A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of HIV-1 Vaccines Based on Chimpanzee Serotypes of Adenovirus Expressing Clade C gp140 and a CH505TF gp120 Protein Boost in Healthy, HIV- Uninfected Adult Participants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: HIV Vaccine Trials Network

FINAL 
November 16, 2022 
Letter of Amendment 2 
Protocol 
Version 1.0 
HVTN 139 
A phase 1 clinical trial to evaluate the safety and 
immunogenicity of HIV-1 vaccines based on chimpanzee 
serotypes of adenovirus expressing clade C gp140 and a 
CH505TF gp120 protein boost in healthy, HIV- uninfected 
adult participants 
DAIDS-ES ID 12052 
A non-IND study 
HIV Vaccine Trials Network (HVTN) Clinical Research Site (CRS) filing 
instructions 
The following information impacts the HVTN 139 study and must be forwarded to your 
Institutional Review Board (IRB)/Ethics Committee (EC) and any other applicable Regulatory 
Entity (RE) as soon as possible for their information and review. Their approval is required 
before implementation. 
Upon receiving final IRB/EC and any other RE approval(s) for this Letter of Amendment 
(LOA), CRSs must implement the LOA immediately. 

Protocol HVTN 139 Version 1.0 
Final Letter of Amendment 2 
November 16, 2022 
HVTN139_v1.0_LOA2_Final 
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Upon receiving final IRB/EC and any other applicable RE approval(s), CRSs are required to 
submit LOA registration documents to the DAIDS Protocol Registration Office (PRO) at the 
Regulatory Support Center (RSC). CRSs will receive an LOA Registration Notification once the 
DAIDS PRO verifies that all the required LOA registration documents have been received and 
are complete. A Registration Notification from the DAIDS PRO is not required prior to 
implementing the LOA. A copy of the LOA Registration Notification, along with this LOA and 
any IRB/EC and RE correspondence, should be retained in the CRS’s regulatory files. 
For additional information on the registration process and specific documents required for LOA 
registration, refer to the current version of the DAIDS Protocol Registration Manual. 
The following information does not affect the sample informed consent. The CRS’s IRB/EC is 
responsible for determining the process of informing study participants of the contents of this 
LOA. 
List of changes 
Item 1 
Revised in Section 5, Objectives and endpoints: secondary objective 4 moved to 
exploratory objective 5 ............................................................................................... 2 
Item 2 
Updated in Section 1.1, Protocol Team: Team membership, contact information, 
and roles ...................................................................................................................... 3 
 
The changes described herein will be incorporated in the next version of Protocol HVTN 139 if it 
undergoes full protocol amendment at a later time. Added text is shown in bold underline and 
deleted text is shown with strikethrough. 
Item 1 
Revised in Section 5, Objectives and endpoints: secondary objective 4 
moved to exploratory objective 5 
The secondary objective 4 has been moved to exploratory objective 5 since the assay 
data is not being used for clinical management of the participant. It will be used for 
research purposes only. Results may be used to identify pre-existing immunity that 
may interfere with other key immunology assessments. 
Tracked revised text in section 5.2: Secondary objectives and endpoints 
Secondary objective 4: 
To evaluate vector-specific antibodies both before and after vaccination.  
Secondary endpoint 4: 
Magnitude of serum antibody neutralization of AdC6 and AdC7 vectors as assessed 
by adenovirus neutralization assay at baseline (Parts A and B), 4 weeks after the first 
vaccination (Parts A and B), and 4 weeks after the second vaccination (Part B) 

Protocol HVTN 139 Version 1.0 
Final Letter of Amendment 2 
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Tracked revised text in section 5.3: Exploratory objectives 
Exploratory objective 5: 
To assess the magnitude of serum antibody neutralization of AdC6 and AdC7 
vector both before and after vaccination.  
Item 2 
Updated in Section 1.1, Protocol Team: Team membership, contact 
information, and roles 
The Protocol Team list has been updated in Section 1.1, Protocol Team. Tracked 
revised text is shown below. Updated protocol team list is appended.   
Tracked revised text under Protocol leadership: 
 
