Open-Label, Dose-Escalating, Phase I Study to Determine Safety and Pharmacokinetic Parameters of Subcutaneous (SC) VRC01, VRC01LS, and VRC07-523LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
 
 
 
P1112 
Open-Label, Dose-Escalating, Phase I Study 
to Determine Safety and Pharmacokinetic 
Parameters of Subcutaneous (SC) VRC01, 
VRC01LS, and VRC07-523LS, Potent Anti-HIV 
Neutralizing Monoclonal Antibodies, in HIV-1-
Exposed Infants 
 
DAIDS Study ID #11903 
 
 
 
This file contains the current IMPAACT P1112 protocol, 
which is composed of the following documents, 
presented in reverse chronological order: 
 
• Letter of Amendment #1, dated 10 June 2020 
• Clarification Memorandum #1, dated 31 March 2020 
• Protocol Version V4.0, dated 06 November 2018 
 

Letter of Amendment #1 
Page 1 of 7 
10 June 2020 
IMPAACT P1112 Protocol Version 4.0 
Letter of Amendment #1 for: 
 
IMPAACT P1112 
Open-Label, Dose-Escalating, Phase I Study to Determine Safety  
and Pharmacokinetic Parameters of Subcutaneous (SC) VRC01, VRC01LS,  
and VRC07-523LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies,  
in HIV-1-Exposed Infants 
 
Version 4.0, dated 6 November 2018 
 
DAIDS Study ID #11903 
IND #113,611 
 
Letter of Amendment Date: 10 June 2020 
 
 
Table of Contents 
 
Information/Instructions to Study Sites from the Division of AIDS ............................................................ 1 
Letter of Amendment Signature Page ........................................................................................................... 2 
Summary of Modifications and Rationale .................................................................................................... 3 
Implementation ............................................................................................................................................. 3 
A. Updates of Protocol Team Roster  .................................................................................................... 3 
B. 
Operational Guidance from Protocol CM #1, dated 31 March 2020 ................................................ 5 
 
 
Information/Instructions to Study Sites from the Division of AIDS 
 
The information contained in this Letter of Amendment (LoA) affects the IMPAACT P1112 study and 
must be submitted to site Institutional Review Boards and/or Ethics Committees (IRBs/ECs) as soon as 
possible for their review and approval. Approval must also be obtained from other site regulatory entities 
if applicable per the policies and procedures of the regulatory entities. All applicable IRB/EC and 
regulatory entity requirements must be followed. 
 
Upon obtaining all required IRB/EC approvals and any other applicable regulatory entity approvals, each 
site should immediately begin implementing this LoA. Sites are required to submit an LoA registration 
packet to the DAIDS Protocol Registration Office (DAIDS PRO) at the Regulatory Support Center. Sites 
will receive a registration notification for the LoA after the DAIDS PRO verifies that all required 
registration documents have been received and are complete. Sites should not await this notification 
before implementing this LoA.  
 
Please file this LoA, all associated IRB/EC and regulatory entity correspondence, and all correspondence 
with the DAIDS PRO in your essential document files for IMPAACT P1112. If the IMPAACT P1112 
protocol is amended in the future, applicable contents of this LoA will be incorporated into the next 
version of the protocol. 
 
 

Letter of Amendment #1 
Page 2 of 7 
10 June 2020 
IMPAACT P1112 Protocol Version 4.0 
IMPAACT P1112 
Open-Label, Dose-Escalating, Phase I Study to Determine Safety  
and Pharmacokinetic Parameters of Subcutaneous (SC) VRC01, VRC01LS,  
and VRC07-523LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies,  
in HIV-1-Exposed Infants 
 
DAIDS Study ID #11903 
 
 
Version 4.0, Letter of Amendment #1 
Letter of Amendment Signature Page 
 
 
I will conduct this 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 Council 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 (e.g., US National Institutes of Health, Division 
of AIDS) and institutional policies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator of Record 
  
 
Date 
 
 
 
 
 
 
 
 
 
 
Name of Investigator of Record  
 
(printed) 
 
 

Letter of Amendment #1 
Page 3 of 7 
10 June 2020 
IMPAACT P1112 Protocol Version 4.0 
Summary of Modifications and Rationale 
 
This LoA updates the protocol team roster and incorporates the contents of protocol Clarification 
Memorandum (CM) #1.  
  
Section A of this LoA includes the protocol team roster updates.  
 
Section B of this LoA incorporates the contents of CM #1, which was issued on 31 March 2020 to 
safeguard the health and well-being of study participants in the context of circulating SARS-CoV-2 and 
the associated COVID-19 pandemic. CM #1 provided operational flexibility for conducting study visits 
and procedures when needed to ensure, when possible, completion of protocol-specified study product 
dosing for participants in Dose Group 5 Cohort 2 and, for all participants, to prioritize the conduct of 
clinically and scientifically important evaluations, particularly those evaluations planned to be conducted 
within 24 weeks of the last dose of study drug and at Week 96. Consistent with the instructions provided 
in CM #1, implementation of Section B of this LoA is expected to be time-limited in relation to the 
COVID-19 pandemic. In consultation with IMPAACT Network leadership and the study Sponsor, the 
IMPAACT P1112 Protocol Team will determine when, in the future, the guidance in Section B is no 
longer applicable. When such a determination is made, study sites will be formally notified and instructed 
to inform IRBs/ECs and other applicable regulatory entities. 
 
Implementation 
 
Updates of the protocol team roster are shown in Section A of this LoA, using strikethrough for deletions 
and bold type for additions where applicable. Operational guidance for conducting study visits and 
procedures during the COVID-19 pandemic is provided in Section B of this LoA; conventions for use of 
strikethrough and bolding do not apply in this section. 
 
