT (+/- SMB) will decide 
the appropriateness of continuing 
enrollment and subsequent product 
administrations in Groups 6 
through 9 without restrictions, and 
beginning enrollment into Group 
10 based on all available safety 
data. 
 
5 
10 
Begins after the 3rd Group 10 participant is enrolled 
(infused) and the solicited AE assessment data through the 
Day 6 visit is reported. 
Review of all cumulative safety data available, including 
the first 3 participants in Group 10 up to and including the 
solicited AE assessment data reported at the Day 6 visit 
after the first study product administration. 
The PSRT (+/- SMB) will decide 
the appropriateness of continuing 
enrollment into Group 10 
without restrictions based on these 
safety data. 
 
aAdditional participants may be enrolled in each group to ensure the availability of safety data from at least 3 
participants in each group.  
11.4 
Safety pause and prompt PSRT AE review 
When a trial is placed on safety pause, all enrollment and study product 
administration with the product related to the event that triggered the pause will 
be held until further notice. The AEs that will lead to a safety pause or prompt 
HVTN 140/HPTN 101 PSRT AE review are summarized in Table 11-2. Study 
product administrations may be suspended for safety concerns other than those 
described in the table, or before pause rules are met, if, in the judgment of the 
HVTN 140/HPTN 101 PSRT, participant safety may be threatened. Criteria for an 
individual participant’s departure from the schedule of study product 
administrations are listed in Section 7.3. 


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Table 11-2 AE notification and safety pause/AE review rules 
Event and 
relationship to study 
products 
Severity 
CRS actiona 
HVTN LOC action b 
SAE, related 
Grade 5 or 
Grade 4 
Phone immediately, email 
and submit forms 
immediately 
Immediate pause 
SAE, not related 
Grade 5 
Phone immediately, email 
and submit forms 
immediately 
Immediate PSRT notification 
SAE, related 
Grade 3, 2, 
or 1 
Email and submit forms 
immediately 
Immediate PSRT notification and 
prompt PSRT AE review to 
consider pause 
AEc, related 
Grade 4 or 
3 
Email and submit forms 
immediately 
Immediate PSRT notification and 
prompt PSRT AE review to 
consider pause 
a Phone numbers and email addresses are found on the Protocol home page on the HVTN Members’ site 
(https://members.hvtn.org/protocols/hvtn140-hptn101). 
b HVTN CSS or HVTN Core designee 
c Does not include subjective Solicited AEs (infusion site pain and/or tenderness, fatigue/malaise, myalgia, 
arthralgia, chills, headache, nausea (unless IV rehydration required), non-exertional dyspnea, generalized 
pruritus, local pruritus [SC infusion only], facial flushing, and unexplained diaphoresis).  
For all safety pauses, HVTN LOC notifies the HVTN 140/HPTN 101 PSRT, 
HVTN Regulatory Affairs, DAIDS Pharmaceutical Affairs Branch (PAB), 
DAIDS Regulatory Affairs Branch (RAB), DAIDS Safety and Pharmacovigilance 
Team (SPT), and participating CRSs. When an immediate safety pause is 
triggered, HVTN LOC notifies the SMB.  
Once a trial is paused, the HVTN 140/HPTN 101 PSRT reviews safety data and 
decides whether the pause can be lifted or permanent discontinuation of study 
product administration is appropriate, consulting the SMB if necessary. HVTN 
LOC notifies the participating CRSs, HVTN Regulatory Affairs, DAIDS PAB, 
DAIDS RAB, and DAIDS SPT of the decision regarding resumption or 
discontinuation of study product administrations. Based on the HVTN 140/HPTN 
101 PSRT assessment, DAIDS RAB notifies the FDA as needed. 
If an immediate HVTN 140/HPTN 101 PSRT notification or prompt HVTN 
140/HPTN 101 PSRT AE review is triggered, HVTN Core notifies the HVTN 
140/HPTN 101 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 140/HPTN 101 PSRT AE review cannot be 
completed within 72 hours of notification (excluding weekends and US federal 
holidays), an automatic safety pause occurs. 
The HVTN and HPTN require that each CRS submit to its IRB/EC and any 
applicable RE protocol-related safety information (such as IND safety reports, 
notification of study-product holds due to the pause rules, unanticipated problems 
involving risks to participants or others, and notification of other unplanned safety 
pauses). CRSs must also follow all applicable RE reporting requirements. 


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In addition, all other AEs are reviewed routinely by the HVTN 140/HPTN 101 
PSRT (see Section 11.5.2). 
11.5 
Review of cumulative safety data 
Routine safety review occurs at the start of enrollment and then throughout the 
study. 
Reviews proceed from a standardized set of protocol-specific safety data reports. 
These reports are produced by the SDMC and include queries to the CRSs. Events 
are tracked by internal reports until resolution.  
11.5.1 
Daily review 
Daily safety reviews are routinely conducted by HVTN Core for events requiring 
expedited reporting to DAIDS, and events that meet safety pause criteria or 
prompt HVTN 140/HPTN 101 PSRT AE review criteria. 
11.5.2 
Weekly review 
During the study product administration phase of the trial, the HVTN 140/HPTN 
101 PSRT reviews clinical safety reports on a weekly basis and conducts calls to 
review the data as appropriate. Following the visit 8 weeks post-final study 
product administration, less frequent reporting and safety reviews may be 
conducted at the discretion of the HVTN 140/HPTN 101 PSRT. HVTN LOC 
reviews reports of clinical and laboratory AEs. Events identified during the 
review that are considered questionable, inconsistent, or unexplained are referred 
to the CRS clinic coordinator for verification. 
11.6 
Study termination 
NIAID reserves the right to terminate or curtail a clinical study for any reason, 
including but not limited to the following (reference: 
https://grants.nih.gov/grants/guide/rfa-files/RFA-AI-12-012.html ): 
• risk to subject safety 
• the scientific question is no longer relevant or the objectives will not be met 
(ie, slow accrual) 
• failure to comply with GCP, U.S. Federal regulations, or Terms and 
Conditions of Award 
• occurrence of unforeseen drug safety issues or data from preclinical studies 
indicate a presence of unanticipated toxicity 


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• risks that cannot be adequately quantified 
• ethical concerns raised by the local community or local medical care/health 
care authorities 
• failure to remedy deficiencies identified through site monitoring 
• substandard data 
• reaching a major study endpoint substantially before schedule with persuasive 
statistical significance. 
This study may also be terminated early by the determination of the HVTN 
140/HPTN 101 PSRT, FDA, a pertinent national regulatory authority, NIH, 
Office for Human Research Protections (OHRP), or study product developer(s). 
In addition, the conduct of this study at an individual CRS may be terminated by 
the determination of the IRB/EC and any applicable RE. 


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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 (ICH E6(R2)), and according to DAIDS, 
HVTN and HPTN policies and procedures as specified in the network-specific 
Manuals of Operations, DAIDS Clinical Research Policies, and Standard 
Procedures Documents including procedures for the following: 
• Protocol registration, activation, and implementation; 
• Informed consent, screening, and enrollment; 
• Study participant reimbursement; 
• Clinical and safety assessments; 
• Safety monitoring and reporting; 
• Data collection, documentation, transfer, and storage; 
• Participant confidentiality; 
• Study follow-up and close-out; 
• Quality control; 
• Protocol monitoring (on-site or remote) and compliance; 
• Advocacy and assistance to participants regarding negative social impacts 
associated with the trial; 
• Risk reduction counseling;  
• Specimen collection, processing, and analysis;  
• Exploratory and ancillary studies and sub-studies, and 
• Destruction of specimens. 
DAIDS, HVTN and HPTN policies and procedures are available for review by 
any IRB/EC/RE upon request. 
Any policies or procedures that vary from DAIDS, HVTN, or HPTN standards or 
require additional instructions (eg, instructions for randomization specific to this 
study) will be described in the HVTN 140/HPTN 101 SSP.  


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12.1 
Social impacts 
It is possible that participants’ involvement in the study could result in social 
impacts. Social harms are negative social impact events and social benefits are 
positive social impact events that a participant reports as affecting them as a result 
of being involved in a research study. It is not the researcher’s opinion of how 
they perceive an event has affected a participant. For example, a participant’s 
involvement in the study could become known to others, and a social harm may 
result (eg, because participants could be perceived as being HIV infected or at 
“high risk” for HIV infection). Participants could be treated unfairly or could have 
problems being accepted by their families and/or communities. Alternatively, a 
social benefit may result (eg, a participant could feel good helping others). 
Social impacts will be collected and reported on CRFs during scheduled visits 
(see Appendix H and Appendix I). 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. A social harm that is reported by the participant and judged by the 
IoR/designee to be serious or unexpected will be reported to the responsible site’s 
IRB at least annually, or according to their individual requirements.  
In the event that a participant reports a social harm, every effort will be made by 
study staff to provide appropriate care and counseling to the participant as 
necessary, and/or referral to appropriate resources for the safety and wellbeing of 
the participant. If CRS staff have questions regarding ways to assist a participant 
dealing with a social impact, a designated NIAID or Network Core representative 
can be contacted. While maintaining participant confidentiality, study sites may 
engage their CAB in exploring the social context surrounding instances of social 
harms to minimize the potential occurrence of such an impact. 
12.2 
Emergency communication with study participants 
As in all clinical research, this study may generate a need to reach participants 
quickly to avoid imminent harm, or to report study findings that may otherwise 
concern their health or welfare. 
When such communication is needed, the 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 CRS 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 Network protocols via clarification memos, letters of 
amendment, or full protocol amendments.  
The version history of, and modifications to, Protocol HVTN 140/HPTN 101 are 
described below. 
Protocol history and modifications 
Date: June 23, 2021 
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 Centers for Disease Control (CDC) Guidelines.  
▪ Revised Recommendations for HIV Testing of Adults, Adolescents, and 
Pregnant Women in Health-Care Settings. Available at 
http://www.cdc.gov/mmwr/PDF/rr/rr5514.pdf.  
▪ Revised Guidelines for HIV Counseling, Testing, and Referral. Available 
at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5019a1.htm 
• Division of AIDS (DAIDS) Clinical Research Policies and Standard 
Procedures Documents. Available at 
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-
procedures  
• Division of AIDS Protocol Registration Manual. Available at 
https://www.niaid.nih.gov/sites/default/files/prmanual.pdf  
• Division of AIDS Table for Grading the Severity of Adult and Pediatric 
Adverse Events. Corrected Version 2.1, July 2017. Available at 
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 at https://rsc.niaid.nih.gov/clinical-research-
sites/manual-expedited-reporting-adverse-events-daids 
• Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. 
Published November 27, 2017. Available at 
https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctca
e_v5_quick_reference_5x7.pdf 
• HVTN Certificate of Confidentiality. Accessible through the HVTN website. 
• HPTN Certificate of Confidentiality. 
• HVTN 140/HPTN 101 Special Instructions. Accessible through the HVTN 
protocol-specific website. 


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• HVTN 140/HPTN 101 Study Specific Procedures. Accessible through the 
HVTN protocol-specific website. 
• HVTN 140/HPTN 101 Site Lab Instructions. Accessible through the HVTN 
protocol-specific website. 
• Ab Manual of Operations. Accessible through the HVTN website. 
• Dangerous Goods Regulations (updated annually), International Air Transport 
Association. Available for purchase at 
https://www.iata.org/publications/dgr/Pages/index.aspx 
• Lab assay algorithm (available upon request) 
• International Council on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6, Guideline for Good Clinical 
Practice: Section 4.8, Informed consent of trial subjects. Available at 
http://www.ich.org/products/guidelines/efficacy/article/efficacy-
guidelines.html 
• Participants’ Bill of Rights and Responsibilities. Accessible through the 
HVTN website. 
• National Institutes of Health (NIH) Policy on Reporting Race and Ethnicity 
Data: Subjects in Clinical Research. Available at 
https://grants.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/score-source-documentation-
requirements.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 
• The Protection of Personal Information Act (POPIA, South Africa, 2013). 
Available at 
https://www.gov.za/sites/default/files/gcis_document/201409/3706726-
11act4of2013protectionofpersonalinforcorrect.pdf  


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See Section 16 for literature cited in the background and statistics sections of this 
protocol. 


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15 
Acronyms and abbreviations 
Ab 
 
antibody 
ADA 
 
anti-drug antibodies 
ADCC 
 
antibody dependent cell mediated cytotoxicity 
ADCP 
 
antibody dependent cellular phagocytosis 
AE 
 
adverse event 
Alk Phos   
alkaline phosphatase 
ALT 
 
alanine aminotransferase 
AMP 
 
Antibody Mediated Prevention 
ANOVA  
analysis of variance 
ART 
 
antiretroviral therapy 
AST 
 
aspartate aminotransferase 
AUC 
 
area-under-the-curve 
AUC-MB  
area-under-the-magnitude-breadth curve 
BAMA 
 
binding antibody multiplex assay 
β-HCG 
 
beta human chorionic gonadotropin 
BIDMC 
 
Beth Israel Deaconess Medical Center 
bnAb 
 
broadly neutralizing HIV-1 antibody 
CAB 
 
Community Advisory Board 
CAVD 
 
Collaboration for AIDS Vaccine Discovery 
CBC 
 
complete blood count 
CDC 
 
US Centers for Disease Control and Prevention 
CFR 
 
Code of Federal Regulations 
cGMP 
 
current Good Manufacturing Practice 
CL 
 
clearance 
Cmax  
 
maximum concentration 
CMIA 
 
chemiluminescent microparticle immunoassay 
CRF 
 
case report form 
CRPMC 
 
NIAID Clinical Research Products Management Center 
CRS 
 
clinical research site 
CSS 
 
Clinical Safety Specialist 
CTCAE 
 
Common Terminology Criteria for Adverse Events 
DAERS 
 
DAIDS Adverse Experience Reporting System 
DAIDS 
 
Division of AIDS (US NIH) 
DHHS 
 
US Department of Health and Human Services 
EAE 
 
adverse events requiring expedited reporting to DAIDS 
EC 
 
Ethics Committee 
EIA 
 
 enzyme immunoassay 
ELISA 
 
enzyme-linked immunosorbent assay 


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Env 
 
HIV envelope protein 
Fc 
 
Fragment crystallizable 
FcRn 
 
Fc-receptor 
FDA 
 
US Food and Drug Administration 
FIH 
 
first-in-human 
Fred Hutch 
Fred Hutchinson Cancer Research Center 
GCP 
 
Good Clinical Practice 
GEE 
 
generalized estimating equation 
GLP 
 
Good Laboratory Practice 
HBsAg 
 
hepatitis B surface antigen 
HCV 
 
hepatitis C virus 
HPTN 
 
HIV Prevention Trials Network 
HVTN 
 
HIV Vaccine Trials Network 
IAVI 
 
International AIDS Vaccine Initiative 
IB 
 
Investigator’s Brochure 
IC 
 
inhibitory concentration 
ICF 
 
informed consent form 
ICH 
 
International Council on Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IgG 
 
immunoglobulin G 
IM 
 
intramuscular 
IND 
 
Investigational New Drug 
IoR 
 
Investigator of Record 
IRB 
 
Institutional Review Board 
IUD 
 
intrauterine device 
IV 
 
intravenous 
LOC 
 
Leadership Operations Center 
mAb 
 
monoclonal antibody 
MAR 
 
missing at random 
M-B 
 
Magnitude-Breadth 
MCAR 
 
missing completely at random 
MITT 
 
modified intent-to-treat 
MOP 
 
Manual of Operations 
MTD 
 
maximum tolerated dose 
nAb 
 
neutralizing antibody 
NAEPP 
 
National Asthma Education and Prevention Program 
NHP 
 
nonhuman primate 
NIAID 
 
National Institute of Allergy and Infectious Diseases (US NIH) 
NIH 
 
US National Institutes of Health 


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NOAEL 
 
no-observed-adverse-effect-level 
NSAID 
 
non-steroidal anti-inflammatory drugs 
OHRP 
 
US Office for Human Research Protections 
PAB 
 
DAIDS Pharmaceutical Affairs Branch 
PCR 
 
polymerase chain reaction 
PD 
 
pharmacodynamics 
PK 
 
pharmacokinetic 
POPIA  
 
Protection of Personal Information Act 
popPK 
 
population PK (pharmacokinetic) 
PP 
 
per-protocol 
PrEP 
 
pre-exposure prophylaxis 
PSRT 
 
Protocol Safety Review Team 
RAB 
 
DAIDS Regulatory Affairs Branch 
RE 
 
regulatory entity 
RSC 
 
DAIDS Regulatory Support Center 
RSV 
 
respiratory syncytial virus 
SAE 
 
serious adverse event 
SAP 
 
Statistical Analysis Plan 
SC 
 
subcutaneous 
SCHARP  
Statistical Center for HIV/AIDS Research and Prevention 
SD 
 
standard deviation 
SDMC 
 
statistical and data management center 
SHIV 
 
simian-human immunodeficiency virus 
SMB 
 
Safety Monitoring Board 
SOP 
 
standard operating procedure 
SPT 
 
DAIDS Safety and Pharmacovigilance Team 
SSP 
 
Study Specific Procedures 
SUSAR 
 
sudden unexpected serious adverse reaction 
TB 
 
tuberculosis 
TCR 
 
tissue cross reactivity 
Tmax 
 
time to Cmax 
USP 
 
United States Pharmacopeia 
UW-VSL  
University of Washington Virology Specialty Laboratory 
VCMP 
 