Protocol Team leader 
 
William Hahn Manuel 
Villaran 
HVTN LOC, Fred Hutch 
206-667-3431 206-667-6757 
whahn@fredhutch.org 
mvillar2@fredhutch.org 
 
Tracked revised text under other contributors to the original protocol: 
 
LOC medical monitor 
William Hahn Manuel 
Villaran  
HVTN LOC, Fred Hutch 
206-667-3431 206-667-6757 
whahn@fredhutch.org 
mvillar2@fredhutch.org 
 
Clinical trials manager 
Julie HuntTaylor Jones-Bradford 
Nelisiwe Xaba  
Michelle Nebergall 
HVTN LOC, Fred Hutch 
Clinical data manager 
Andrea Repetto, Bhavesha O’Byrne 
HVTN SDMC, Fred Hutch 
 
Statistical research 
associate 
 
 
Hua Zheng Xue Han 
HVTN SDMC, Fred Hutch 
Laboratory Center 
Representative  
Lisa Sanders Jen Hanke 
HVTN Laboratory Center,  
Fred Hutch 
  
Associate Director of 
Regulatory affairs 
associate 
Megan Brandon 
HVTN LOC, Fred Hutch 
  
Protocol development 
managers 
Rufi Dalvi  
Kajari Mondal 
Daciana Margineantu  
HVTN LOC, Fred Hutch 
Project coordinator 
Anders McConachie 
Haven Wilvich 
HVTN LOC, Fred Hutch 

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1.1 
Protocol Team 
Protocol leadership 
Chair 
Ameena Goga 
HIV Prevention Research Unit, 
South African Medical Research 
Council 
Ameena.Goga@mrc.ac.za 
+2712 339 8524 
+2782 302 3168 
Statistician 
Youyi Fong 
HVTN SDMC, Fred Hutch 
206-667-1093 
yfong@fredhutch.org 
Co-chair 
Steven Innes  
Emavundleni Research Centre 
+27 21 650 5851 
+27 74 764 5253 
Steven.Innes@hiv-research.org.za 
DAIDS Medical 
officer 
Edith Swann 
DAIDS, NIAID 
240-627-3035 
301-332-6435-BB 
swanne@niaid.nih.gov  
Protocol Team leader 
Manuel Villaran 
HVTN LOC, Fred Hutch 
206-667-6757 
mvillar2@fredhutch.org 
Laboratory lead 
Stephen De Rosa 
HVTN Laboratory Center 
206-667-1681 
sderosa@fredhutch.org 
Other contributors to the original protocol 
LOC medical monitor 
Manuel Villaran 
HVTN LOC, Fred Hutch 
206-667-6757 
mvillar2@fredhutch.org 
DAIDS Product Lead 
Michael Pensiero 
DAIDS, NIAID 
301-435-3749 
mpensiero@niaid.nih.gov 
Study product 
developer 
representatives 
Hildegund Ertl 
Wistar Institute Vaccine and 
Immunotherapy Center 
Emmanuel (Chip) Walter 
Duke Human Vaccine Institute 
Zachary Sagawa 
Infectious Disease Research 
Institute 
DAIDS protocol 
pharmacist 
Oladapo Alli 
DAIDS, NIAID 
240-627-3593 
SDMC Associate 
director of lab science 
April Randhawa 
HVTN SDMC, Fred Hutch 
Laboratory Center 
Representative 
Jen Hanke 
HVTN Laboratory Center,  
Fred Hutch 
Clinical trials manager 
Taylor Jones-Bradford 
Nelisiwe Xaba  
Michelle Nebergall 
HVTN LOC, Fred Hutch 
Associate Director of 
Regulatory affairs  
Megan Brandon 
HVTN LOC, Fred Hutch 
Clinical safety specialist 
Maija Anderson 
HVTN LOC, Fred Hutch 
 