A. Updates of Protocol Team Roster  
 
To reflect current membership, the protocol title page and protocol team roster are updated as follows:  
 
Protocol Title Page 
 
NIAID Medical Officers: 
Mary Elizabeth Smith, MD 
 
 
 
 
Dwight Yin, MD, MPH 
 
NICHD Medical Officer: 
Rohan Hazra, MD Sai Majji, PhD 
 
Clinical Trials Specialists:  
Charlotte Perlowski, MSPH 
 
 
 
 
Patricia Morgan, MS, PA Emily Brown, MA 
 

Letter of Amendment #1 
Page 4 of 7 
10 June 2020 
IMPAACT P1112 Protocol Version 4.0 
Protocol Team Roster 
 
NIAID Medical Officers 
Dwight Yin, MD, MPH 
Maternal Adolescent and Pediatric Research 
Branch, Prevention Sciences Program 
DAIDS/NIAID/NIH 
5601 Fishers Lane, Room 8B37, MSC 9831 
Rockville, MD 20852 
Phone: (240) 292-4791 
Email: dwight.yin@nih.gov  
 
NICHD Medical Officer 
Rohan Hazra, MD  
Chief, Maternal and Pediatric Infectious Disease 
Branch 
Eunice Kennedy Shriver National Institute of 
Child Health and Human Development  
6710B Rockledge Drive, Room 2113, MSC 7002 
Bethesda, MD 20817 
Phone: (301) 435-6868  
Email: hazrar@mail.nih.gov 
Sai Majji, PhD 
Maternal and Pediatric Infectious Disease 
Branch 
Eunice Kennedy Shriver National Institute of 
Child Health and Human Development 
6710B Rockledge Drive Room 2159C 
Bethesda, MD 20817 
Phone: 301-402-8048 
Email: sai.majji@nih.gov 
 
Clinical Trials Specialists 
Charlotte Perlowski, MSPH 
FHI 360 
359 Blackwell St., Suite 200 
Durham, NC 22701 USA 27701 
Phone: (919) 544-7040 x11480 
Email: cperlowski@fhi360.org 
 
Patricia Morgan, MS, PA 
FHI 360 
359 Blackwell St 
Durham, NC 27701, USA 
Phone: (919) 475-3131 
E-mail: pmorgan@fhi360.org 
Emily Brown, MA 
FHI 360 
359 Blackwell St., Suite 200 
Durham, NC 27701 
Phone: (919) 544-7040 x11123 
Email: embrown@fhi360.org  
 
Protocol Statisticians 
Petronella Muresan, MS 
Center for Biostatistics in AIDS Research 
(CBAR) 
Harvard T.H. Chan School of Public Health 
Statistical and Data Management Center 
(SDMC) 
Frontier Science Foundation 
1371 Beacon Street, Suite #203 
Brookline, MA 02446 
Phone: (617) 632-2000, ext. 4031 
E-mail: petronm@sdac.harvard.edu 
 
Protocol Data Managers 
Bonnie Zimmer 
Frontier Science and Technology Research 
Foundation, Inc. 
4033 Maple Road 
Amherst, NY 14226-1056 
Phone: (716) 834-0900 x 7260 
Fax: (716) 834-8432 
E-mail: zimmer@fstrf.org 
Bobbie Graham 
Frontier Science Foundation 
Amherst, NY 14226-1056 
Phone: (716) 834-0900 x7265 
Fax: (716) 834-8432 
Email: graham@frontierscience.org 
 
Benjamin Johnston 
Frontier Science and Technology Research 
Foundation, Inc. Frontier Science Foundation 
4033 Maple Road  
Amherst, NY 14226-1056 
Phone: (716) 834-0900 x 7407 
Fax: (716) 834-8432 
Email: johnston@fstrf.org 
johnston@frontierscience.org 
 

Letter of Amendment #1 
Page 5 of 7 
10 June 2020 
IMPAACT P1112 Protocol Version 4.0 
Laboratory Center Representatives 
Dale Dayton, RN, CCRA 
University of California Los Angeles 
MacDonald Research Laboratories 
675 Charles E. Young Drive South 
Los Angeles, CA 90095 
Phone: 301-742-9077 
ddayton@impaactlabcenter.org  
 
Laboratory Data Coordinator Manager 
Frederic Bone 
Frontier Science and Technology Research 
Foundation, Inc. Frontier Science Foundation 
4033 Maple Rd.  
Amherst, NY 14226-1056 
Phone: (716) 834-0900 x 7407 7306 
Fax: (716) 834-8432 
E-mail: bone@fstrf.org 
bone@frontierscience.org 
 
IMPAACT Community Program Associate 
Jonathan Lucas, MPH 
FHI 360 
359 Blackwell St., Suite 200 
Durham, NC 27701 
Phone: (919) 544-7040 x11458 
Email: jlucas@fhi360.org 
IMPAACT Community Advisory Board 
(ICAB) Representative 
Maximina Jokonya 
Africaid, Zvandiri 
12 Stone Ridge Way 
Avondale, Harare, Zimbabwe 
Phone: +263 773 583 629 
Email: maxminaj@gmail.com 
 
B. Operational Guidance from Protocol CM #1, dated 31 March 2020 
 
This CM provides operational guidance to study sites from the IMPAACT P1112 Protocol Team. The 
Protocol Team acknowledges that the extent to which site operations may be disrupted by the COVID-19 
pandemic may vary across sites and over time. All sites should follow applicable government, health 
authority, and institutional policies with respect to conduct of study visits and procedures, with 
utmost importance placed on the health and well-being of study participants and study staff. Site 
investigators should continue to follow current protocol specifications for communication with the 
Protocol Team and should contact the Protocol Team (impaact.teamp1112@fstrf.org) with any questions 
or concerns regarding this CM or management of study participants. 
 
Visit Scheduling 
• 
Sites should utilize the allowable visit windows currently specified in the protocol V4.0 to permit 
continued completion of in-person visits through 24 weeks after the last dose of study drug and at 
Week 96. Sites should consider current or anticipated operational disruptions or closures when 
scheduling visits and should schedule visits early or late in the allowable window, as appropriate. 
Visits conducted outside of the allowable window would also be preferred to completely missed 
visits. 
• 
Effective with the issuance of this CM, for Dose Group 5 Cohort 1, the allowable window for visits 
beyond 24 weeks after the last dose of study drug and prior to Week 96 (i.e., visits at Week 36, Week 
48, Week 60, Week 72, and Week 84 for all Dose Group 5 Cohort 1 participants) are broadened to ±6 
weeks. The current V4.0 protocol-specified visit windows remain the target for these visits, and sites 
are encouraged to continue scheduling within these target windows whenever possible. 