Vaccine Clinical Materials Program 
Vd 
 
volume of distribution 
VRC 
 
Vaccine Research Center (NIAID) 
VRP 
 
Vaccine Research Program  
VTRB 
 
Vaccine Translational Research Branch  


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Appendix A 
Sample informed consent form for Part A 
Title: A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, 
and pharmacokinetics of PGDM1400LS alone and in combination with VRC07-
523LS and PGT121.414.LS in healthy, HIV-uninfected adult participants 
Protocol number: HVTN 140/HPTN 101 
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. 
Key Information 
These are some of the things you should know about this study: 
• The purpose of this part of the study is to understand how the body’s immune 
system responds to a new lab-made antibody against HIV. We also want to 
see if the way the antibody is given affects the immune response.We will also 
look at whether the antibody is safe to give to people and does not make them 
too uncomfortable.  
• If you choose to join, we will ask you to come to several study visits over 
about 6 months. At one of these visits you will get the study antibody in a vein 
(by IV infusion) or under the skin (by subcutaneous infusion, called SC). We 
will take blood from you at each study visit to see how your body responds to 
the study antibody and how much antibody is in your blood. We will test you 
for HIV and other sexually transmitted infections (STIs) and pregnancy (if 
applicable). We will ask you to complete questionnaires and you will have 
physical exams.  
• Some general risks of antibodies include fever, chills, shaking, nausea, 
vomiting, pain, headache, dizziness, fatigue, flushing, diarrhea, trouble 
breathing, high or low blood pressure, itchiness and rash. There may be other 
side effects that we don’t yet know about, even serious ones. Because this is 
the first time this study antibody is being given to people, we do not know 
what all of the risks may be. We think that the risks will be similar to these 
general risks. 
• There is no direct benefit to you from being in the study.  
• Whether to take part in this study is your choice. You do not have to take part 
in the study and you are free to stop at any time. 


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• The rest of this form provides a more complete description of this study. 
Please read it carefully. 
 
About the study 
The HIV Vaccine Trials Network (HVTN), the HIV Prevention Trials Network 
(HPTN), and [Insert site name] are doing a study to test a combination of different 
antibodies against HIV. HIV is the virus that causes AIDS. Antibodies are made 
by the body as one way to respond to or fight infection. Researchers can also 
make antibodies in laboratories and give them to people by infusions into a vein 
or under the skin. We will tell you more about these procedures below. 
Antibodies have been used successfully to prevent or treat other health problems, 
such as COVID-19 caused by SARS-CoV-2 infection, and respiratory infections 
in babies caused by RSV (respiratory syncytial virus). 
About 95 people will take part in this study at multiple clinics. 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.  
There are 2 parts of this study, Part A and Part B. About 15 people will take part 
in Part A of this study to test one study antibody. After we see the results from 
Part A, we will decide whether or not to do Part B of the study, that will test a 
combination of 3 antibodies. If we decide to do Part B, 80 more people will join. 
You are being invited to join Part A of the study.  
1. We are doing this part of the study to answer several questions. 
• Is the new study antibody safe to give to people by itself at different doses? 
• Are people able to take the new study antibody without becoming too 
uncomfortable? 
• How do people’s immune systems respond to the new study antibody? (Your 
immune system protects you from disease.) 
• Does the method of giving the new study antibody change the body’s 
response?  
• How much of the antibody remains in the body as time passes? 
2. The study antibody cannot give you HIV. 
The study antibody is not made from actual HIV. It is impossible for the study 
antibody to give you HIV. Also, it cannot cause you to give HIV to someone else. 


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We do not know if the study antibody will decrease, increase, or not change your 
risk of getting HIV if you are exposed to the virus. 
3. This study antibody is experimental. 
The study antibody is called PGDM1400LS. From here on, we will call it the 
study antibody. It is an experimental HIV prevention product. That means we do 
not know if it will be safe to use in people, or if it will work to prevent HIV 
infection. This antibody is used only in research studies. 
The antibody was developed by the National Institute of Allergy and Infectious 
Diseases (NIAID).  
This study antibody has not been given to people before. An earlier version of the 
study antibody called PGDM1400 has been given to 53 people in 3 other studies. 
One of these studies is still ongoing, but so far there have been no safety 
concerns. Nine people have been given PGDM1400 alone and 44 have been given 
PGDM1400 in combination with other antibodies. The new version of the study 
antibody used in this study has been changed so that it will last longer in the body.  
Antibodies given to a person usually do not last in the body more than a few 
months. One of the goals of this study is to see how long this antibody will stay in 
the body. We don’t know yet how long it will last, but we think it may be several 
months.  
Risks of the study antibody: 
This section lists the side effects we know about. There may be others that we 
don’t yet know about, even serious ones. We will tell you if we learn about any 
new side effects.  
Because this is the first time the antibody is being given to people, we do not 
know what all of the risks may be. We think that the risks will be similar to the 
general risks described below. 
General risks of antibodies: 
Other kinds of antibodies used for other health problems have caused fever, chills, 
itchiness, rash, hives, redness in cheeks and neck, lip or face swelling, nausea, 
vomiting, pain, diarrhea, fatigue, flushing, headache, dizziness, shaking, trouble 
breathing, high or low blood pressure, racing heartbeat, and chest pain. These 
reactions may be related to how an antibody is made, what it targets, or how fast 
the antibody product is given. At times the side effects include reactions at the 
injection site (pain, redness, bruising, swelling, hardening). Most side effects 
happen within the first 24 hours. 
Rarely, some antibodies for other diseases have caused 2 kinds of side effects that 
may be life-threatening:  


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• Anaphylaxis – a physical reaction that may include hives or rash, mouth and 
face swelling, low blood pressure, and trouble breathing, possibly leading to 
low blood oxygen. This may occur soon after getting an antibody. 
• Serum Sickness – a physical reaction that includes hives or rash, fever, big 
lymph nodes, muscle and joint pain, chest discomfort and shortness of breath. 
This may occur several days to a few weeks after getting an antibody. 
These rare side effects have not been seen in other studies with similar 
experimental antibodies against HIV. Please tell us if you have ever had a reaction 
similar to anaphylaxis or serum sickness. 
Rarely, antibodies approved for treatment of other diseases have been linked to 
other effects like cancer, increased bleeding, increased infections, heart and liver 
toxicity, and problems with blood clotting and immune response. These rare side 
effects and reactions have not been seen in other studies with similar experimental 
antibodies against HIV.  
Joining the study 
4. It is completely up to you whether or not to join the study.  
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. 
If you join this study, you may not be allowed to join some other 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. Remainder of paragraph for South African sites. We check to make sure that 
you are not in more than one study by taking your fingerprint on an electronic 
system. This information is only accessed by a few members of the study team 
using a secure password. 
You should not donate blood or tissue during the study. 
If you choose not to join this study, you may be able to join another study. 
Site: Remove item 5 if you use a separate screening consent that covers these 
procedures. 
5. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, HIV test and health history. A physical exam 
may include, but is not limited to: 
• Checking your weight, temperature and blood pressure 


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• Looking in your mouth and throat 
• Checking your veins to see how easy it might be to start an infusion 
• Looking at your skin 
• Listening to your heart and lungs 
• Feeling your abdomen (stomach and liver) 
• Asking you about any symptoms of COVID-19 that you may have 
• Asking you about vaccines you have gotten recently 
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 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. If you 
have had your uterus or ovaries removed (a hysterectomy or oophorectomy), and 
this is verified by medical records, you are not required to have a pregnancy test.  
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
Site: adapt the following section so it is applicable to the care available at your site 
6. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 
7. If you were assigned female sex at birth and could become pregnant, you 
must agree to use birth control to join this study. 
Site: If you want to include Appendix C, Approved birth control methods (for sample 
informed consent form), in this consent form, paste it below and delete paragraph 
below. 
You should not become pregnant during the study because we do not know how 
the study antibody could affect the developing baby. You must agree to use 
effective birth control from 21 days before your infusion until your last required 
clinic visit. We will talk to you about effective birth control methods. They are 
listed on a handout that we will give to you.  


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Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
8. You will come to the clinic for 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.) 
Most of the visits will be 1-2 months apart. After you get the study antibody, we 
will ask you to come to the clinic for follow up visits 3 days later and 6 days later 
to draw your blood. We will do this so that we can look at how your body 
responds to the study product. Visits can last from [#] to [#] hours. 
Site: Please adjust the first sentence in the paragraph below to reflect whether you 
assess COVID-19 symptoms by phone/email/text message prior to the scheduled visit, 
or if symptom assessment occurs at the visit itself. You can also add a description of 
how symptoms are monitored upon arrival at your location, such as temperature 
screening in the building lobby, etc., so that participants know what to expect. 
You may have to come for more visits if you have a lab or health issue. 
We may contact you after the study ends (for example, to tell you about the study 
results). 
 
9. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for participants who 
could become pregnant). 
US sites: Include the following paragraph. You can remove the box around the text. 
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. 


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10. We will give you the study antibody by IV infusion or SC infusion at your 
enrollment visit. 
For the IV infusion, we will use a sterile needle to place a small plastic tube into a 
vein in your arm or hand. The small plastic tube is connected to a small bag of 
fluid that contains the study antibody. A pump controls how fast the fluid drips 
from the bag, through the tube, and into your vein. The IV infusion will take 
about 1 hour.  
When getting a subcutaneous (SC) infusion, sterile needles are put under the skin 
on your abdomen, arm, or thigh. The dose of the antibody will be divided and 
given in 2 or 3 locations at the same time. A pump is used to control how fast the 
study antibody is injected through the needles. The infusion will take between 15-
90 minutes depending on which group you are in and depending on your weight. 
If you have any symptoms while you are getting the study antibody, tell the study 
staff. Slowing or stopping the flow rate may help improve the symptoms. 
11. We will give you the study antibody at one visit. 
You will be in one of 5 groups. You will get 1 infusion during the study as shown 
in the table below. 
People in Group 1 will be enrolled first, and the safety will be reviewed before 
enrollment starts in Group 2 and 3. Safety for Groups 2 and 3 will be reviewed 
before enrollment begins in Groups 4 and 5. Enrollment in Groups 2 and 3, and 
Groups 4 and 5 is completely random, like flipping a coin. We have no say in how 
people are assigned to these groups. Neither do you. 
 
 
 
 
Infusion schedule:  
Group 
Number of 
participants 
Dose 
How it is given 
Enrollment Visit 
 
 
 
 
 
1 
3 
lower 
IV 
PGDM1400LS 
 
 
 
 
 
2 
3 
medium 
IV 
PGDM1400LS 
 
 
 
 
 
3 
3 
medium 
SC 
PGDM1400LS 
 
 
 
 
 
4 
3 
higher 
IV 
PGDM1400LS 
 
 
 
 
 
5 
3 
higher  
SC 
PGDM1400LS 
You will have to wait in the clinic for about 1 hour after the infusion to see if 
there are any problems. We will collect a blood sample about 1 hour after the 
infusion. Then for that night and for 3 more days, you will need to keep track in a 
diary of how you are feeling and if you have any symptoms. Site: Customize the 
next sentence based on how you collect reactogenicity information. We will 
review the diary with you during the visits after you get an infusion. You will turn 


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in the diary by the Day 6 visit. Contact the clinic staff if you have any issues or 
concerns after getting an infusion. If you have a problem, we will continue to 
check on you until it goes away. 
12. In addition to giving you the study antibody we will: 
• Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV 
• Do physical exams 
• Do pregnancy tests if you were assigned female sex at birth 
• Ask questions about your health, including medications you may be taking, 
including PrEP  
• Ask questions about any personal problems or benefits you may have from 
being in the study 
• Ask questions about your experience getting infusions 
• 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 25 mL and 105 mL (a little less than 2 tablespoons 
to about 1/2 cup). Your body will make new blood to replace the blood we take 
out.  
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 
Site: Insert Appendix E, 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.  
Some procedures may be done remotely, such as by phone, text message, email or 
video calls. This could happen instead of or in combination with in-person visits 
at the study clinic. Some study procedures might also take place in other 
locations, such as outdoor tents or mobile clinics. The staff will tell you more 
about the options they plan to use to protect everyone’s safety. 


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13. Getting a COVID-19 vaccine while you are in this study is allowed. 
To be sure that we can answer the study questions, we will not give the study 
infusion within 7 days before or after you get a COVID-19 vaccine. If you are 
planning to get a COVID-19 vaccine, please tell us so that we can schedule your 
study visits with this in mind. 
14. We will counsel you about protecting yourself from HIV. 
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 acquiring HIV low.  
15. We will test your samples. 
We will send your samples (without your name) to labs approved by the HVTN 
and HPTN for this study, which are located in the United States and South Africa. 
In rare cases, some of your samples may be sent to labs approved by the HVTN 
and HPTN 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. 
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 and HPTN 
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 and HPTN 
want to use them in other studies and share them with other researchers.  
The HVTN and HPTN call these samples “extra samples”. The HVTN and HPTN 
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. 