Community engagement 
unit representative 
Baepanye Kagisho 
HVTN LOC, Fred Hutch 
Regional Medical Liaison 
Azwi Takalani 
HVTN LOC, Fred Hutch 
Community 
educator/recruiter 
Mduduzi Ngubane 
Isipingo South African Medical 
Research Council  
Clinic coordinator 
Brodie Daniels 
Isipingo South African Medical 
Research Council  
Community Advisory 
Board (CAB) member 
Sphelelo Mqadi 
Isipingo South African Medical 
Research Council  
Clinical data manager 
Andrea Repetto,  
HVTN SDMC, Fred Hutch 
 
Protocol development 
managers 
Rufi Dalvi 
Kajari Mondal 
HVTN LOC, Fred Hutch 
Statistical research 
associate 
Xue Han 
HVTN SDMC, Fred Hutch 
Project coordinator 
Anders McConachie 
HVTN LOC, Fred Hutch 

Protocol HVTN 139 Version 1.0 
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Protocol modification history 
Protocol modifications are made to HVTN protocols via clarification memos, letters of 
amendment, or full protocol amendments. HVTN protocols are modified and distributed 
according to the standard HVTN procedures as described in the HVTN Manual of Operations 
(MOP). 
The version history of, and modifications to, Protocol HVTN 139 are described below. 
Date: November 16, 2022 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 2 
Item 1 
Revised in Section 5, Objectives and endpoints: secondary objective 4 moved to 
exploratory objective 5 
Item 2 
Updated in Section 1.1, Protocol Team: Team membership, contact information, 
and roles 
Date: May 19, 2022 
Protocol version: Version 1.0 
Protocol modification: Clarification Memo 2 
Item 1 
Updated in Appendix H, Laboratory procedures Part B; Appendix J, 
Procedures at HVTN CRS for Part B; and Appendix L, HVTN 139 Visit 
Windows for Part B: visit numbers for Part B 
Date: March 07, 2022 
Protocol version: Version 1.0 
Protocol modification: Clarification Memo 1 
Item 1 
Updated in Section 8.3.1, AdC6-HIVgp140; Section 8.3.2, AdC7-HIVgp140; and 
8.3.4, Placebo for AdC6-HIVgp140 and AdC7-HIVgp140: label of study 
products 
Date: June 15, 2021 
Protocol version: Version 1.0 
Protocol modification: Letter of Amendment 1 
Item 1 
Revised in Section 4.10.1, Clinical studies of Chimpanzee Ad vectors targeting 
diverse pathogens, Section 4.11, Potential risks of study products and 
administration, Appendices A and B, Sample Informed Consent Form for Part A 
and Part B (section 4), and Appendix N, Adverse events of special interest: risks 
of AdC6 and AdC7 study products 
Item 2 
Revised in Appendix A, Sample Informed Consent Form for Part A, Sections 4 
and 17: study product developer information 

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Final Letter of Amendment 2 
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Item 3 
Revised in Appendix B, Sample Informed Consent Form for Part B, Section 4: 
study product developer information 
Item 4 
Revised Section 1.1, Protocol Team, Protocol Team Leadership: Co-Chair and 
member contact information 
Item 5 
Clarified in Section 9, Clinic Procedures: procedures for data entry into the 
study database and reference to the HVTN HIV testing algorithm 
Item 6 
Clarified in Section 12, Protocol conduct: protocol monitoring 
Item 7 
Updated Section 14, Document references (other than literature citations): the 
URL for requirements for source documentation 
Date: February 23, 2021 
Protocol version: Version 1.0 
Protocol modification: N/A 
Original protocol 
 
 

Protocol HVTN 139 Version 1.0 
Final Letter of Amendment 2 
November 16, 2022 
HVTN139_v1.0_LOA2_Final 
Page 7 of 7 
Protocol signature page 
A phase 1 clinical trial to evaluate the safety and immunogenicity of HIV-1 vaccines based on 
chimpanzee serotypes of adenovirus expressing clade C gp140 and a CH505TF gp120 protein 
boost 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 (US) 
Health and Human Service regulations (45 CFR 46); applicable US Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (eg, US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
 
 
 
 
Investigator of Record Name (print) 
 
Investigator of Record Signature 
 
Date 
 
 
DAIDS Protocol Number: HVTN 139 
DAIDS Protocol Version: Version 1.0 
Protocol Date: February 23, 2021