Letter of Amendment #1 
Page 6 of 7 
10 June 2020 
IMPAACT P1112 Protocol Version 4.0 
• 
Effective with the issuance of this CM, for Dose Group 5 Cohort 2, the allowable window for visits 
beyond 24 weeks after the last dose of study drug and prior to Week 96 (i.e., visits at Week 48, Week 
60, Week 72, and Week 84 for all Dose Group 5 Cohort 2 participants and also the visit at Week 36 
for Dose Group 5 Cohort 2 participants who do not receive a dose of study drug at Week 12) are 
broadened to ±6 weeks. The current V4.0 protocol-specified visit windows remain the target for these 
visits, and sites are encouraged to continue scheduling within these target windows whenever 
possible. 
 
Prioritization of Study Visit Procedures 
• 
Sites with full capacity to conduct in-person study visits at the study clinic through 24 weeks after the 
last dose of study drug and at Week 96 (to confirm end-of-study HIV infection status) should 
continue to do so in full compliance with the protocol. 
• 
Sites with limited capacity to conduct in-person study visits at the study clinic through 24 weeks after 
the last dose of study drug and at Week 96 should prioritize: 
− 
administration of study drug at Week 12 to Dose Group 5 Cohort 2 participants who have not had 
complete cessation of breastfeeding, if the site is reasonably confident that the completion of the 
subsequent safety and other assessments will be possible. 
− 
conduct of laboratory evaluations per the “priority for blood samples” listings in the protocol 
Schedules of Evaluations. If it is not possible to perform these tests consistent with the site’s 
approved Protocol Analyte List (PAL), tests may be performed in alternative settings using 
alternate assays (alternate laboratories must adhere to local regulations for clinical laboratory 
testing). 
• 
Sites may also conduct study visits, in full or in part, beyond 24 weeks after the last dose of study 
drug and prior to Week 96, off-site if permitted by applicable government, health authority, and 
institutional policies. Where this option is permitted, site staff should communicate with 
parents/guardians to determine in advance where and when such visits will take place, with adequate 
protections for safety, privacy, and confidentiality. Off-site visit procedures should be conducted by 
site staff who are adequately qualified and trained to conduct the procedures, with attention paid to 
occupational health, biohazard containment, and specimen and data chain of custody. These staff 
should also be adequately trained and qualified to immediately manage any adverse events and/or 
social impacts that may occur during the visits. If adverse events requiring further evaluation or 
management are identified during an off-site visit, study staff conducting the visit should arrange for 
appropriate clinical management, in consultation with the IoR or designee, as needed. 
• 
Sites with no ability to conduct in-person study visits, either at the study clinic or off-site, should 
consider whether any study procedures can be conducted remotely (e.g., by telephone). Evaluations 
should be prioritized as follows (as applicable for the individual participant and scheduled study visit 
in question): 
1. Medical history taking 
2. Review of any injection site reactions 
 
Study Drug Supply 
• 
No changes in procedures for preparing, dispensing, or administering study product (VRC07-523LS) 
are planned. These procedures must be performed on-site to ensure adherence to product temperature 
requirements. In addition, study product must be administered in a clinical setting to ensure 
appropriate management in the rare event of an acute hypersensitivity reaction. 
 
Documentation 
• 
Site-specific contingency plans, and the implementation thereof, should be documented in essential 
document files for IMPAACT P1112. 

Letter of Amendment #1 
Page 7 of 7 
10 June 2020 
IMPAACT P1112 Protocol Version 4.0 
• 
Documentation should be entered in participant study charts in real-time should any of the following 
occur: 
- Missed visits 
- Out-of-window visits 
- Off-site visits (document the location of the visit) 
- Incomplete or partial visits (document which procedures were performed and which were not) 
- Remote contacts performed in lieu of in-person visits (document method used to complete the 
contact and which procedures were performed) 
- Any other participant contacts 
- Use of alternate laboratories or alternate laboratory assays 
- Non-standard provision of study drug 
• 
In consultation with the Division of AIDS, the IMPAACT Network is developing comprehensive 
guidance for documenting and/or reporting protocol deviations that may occur due to limited site 
capacity to conduct study visits or procedures during the COVID-19 pandemic. Similar guidance will 
be provided for documentation of use of alternate laboratories or alternate laboratory assays. Once 
this Network-level guidance is available, it will be provided in a separate communication to all sites. 
 

Clarification Memorandum #1 
Page 1 of 3 
31 March 2020 
IMPAACT P1112 Protocol Version 4.0 
Clarification Memorandum #1 for:  
 
IMPAACT P1112 
Open-Label, Dose-Escalating, Phase I Study to Determine Safety and Pharmacokinetic 
Parameters of Subcutaneous (SC) VRC01, VRC01LS, and VRC07-523LS, Potent Anti-HIV 
Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants 
 
Version 4.0, dated 6 November 2018 
 
DAIDS Study ID #11903 
IND #113,611 
 
Clarification Memorandum Date: 31 March 2020 
 
 
Summary of Clarifications 
 
This Clarification Memorandum (CM) is being issued to safeguard the health and well-being of 
IMPAACT P1112 study participants in the context of circulating severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease (COVID-19) pandemic.  
 
As the study Sponsor, the Division of AIDS (DAIDS) has determined that this CM should be 
implemented immediately upon issuance. Consistent with United States Food and Drug Administration 
guidance, institutional review board/ethics committee (IRB/EC) approval of this CM is not required by 
the Division of AIDS prior to implementation. However, given the context of the COVID-19 pandemic 
and the importance of the guidance provided in this CM, sites should submit this CM to IRBs/ECs for 
their information or, if required by the IRBs/ECs, for their review and approval.  
 
The purpose of this CM is to provide operational flexibility for conducting study visits and procedures 
when needed to ensure, when possible, completion of protocol-specified study product dosing for 
participants in Dose Group 5 Cohort 2 and, for all participants, to prioritize the conduct of clinically and 
scientifically important evaluations, particularly those evaluations planned to be conducted within 24 
weeks of the last dose of study drug and at Week 96. 
 
Implementation of this CM is expected to be time-limited in relation to the COVID-19 pandemic. In 
consultation with IMPAACT Network leadership and the study Sponsor, the IMPAACT P1112 Protocol 
Team will determine when, in the future, the guidance provided in this CM is no longer applicable. When 
such a determination is made, study sites will be formally notified and instructed to inform their 
IRBs/ECs. 
 
Please file this CM and any applicable IRB/EC correspondence in your essential document files for 
IMPAACT P1112. 
 