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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. [Site: choose one of the following two sentences. African sites 
should choose the sentence referencing the repository in South Africa. All other 
sites should choose the sentence referencing the repository in the United States.] 
Your samples will be stored in the HVTN repository in South Africa. Your 
samples will be stored in the HVTN repository in the United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN or HPTN sell my samples and information? No, but the HVTN 
and HPTN may share your samples with HVTN, HPTN, 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 and HPTN. Also, the researcher’s institutional review board (IRB) 
or ethics committee (EC) will review their plan. [Site: If review by your 
institution’s IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs 
protect the rights and well-being of people in research. If the research plan is 
approved, the HVTN will send your samples to the researcher’s location.  
What information is shared with HVTN, HPTN, or other researchers? The 
samples and information will be labeled with a code number. The key to the code 
will stay at this clinic. It will not be shared with the HVTN, HPTN, other 
researchers, or with anyone else who does not need to know your name. 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 antibody 
you received and how your body responded to the studyantibody.  


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What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, antibodies, the immune system, and other 
diseases.  
Researchers may also do genetic testing on your samples. If you agree, your 
samples could also be used for genome wide studies. In these studies, researchers 
will look at all of your genes (your genome). The researchers compare the 
genomes of many people, looking for common patterns of genes that could help 
them understand diseases. The researchers may put the information from the 
genome-wide studies into a protected database so that other researchers can 
access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks.  
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• Any regulatory agency that reviews clinical trials 
• The researcher’s Institutional Review Board or Ethics Committee 
• The people who work with the researcher  
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
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. 


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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, people who work for them, and their 
study monitors, 
• The US Food and Drug Administration, 
• Any regulatory agency that reviews clinical trials, 
• Non-US Sites must include; US sites may but are not required to 
include:[Insert name of local IRB/EC] , 
• [Insert name of local and/or national regulatory authority as appropriate], 
• The HVTN, HPTN and people who work for them,  
• The 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. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared. At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements, including SARS-CoV-
2/COVID-19. Bulleted examples should include all appropriate cases (reportable 
communicable disease, risk of harm to self or others, etc.). If your site does not have 
public health or legal reporting requirements, you may delete the last sentence in the 
paragraph above, along with the bullets below. 
• [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. 


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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. 
18. If you become pregnant or acquire HIV, we may ask you to stay in the study 
to complete other study procedures. 
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. 
If you get HIV while in the study, we will also take fewer samples, and we will 
help you get care and support. We will encourage you to stay in the study for up 
to 6 months after your last infusion or last scheduled protocol clinic visit 
whichever comes first. We will discuss your study options with you. We will 
counsel you about having HIV and about telling your partner(s). Site: Modify the 
following sentence as appropriate. We will not provide or pay for any of your 
HIV care directly.  
19. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, 
• the study is stopped for any reason. 
Other Risks 
20. There are other risks to being in this study. 
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of giving blood:  


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Giving blood can cause bruising, pain, fainting, soreness, redness, swelling, 
itching, bleeding, and infection (rarely). Giving blood can cause a low blood cell 
count (anemia), making your feel tired.  
Risks of SC infusion procedures:  
Getting a SC infusion may cause bruising, pain, fainting, soreness, redness, 
swelling, itching, a sore, bleeding, blood clots, forming a bump under the skin, 
and (rarely) muscle damage, or infection where you got the SC infusion.  
Risks of IV infusion procedures: 
Getting an IV may cause stinging, discomfort, pain, soreness, redness, bruising, 
itching, rash and swelling where the needle goes into the skin. Rarely, needle 
sticks can result in a blood clot or infection. 
Personal problems/discrimination: 
Some people who join HVTN and HPTN studies report personal problems or 
discrimination because of joining an HIV prevention study. Family or friends may 
worry, get upset or angry, or assume that you have HIV or are at high risk and 
treat you unfairly as a result. Rarely, a person has lost a job because the study 
took too much time away from work, or because their employer thought they had 
HIV.  
HIV testing: 
HIV antibody tests are the usual way to test for HIV infections. We are still 
learning how HIV tests perform when people are given monoclonal antibodies. 
We have used several common HIV antibody tests to test samples of blood 
containing antibodies similar to the study antibody. We found that very high 
levels of these similar antibodies can cause positive or uncertain results on some 
HIV tests. You may have such high levels for a short time after you get the study 
antibody. This means that for a few days after getting the study antibody, some 
HIV tests might 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 truly detect HIV. They can also tell if someone does not have 
HIV. We do not expect you to have any problems with HIV testing after the study 
ends. 
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 have HIV. If you feel embarrassed or anxious, please tell us and we will try to 
help you. 


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Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it.  
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you.  
U.S. Sites, include the following paragraph In the very unlikely event that your 
genetic information becomes linked to your name, a federal law called the 
Genetic Information Nondiscrimination Act (GINA) helps protect you. GINA 
keeps health insurance companies and employers from seeing results of genetic 
testing when deciding about giving you health insurance or offering you work. 
GINA does not help or protect you against discrimination by companies that sell 
life, disability or long-term care insurance. 
Unknown risks:  
We do not know if the study antibody will increase, decrease, or not change your 
risk of getting HIV if you are exposed. If you get HIV, we do not know how the 
study antibody might affect your HIV infection or how long it takes to develop 
AIDS. 
We do not know if getting this study antibody will affect how you respond to any 
future approved HIV antibody or vaccine. Currently, no HIV antibody or vaccine 
has been approved for use. 
We do not know how the study antibody will affect a pregnant participant or a 
developing baby.  
Benefits 
21. The study may not benefit you. 
We do not expect the study antibody to benefit you in any way. However, being 
in the study might still help you in some ways. The counseling that you get as part 
of the study may help you avoid getting HIV. The lab tests and physical exams 
that you get while in this study might detect health problems you don’t yet know 
about.  


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When asked, most study participants say that participating in a study made them 
feel good about helping others, increased their knowledge about HIV, and 
improved their self-esteem. 
This study may help in the search for an antibody or vaccine to prevent HIV. 
However, if the study antibody or a vaccine later become approved and sold, there 
are no plans to share any money with you.  
Your rights and responsibilities 
22. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Bill of Rights and Responsibilities for HIV Research. We will give 
you a copy of it. 
Leaving the study 
23. Tell us if you decide to leave the study.  
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know.  
Previously collected information about you will remain in the study records and 
will be included in the analysis of results. Your information can not be removed 
from the study records. 
We may 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 may also ask about any 
personal problems or benefits you have experienced from being in the study. We 
believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text. You can remove 
the box around the text. 
24. If you get sick or injured during the study, contact us immediately. 
2 paragraphs below for all sites. 
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 


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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, the HVTN has a process to decide if it 
is related to the study product 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. 
Next paragraph for non-US sites. 
Sites: adjust the language in this paragraph so it is applicable to your site. Note 
that the ABPI guidelines apply to South Africa only. In this study, our clinic has 
insurance to cover your medical treatment in the case of a study-related injury. 
We will follow the Association of the British Pharmaceutical Industry guidelines 
for payment of study-related injury. We can give you a copy of these guidelines. 
In rare cases, the insurance funds may not be enough.  
In this situation, 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/or your health insurance will be responsible for treatment costs. 
Next paragraph for US sites. 
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/or your health 
insurance will be responsible for treatment costs. 
 
2 paragraphs below for all sites. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV prevention study. Or you might lose wages because you cannot 
go to work. However, there are no funds to pay for these kinds of injuries, even if 
they are study related. 
You may disagree with the decision about whether your injury is study related. If 
you wish, 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. 
 


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Questions  
25. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 
Paragraph for South African sites. The study has been structured in accordance 
with the Declaration of Helsinki (last updated October 2013) which deals with the 
recommendations guiding doctors in biomedical research involving human 
participants, the Ethics in Health Research: Principles, Structures and Processes 
Second Edition 2015, and Guidelines for Good Practice in the Conduct of Clinical 
Trials in Human Participants in South Africa. We can provide you with copies of 
these guidelines if you wish to review them. In addition, the recent Protection of 
Personal Information Act (POPIA) ensures that all South African institutions 
conduct themselves in a responsible manner when collecting, processing, storing 
and sharing another entity’s personal information by holding them accountable 
should they abuse or compromise your personal information in any way.If you 
want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Remainder of section for South African sites only.  
You can reach a study staff member 24 hours a day at [telephone number].  
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 
you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Health Products Regulatory Authority (SAHPRA) at: 
The Chief Executive Officer 
Dr Boitumelo Semete-Makokotlela 
South African Health Products Regulatory Authority Private Bag X828 
PRETORIA 
0001 
Tel: (012) 501 0410 
e-mail: Boitumelo.Semete@sahpra.org.za 


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 Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
26. In Section 16 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN and HPTN keep track of your decision 
about how your samples and information can be used. You can change your 
mind after signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to HIV, 
vaccines, antibodies, the immune system, and other diseases. This may include genetic 
testing.  
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 or genome wide studies.  
 
27. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
• You have read this consent form, or someone has read it to you. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 
You will not be giving up any of your rights by signing this consent form. 


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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 B 
Sample informed consent form for Part B 
Title: A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, 
and pharmacokinetics of PGDM1400LS alone and in combination with VRC07-
523LS and PGT121.414.LS in healthy, HIV-uninfected adult participants 
Protocol number: HVTN 140/HPTN 101 
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. 
Key Information 
These are some of the things you should know about this study: 
• The purpose of this part of the study is to understand how the body’s immune 
system responds to lab-made antibodies against HIV when they are given in 
combination at different doses. We also want to see if the way the antibodies 
is given affects the immune response. 
• We also want to see if the antibodies are safe to give to people and do not 
make them too uncomfortable.  
• If you choose to join, we will ask you to come to several study visits over 
about 10 months. At 2 of these visits you will get the study antibodies in a 
vein (by IV infusion) or under the skin (by subcutaneous infusion, called SC). 
We will take blood from you at each study visit to see how your body 
responds to the study antibodies and how much of the antibody combination 
remains in your blood. We will test you for HIV and other sexually 
transmitted infections (STIs) and pregnancy (if applicable). We will ask you 
to complete questionnaires and you will have physical exams.  
• Some general risks of antibodies include fever, chills, shaking, nausea, 
vomiting, pain, diarrhea, headache, dizziness, fatigue, flushing, trouble 
breathing, high or low blood pressure, itchiness and rash. There may be other 
side effects that we don’t yet know about, even serious ones. Because this is 
the first time that one of the study antibodies is being given to people, and the 
first time this combination of antibodies is being given to people, we do not 
know what all of the risks may be. We think that the risks will be similar to 
these general risks. 
• There is no direct benefit to you from being in the study.  


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• Whether to take part in this study is your choice. You do not have to take part 
in the study and you are free to stop at any time. 
• The rest of this form provides a more complete description of this study. 
Please read it carefully. 
 
About the study 
The HIV Vaccine Trials Network (HVTN), the HIV Prevention Trials Network 
(HPTN), and [Insert site name]  are doing a study to test a combination of 
antibodies against HIV. HIV is the virus that causes AIDS. Antibodies are made 
by the body as one way to respond to or fight infection. Researchers can also 
make antibodies in laboratories and give them to people by infusion into a vein or 
under the skin. We will tell you more about these procedures below. Antibodies 
have been used successfully to prevent or treat other health problems, such as 
COVID-19 caused by the SARS-CoV-2 virus, and respiratory infections in babies 
caused by RSV (respiratory syncytial virus). 
About 95 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.  
There are 2 parts of this study, Part A and Part B. In Part A, we gave different 
doses of one of the study antibodies to 15 people. People in Part A got the study 
antibody one time. Part A was the first time that antibody has been tested in 
people. The results of Part A show that it is safe to move ahead with Part B of the 
study. In Part B, we will give about 80 more people a combination of three study 
antibodies, including the antibody tested in Part A.  
You are being invited to join part B of the study.  
1. We are doing this part of the study to answer several questions. 
• Are the study antibodies safe to give to people together at different doses? 
• Are people able to take the study antibodies without becoming too 
uncomfortable? 
• How do people’s immune systems respond to the study antibodies? (Your 
immune system protects you from disease.) 
• Does the method of giving the study antibodies change the body’s response?  
• How much of the antibodies remain in the body as time passes? 


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2. The study antibodies cannot give you HIV. 
The study antibodies are not made from actual HIV. It is impossible for the study 
antibodies to give you HIV. Also, they cannot cause you to give HIV to someone 
else. We do not know if the study antibodies will decrease, increase, or not 
change your risk of getting HIV if you are exposed to the virus. 
3. These study antibodies are experimental. 
The study antibodies are called PGDM1400LS, VRC07-523LS, and 
PGT121.414.LS. From here on, we will call them the study antibodies. They are 
experimental HIV prevention products. That means we do not know if they will 
be safe to use in people, or if they will work to prevent HIV infection. These 
antibodies are used only in research studies. 
The 3 study antibodies were developed by researchers with the National Institute 
of Allergy and Infectious Diseases (NIAID) and the Collaboration for AIDS 
Vaccine Discovery. Researchers at Beth Israel Deaconess Medical Center in 
Boston, MA were also involved in developing PGT121.414.LS.  
The study antibody PGDM1400LS has only been given to the 15 people who 
were enrolled in Part A. A review of the safety information from these 
participants shows that it is safe to continue with Part B of the study. An earlier 
version of the study antibody called PGDM1400 has been given to 53 people in 3 
other studies. One of these studies is still ongoing, but so far there have been no 
safety concerns. Nine people have been given PGDM1400 alone and 44 have in 
combination with other antibodies. PGDM1400LS is a new version of 
PGDM1400 and has been changed so that it will last longer in the body. 
The other 2 antibodies have been given to 231 people in 6 studies. VRC07-523LS 
has been given alone to 173 people and in combination with other antibodies to 49 
people. PGT121.414.LS has only been given to 9 people. An earlier version of the 
study antibody called PGT121 has been given alone to 41 people and in 
combination with other antibodies to 47 people, in 4 studies. PGT121.414.LS is a 
new version of PGT121 and has been changed so that it will last longer in the 
body. 
Antibodies given to a person usually do not last in the body more than a few 
months. One of the goals of this study is to see how long these study antibodies 
will stay in the body. We don’t know yet how long they will last, but we think it 
may be several months.  
Risks of the study antibodies: 
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. Based on what we have seen so far in ongoing studies, we think 
that the risks will be similar to the general risks described below.  