 
 
 

Clarification Memorandum #1 
Page 2 of 3 
31 March 2020 
IMPAACT P1112 Protocol Version 4.0 
Implementation 
 
This CM provides operational guidance to study sites from the IMPAACT P1112 Protocol Team. The 
Protocol Team acknowledges that the extent to which site operations may be disrupted by the COVID-19 
pandemic may vary across sites and over time. All sites should follow applicable government, health 
authority, and institutional policies with respect to conduct of study visits and procedures, with 
utmost importance placed on the health and well-being of study participants and study staff. Site 
investigators should continue to follow current protocol specifications for communication with the 
Protocol Team and should contact the Protocol Team (impaact.teamp1112@fstrf.org) with any questions 
or concerns regarding this CM or management of study participants.  
 
Visit Scheduling 
• 
Sites should utilize the allowable visit windows currently specified in the protocol V4.0 to permit 
continued completion of in-person visits through 24 weeks after the last dose of study drug and at 
Week 96. Sites should consider current or anticipated operational disruptions or closures when 
scheduling visits and should schedule visits early or late in the allowable window, as appropriate. 
Visits conducted outside of the allowable window would also be preferred to completely missed 
visits.   
• 
Effective with the issuance of this CM, for Dose Group 5 Cohort 1, the allowable window for visits 
beyond 24 weeks after the last dose of study drug and prior to Week 96 (i.e., visits at Week 36, Week 
48, Week 60, Week 72, and Week 84 for all Dose Group 5 Cohort 1 participants) are broadened to ±6 
weeks.  The current V4.0 protocol-specified visit windows remain the target for these visits, and sites 
are encouraged to continue scheduling within these target windows whenever possible.  
• 
Effective with the issuance of this CM, for Dose Group 5 Cohort 2, the allowable window for visits 
beyond 24 weeks after the last dose of study drug and prior to Week 96 (i.e., visits at Week 48, Week 
60, Week 72, and Week 84 for all Dose Group 5 Cohort 2 participants and also the visit at Week 36 
for Dose Group 5 Cohort 2 participants who do not receive a dose of study drug at Week 12) are 
broadened to ±6 weeks. The current V4.0 protocol-specified visit windows remain the target for these 
visits, and sites are encouraged to continue scheduling within these target windows whenever 
possible.  
 
Prioritization of Study Visit Procedures 
• 
Sites with full capacity to conduct in-person study visits at the study clinic through 24 weeks after the 
last dose of study drug and at Week 96 (to confirm end-of-study HIV infection status) should 
continue to do so in full compliance with the protocol. 
• 
Sites with limited capacity to conduct in-person study visits at the study clinic through 24 weeks after 
the last dose of study drug and at Week 96 should prioritize:  
− 
administration of study drug at Week 12 to Dose Group 5 Cohort 2 participants who have not had 
complete cessation of breastfeeding, if the site is reasonably confident that the completion of the 
subsequent safety and other assessments will be possible.  
− 
conduct of laboratory evaluations per the “priority for blood samples” listings in the protocol 
Schedules of Evaluations. If it is not possible to perform these tests consistent with the site’s 
approved Protocol Analyte List (PAL), tests may be performed in alternative settings using 
alternate assays (alternate laboratories must adhere to local regulations for clinical laboratory 
testing). 
• 
Sites may also conduct study visits, in full or in part, beyond 24 weeks after the last dose of study 
drug and prior to Week 96, off-site if permitted by applicable government, health authority, and 
institutional policies. Where this option is permitted, site staff should communicate with 
parents/guardians to determine in advance where and when such visits will take place, with adequate 
protections for safety, privacy, and confidentiality. Off-site visit procedures should be conducted by 

Clarification Memorandum #1 
Page 3 of 3 
31 March 2020 
IMPAACT P1112 Protocol Version 4.0 
site staff who are adequately qualified and trained to conduct the procedures, with attention paid to 
occupational health, biohazard containment, and specimen and data chain of custody. These staff 
should also be adequately trained and qualified to immediately manage any adverse events and/or 
social impacts that may occur during the visits. If adverse events requiring further evaluation or 
management are identified during an off-site visit, study staff conducting the visit should arrange for 
appropriate clinical management, in consultation with the IoR or designee, as needed.  
• 
Sites with no ability to conduct in-person study visits, either at the study clinic or off-site, should 
consider whether any study procedures can be conducted remotely (e.g., by telephone). Evaluations 
should be prioritized as follows (as applicable for the individual participant and scheduled study visit 
in question):  
1. Medical history taking 
2. Review of any injection site reactions 
 
Study Drug Supply 
• No changes in procedures for preparing, dispensing, or administering study product (VRC07-523LS) 
are planned. These procedures must be performed on-site to ensure adherence to product temperature 
requirements. In addition, study product must be administered in a clinical setting to ensure 
appropriate management in the rare event of an acute hypersensitivity reaction. 
 
Documentation 
• 
Site-specific contingency plans, and the implementation thereof, should be documented in essential 
document files for IMPAACT P1112.  
• 
Documentation should be entered in participant study charts in real-time should any of the following 
occur: 
- Missed visits  
- Out-of-window visits 
- Off-site visits (document the location of the visit) 
- Incomplete or partial visits (document which procedures were performed and which were not) 
- Remote contacts performed in lieu of in-person visits (document method used to complete the 
contact and which procedures were performed) 
- Any other participant contacts  
- Use of alternate laboratories or alternate laboratory assays 
- Non-standard provision of study drug  
• 
In consultation with the Division of AIDS, the IMPAACT Network is developing comprehensive 
guidance for documenting and/or reporting protocol deviations that may occur due to limited site 
capacity to conduct study visits or procedures during the COVID-19 pandemic. Similar guidance will 
be provided for documentation of use of alternate laboratories or alternate laboratory assays. Once 
this Network-level guidance is available, it will be provided in a separate communication to all sites.  