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General risks of antibodies: 
Other kinds of antibodies used for other health problems have caused fever, chills, 
itchiness, rash, hives, redness in cheeks and neck, lip or face swelling, nausea, 
vomiting, diarrhea, pain, headache, fatigue, flushing, dizziness, shaking, trouble 
breathing, high or low blood pressure, racing heartbeat, and chest pain. These 
reactions may be related to how an antibody is made, what it targets, or how fast 
the antibody product is given. At times the side effects include reactions at 
injection site (pain, redness, bruising, swelling, hardening). Most side effects 
happen within the first 24 hours. 
Rarely, some antibodies for other diseases have caused 2 kinds of side effects that 
may be life-threatening:  
• Anaphylaxis – a physical reaction that may include hives or rash, mouth and 
face swelling, low blood pressure, and trouble breathing, possibly leading to 
low blood oxygen. This may occur soon after getting an antibody. 
• Serum Sickness – a physical reaction that includes hives or rash, fever, big 
lymph nodes, muscle and joint pain, chest discomfort and shortness of breath. 
This may occur several days to a few weeks after getting an antibody. 
These rare side effects have not been seen in other studies with similar 
experimental antibodies against HIV. Please tell us if you have ever had a reaction 
similar to anaphylaxis or serum sickness. 
Rarely, antibodies approved for treatment of other diseases have been linked to 
other effects like cancer, increased bleeding, increased infections, heart and liver 
toxicity, and problems with blood clotting and immune response. These rare side 
effects and reactions have not been seen in other studies with these study 
antibodies or similar experimental antibodies against HIV.  
Joining the study 
4. It is completely up to you whether or not to join the study.  
Take your time in deciding. If it helps, talk to people you trust, such as your 
doctor, friends or family. If you decide not to join this study, or if you leave it 
after you have joined, your other care at this clinic and the benefits or rights you 
would normally have will not be affected. 
If you join this study, you may not be allowed to join some other 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. Site: Remainder of paragraph for South African sites. We check to make 
sure that you are not in more than one study by taking your fingerprint on an 
electronic system. This information is only accessed by a few members of the 
study team using a secure password. 


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You should not donate blood or tissue during the study. 
If you choose not to join this study, you may be able to join another study. 
Site: Remove item 5 if you use a separate screening consent that covers these 
procedures. 
5. If you want to join the study, we will screen you to see if you are eligible. 
Screening involves a physical exam, HIV test and health history. A physical exam 
may include, but is not limited to: 
• Checking your weight, temperature and blood pressure 
• Looking in your mouth and throat 
• Checking your veins to see how easy it might be to start an infusion 
• Looking at your skin  
• Listening to your heart and lungs 
• Feeling your abdomen (stomach and liver) 
• Asking you about any symptoms of COVID-19 that you may have 
• Asking you about vaccines you have gotten recently. 
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 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. If you 
have had your uterus or ovaries removed (a hysterectomy or oophorectomy), and 
this is verified by medical records, you are not required to have a pregnancy test.  
We will review the screening results with you. The screening results may show 
you are not eligible to join the study, even if you want to.  
Site: adapt the following section so it is applicable to the care available at your site 
6. If we find that you have a health problem during screening or during the 
study, we will tell you about the care that we can give here for free. 
For the care that we cannot give, we will explain how we will help you get care 
elsewhere. For health problems that are unrelated to the study, we will not pay for 
care. 


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7. If you were assigned female sex at birth and could become pregnant, you 
must agree to use birth control to join this study. 
Site: If you want to include Appendix C, 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 antibodies could affect the developing baby. You must agree to use 
effective birth control from 21 days before your first infusion until your last 
required clinic visit. We will talk to you about effective birth control methods. 
They are listed on a handout that we will give to you.  
Being in the study 
If you meet the study requirements and want to join, here is what will happen: 
8. You will come to the clinic for 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.) 
Most of the visits will be 1-2 months apart. After you get the study antibodies, we 
will also ask you to come to the clinic for follow-up visits about 3 and 6 days after 
the first infusion to take your blood. We will do this so that we can look at how 
your body responds to the study products. Visits can last from [#] to [#] hours. 
Site:Please adjust the first sentence in the paragraph below to reflect whether you 
assess COVID-19 symptoms by phone/email/text message prior to the scheduled 
visit, or if symptom assessment occurs at the visit itself. You can also add a 
description of how symptoms are monitored upon arrival at your location, such as 
temperature screening in the building lobby, etc., so that participants know what 
to expect. 
You may have to come for more visits if you have a lab or health issue. 
We may contact you after the study ends (for example, to tell you about the study 
results). 
9. We will give you [Site: Insert compensation] for each study visit you 
complete. 
This amount is to cover the costs of [Site: Insert text] 
Site: Insert any costs to participants (eg, birth control costs for participants who 
could become pregnant). 


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US sites: Include the following paragraph. You can remove the box around the text. 
Payments you receive for being in the study may be taxable. We may need to ask 
you for your Social Security number for tax reasons. 
You do not have to pay anything to be in this study. 
10. We will give you the study antibodies by IV infusion or SC infusion. 
For the IV infusion, we will use a sterile needle to place a small plastic tube into a 
vein in your arm or hand. The small plastic tube is connected to a small bag of 
fluid that contains the study antibody. A pump controls how fast the fluid drips 
from the bag, through the tube, and into your vein. Each antibody will be given in 
a separate infusion, one after the other. If you have any symptoms while you are 
getting the study antibodies, tell the study staff. Slowing or stopping the flow rate 
may help improve the symptom. 
At the first visit, the IV infusions will take about one hour for each study antibody 
(total of about 3 hours). The second IV infusion visit will take about 15 - 30 
minutes for each study antibody (total of about 1 1/2 hours). 
When getting a subcutaneous (SC) infusion, sterile needles are put under the skin 
on your abdomen, arm, or thigh. The dose of each antibody will be divided and 
given in 2 or 3 locations at the same time. A pump is used to control how fast the 
study antibody is injected through the needles. Each antibody will be given 
separately, one after the other, and you’ll be able to get up and move around in 
between infusions. The infusion of the three study antibodies will take between 45 
minutes – 2 hours depending on which group you are in and depending on your 
weight. 
The highest dose of antibodies given to some people in this study is more than the 
highest dose of these antibodies given in previous studies. However, it is less than 
the amount of other licensed antibodies given to treat other illnesses.  
11. We will give you the study antibodies on a schedule. 
You will be in either group 6, 7, 8, 9 or 10. (Groups 1-5 were in Part A of the 
study.) You will get 2 infusions during the study as shown in the table below. The 
difference between the groups is the dose of study antibodies being given and the 
way they are being given. Some people will get a fixed dose of antibodies and 
some people will get a dose of antibodies based on their body weight.  
Because this is the first time the antibodies are being given to people in this 
combination, the study has planned a pause when safety information will be 
reviewed to decide if it is safe to continue the study. The pause will be after the 
first 8 participants in Groups 6-9, with two participants per group, have had their 
first infusion. If the safety review of these participants shows it is safe to continue, 
then enrollment will resume for the rest of the participants in Groups 6-9 as well 


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as Group 10. You have an equal chance of being in Groups 6-9. Whether you are 
enrolled in Groups 6-9 or Group 10 will depend on when you join the study. 
 
 
 
 
 
Infusion schedule  
Group 
Number of 
participants 
Dose 
How it is 
given 
Enrollment Visit 
4 months later 
 
 
 
 
 
 
6 
16 
medium dose 
weight based 
IV 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
 
 
 
 
 
7 
16 
medium dose 
weight based 
SC 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
 
 
 
 
 
8 
16 
medium dose 
fixed 
IV 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
 
 
 
 
 
9 
16 
medium dose 
fixed 
SC 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
 
 
 
 
 
10 
16 
higher dose 
weight based 
IV 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS 
 
You will have to wait in the clinic for about 1 hour after your last infusion to see 
if there are any problems. We will collect a blood sample about 1 hour after the 
infusion. Then for that night and for 3 more days, you will need to keep track in a 
diary about how you are feeling and if you have any symptoms. Site: Customize 
the next sentence based on how you collect reactogenicity information. We will 
review the diary with you during the 2 visits after you get an infusion. You will 
turn in the diary by the Day 6 visit after the first infusion. We will contact you 
about 4 days after the second infusion to collect the information from your diary. 
Contact the clinic staff if you have any issues or concerns after getting an 
infusion. If you have a problem, we will continue to check on you until it goes 
away. 
12. In addition to giving you the study antibodies we will: 
• Do regular HIV testing, as well as counseling on your results and on how to 
avoid getting HIV 


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• Do physical exams 
• Do pregnancy tests if you were assigned female sex at birth 
• Ask questions about your health, including medications you may be taking, 
including PrEP  
• Asking you about any symptoms of COVID-19 that you may have 
• Ask questions about any personal problems or benefits you may have from 
being in the study 
• Ask questions about your experience getting infusions/injections 
• 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 25 mL and 105 mL (a little less than 2 tablespoons 
to about 1/2 cup). Your body will make new blood to replace the blood we take 
out.  
Site: You may want to add a sentence to the end of the previous paragraph 
contextualizing the blood volumes described (eg, “To compare, people who donate 
blood in the US can give a total of about 500 mL in an 8-week period.”). Modify the 
example for cultural relevance and alter blood volumes as necessary. 
Site: Insert Appendix E, 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. 
Some procedures may be done remotely, such as by phone, text message, email or 
video calls. This could happen instead of or in combination with in-person visits 
at the study clinic. Some study procedures might also take place in other 
locations, such as outdoor tents or mobile clinics. The staff will tell you more 
about the options they plan to use to protect everyone’s safety. 
13.  Getting a COVID-19 vaccine while you are in this study is allowed. 
To be sure that we can answer the study questions, we will not give the study 
infusion within 7 days before or after youget a COVID-19 vaccine. If you are 
planning to get a COVID-19 vaccine, please tell us so that we can schedule your 
study visits with this in mind. 


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14. We will counsel you about protecting yourself from HIV. 
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 acquiring HIV low.  
15. We will test your samples. 
We will send your samples (without your name) to labs approved by the HVTN 
and HPTN for this study, which are located in the United States and South Africa. 
In rare cases, some of your samples may be sent to labs approved by the HVTN 
and HPTN 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. 
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 and HPTN 
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 and HPTN 
want to use them in other studies and share them with other researchers.  
The HVTN and HPTN call these samples “extra samples”. The HVTN and HPTN 
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. [Site: choose one of the following two sentences. African sites 
should choose the sentence referencing the repository in South Africa. All other 


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sites should choose the sentence referencing the repository in the United States.] 
Your samples will be stored in the HVTN repository in South Africa. Your 
samples will be stored in the HVTN repository in the United States. 
How long will the samples be stored? There is no limit on how long your extra 
samples will be stored. [Site: Revise the previous sentence to insert limits if your 
regulatory authority imposes them.] 
Will I be paid for the use of my samples? No. Also, a researcher may make a new 
scientific discovery or product based on the use of your samples. If this happens, 
there is no plan to share any money with you. The researcher is not likely to ever 
know who you are. 
Will I benefit from allowing my samples to be used in other studies? Probably not. 
Results from these other studies are not given to you, this clinic, or your doctor. 
They are not part of your medical record. The studies are only being done for 
research purposes. 
Will the HVTN or HPTN sell my samples and information? No, but the HVTN 
and HPTN may share your samples with HVTN, HPTN, 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 and HPTN. Also, the researcher’s institutional review board (IRB) 
or ethics committee (EC) will review their plan. [Site: If review by your 
institution’s IRB/EC/RE is also required, insert a sentence stating this.] IRBs/ECs 
protect the rights and well-being of people in research. If the research plan is 
approved, the HVTN will send your samples to the researcher’s location.  
What information is shared with HVTN, HPTN, or other researchers? The 
samples and information will be labeled with a code number. The key to the code 
will stay at this clinic. It will not be shared with the HVTN, other researchers, or 
with anyone else who does not need to know your name. 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 antibodies you received 
and how your body responded to the studyantibodies.  
What kind of studies might be done with my extra samples and information? The 
studies will be related to HIV, vaccines, antibodies, the immune system, and other 
diseases.  
Researchers may also do genetic testing on your samples. 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 


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them understand diseases. The researchers may put the information from the 
genome-wide studies into a protected database so that other researchers can 
access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks.  
Who will have access to my information in studies using my extra samples?  
People who may see your information are: 
• Researchers who use your extra samples and information for other research 
• Government agencies that fund or monitor the research using your extra 
samples and information 
• Any regulatory agency that reviews clinical trials 
• The researcher’s Institutional Review Board or Ethics Committee 
• The people who work with the researcher  
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
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. 
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, people who work for them, and their 
study monitors, 
• The US Food and Drug Administration, 
• Any regulatory agency that reviews clinical trials, 


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• Non-US Sites must include; US sites may but are not required to 
include:[Insert name of local IRB/EC] , 
• [Insert name of local and/or national regulatory authority as appropriate], 
• The HVTN, HPTN and people who work for them,  
• The 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. If you are found to have a medical 
condition that we are required to report by law, then some of your information 
may be shared. At this clinic, we have to report the following information:  
Site: Include any public health or legal reporting requirements, including SARS-CoV-
2/COVID-19. Bulleted examples should include all appropriate cases (reportable 
communicable disease, risk of harm to self or others, etc.). If your site does not have 
public health or legal reporting requirements, you may delete the last sentence in the 
paragraph above, along with the bullets below. 
• [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. There are several reasons why we may stop your infusions. We may stop 
them even if you were scheduled for more infusions. 
If we stop your infusions, we may ask you to stay in the study to complete other 
study procedures. 
We will stop your infusions 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. 
We will stop your infusions if you enroll in a different research study where you 
get another study product. We will encourage you to stay in the study if you 
choose. 
We will stop your infusions if you acquire HIV. We will also take fewer samples, 
and we will help you get care and support. We will encourage you to stay in the 
study for up to 16 weeks after your last infusion or last scheduled protocol clinic 
visit, whichever comes first. We will discuss your study options with you. We 
will counsel you about having HIV and about telling your partner(s). Site: Modify 
the following sentence as appropriate. We will not provide or pay for any of your 
HIV care directly. 
In the unlikely event that you have a bad reaction to a study infusion, we may stop 
your infusions.  
19. We may take you out of the study at any time.  
We may take you out of the study if: 
• you do not follow instructions, 
• we think that staying in the study might harm you, 
• the study is stopped for any reason. 
Other Risks 
20. There are other risks to being in this study. 
This section describes the other risks and restrictions we know about. There may 
also be unknown risks, even serious ones. We will tell you if we learn anything 
new that may affect your willingness to stay in the study. 
Risks of giving blood:  


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Giving blood can cause bruising, pain, fainting, soreness, redness, swelling, 
itching, bleeding, and infection (rarely). Giving blood can cause a low blood cell 
count (anemia), making your feel tired.  
Risks of SC infusion procedures:  
Getting a SC infusion may cause bruising, pain, fainting, soreness, redness, 
swelling, itching, a sore, bleeding, blood clots, forming a bump under the skin, 
and (rarely) muscle damage, or infection where you got the SC infusion.  
Risks of IV infusion procedures: 
Getting an IV may cause stinging, discomfort, pain, soreness, redness, bruising, 
itching, rash and swelling where the needle goes into the skin. Rarely, needle 
sticks can result in a blood clot or infection. 
Personal problems/discrimination: 
Some people who join HVTN and HPTN studies report personal problems or 
discrimination because of joining an HIV prevention study. Family or friends may 
worry, get upset or angry, or assume that you have HIV or are at high risk and 
treat you unfairly as a result. Rarely, a person has lost a job because the study 
took too much time away from work, or because their employer thought they had 
HIV.  
HIV testing: 
HIV antibody tests are the usual way to test for HIV infections. We are still 
learning how HIV tests perform when people are given monoclonal antibodies. 
We have used several common HIV antibody tests to test samples of blood 
containing antibodies similar to the study antibodies. We found that very high 
levels of these similar antibodies can cause positive or uncertain results on some 
HIV tests. You may have such high levels for a short time after you get the study 
antibodies. This means that for a few days after getting the study antibodies, some 
HIV tests might 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 truly detect HIV. They can also tell if someone does not have 
HIV. We do not expect you to have any problems with HIV testing after the study 
ends. 
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 have HIV. If you feel embarrassed or anxious, please tell us and we will try to 
help you. 


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Risks of disclosure of your personal information: 
We will take several steps to protect your personal information. Although the risk 
is very low, it is possible that your personal information could be given to 
someone who should not have it. If that happened, you could face discrimination, 
stress, and embarrassment. We can tell you more about how we will protect your 
personal information if you would like it.  
Risks of genetic testing: 
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 
test results from the genetic testing. The results are not part of your study records 
and are not given to you.  
U.S. Sites, include the following paragraph In the very unlikely event that your 
genetic information becomes linked to your name, a federal law called the 
Genetic Information Nondiscrimination Act (GINA) helps protect you. GINA 
keeps health insurance companies and employers from seeing results of genetic 
testing when deciding about giving you health insurance or offering you work. 
GINA does not help or protect you against discrimination by companies that sell 
life, disability or long-term care insurance. 
Unknown risks:  
We do not know if the study antibodies will increase, decrease, or not change 
your risk of getting HIV if you are exposed. If you get HIV, we do not know how 
the study antibodies might affect your HIV infection or how long it takes to 
develop AIDS. 
We do not know if getting these study antibodies will affect how you respond to 
any future approved HIV antibody or vaccine. Currently, no HIV antibody or 
vaccine has been approved for use. 
We do not know how the study antibodies will affect a pregnant participant or a 
developing baby.  
Benefits 
21. The study may not benefit you. 
We do not expect the study antibodies 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.  


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When asked, most study participants say that participating in a study made them 
feel good about helping others, increased their knowledge about HIV, and 
improved their self-esteem. 
This study may help in the search for an antibody or vaccine to prevent HIV. 
However, if the study antibodies or a vaccine later become approved and sold, 
there are no plans to share any money with you.  
Your rights and responsibilities 
22. If you join the study, you have rights and responsibilities. 
You have many rights that we will respect. You also have responsibilities. We list 
these in the Bill of Rights and Responsibilities for Research. We will give you a 
copy of it. 
Leaving the study 
23. Tell us if you decide to leave the study.  
You are free to leave the study at any time and for any reason. Your care at this 
clinic and your legal rights will not be affected, but it is important for you to let us 
know.  
Previously collected information about you will remain in the study records and 
will be included in the analysis of results. Your information can not be removed 
from the study records. 
We may 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 may also ask about any 
personal problems or benefits you have experienced from being in the study. We 
believe these steps are important to protecting your health, but it is up to you 
whether to complete them. 
Injuries 
Sites: Approval from HVTN Regulatory Affairs (at vtn.core.reg@hvtn.org) is needed 
for any change (other than those that the instructions specifically request or those 
previously approved by HVTN Regulatory Affairs) to the boxed text. You can remove 
the box around the text. 
24. If you get sick or injured during the study, contact us immediately. 
2 paragraphs below for all sites. 
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 


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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, the HVTN has a process to decide if it 
is related to the [study product(s)]  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. 
Next paragraph for non-US sites. 
Sites: adjust the language in this paragraph so it is applicable to your site. Note 
that the ABPI guidelines apply to South Africa only. In this study, our clinic has 
insurance to cover your medical treatment in the case of a study-related injury. 
We will follow the Association of the British Pharmaceutical Industry guidelines 
for payment of study-related injury. We can give you a copy of these guidelines. 
In rare cases, the insurance funds may not be enough.  
In this situation, 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/or your health insurance will be responsible for treatment costs. 
Next paragraph for US . 
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/or your health 
insurance will be responsible for treatment costs. 
 
2 paragraphs below for all sites. 
Some injuries are not physical. For example, you might be harmed emotionally by 
being in an HIV prevention study. Or you might lose wages because you cannot 
go to work. However, there are no funds to pay for these kinds of injuries, even if 
they are study related. 
You may disagree with the decision about whether your injury is study related. If 
you wish, 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. 
 


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Questions  
25. If you have questions or problems at any time during your participation in 
this study, use the following important contacts. 
If you have questions about this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have any symptoms that you think may be related to this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
This study has been reviewed and approved by a committee called the 
[name of local IRB/EC]. If you have questions about your rights as a research 
participant, or problems or concerns about how you are being treated in this study, 
contact [name or title and telephone number of person on IRB/EC] , at the 
committee. 
US sites include if this sIRB will be used: This study has been reviewed and 
approved by a committee called the Fred Hutchinson Cancer Research Center 
Institutional Review Board. If you have questions about your rights as a research 
participant, or problems with or concerns about how you are being treated in this 
study, contact the Director at 206-667-5900 or irodirector@fredhutch.org. 
Paragraph for South African sites. The study has been structured in accordance 
with the Declaration of Helsinki (last updated October 2013) which deals with the 
recommendations guiding doctors in biomedical research involving human 
participants, the Ethics in Health Research: Principles, Structures and Processes 
Second Edition 2015, and Guidelines for Good Practice in the Conduct of Clinical 
Trials in Human Participants in South Africa. We can provide you with copies of 
these guidelines if you wish to review them. In addition, the recent Protection of 
Personal Information Act (POPIA) ensures that all South African institutions 
conducts themselves in a responsible manner when collecting, processing, storing 
and sharing another entity’s personal information by holding them accountable 
should they abuse or compromise your personal information in any way.If you 
want to leave this study, contact 
[name or title and telephone number of the investigator or other study staff]. 
Remainder of section for South African sites only.  
You can reach a study staff member 24 hours a day at [telephone number].  
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 
you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Health Products Regulatory Authority (SAHPRA) at: 


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The Chief Executive Officer 
Dr Boitumelo Semete-Makokotlela 
South African Health Products Regulatory Authority Private Bag X828 
PRETORIA 
0001 
Tel: (012) 501 0410 
e-mail: Boitumelo.Semete@sahpra.org.za 
 Your permissions and signature  
Site: Delete this section if using a separate consent for use of samples and 
information in other studies 
26. In Section 16 of this form, we told you about possible other uses of your extra 
samples and information, outside this study. Please choose only one of the 
options below and write your initials or make your mark in the box next to it. 
Whatever you choose, the HVTN and HPTN keep track of your decision 
about how your samples and information can be used. You can change your 
mind after signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to HIV, 
vaccines, antibodies, the immune system, and other diseases. This may include genetic 
testing.  
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 or genome wide studies.  
 
27. If you agree to join this study, you will need to sign or make your mark 
below. Before you sign or make your mark on this consent form, make sure 
of the following: 
• You have read this consent form, or someone has read it to you. 
• You feel that you understand what the study is about and what will happen to 
you if you join. You understand what the possible risks and benefits are. 
• You have had your questions answered and know that you can ask more. 
• You agree to join this study. 


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You will not be giving up any of your rights by signing this consent form. 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form. 
 
 


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Appendix C 
Approved birth control methods for persons 
assigned female sex at birth (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 antibodies could affect the developing baby. 
You must agree to use effective birth control from 21 days before your first 
infusion until last scheduled protocol clinic visit.  
Effective birth control means using one 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; 
• Internal or external 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). 


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Remember: If you are having sex, internal and external condoms (also known as 
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 studyinfusion. 
 


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Appendix D 
Sample consent form for use of samples and 
information in other studies 
Title: A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, 
and pharmacokinetics of PGDM1400LS alone and in combination with VRC07-
523LS and PGT121.414.LS in healthy, HIV-uninfected adult participants 
Protocol number: HVTN 140/HPTN 101 
Site: [Insert site name] 
When samples are no longer needed for this study, the HVTN and HPTN want to 
use them in other studies and share them with other researchers. The HVTN and 
HTPN call these samples called “extra samples.” The HVTN and HPTN will only 
allow your extra samples to be used in other studies if you agree to this. You will 
mark your decision at the end of this form. If you have any questions, please ask.  
1. Do I have to agree?  
No. You are free to say yes or no, or to change your mind after you sign this form. 
At your request, we will destroy all extra samples that we have. Your decision 
will not affect your being in this study or have any negative consequences here.  
2. Where are the samples stored?  
Extra samples are stored in a secure central place called a repository. [Site: 
choose one of the following two sentences. African sites should choose the 
sentence referencing the repository in South Africa. All other sites should choose 
the sentence referencing the repository in the United States.] Your samples will 
be stored in the HVTN repository in South Africa. Your samples will be stored in 
the HVTN repository in the United States. 
3. How long will the samples be stored?  
There is no limit on how long your extra samples will be stored. [Site: Revise the 
previous sentence to insert limits if your regulatory authority imposes them.] 
4. Will I be paid for the use of my samples?  
No. Also, a researcher may make a new scientific discovery or product based on 
the use of your samples. If this happens, there is no plan to share any money with 
you. The researcher is not likely to ever know who you are. 
5. Will I benefit from allowing my samples to be used in other studies?  
Probably not. Results from these other studies are not given to you, this clinic, or 
your doctor. They are not part of your medical record. The studies are only being 
done for research purposes. 


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6. Will the HVTN or HPTN sell my samples and information?  
No, but the HVTN and HPTN may share your samples with HVTN, HPTN, 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 and HPTN. Also, the researcher’s institutional 
review board (IRB) or ethics committee (EC) will review their plan. [Site: If 
review by your institution’s IRB/EC/RE is also required, insert a sentence stating 
this.] IRBs/ECs protect the rights and well-being of people in research. If the 
research plan is approved, the HVTN will send your samples to the researcher’s 
location. 
8. What information is shared with HVTN, HPTN, 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 antibodies you 
received and how your body responded to the studyantibodies.  
9. What kind of studies might be done with my extra samples and information?  
The studies will be related to HIV, vaccines, antibodies, the immune system, and 
other diseases.  
Researchers may also do genetic testing on your samples.  
If you agree, your samples could also be used for genome wide studies. In these 
studies, researchers will look at all of your genes (your genome). The researchers 
compare the genomes of many people, looking for common patterns of genes that 
could help them understand diseases. The researchers may put the information 
from the genome-wide studies into a protected database so that other researchers 
can access it, but your name and other personal information will not be included. 
Usually, no one would be able to look at your genome and link it to you as a 
person. However, if another database exists that also has information on your 
genome and your name, someone might be able to compare the databases and 
identify you. If others found out, it could lead to discrimination or other problems. 
The risk of this is very small. There may be other unknown risks. 
10. What are the risks of genetic testing?  
It is unlikely, but the genetic tests done on your samples could show you may be 
at risk for certain diseases. If others found out, it could lead to discrimination or 
other problems. However, it is almost impossible for you or others to know your 


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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 Institutional Review Board or Ethics Committee 
• The people who work with the researcher  
All of these people will do their best to protect your information. The results of 
any new studies that use your extra samples and information may be published. 
No publication will use your name or identify you personally. 
Questions  
12. If you have questions or problems about allowing your samples and 
information to be used in other studies, use the following important contacts. 
If you have questions about the use of your samples or information or if you want 
to change your mind about their use, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you think you may have been harmed because of studies using your samples or 
information, contact 
[name or title and telephone number of the investigator or other study staff]. 
If you have questions about your rights as a research participant, contact 
[name or title and telephone number of person on IRB/EC . 


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Paragraph for South African sites. The study has been structured in accordance 
with the Declaration of Helsinki (last updated October 2013) which deals with the 
recommendations guiding doctors in biomedical research involving human 
participants, the Ethics in Health Research: Principles, Structures and Processes 
Second Edition 2015, and Guidelines for Good Practice in the Conduct of Clinical 
Trials in Human Participants in South Africa. We can provide you with copies of 
these guidelines if you wish to review them. 
Remainder of section for South African sites only.  
You can reach a study staff member 24 hours a day at [telephone number].  
If you have questions about this trial you should first discuss them with your 
doctor or the ethics committee (contact details as provided on this form). After 
you have consulted your doctor or the ethics committee and if they have not 
provided you with answers to your satisfaction, you should write to the South 
African Health Products Regulatory Authority (SAHPRA) at: 
The Chief Executive Officer 
Dr Boitumelo Semete-Makokotlela 
South African Health Products Regulatory Authority Private Bag X828 
PRETORIA 
0001 
Tel: (012) 501 0410 
e-mail: Boitumelo.Semete@sahpra.org.za 
 
 


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13. Please choose only one of the options below and write your initials or make 
your mark in the box next to it. Whatever you choose, the HVTN and HPTN 
keep track of your choice about how your samples and information can be 
used. You can change your mind after signing this form. 
 
 
I allow my extra samples and information to be used for other studies related to HIV, 
vaccines, antibodies, the immune system, and other diseases. This may include genetic 
testing.  
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 or genome wide studies.  
 
 
 
 
 
 
 
 
 
 
Participant’s name (print) 
 
Participant’s signature or mark 
 
Date 
 
Time 
 
 
 
 
 
 
 
Clinic staff conducting consent 
discussion (print) 
 
Clinic staff signature 
 
Date 
 
Time 
For participants who are unable to read or write, a witness should complete the 
signature block below: 
 
 
 
 
 
 
 
Witness’s name (print) 
 
Witness’s signature  
 
Date 
 
Time 
*Witness is impartial and was present for the entire discussion of this consent form.