 
IMPAACT P1112 
 
Open-Label, Dose-Escalating, Phase I Study to Determine Safety and Pharmacokinetic 
Parameters of Subcutaneous (SC) VRC01, VRC01LS, and VRC07-523LS, Potent Anti-HIV 
Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants 
 
(DAIDS ID Document ID # 11903) 
 
A Multicenter, Domestic and International Trial of the  
International Maternal Pediatric Adolescent AIDS  
Clinical Trials (IMPAACT) Network 
 
Sponsored by: 
 
The National Institute of Allergy and Infectious Diseases (NIAID) 
The Eunice Kennedy Shriver National Institute of Child Health and Human Development 
(NICHD) 
The National Institute of Mental Health (NIMH) 
 
 
IND# 113,611 
 
 
The IMPAACT Prevention Scientific Committee Chair: Lynda Stranix-Chibanda 
 
 
 
Protocol Chair: 
Coleen Cunningham, MD 
 
Protocol Vice Chair:  
Elizabeth McFarland, MD 
 
NIAID Medical Officer:  
Mary Elizabeth Smith, MD 
 
NICHD Medical Officer: 
Rohan Hazra, MD 
 
Clinical Trials Specialist:  
 
Charlotte Perlowski, MSPH 
 
 
Patricia Morgan, MS, PA 
 
 
 
 
Version 4.0 
06 November 2018
 
 

 
 
IMPAACT P1112 Version 4.0 
Page 2 of 144  
06 November 2018 
All questions concerning this protocol should be sent via e-mail to 
impaact.teamP1112@fstrf.org.  Remember to include the participant’s PID when 
applicable.  The appropriate team member will respond to questions via e-mail with a 
"cc" to impaact.teamP1112@fstrf.org.  A response should generally be received within 
24 hours (Monday - Friday).  For protocol registration questions, e-mail protocol@tech-
res.com or call 301-897-1707.  Protocol registration material should be submitted via the 
DAIDS Protocol Registration System (DPRS):  https://rsc.niaid.nih.gov/clinical-research-
sites/protocol-registration or can be sent via e-mail to epr@tech-res.com.  For Expedited 
Adverse Event (EAE) questions, e-mail DAIDSRSCSafetyOffice@tech-res.com or call 
1-800-537-9979 or 1-301-897-1709 or fax 1-800-275-7619 or 301-897-1710.  To order 
study agent, call the Clinical Research Products Management Center at (301) 294-0741.  
For randomization or enrollment questions, contact the Data Management Center at 716-
834-0900 or by email at rando.support@fstrf.org.   
 
IMPAACT P1112 PROTOCOL TEAM ROSTER 
 
Protocol Chair 
Coleen Cunningham, MD 
Duke University 
T915, Children's Health Center 
Erwin Road,  
Box 3352 DUMC 
Durham, NC 27710 
Phone: (919) 668-4851 
E-mail: coleen.cunningham@duke.edu 
 
Protocol Co-Vice-Chair and 
Immunologist 
Elizabeth (Betsy) J. McFarland, MD 
Professor of Pediatrics  
University of Colorado Denver  
Pediatric Infectious Diseases  
The Children's Hospital  
13132 E. 16th Avenue, B055  
Aurora, CO 80045 
Phone: (303) 724-3447 
E-mail: betsy.mcfarland@ucdenver.edu 
 
NIAID Medical Officer  
Mary Elizabeth (Betsy) Smith, MD 
Maternal Adolescent and Pediatric 
Research Branch 
DAIDS/NIAID/NIH/DHHS 
5601 Fishers Lane 
Rockville, MD 20852 
Phone: 1-240-292-4788 
E-mail: betsysmith@niaid.nih.gov 
 
NICHD Medical Officer 
Rohan Hazra, MD  
Chief, Maternal and Pediatric Infectious 
Disease Branch  
Eunice Kennedy Shriver National 
Institute of Child Health & Human 
Development  
6710B Rockledge Drive, Room 2113 
Bethesda, MD 20817 
Phone: (301) 435-6868 
E-mail: hazrar@mail.nih.gov  
 
Clinical Trials Specialists 
Charlotte Perlowski, MSPH 
FHI 360 
359 Blackwell St  
Durham, NC 22701, USA 
Phone: (919) 544-7040 x 11480  
E-mail: cperlowski@fhi360.org  
 
Patricia Morgan, MS, PA 
FHI 360 
359 Blackwell St  
Durham, NC 22701, USA 
Phone: (919) 475-3131 
E-mail: pmorgan@fhi360.org 
 
 

 
 
IMPAACT P1112 Version 4.0 
Page 3 of 144  
06 November 2018 
Protocol Statisticians 
Petronella Muresan, MS 
Center for Biostatistics in AIDS 
Research (CBAR) 
Harvard T.H. Chan School of Public 
Health 
1371 Beacon Street, Suite #203 
Brookline, MA 02446 
Phone: (617) 632-2000, ext. 4031 
E-mail: petronm@sdac.harvard.edu 
 
Protocol Data Managers 
 Bonnie Zimmer 
Frontier Science and Technology 
Research Foundation, Inc. 
4033 Maple Road 
Amherst, NY  14226-1056 
Phone: (716) 834-0900 x 7260 
Fax: (716) 834-8432 
E-mail:  zimmer@fstrf.org 
 
Benjamin Johnston 
Frontier Science and Technology 
Research Foundation, Inc. 
4033 Maple Road 
Amherst, NY  14226-1056 
Phone: (716) 834-0900 x 7407 
Fax: (716) 834-8432 
E-mail: johnston@fstrf.org  
 
Protocol Pharmacist 
Lynette Purdue, PharmD 
Division of AIDS 
5601 Fishers Lane 
Rockville, MD 20852 
Phone: 1-240-627-3061 
E-mail: lpurdue@niaid.nih.gov 
Protocol Virologist 
Grace Aldrovandi, MD, CM 
Professor 
IMPAACT Virology Laboratory 
130 Children's Hospital of Los Angeles 
4546 Sunset Blvd, MS 51 
Smith Research Tower  
Room 902 
Los Angeles, CA 90027 
Phone: (323) 361-8501 
E-mail: gracea@mac.com  
 
Protocol Pharmacologist 
Edmund Capparelli, PharmD 
Pediatric Pharmacology Research Unit 
University of California, San Diego 
7910 Frost Street #360 
San Diego, CA  92123 
Phone: (858) 246-0009 
E-mail:  ecapparelli@ucsd.edu 
 
Laboratory Center Representatives 
Dale Dayton, RN, CCRA 
University of California Los Angeles 
MacDonald Research Laboratories 
675 Charles E. Young Drive South 
Los Angeles, CA 90095 
Phone:  301-742-9077 
ddayton@impaactlabcenter.org 
 
Nicole Tobin, MD 
University of California Los Angeles 
MacDonald Research Laboratory  
675 Charles E. Young Drive South 
Los Angeles, CA 90095 
Phone: (310) 825-7708 
Fax: (310) 206-4764 
ntobin@impaactlabcenter.org 

 
 