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 180 of 195 
Appendix E 
Table of procedures (for sample informed consent form) 
 
For Part A 
 
 
Time after enrollment infusion visit 
Procedure 
Screening 
visit(s) 
Infusion 
visit 
 3 
days 
6 
days 
1 
month 
2 
months 
4 
months 
6 
months 
Infusion 
 
√ 
 
 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
 
Urine test 
√ 
 
 
 
 
√ 
 
√ 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Pregnancy test 
(participants assigned 
female sex at birth)* 
√ 
√ 
 
 
 
 
 
√ 
HIV testing and pretest 
counseling 
√ 
 
 
 
 
 
√ 
√ 
Risk reduction 
counseling 
√ 
√ 
 
 
√ 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
 
 
√ 
√ 
√ 
√ 
 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
* Persons who had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records), are not required to have a pregnancy test. 
 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 181 of 195 
For Part B 
 
 
 
Time after first infusion visit 
Procedure 
Screening 
visit(s) 
First 
infusion 
visit 
 3 
days 
6 
days 
1 
month 
2 
months 
4 
months 
4 
months 
+ 4 
days 
6 
months 
8 
months 
10 
months 
Infusion 
 
√ 
 
 
 
 
√ 
 
 
 
 
Medical history 
√ 
 
 
 
 
 
 
 
 
 
 
Complete physical 
√ 
 
 
 
 
 
 
 
 
 
√ 
Brief physical 
 
√ 
√ 
√ 
√ 
√ 
√ 
 
√ 
√ 
 
Urine test 
√ 
 
 
 
 
√ 
 
 
√ 
 
√ 
Blood drawn 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
√ 
√ 
√ 
Pregnancy test 
(participants assigned 
female sex at birth)* 
√ 
√ 
 
 
 
 
√ 
 
 
 
√ 
HIV testing and pretest 
counseling 
√ 
 
 
 
 
 
√ 
 
 
√ 
√ 
Risk reduction 
counseling 
√ 
√ 
 
 
√ 
√ 
√ 
 
√ 
√ 
√ 
Interview/questionnaire 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Not shown in this table is a time after all study participants have completed their last scheduled visit when you can find out what products you received.  
* Persons who had a hysterectomy (removal of the uterus) or removal of both ovaries (verified by medical records), are not required to have a pregnancy test. 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 182 of 195 
Appendix F 
 Laboratory procedures for Part A 
 
Visit:
1
2
3
4
5
6
7
8
9
Day:
Screening 
visit3
D0
D3
D6
D28
D56
D112
D116
D168
Week:
W0
W4
W8
W16
W24
Study Product 
Administration
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. capacity)4
PGDM1400LS
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
—
—
—
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
Syphilis9
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
HIV diagnostics 7
UW-VSL / 
HSML-NICD
UW-VSL / HSML-
NICD
EDTA
10mL
—
—
—
—
—
—
—
10
Safety labs10
CBC/ Differential
Local lab
Local lab
EDTA
5mL
5
5
—
—
—
5
—
5
Chemistry Panel5
Local lab
Local lab
SST
5mL
5
5
—
—
—
5
—
5
Drug concentrations/detection
PGDM1400LS concentration
CSR
HVTN Labs
SST
8.5mL
—
y
y
y
y
y
y
y
Humoral assays
HIV-1 neutralizing Ab 
CSR
HVTN Labs
SST
8.5mL
—
y
y
y
y
y
y
y
Non-neutralizing antiviral 
assays
CSR
HVTN Labs
SST
8.5mL
—
y
y
y
y
y
y
y
Anti-Drug Antibody (ADA)
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
y
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
—
y
Ab Reaction11
Tryptase / C3 and C4 
Complement / Cytokines
CSR
ARUP
SST
8.5mL
—
See footnote 12
—
—
See 
footnote 
12
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
See footnote y
—
—
—
—
—
—
STORAGE
Serum 
CSR
—
SST
8.5mL
—
76.514
42.5
42.5
42.5
42.5
42.5
42.5
Visit total
25
86.5
42.5
42.5
42.5
52.5
42.5
62.5
56-Day total13
 
25
112
154.0
197
239
292
95
105
URINE COLLECTION10
Urine dipstick8
Local lab
Local lab
X
—
—
—
—
X
—
X
Pregnancy test6
Local lab
Local lab
X
X15
—
—
—
—
—
X
See footnote 12


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 183 of 195 
Footnotes for Appendix F 
 
Greyed-out column does not apply to Part A. 
1CSR = central specimen repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA); 
HSML-NICD = HIV Sero-Molecular Laboratory-National Institute for Communicable Diseases (Johannesburg, South Africa) 
2HVTN Laboratories include: Duke University Medical Center (Durham, North Carolina, USA); South African Immunology Laboratory-
National Institute for Communicable Diseases (SAIL-NICD, Johannesburg, South Africa); Dartmouth College (Hanover, New 
Hampshire, USA).Non-HVTN laboratories: ARUP Laboratories (Salt Lake City, Utah, USA). 
3Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration.  
4Local labs may assign appropriate alternative specimen type or tube types for locally performed tests. 
5Chemistry panels are defined in Section 9.2 (pre-enrollment), and Sections 9.3 and 9.4 (enrollment and follow-up). 
6For participants assigned female sex at birth, pregnancy test must be performed on urine or blood specimens on the day of study product 
administration with negative results received prior to administration. Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
7At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.10), blood should be drawn 
for HIV diagnostic testing, as shown for visit 15 above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood 
for HIV diagnostic testing (see Section 9.12). 
8And microscopy if needed. 
9Syphilis testing will be done by serology.  
10For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, 
urinalysis and pregnancy tests will be collected. 
11To investigate Ab administration-related clinical reactions, assays may be performed on serum samples taken prior to the study product 
administration associated with the reaction and collected after the onset of reaction. Refer to the SSP for more information. 
12SST blood will be collected at specific time points after the onset of any Ab reaction. Refer to the SSP for more information. 
13The 56-day total blood volume does not include up to 34mL SST blood collected for any Ab reaction; however, the 56-day limit is not 
exceeded at any visit by the possible collection of SST blood for an Ab reaction. 
14Of this volume, 8.5mL of SST blood will be collected post study product administration (see SSP for details).  
15 Pregnancy test at enrollment does not need to be performed if negative results are received from screening pregnancy test conducted 
within 48 hours prior to study product administration. 
y = SST blood collected for serum storage will also cover specimen needs for drug concentrations, HIV-1 neutralizing Ab assays, non-
neutralizing antiviral assays, and ADA detection and functional assays (including for any Ab reactions); no separate blood draw is needed. 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 184 of 195 
Appendix G 
Laboratory procedures for Part B 
 
Study Product 
Administration #1
Study Product 
Administration #2
Procedure
Ship to1
Assay location2
Tube 
Type4
Tube size
(vol. 
capacity)4
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS
PGDM1400LS + 
VRC07-523LS + 
PGT121.414.LS
BLOOD COLLECTION
Screening/Diagnostic
Screening HIV test
Local lab
Local lab
EDTA
5mL
5
—
—
—
—
—
—
—
—
—
—
HBsAg/anti-HCV
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
Syphilis9
Local lab
Local lab
SST
5mL
5
—
—
—
—
—
—
—
—
—
—
HIV diagnostics 7
UW-VSL / 
HSML-NICD
UW-VSL / HSML-
NICD
EDTA
10mL
—
—
—
—
—
—
10
—
—
—
10
Safety labs10
CBC/ Differential
Local lab
Local lab
EDTA
5mL
5
5
—
—
—
5
5
—
5
—
5
Chemistry Panel5
Local lab
Local lab
SST
5mL
5
5
—
—
—
5
5
—
5
—
5
Drug concentrations/detection
PGDM1400LS, VRC07-
523LS, PGT121.414.LS 
concentrations
CSR
HVTN Labs
SST
8.5mL
—
y
y
y
y
y
y
—
y
y
y
Humoral assays
HIV-1 neutralizing Ab 
CSR
HVTN Labs
SST
8.5mL
—
y
y
y
y
y
y
—
y
y
y
Non-neutralizing antiviral 
assays
CSR
HVTN Labs
SST
8.5mL
—
y
y
y
y
y
y
—
y
y
y
Anti-Drug Antibody (ADA)
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
y
—
—
—
y
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
y
—
—
—
—
y
—
—
—
y
Ab Reaction11
Tryptase / C3 and C4 
Complement / Cytokines
CSR
ARUP
SST
8.5mL
—
See footnote 12
—
—
—
ADA detection assays 
(screening, confirmatory, 
titration)
CSR
HVTN Labs 
SST
8.5mL
—
See footnote y
—
—
—
—
See footnote y
—
—
—
—
ADA functional assay
CSR
HVTN Labs
SST
8.5mL
—
See footnote y
—
—
—
—
See footnote y
—
—
—
—
STORAGE
Serum 
CSR
—
SST
8.5mL
—
76.514
42.5
42.5
42.5
42.5
5114
—
42.5
42.5
42.5
Visit total
 
25
86.5
42.5
42.5
42.5
52.5
71
0
52.5
42.5
62.5
56-Day total13
 
25
112
154
197
239
292
71
71
124
95
105
URINE COLLECTION10
Urine dipstick8
Local lab
Local lab
X
—
—
—
—
X
—
—
X
—
X
Pregnancy test6
Local lab
Local lab
X
X15
—
—
—
—
X
—
—
—
X
See footnote 12
See footnote 12


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 185 of 195 
Footnotes for Appendix G 
 
1CSR = central specimen repository; UW-VSL = University of Washington Virology Specialty Laboratory (Seattle, Washington, USA); 
HSML-NICD = HIV Sero-Molecular Laboratory-National Institute for Communicable Diseases (Johannesburg, South Africa) 
2HVTN Laboratories include: Duke University Medical Center (Durham, North Carolina, USA); South African Immunology Laboratory-
National Institute for Communicable Diseases (SAIL-NICD, Johannesburg, South Africa); Dartmouth College (Hanover, New 
Hampshire, USA). Non-HVTN laboratories: ARUP Laboratories (Salt Lake City, Utah, USA) 
3Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration.  
4Local labs may assign appropriate alternative specimen type or tube types for locally performed tests. 
5Chemistry panels are defined in Section 9.2 (pre-enrollment), and Sections 9.3 and 9.4 (enrollment and follow-up).  
6For participants assigned female sex at birth, pregnancy test must be performed on urine or blood specimens on the day of study product 
administration with negative results received prior to administration. Persons who are NOT of reproductive potential due to having 
undergone hysterectomy or bilateral oophorectomy (verified by medical records), are not required to undergo pregnancy testing. 
7At an early termination visit for a withdrawn or terminated participant who is not HIV-infected (see Section 9.10), blood should be drawn 
for HIV diagnostic testing, as shown for visit 20 above. If a participant has a confirmed diagnosis of HIV infection, do not collect blood 
for HIV diagnostic testing (see Section 9.12). 
8And microscopy if needed. 
9Syphilis testing will be done by serology.  
10For participants with confirmed diagnosis of HIV infection, only specimens required for protocol-specified safety laboratory tests, 
urinalysis and pregnancy tests will be collected. 
11To investigate Ab administration-related clinical reactions, assays may be performed on serum samples taken prior to the study product 
administration associated with the reaction and collected after the onset of reaction. Refer to the SSP for more information. 
12SST blood will be collected at specific time points after the onset of any Ab reaction. Refer to the SSP for more information. 
13The 56-day total blood volume does not include up to 51mL SST blood collected for any Ab reaction; however, the 56-day limit is not 
exceeded at any visit by the possible collection of SST blood for an Ab reaction. 
14Of this volume, 8.5mL of SST blood will be collected post study product administration (see SSP for details). 
15Pregnancy test at enrollment does not need to be performed if negative results are received from screening pregnancy test conducted 
within 48 hours prior to study product administration . 
16Phone contact only. No specimen collection at this visit.  
y = SST blood collected for serum storage will also cover specimen needs for drug concentrations, HIV-1 neutralizing Ab assays, non-
neutralizing antiviral assays, and ADA detection and functional assays (including for any Ab reactions); no separate blood draw is needed. 
 
 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 186 of 195 
Appendix H 
Procedures at HVTN CRS for Part A 
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
09 
Post 
Day: 
 
D0 
D3 
D6 
D28 
D56 
D112 
D116 D168 
 
Week: 
 
W0 
W0 
W0 
W4 
W8 
W16 
W16 
W24 
 
Procedure 
Scr 
Inf 
 
 
 
 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
 
X 
— 
Confirm eligibility, obtain demographics, 
randomize  
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
Infusion 
— 
X 
— 
— 
— 
— 
— 
 
— 
— 
Solicited AE assessment3 
— 
X 
X3 
X3 
— 
— 
— 
 
— 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
 
— 
— 
Risk reduction counseling4 
X 
X 
— 
— 
X 
X 
X 
 
X 
— 
Contraception status assessment5 
X 
X 
— 
— 
X 
X 
X 
 
X 
— 
Social impact assessment 
— 
X 
— 
— 
X 
X 
X 
 
X 
— 
Behavioral risk assessment questionnaire6 
X 
— 
— 
— 
— 
— 
— 
 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
X 
— 
 
X 
— 
Acceptability questionnaire 
— 
X 
— 
— 
— 
— 
— 
 
— 
— 
Outside testing questionnaire 
— 
— 
— 
— 
— 
— 
— 
 
X 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
 
X 
— 
Intercurrent illness/Unsolicited AE assessment 
— 
X 
X 
X 
X 
X 
X 
 
X 
— 
HIV infection assessment7 
X 
— 
— 
— 
— 
— 
X 
 
X 
— 
Confirm HIV test results provided to participant 
— 
X 
— 
— 
— 
— 
— 
 
X 
X 
Specimen collection 8 
X 
X 
X 
X 
X 
X 
X 
 
X 
— 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 187 of 195 
Greyed-out column does not apply to Part A. 
Footnotes for Appendix H 
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 
2 Specimens collected at Day 0 may be obtained within the 14 days prior to study product administration, except for a pregnancy test, which must 
be performed on urine or blood specimens within 48 hours prior to study product administration with negative results received prior to study 
product administration. 
3 Solicited AE assessments are performed daily for at least 3 full days following study product administration. CRS staff will review and reconcile 
the diary with the participant and then report Solicited AEs. Participant diary reconciliation may happen as the data is available (see the HVTN 
140/HPTN 101 SSP). 
4 Includes transmission risk reduction counseling for HIV-infected participants. 
5 Contraception status assessment is required only for participants who were assigned female sex at birth and who are capable of becoming 
pregnant. 
6 Not applicable to HIV-infected participants. 
7 Includes pretest counseling and HIV testing. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to 
participant. Not applicable for participants diagnosed with HIV infection. 
8 For specimen collection requirements, see Appendix F. 
 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 188 of 195 
Appendix I 
Procedures at HVTN CRS for Part B  
 
Visit 
011 
022 
03 
04 
05 
06 
07 
08 
09 
10 
11 
Post 
Day: 
 
D0 
D3 
D6 
D28 
D56 
D112 
D116 
D168 
D224 
D280 
 
Week: 
 
W0 
W0 
W0 
W4 
W8 
W16 
W16 
W24 
W32 
W40 
 
Procedure 
Scr 
Inf 1 
 
 
 
 
Inf 2 
Phone 
contact 
 
 
 
 
Study procedures 
 
 
 
 
 
 
 
 
 
 
 
 
Signed screening consent (if used) 
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
— 
— 
Assessment of understanding 
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
— 
— 
Signed protocol consent 
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
— 
— 
Medical history  
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
— 
— 
Complete physical exam 
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
X 
— 
Confirm eligibility, obtain demographics, randomize  
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
— 
— 
Infusion 
— 
X 
— 
— 
— 
— 
X 
 
— 
— 
— 
— 
Solicited AE assessment3 
— 
X 
 X3 
 X3 
— 
— 
X3 
X3 
X3 
— 
— 
— 
Abbreviated physical exam 
— 
X 
X 
X 
X 
X 
X 
 
X 
X 
— 
— 
Risk reduction counseling4 
X 
X 
— 
— 
X 
X 
X 
 
X 
X 
X 
— 
Contraception status assessment5 
X 
X 
— 
— 
X 
X 
X 
 
X 
X 
X 
— 
Social impact assessment 
— 
X 
— 
— 
X 
X 
X 
 
X 
X 
X 
— 
Behavioral risk assessment questionnaire6 
X 
— 
— 
— 
— 
— 
— 
 
— 
— 
X 
— 
Social impact assessment questionnaire 
— 
— 
— 
— 
— 
X 
— 
 
X 
— 
X 
— 
Acceptability questionnaire 
— 
X 
— 
— 
— 
— 
X 
 
— 
— 
— 
— 
Outside testing questionnaire 
— 
— 
— 
— 
— 
— 
— 
 
— 
— 
X 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
— 
Intercurrent illness/Unsolicited AE assessment 
— 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
— 
HIV infection assessment7 
X 
— 
— 
— 
— 
— 
X 
 
— 
X 
X 
— 
Confirm HIV test results provided to participant 
— 
X 
— 
— 
— 
— 
— 
 
X 
— 
X 
X 
Specimen collection 8 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
— 
 
 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 189 of 195 
 
Footnotes for Appendix I 
1 Screening may occur over the course of several contacts/visits up to and including day 0 prior to study product administration. 
2 Specimens collected at Day 0 may be obtained within the 14 days prior to study product administration, except for a pregnancy test, which must be performed 
on urine or blood specimens within 48 hours prior to study product administration with negative results received prior to study product administration. 
3 Solicited AE assessments are performed daily for at least 3 full days following study product administration. CRS staff will review and reconcile the diary 
with the participant and then report Solicited AEs. Participant diary reconciliation may happen as the data is available (see the HVTN 140/HPTN 101 SSP). 
For Part B participants’ second infusion solicited AE data collection: remote documentation of the participant diary may occur after the solicited AE 
assessment period and the next clinic visit (Visit 9), ideally within 2 weeks post-infusion (see the HVTN 140/HPTN 101 SSP). 
4 Includes transmission risk reduction counseling for HIV-infected participants. 
5 Contraception status assessment is required only for participants who were assigned female sex at birth and who are capable of becoming pregnant. 
6 Not applicable to HIV-infected participants. 
7 Includes pretest counseling and HIV testing. A subsequent follow-up contact is conducted to provide post-test counseling and to report results to participant. 
Not applicable for participants diagnosed with HIV infection. 
8 For specimen collection requirements, see Appendix G. 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 190 of 195 
Appendix J 
HVTN low risk guidelines for the US 
The following are intended as guidelines for the investigator to help identify potential 
vaccine trial participants at “low risk” for HIV infection. These guidelines are based on 
behaviors within the last 6-12 months prior to enrollment; however, it may be appropriate to 
consider a person’s behavior over a longer period of time than specified to assess the 
person’s likelihood of maintaining low risk behavior. Some volunteers may not be 
appropriate for enrollment even if they meet these guidelines. These guidelines should be 
supplemented and interpreted with local epidemiologic information about HIV prevalence in 
your area and community networks. The investigator may review the risk level of any 
volunteer with the site PI and/or the Protocol Safety Review Team. 
 