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Laboratory Technologist 
Paul Harding, MS 
Pediatric Infectious Disease 
University of Colorado Denver 
Mail Stop 8604    Building P15   
12700 E. 19th Ave    Room # 11460-A 
Aurora, CO 80045 
Office: (303) 724-3404  
Lab: (303) 724-3407  
E-mail: paul.harding@ucdenver.edu 
 
Laboratory Data Coordinator 
Frederic Bone 
Frontier Science and Technology 
Research Foundation  
4033 Maple Rd. 
Amherst, NY 14226-1056 
Phone: 716-834-0900 x 7306 
E-mail: bone@fstrf.org   
 
Investigators 
Barney S. Graham, MD, PhD 
Chief, Clinical Trials Core 
Chief, Viral Pathogenesis Laboratory 
and Translational Science Core 
Vaccine Research Center, NIAID, NIH 
40 Convent Drive, MSC 3017 
Bldg 40, Room 2502 
Bethesda, MD 20892-3017 
Phone: (301) 594-8468 
E-mail: bgraham@mail.nih.gov  
URL: 
https://www.niaid.nih.gov/about/vrc 
 
John Mascola, MD 
Vaccine Research Center, NIAID, NIH 
40 Convent Drive 
Bldg. 40, Room 4502 
Bethesda, MD 20814 
Phone: (301) 594-8487 
Fax: (301) 480-2788 
E-mail: jmascola@nih.gov 
 
Westat Clinical Research Associate 
Kathryn Myers, BA 
Westat Inc 
1441 West Montgomery Ave. WB215 
Rockville, MD 20850 
Phone: (301) 610-8803 
Fax: (301) 279-4545 
E-mail: KathrynMyers@westat.com 
 
 

 
 
 
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TABLE OF CONTENTS 
 
GLOSSARY OF TERMS ................................................................................................9 
SCHEMA ........................................................................................................................11 
1 
INTRODUCTION .................................................................................................16 
1.1 
Background ......................................................................................................16 
1.2 
Rationale ..........................................................................................................35 
2 
STUDY OBJECTIVES .........................................................................................43 
2.1 
Primary Objectives...........................................................................................43 
2.2 
Secondary Objectives.......................................................................................44 
2.3 
Exploratory ......................................................................................................44 
3 
STUDY DESIGN ...................................................................................................44 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS.............................49 
4.1 
Maternal Inclusion Criteria ..............................................................................49 
4.2 
Maternal Exclusion Criteria .............................................................................50 
4.3 
Infant Inclusion Criteria ...................................................................................50 
4.4 
Infant Exclusion Criteria ..................................................................................51 
4.5 
Concomitant Medication Guidelines ...............................................................52 
4.6 
Enrollment Procedures .....................................................................................52 
4.7 
Co-enrollment Procedures ...............................................................................53 
5 
STUDY TREATMENT .........................................................................................54 
5.1 
Drug Regimens, Administration and Duration ................................................54 
5.2 
Drug Formulation.............................................................................................55 
5.3 
Thawing Instructions .......................................................................................56 
5.4 
Study Product Preparation ...............................................................................56 
5.5 
Study Product Administration..........................................................................56 
5.6 
Drug Supply, Distribution and Pharmacy ........................................................57 
6 
PARTICIPANT MANAGEMENT ......................................................................57 
6.1 
Toxicity Management ......................................................................................57 
6.2 
Study Management Plan ..................................................................................59 
6.3 
Criteria for Treatment Pause for Individual Participants .................................60 
6.4 
Criteria for Treatment Discontinuation ............................................................61 
6.5 
Criteria for Study Discontinuation ...................................................................61 
6.6 
If an Infant is Determined to be HIV-Infected.................................................61 
7 
EXPEDITED ADVERSE EVENT REPORTING..............................................61 
7.1 
Adverse Event Reporting to DAIDS ................................................................61 
7.2 
Reporting Requirements for this Study............................................................62 
7.3 
Grading Severity of Events ..............................................................................62 
7.4 
Expedited AE Reporting Period.......................................................................62 
8 
STATISTICAL CONSIDERATIONS .................................................................63 
8.1 
General Design Issues ......................................................................................63 
8.2 
Outcome Measures...........................................................................................65 
8.3 
Randomization and Stratification ....................................................................66 
8.4 
Sample Size and Accrual .................................................................................66 
8.5 
Monitoring .......................................................................................................67 
8.6 
Analyses ...........................................................................................................71 

 
 
 
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8.7 
Secondary Analyses .........................................................................................73 
8.8 
Exploratory Analyses .......................................................................................74 
9 
CLINICAL PHARMACOLOGY PLAN ............................................................74 
9.1 
Pharmacology Objectives ................................................................................74 
9.2 
Primary and Secondary Data ...........................................................................74 
9.3 
Study Design, Modeling and Data Analysis ....................................................75 
9.4 
Anticipated Outcomes ......................................................................................80 
10 
HUMAN SUBJECTS ............................................................................................81 
10.1 
Institutional Review Board and Informed Consent .........................................81 
10.2 
Participant Confidentiality ...............................................................................82 
10.3 
Study Discontinuation ......................................................................................82 
11 
PUBLICATION OF RESEARCH FINDINGS ..................................................82 
12 
BIOHAZARD CONTAINMENT ........................................................................82 
13 
REFERENCES ......................................................................................................83 
APPENDIX IA: Maternal Schedule of Evaluations (all dose groups) ......................87 
APPENDIX IB: Infant Schedule of Evaluations (Dose Groups 1 and 2) ..................88 
APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)191 
APPENDIX ID: Schedule of Evaluations (Dose Group 3) .........................................93 
APPENDIX IE: Schedule of Evaluations (Dose Group 4, Cohort 1: non-
breastfeeding) .......................................................................................................96 
APPENDIX IF: Schedule of Evaluations (Dose Group 4, Cohort 2: breastfeeding)
 
99 
APPENDIX IG: Schedule of Evaluations (Dose Group 5, Cohort 1: non-
breastfeeding) .....................................................................................................102 
APPENDIX IH: Schedule of Evaluations (Dose Group 5, Cohort 2: breastfeeding)
 
105 
APPENDIX IIA: IMPAACT P1112 Sample Informed Consent Template: Dose 
Group 5, Cohort 1 (Non-breastfeeding) ...........................................................108 
APPENDIX IIB: IMPAACT P1112 Sample Informed Consent Template: Dose 
Group 5, Cohort 2 (breastfeeding) ...................................................................123 
 