A volunteer may be appropriate for inclusion if he/she/they meets these guidelines: 
A. For US volunteers NOT on stable Pre-exposure prophylaxis (PrEP) 
1. SEXUAL BEHAVIORS 
In the last 12 months did not: 
• Have oral, vaginal or anal intercourse with an HIV-infected partner, or a 
partner who uses injection drugs  
• Give or receive money, drugs, gifts or services in exchange for oral, vaginal or 
anal sex 
AND 
 
In the last 6 months has abstained from penile/anal or penile/vaginal intercourse, OR 
 
In the last 6 months: 
• Had 4 or fewer partners of the opposite birth sex for vaginal and/or anal 
intercourse, OR 
 
Is an MSM (person born male with partner(s) born male) who, in the last 12 months: 
• Had 2 or fewer MSM partners for anal intercourse and had no unprotected 
anal sex with MSM, OR 
•  Had unprotected anal intercourse with only 1 MSM partner, within a 
monogamous relationship lasting at least 12 months (during which neither 
partner had any other partners). If the monogamous relationship ended, the 
volunteer may then have had protected anal intercourse with 1 other MSM 
partner (total 2 or fewer partners in the last 12 months).  
 
Is a transgender person, regardless of the point on the transition spectrum, having sex 
with men (born male) and/or other transgender persons, who in the last 12 months: 
• Had 2 or fewer partners for anal or vaginal intercourse, and had no 
unprotected anal or vaginal sex, OR  
• Had unprotected anal or vaginal intercourse sex with 1 partner only within a 
monogamous relationship lasting at least 12 months (during which neither 
partner had any other partners). If the monogamous relationship ended, may 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 191 of 195 
then have had protected anal or vaginal sex with 1 other partner (total 2 or 
fewer partners in the last 12 months). 
AND 
Uses or intends to use condoms in situations which may include penile/anal or 
penile/vaginal intercourse with new partners of unknown HIV status, occasional 
partners, 
partners outside a primary relationship, and/or partners known to have other 
partners. 
 
2. NON-SEXUAL BEHAVIORS 
In the last 12 months did not: 
• Inject drugs or other substances without a prescription 
• Use cocaine, methamphetamine, or excessive alcohol, which in the 
investigator’s judgment, rendered the participant at greater than low risk for 
acquiring HIV infection. 
The investigator’s judgment should consider local epidemiologic information 
about HIV prevalence in the area and community networks. 
A volunteer is NOT appropriate for inclusion if he/she: 
 
Acquired an STI (ie, new infection) in the last 12 months: 
 
• Syphilis  
• Gonorrhea  
• Non-gonococcal urethritis  
• Herpes Simplex Virus type 2 (HSV2)  
• Chlamydia  
• Pelvic inflammatory disease (PID)  
• Trichomonas  
• Mucopurulent cervicitis  
• Epididymitis  
• Proctitis  
• Lymphogranuloma venereum  
• Chancroid  
• Hepatitis B 
B. For US volunteers on Pre-exposure prophylaxis (PrEP) 
1. PrEP ASSESSMENT 
• Reports equal to or greater than six months of protective PrEP use 
• Commits to maintaining protective PrEP use throughout trial 
• Participant reports equal to or greater than 70% when asked the following:  
“Thinking about the past 4 weeks, what percent of the time were you able to take 
all your PrEP medications?” 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 192 of 195 
2. SEXUAL BEHAVIORS 
Persons stably taking PrEP as described above for 6 months or longer are 
considered low risk of HIV infection, regardless of any sexual behavior that might 
otherwise be associated with high risk of HIV exposure. 
 
2. NON-SEXUAL BEHAVIORS 
In the last 12 months did not: 
• Inject drugs or other substances without a prescription 
• Use cocaine, methamphetamine, or excessive alcohol, which in the 
investigator’s judgment, rendered the participant at greater than low risk for 
acquiring HIV infection. 
The investigator’s judgment should consider local epidemiologic information about 
HIV prevalence in the area and community networks. 


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HVTN140_HPTN101_ v1.0_FINAL / Page 193 of 195 
Appendix K 
HVTN low risk guidelines for Southern Africa 
 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 194 of 195 
Appendix L 
Visit windows 
Part A 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target 
Day 
Target 
Day 
Upper 
Target Day 
Upper 
Allowable 
Window  
01.0 
Screening 
-56 
- 
 
- 
- 
02.0 
Enrollment¹ 
Infusion 
- 
- 
0 
- 
- 
03.0 
3 days post infusion 
-1 
- 
3 
- 
+1 
04.0 
 
6 days post infusion 
-1 
- 
6 
- 
+2 
05.0 
4 weeks post infusion 
-7 
-3 
28 
+3 
+7 
06.0 
8 weeks post infusion 
-7 
-3 
56 
+3 
+7 
07.0 
16 weeks post infusion 
-7 
-3 
112 
+3 
+7 
08.0 
 
 
 
 
 
 
09.0 
24 weeks post infusion 
-7 
-3 
168 
+3 
+7 
Greyed-out visit does not apply to Part A. 
Part B 
Visit 
Number 
Visit Type 
Lower 
Allowable 
Window  
Lower 
Target 
Day 
Target 
Day 
Upper 
Target Day 
Upper 
Allowable 
Window  
01.0 
Screening 
-56 
- 
 
- 
- 
02.0 
Enrollment 
Infusion #1 
- 
- 
0 
- 
- 
03.0 
3 days post infusion #1 
-1 
- 
3 
- 
+1 
04.0 
 
6 days post infusion #1 
-1 
- 
6 
- 
+2 
05.0 
4 weeks post infusion #1 
-7 
-3 
28 
+3 
+7 
06.0 
8 weeks post infusion #1 
-7 
-3 
56 
+3 
+7 
07.0 
Infusion #2 
-14 
-7 
112 
+7 
+14 
08.0 
4 days post infusion #2 
- 
- 
116 
+7 
- 
09.0 
8 weeks post infusion #2 
-7 
-3 
168 
+3 
+7 
10.0 
16 weeks post infusion #2 
-7 
-3 
224 
+3 
+7 
11.0 
24 weeks post infusion #2 
-7 
-3 
280 
+3 
+7 


HVTN 140/HPTN 101 Version 1.0 / June 23, 2021 
 
HVTN140_HPTN101_ v1.0_FINAL / Page 195 of 195 
Appendix M 
Protocol Signature Page 
 
A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, and 
pharmacokinetics of PGDM1400LS alone and in combination with VRC07-
523LS and PGT121.414.LS in healthy, HIV-uninfected adult participants 
I will conduct the study in accordance with the provisions of this protocol and all 
applicable protocol-related documents. I agree to conduct this study in 
compliance with United States (U.S.) Health and Human Service regulations (45 
CFR 46); applicable U.S. Food and Drug Administration regulations; standards of 
the International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice 
(E6(R2)); 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 140/HPTN 101 
DAIDS Protocol Version: Version 1.0 
Protocol Date: June 23, 2021 
 

SAP_001.pdf: 
Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
 
Version 1.0, 16-Nov-2021 
Page 1 of 14 
 
STATISTICAL ANALYSIS PLAN  
Protocol HVTN 140/HPTN 101 
Version 1.0 
 
A phase 1 dose-escalation clinical trial to evaluate the 
safety, tolerability, and pharmacokinetics of 
PGDM1400LS alone and in combination with VRC07-
523LS and PGT121.414.LS in healthy, HIV-uninfected 
adult participants 
Date: 
Nov 16, 2021 
Version 1.0 
Prepared by 
Protocol Statisticians 
Kevin Gillespie, MS 
 
 
 
Chenchen Yu, MS  
 
 
 


Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 2 of 14 
 
Approval Signature Page 
 
HVTN 140/HPTN 101  
Statistical Analysis Plan 
 
 
 A phase 1 dose-escalation clinical trial to evaluate the safety, 
tolerability, and pharmacokinetics of PGDM1400LS alone and 
in combination with VRC07-523LS and PGT121.414.LS in 
healthy, HIV-uninfected adult participants 
 
I have read this Statistical Analysis Plan and approve its contents. 
See appended email signature 
______________________________ 
 
 
 
_____________________ 
Kevin Gillespie, MS                                                                     
Date 
Statistical Research Associate 
Fred Hutchinson Cancer Research Center, SCHARP 
 
See appended email signature 
______________________________ 
 
 
 
_____________________ 
Chenchen Yu, MS                                                                     
Date 
Statistical Research Associate 
Fred Hutchinson Cancer Research Center, SCHARP 
 
 
 
 
 
 


Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 3 of 14 
SAP Modification History 
The version history of, and modifications to, this statistical analysis plan are described below. 
 
SAP Version 
Date 
Modification 
0.0 
05 Nov 2021 
First draft concerning only the analysis of safety endpoints.  
1.0 
16 Nov 2021 
Incorporated review comments 
 
 


Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 4 of 14 
Table of Contents 
 
1 
OVERVIEW ...................................................................................................................................... 5 
2 
PROTOCOL SUMMARY ................................................................................................................. 5 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................... 7 
3.1. 
PRIMARY OBJECTIVE: .................................................................................................................. 7 
3.2. 
SECONDARY OBJECTIVE:............................................................................................................ 7 
3.3. 
EXPLORATORY OBJECTIVE: ....................................................................................................... 8 
4 
COHORT DEFINITION .................................................................................................................... 9 
5 
POTENTIAL CONFOUNDERS ....................................................................................................... 9 
6 
RANDOMIZATION ........................................................................................................................... 9 
7 
BLINDING ...................................................................................................................................... 10 
8 
STATISTICAL ANALYSIS............................................................................................................. 10 
8.1 
Analysis variables ............................................................................................................. 10 
8.2 
Analysis tools .................................................................................................................... 10 
8.3 
Baseline comparability ...................................................................................................... 10 
8.4 
Safety/tolerability analysis ................................................................................................. 11 
8.4.1 
Solicited AEs ........................................................................................................ 11 
8.4.2 
SAEs and Unsolicited AEs ................................................................................... 11 
8.4.3 
Local laboratory values ........................................................................................ 11 
8.4.4 
Reasons for study product administration discontinuation and early study 
termination ........................................................................................................... 11 
8.5 
Analyses prior to end of scheduled follow-up visits .......................................................... 12 
8.5.1 
Safety ................................................................................................................... 12 
9 
SAFETY TABLES AND FIGURES ................................................................................................ 13 
9.1 
List of Tables ..................................................................................................................... 13 
9.2 
Participant Listings ............................................................................................................ 13 
9.3 
List of Graphs .................................................................................................................... 14 
10 
REFERENCES ............................................................................................................................... 14 
 
 
 


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1 
OVERVIEW 
The following describes the Statistical Analysis Plan (SAP) for the analysis of data from HVTN 
140 for Safety Monitoring Board (SMB) reports, the Final Study Report (FSR) for Safety, 
Protocol Team (PT) reports for immunogenicity data, and the FSR for Immunogenicity. As 
detailed in SCHARP SOP-0013, Revision 5 (effective date: August 15, 2016), this SAP is 
required prior to the first analysis and must be approved by the lead protocol statistician. SMB 
reporting begins shortly after enrollment opens, and subsequent revisions are expected to describe 
analysis of immunogenicity data. The SAP will be reviewed prior to the first SMB report and 
before the final analysis with all major revisions of the plan archived.  
2 
PROTOCOL SUMMARY 
A phase 1 dose-escalation clinical trial to evaluate the safety, tolerability, and 
pharmacokinetics of PGDM1400LS alone and in combination with VRC07-523LS and 
PGT121.414.LS in healthy, HIV-uninfected adult participants 
Study Products 
• 
PGDM1400LS: a human mAb that targets the HIV-1 V2 glycan, centered on N160. It is a 
derivative of PGDM1400 that was engineered to improve in vivo elimination half-life. It 
has been developed by the Vaccine Research Program (VRP) of the National Institute of 
Allergy and Infectious Diseases (NIAID). PGDM1400LS was manufactured under 
current Good Manufacturing Practice (cGMP) standards at Just-Evotec (Seattle, 
Washington) under contract to DAIDS’s Vaccine Translational Research Branch 
(VTRB). The drug product was filled and released at the VRC Pilot Plant, operated under 
contract by Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, 
Inc., Frederick, MD. The drug product is provided at 100 mg/mL as 10 mL glass vials 
with a 4.75 mL fill volume. 
• 
PGT121. 414.LS: is a human mAb that targets the HIV-1 V3 glycan, centered on N332. 
It is a derivative of PGT121 that was engineered for improved manufacturing, stability 
and in vivo elimination half-life by Just Biotherapeutics in collaboration with Dan 
Barouch and Collaboration for AIDS Vaccine Discovery (CAVD) investigators. The drug 
substance was manufactured under cGMP standards at Just Biotherapeutics under 
contract to DAIDS’s VTRB. The drug product was filled and released by the VRC and 
VCMP, Leidos Biomedical Research, Inc., Frederick, MD. Product is provided at 100 
mg/mL as 10 mL glass vials with a 4.75 mL fill volume. 
• 
VRC-HIVMAB075-00-AB (VRC07-523LS): is a human mAb that targets the HIV-1 
CD4 binding site. It was developed by the VRC/NIAID/NIH and manufactured under 
cGMP standards at the VRC Pilot Plant operated under contract by the VCMP, Leidos 
Biomedical Research, Inc., Frederick, MD. Product is provided at 100 ± 10 mg/mL as 10 
mL glass vials with a 6.25 ± 0.1 mL fill volume and 3 mL glass vials with a 2.25 mL ± 
0.1 mL fill volume. 
Participants  
• 
About 95 healthy, HIV-1–uninfected volunteers aged 18 through 50 years 
 