 
 

 
 
 
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LIST OF FIGURES AND TABLES 
 
Figure 1: Overview of Study Design ................................................................................ 15 
Figure 2: Breadth Potency Curves for VRC01 Data. ........................................................ 19 
Figure 3: Comparison of Infant SC 20mg/kg and Adult IV 40mg/kg of VRC 01............ 41 
Figure 4: VRC01 and VRC01LS levels following IV administration in adults ............... 41 
Figure 5: VRC01, VRC01LS and VRC07-523LS levels following IV administration of 
20 mg/kg in adults ............................................................................................................. 42 
Figure 6: Modeling of VRC07-523LS levels.................................................................... 42 
Figure 7: Predicted VRC01, VRC01LS, and VRC07-523LS Concentrations.................. 77 
Figure 8: Expected Day 28 VRC01 Concentrations ......................................................... 80 
Figure 9: Expected VRC01 Concentrations ...................................................................... 81 
 
 
Table 1: Breadth and Potency of VRC01 neutralization of tier 2 virus ............................ 18 
Table 2: Potency and Breadth of HIV-1 Neutralization of VRC01 and VRC07-523LS 
(Development-Grade Material) ......................................................................................... 21 
Table 3: Planned or completed studies of VRC01, VRC01LSand VRC07-523LS .......... 23 
Table 4: Adverse Events Occurring at a Rate of 1% or Greater in Infantsϯ Receiving 
Palivizumab or Placebo..................................................................................................... 33 
Table 5: Description of Dose Groups ............................................................................... 48 
Table 6: Probability of Meeting Safety Review Trigger Under Potential Rates of True 
Toxicity (N=6) .................................................................................................................. 70 
Table 7: Exact 90% Confidence Intervals around Potential Proportions of Participants 
Exhibiting Grade 3 or Higher Adverse Events (N=8, 10 and 13) ..................................... 72 
Table 8: Exact 90% Confidence Intervals around Potential Rates of PK Success (N=8, 10 
and 13) .............................................................................................................................. 73 
 

 
 
 
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IMPAACT P1112 
Open-Label, Dose-Escalating, Phase I Study to Determine Safety and 
Pharmacokinetic Parameters of Subcutaneous (SC) VRC01, VRC01LS, and 
VRC07-523LS, Potent Anti-HIV Neutralizing Monoclonal Antibodies, in HIV-1-
Exposed Infants 
 
DAIDS Study ID #11903 
 
Version 4.0 
Protocol Signature Page 
 
 
I will conduct this 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 (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
__ 
 
Signature of Investigator of Record 
  
 
Date 
 
 
 
 
 
 
 
 
 
 
Name of Investigator of Record  
 
(printed) 
 

 
IMPAACT P1112 Version 4.0 
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06 November 2018 
GLOSSARY OF TERMS 
 
AE 
 
Adverse Event/Adverse Experience 
AIDS  
Acquired Immune Deficiency Syndrome 
ANA  
Antinuclear antibody activity  
aPTT  
Activated Partial thromboplastin time 
ART  
Antiretroviral therapy 
ARV  
Antiretroviral 
AUC   
Area-Under-the-Curve  
CAP  
College of American Pathologists 
CDR  
Complementarity Determining Regions 
CLIA  
Clinical Laboratory Improvement Amendments 
CRF 
 
Case Report Form 
CRPMC 
Clinical Research Products Management Center 
DAERS 
DAIDS Adverse Experience Reporting System 
DAIDS 
Division of AIDS 
DNA  
Deoxyribonucleic Acid  
DPRS  
DAIDS Protocol Registration System 
EAE 
 
Expedited Adverse Event 
EIA 
 
Enzyme Immunoassay 
EC 
 
Ethics Committee  
GCP  
Good Clinical Practice 
GMP  
Good Manufacturing Practice 
HAART 
Highly active antiretroviral therapy  
HBIG  
Hepatitis B immune globulin  
HIV 
 
Human Immunodeficiency Virus 
IC50  
Half maximal inhibitory concentration 
Ig 
 
Immunoglobulin 
IM 
 
Intramuscular 
IMPAACT  
International Maternal Pediatric Adolescent AIDS Clinical Trials Group 
IRB 
 
Institutional Review Board 
IV  
 
Intravenous 
LPC 
 
Laboratory Processing Chart  
mAb  
Monoclonal antibody 
MTCT  
Mother to child transmission 
N 
 
Number (typically refers to participants) 
NAT  
Nucleic Acid Testing 
NIAID  
National Institute of Allergy and Infectious Diseases 
NICHD 
Eunice Kennedy Shriver National Institute of Child Health and Human 
Development 
NIH 
National Institutes of Health 
NVP  
Nevirapine 
OHRP  
Office for Human Research Protections 
PBMC  
Peripheral Blood Mononuclear Cell 
PCR 
 
Polymerase Chain Reaction 
PID 
 
Patient Identifier 

 
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06 November 2018 
PK 
 
Pharmacokinetic 
PRO  
Protocol Registration Office 
PROM  
Premature rupture of membranes 
PTT 
 
Partial thromboplastin time 
RE 
 
Regulatory Entity 
RNA   
Ribonucleic Acid 
RSC 
 
Regulatory Support Center 
RSV  
Respiratory syncytial virus 
SADR  
Suspected Adverse Drug Reaction 
SAE 
 
Serious Adverse Event/Serious Adverse Experience 
SC 
 
Subcutaneous 
SDAC  
Statistical and Data Analysis Center 
SHIV  
Simian Human Immunodeficiency Virus 
SMC   
Safety Monitoring Committee 
SUSAR 
Suspected, Unexpected Serious Adverse Reactions 
TCID  
Tissue Culture Infectious Doses 
T1/2 
 
Half-life 
UNAIDS 
United Nations AIDS Organization 
VRC  
Vaccine Research Center 
VRC01 
Human monoclonal antibody (VRC-HIVMAB-060-00-AB) 
VRC01LS 
Human monoclonal antibody (VRC-HIVMAB-080-00-AB) 
VRC07-523LS Human monoclonal antibody (VRC-HIVMAB075-00-AB) 
WHO  
World Health Organization 