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Version 1.0, 16-Nov-2021 
Page 6 of 14 
  
Study arm  
N*  
Dose  
Route  
Month 0  
Month 4  
Part A  
Group 1  
3  
5 mg/kg  
IV  
PGDM1400
LS  
-  
Group 21  
3  
20 mg/kg  
IV  
PGDM1400
LS  
-  
Group 31  
3  
20 mg/kg  
SC  
PGDM1400
LS  
-  
Group 42  
3  
40 mg/kg  
IV  
PGDM1400
LS  
-  
Group 52  
3  
40 mg/kg  
SC  
PGDM1400
LS  
-  
Part B**  
Group 63  
16  
20 mg/kg +  
20 mg/kg +  
20 mg/kg  
IV  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
Group 73  
16  
20 mg/kg +  
20 mg/kg +  
20 mg/kg  
SC  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
Group 83  
16  
1.4 g +  
1.4 g +  
1.4 g  
IV  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
Group 93  
16  
1.4 g +  
1.4 g +  
1.4 g  
SC  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
Group 104  
16  
40 mg/kg +  
40 mg/kg +  
40 mg/kg  
IV  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
PGDM1400
LS + 
VRC07-
523LS + 
PGT121.414.
LS  
Total  
95  
IV = intravenous infusion; SC = subcutaneous infusion; *additional participants may be enrolled to ensure the 
availability of safety data from at least 3 participants in each group;**antibodies will be administered sequentially as 
3 separate infusions; + sign = “and”.  
1Opening enrollment in Groups 2 & 3 follows review of safety data for participants in Group 1. Details are described 
in Section 11.3.1.  
2Opening enrollment in Group 4 & 5 follows review of safety data for participants in Groups 1- 3.  
3Opening enrollment in Groups 6, 7, 8, and 9 follows review of safety data for participants in Part A.  
4Opening enrollment in Group 10 follows review of safety data for participants from Groups 1-9. 


Protocol HVTN 140/HPTN 101 
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Page 7 of 14 
3 
OBJECTIVES AND ENDPOINTS 
3.1. Primary objective: 
Primary objective 1: 
To evaluate the safety and tolerability of PGDM1400LS when administered via intravenous 
(IV) or subcutaneous (SC) routes (Part A) and of PGDM1400LS, VRC07-523LS and 
PGT121.414.LS when administered in sequence IV or SC (Part B) 
Primary endpoints 1: 
• 
Local and systemic Solicited AEs, laboratory measures of safety, Unsolicited AEs, 
and SAEs 
• 
Early discontinuation of administration and reason(s) for discontinuation and early 
study termination 
Primary objective 2: 
To evaluate the serum concentrations and pharmacokinetics of PGDM1400LS after a single 
administration (Part A) and of PGDM1400LS, VRC07-523LS, and PGT121.414.LS after 
each three-mAb administration (Part B) 
Primary endpoint 2: 
Serum concentrations of PGDM1400LS, VRC07-523LS and PGT121.414.LS at prespecified 
timepoints among participants who received all scheduled product administrations 
Primary objective 3: 
To evaluate the individual mAb-specific serum neutralizing activity after single product 
administration of PGDM1400LS (Part A) and after each three-mAb administration of 
PGDM1400LS, VRC07-523LS and PGT121.414.LS (Part B) 
Primary endpoint 3: 
Magnitude and breadth of neutralizing activity measured with Env pseudotyped viruses 
specific for either PGDM1400LS, VRC07-523LS or PGT121.414LS in TZM-bl cells at 
prespecified timepoints among participants who received all scheduled product 
administrations 
3.2. Secondary objective: 
Secondary objective 1: 
To correlate serum concentrations of PGDM1400LS, VRC07-523LS and PGT121.414.LS 
with corresponding virus neutralization titers in serum 
Secondary endpoints 1: 


Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 8 of 14 
• 
Serum concentrations of PGDM1400LS, VRC07-523LS and PGT121.414.LS at 
prespecified timepoints for all participants in all groups regardless of how many 
product administrations and how much product they received 
• 
Magnitude of serum neutralizing activity measured with mAb-specific Env-
pseudotyped viruses in TZM-bl cells at prespecified timepoints for all participants in 
all groups regardless of how many product administrations and how much product 
they received 
Secondary objective 2: 
To determine whether the mAbs maintain their expected combined magnitude and breadth of 
serum neutralizing activity after each PGDM1400LS, VRC07-523LS and PGT121.414.LS 
three-mAb administration (Part B) as predicted by the known magnitude and breadth of 
neutralization of the corresponding mAb combinations as non-infused clinical products 
Secondary endpoint 2: 
Magnitude of neutralizing activity against a panel of Env-pseudotyped reference viruses that 
are sensitive to all three bnAbs in TZM-bl cells at selected timepoints for all participants in 
all groups regardless of how many product administrations and how much product they 
received 
Secondary objective 3: 
To determine whether anti-drug antibodies (ADA) are present 
Secondary endpoint 3: 
ADA titers in each group measured at prespecified timepoints for all participants in all groups 
regardless of how many product administrations and how much product they received 
Secondary objective 4: 
To evaluate the impact of body weight and other baseline covariates on the pharmacokinetics 
of PGDM1400LS, VRC07-523LS and PGT121.414.LS in both the weight-based and fixed-
dose groups. 
Secondary endpoint 4: 
Serum concentrations of PGDM1400LS, VRC07-523LS and PGT121.414.LS at prespecified 
timepoints 
3.3. Exploratory objective: 
 Exploratory objective 1: 
To determine whether any confirmed positive ADA samples have functional activity that impacts 
the neutralizing activity of PGDM1400LS, VRC07-523LS and PGT121.414.LS 
Exploratory objective 2: 


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Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 9 of 14 
To further evaluate non-neutralizing anti-viral activities, additional assays (eg, ADCC, ADCP, 
virion capture) may be performed for activities that the PGDM1400LS, VRC07-523LS and 
PGT121.414.LS are shown to exhibit in vitro 
Exploratory objective 3: 
To conduct analyses related to predicting serum neutralization over time against a set of 
potentially exposing viruses in a future efficacy trial for ranking and down-selecting bnAb 
regimens 
Exploratory objective 4: 
To conduct analyses related to furthering the understanding of HIV, passive immunity, 
immunology, vaccines, and clinical trial conduct. 
 
 
4 
COHORT DEFINITION 
Participants  
About 95 healthy, HIV-1–uninfected volunteers aged 18 through 50 years  
Design  
Multicenter, randomized, open-label study  
Duration per participant  
6 months per participant in Part A and 10 months per participant in Part B of scheduled clinic 
visits  
Estimated total study duration  
14 months (includes enrollment, planned safety holds, and follow-up) 
5 
POTENTIAL CONFOUNDERS 
Characterization of the safety of the vaccine is susceptible to confounding by adverse events not 
related to the vaccine that by chance occur more often in one arm of the trial than another. 
Therefore analyses involving adverse events will incorporate the reported relationship to product 
as assessed by HVTN staff. 
6 
RANDOMIZATION 
There will be no randomization for Group 1 as they will be enrolled first. Contingent on safety 
data from Group 1, Groups 2 and 3 will be randomized and enrolled simultaneously. Contingent 
on safety data from Groups 2 and 3, Groups 4 and 5 will be randomized and enrolled 
simultaneously. Contingent on data from Part A, Groups 6, 7, 8, and 9 will be randomized in 
blocks to ensure balance across groups for simultaneous enrollment. There will be no 
randomization for Group 10. A participant’s randomization assignment will be computer 
generated and provided to the CRS pharmacist through a web-based randomization system. 


Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 10 of 14 
7 
BLINDING 
Participants and CRS staff will be unblinded to participant treatment arm assignments. 
Laboratory Center staff will be unblinded to whether a sample is from Part A or Part B, but 
will remain blinded to treatment assignment within Part A or Part B during sample analysis. 
8 
STATISTICAL ANALYSIS 
All safety data from enrolled participants will be analyzed according to the initial randomization 
assignment regardless of how many study product administrations and how much study product 
they received. Analyses of safety data are modified intent-to-treat (MITT) in that individuals who 
are randomized but not enrolled do not contribute data and hence are excluded. Because of the 
brief length of time between randomization and enrollment—typically no more than 4 working 
days—very few such individuals are expected.  
The primary analysis of mAb concentration and anti-viral functional activity data are per-protocol 
(PP) in that only individuals who receive the expected mAb at the expected dose level within the 
expected visit window contribute data. Secondary analysis will also involve the MITT cohort, and 
when necessary account for the actual specimen collection time, and the actual time and dose 
amount of each product administration. 
Analyses for primary endpoints will be performed using SAS and R. Additional software may be 
used to perform non-compartmental PK and population PK analyses (eg, Monolix). All other 
descriptive and inferential statistical analyses will be performed using SAS, StatXact, or R 
statistical software. 
No formal multiple comparison adjustments will be employed for multiple primary or secondary 
endpoints. However, multiplicity adjustments will be made for certain primary or secondary 
endpoint assays, as discussed below, when the assay endpoint is viewed as a collection of 
hypotheses (eg, testing multiple pseudo-viruses to determine a positive antiviral functional 
activity response). Unless otherwise noted, all statistical tests will be 2-sided and will be 
considered statistically significant if p < 0.05. 
8.1 
Analysis variables 
The analysis variables consist of baseline participant characteristics, safety, mAb concentration, 
mAb functionality, and ADA for primary- and secondary-objective analyses. 
8.2 
Analysis tools 
Analyses for primary endpoints will be performed in SAS (v9.4). All other descriptive and 
inferential statistical analyses will be performed using SAS, Monolix, and/or R statistical 
software. 
8.3 
Baseline comparability  
Treatment arms will be compared for baseline participant characteristics using descriptive 
statistics. 


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Version 1.0, 16-Nov-2021 
Page 11 of 14 
8.4 
Safety/tolerability analysis 
Since enrollment is concurrent with receiving the first study product administration, all 
participants will have received at least 1 product administration and therefore will provide some 
safety data. 
8.4.1 
Solicited AEs  
The number and percentage of participants experiencing each type of Solicited AE sign or 
symptom (see Section 11.2.2) will be tabulated by severity and treatment arm and the 
percentages displayed graphically by arm. For a given sign or symptom, each participant’s 
Solicited AEs will be counted once under the maximum severity for all 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. Kruskal-Wallis tests 
will be used to test for differences in severity between arms. 
8.4.2 
SAEs and Unsolicited AEs 
Unsolicited AEs (see Section 11.2.2) will be summarized using MedDRA System Organ Class 
and preferred terms. Tables will show by treatment arm the number and percentage of 
participants experiencing an Unsolicited AE within a System Organ Class or within preferred 
term category by severity or by relationship to study product. For the calculations in these tables, 
a participant with multiple Unsolicited AEs within a category will be counted once under the 
maximum severity or the strongest recorded causal relationship to study product. Formal 
statistical testing comparing arms is not planned since interpretation of differences must rely 
heavily upon clinical judgment. 
A listing of SAEs reported to the DAIDS Regulatory Support Center (RSC) Safety Office will 
provide details of the events including severity, relationship to study product, time between onset 
and last study product administration, and number of study product administrations received. 
8.4.3 
Local laboratory values 
Box plots of local laboratory values will be generated for baseline values and for values measured 
during the course of the study by treatment arm and visit. Each box plot will show the first 
quartile, the median, and the third quartile. Outliers (values outside the box plot) will also be 
plotted. If appropriate, horizontal lines representing boundaries for abnormal values will be 
plotted. 
For each local laboratory measure, summary statistics will be presented by treatment arm and 
timepoint, as well as changes from baseline for postenrollment values. In addition, the number 
(percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria 
or above as specified in the Division of AIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events (see Section 9.8) will be tabulated by treatment arm for each poststudy 
product administration timepoint. Reportable clinical laboratory abnormalities without an 
associated clinical diagnosis will also be included in the tabulation of AEs described above. 
8.4.4 
Reasons for study product administration discontinuation and early study termination 
The number and percentage of participants who discontinue study product administration and 
who terminate the study early will be tabulated by reason and treatment arm. 


Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 12 of 14 
8.5 
Analyses prior to end of scheduled follow-up visits 
Any analyses conducted prior to the end of the scheduled follow-up visits should not compromise 
the integrity of the trial in terms of participant retention or other study endpoint assessments. 
8.5.1 
Safety 
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 140/HPTN 101 PSRT. 


Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 13 of 14 
9 
SAFETY TABLES AND FIGURES 
9.1 
List of Tables 
• 
Enrollment Report 
• 
Demographics and Study Product Administration Frequencies 
• 
Overall Protocol Status 
• 
Discontinuation Status 
• 
Study Product Administration Errors 
• 
Maximum Local and Systemic Solicited AE Summaries 
• 
Severe or Life-threatening Local Solicited AE's 
• 
Moderate, Severe, and Life-threatening Erythema / Induration 
• 
Adverse Experiences by Body System and Severity – By Decreasing Frequency 
• 
Adverse Experiences by Preferred Term and Severity – By Decreasing Frequency – Includes 
Severe, Life-threatening or Fatal Events Only 
• 
Adverse Experiences by Preferred Term and Severity – By Decreasing Frequency – Includes 
Events of All Severities 
• 
Adverse Experiences by Preferred Term and Relationship to Study Product – By Decreasing 
Frequency – Includes Related Events Only 
• 
Adverse Experiences by Preferred Term and Relationship to Study Product – By Decreasing 
Frequency – Includes Events of Any Relationship 
• 
Severe, Life-Threatening, or Fatal Adverse Events  
• 
Related Events 
 
9.2 
Participant Listings 
The following listings of participant-level data are included in the SMB reports. 
• 
Discontinuations 
• 
Pregnancies 
• 
Severe or Life-Threatening Local and Systemic Solicited AEs 
• 
Moderate or Severe Erythema and Induration 
• 
Expedited Adverse Experiences (EAEs)  
• 
Severe, Life-Threatening, or Fatal Adverse Experiences 
• 
Adverse Experiences with Relationship to Study Product (Grade 2 or higher)  
• 
Study Product Administration Errors 
• 
HIV Infection Results from Lab and Reported by Site 
• 
mAb Reactions 
 


Protocol HVTN 140/HPTN 101 
Statistical Analysis Plan 
Version 1.0, 16-Nov-2021 
Page 14 of 14 
9.3 
List of Graphs 
• 
Maximum Local Solicited AEs 
• 
Maximum Systemic Solicited AEs  
• 
Boxplots for Alkaline Phosphatase, AST, ALT, Creatinine, WBC, Hemoglobin, Platelets, 
Lymphocyte Count, Neutrophil Count 
10 REFERENCES 
1. Agresti A, Coull BA. Approximate is better than "exact" for interval estimation of binomial     
proportions. Am Stat 1998;52:119-26.