 
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06 November 2018 
SCHEMA 
 
Open-Label, Dose-Escalating, Phase I Study to Determine Safety and Pharmacokinetic 
Parameters of Subcutaneous (SC) VRC01, VRC01LS, and VRC07-523LS, Potent Anti-
HIV Neutralizing Monoclonal Antibodies, in HIV-1-Exposed Infants 
 
DESIGN:  
 Open-label, dose-escalating, Phase 1, multicenter trial of VRC01 
(VRC-HIVMAB-060-00-AB), VRC01LS (VRCHIVMAB080-00-
AB), and VRC07-523LS (VRC-HIVMAB075-00-AB) 
 
SAMPLE SIZE:   N=79 mother-infant pairs, 13 per Dose Groups 1, 2 and 3; 20 per 
Dose Groups 4 and 5 (10 per each cohort) 
 
Description of Dose Groups 
 
N 
Dose of VRC01, VRC01LS, or VRC07-523LS 
Dose Group 1 
13 
20 mg/kg SC X1 VRC01 
Dose Group 2 
13 
40 mg/kg SC X1 VRC01 
Dose Group 3 
13 
40 mg/kg SC for initial dose 
20 mg/kg SC monthly of VRC01 for at least 6 
months (24 weeks) and no more than 18 months 
(72 weeks) while breastfeeding 
Dose Group 4 
10 
 
 
 
 
 
10 
Cohort 1: Non-breastfeeding 
Single dose at birth of VRC01LS to be 
administered SC; dose is based on weight: 
< 4.5 kg: 80 mg 
≥ 4.5 kg: 100 mg 
 
Cohort 2: Breastfeeding 
Initial dose at birth of VRC01LS to be 
administered SC; dose is based on weight: 
< 4.5 kg: 80 mg 
≥ 4.5 kg: 100 mg 
 
Second dose of 100 mg VRC01LS at Week 12 to 
be administered SC if the infant has not achieved 
complete cessation of breastfeeding 
Dose Group 5 
10 
 
 
 
 
 
10 
Cohort 1: Non-breastfeeding 
Single dose at birth of VRC07-523LS to be 
administered SC; dose is based on weight: 
< 4.5 kg: 80 mg 
≥ 4.5 kg: 100 mg 
 
Cohort 2: Breastfeeding 
Initial dose at birth of VRC07-523LS to be 
administered SC; dose is based on weight: 
< 4.5 kg: 80 mg 
≥ 4.5 kg: 100 mg 
 
Second dose of 100 mg VRC07-523LS at Week 
12 to be administered SC if the infant has not 
achieved complete cessation of breastfeeding 

 
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06 November 2018 
 
POPULATION:  Infants born to HIV-1-infected women who meet all maternal 
inclusion and no maternal exclusion criteria and who are ≥ 36 weeks 
gestation; ≥ 2kg birth weight; and meet the study definition of 
increased risk of HIV infection.  Additional exclusion criteria for 
infants also apply (see Section 4).  The mothers are enrolled as well, 
but only the infants receive the VRC01/VRC01LS/VRC07-523LS 
immunization(s) and are followed on the study.  All infants receive 
prophylactic antiretroviral therapy (ART) treatment per local 
standard of care.   
 
REGIMEN:    
Infants in Dose Group 1 received a single VRC01 (human 
monoclonal antibody) 20 mg/kg subcutaneous injection less than 72 
hours after birth.  
  
Dose Group 2 opened after 13 infants had been accrued into Dose 
Group 1 and 6 of those had been immunized, completed 28 days of 
follow-up and passed a safety assessment.  Infants in Dose Group 2 
received a single subcutaneous VRC01 dose of 40 mg/kg less than 
72 hours after birth.   
 
Dose Group 3 opened after 6 infants in Dose Group 2 had been 
immunized, completed 28 days of follow-up and passed a safety 
assessment.  Infants in Dose Group 3 received a subcutaneous 
VRC01 dose of 40 mg/kg less than 5 days after birth for the initial 
dose and 20 mg/kg SC monthly.  There have been and will be formal 
safety reviews of data from adult and pediatric protocols of VRC01 
(from P1112 database and most recent safety reports available from 
other protocols) every 6 months beginning after the first participant 
in Dose Group 3 reaches the Week 24 milestone.   
 
In Dose Group 4, infants enrolled into one of two separate cohorts: 
Dose Group 4, Cohort 1 opened after Version 3.0 was released and 
safety data – as shown in Error! Reference source not found.  – 
was reviewed and revealed no signal. Dose Group 4: Cohort 2 
(breastfeeding) opened after six infants in Dose Group 4, Cohort 1 
were immunized, completed 28 days of follow-up, and passed a 
safety assessment.  Non-breastfeeding infants in Dose Group 4, 
Cohort 1 received a single subcutaneous VRC01LS dose (< 4.5 kg: 
80 mg; ≥ 4.5 kg: 100 mg) as soon as possible and less than 72 hours 
after birth.  Breastfeeding infants in Dose Group 4, Cohort 2 
received subcutaneous VRC01LS (< 4.5 kg: 80 mg; ≥ 4.5 kg: 100 
mg) as soon as possible and no longer than 5 days after birth for the 
initial dose and a second dose (100 mg) at Week 12 if the infant has 
not achieved complete cessation of breastfeeding.  Complete 

 
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06 November 2018 
cessation of breastfeeding is defined as no exposure to breastmilk for 
28 days. 
 
In Dose Group 5, infants will enroll into one of two separate cohorts: 
Cohort 1 (non-breastfeeding) or Cohort 2 (breastfeeding). Non-
breastfeeding infants in Dose Group 5, Cohort 1 will receive a single 
subcutaneous VRC07-523LS dose (< 4.5 kg: 80 mg; ≥ 4.5 kg: 100 
mg) as soon as possible and less than 72 hours after birth. 
Breastfeeding infants in Dose Group 5, Cohort 2 will receive 
subcutaneous VRC07-523LS (< 4.5 kg: 80 mg; ≥ 4.5 kg: 100 mg) as 
soon as possible and no longer than 5 days after birth for the initial 
dose and a second dose (100 mg) at Week 12 if the infant has not 
achieved complete cessation of breastfeeding. Complete cessation of 
breastfeeding is defined as no exposure to breastmilk for 28 days. 
Dose Group 5, Cohort 1 will open as soon as Version 4.0 has been 
released and interim safety data – as shown in Error! Reference 
source not found. – have been reviewed and reveal no signal. Dose 
Group 5, Cohort 2 will open as soon as six infants in Dose Group 5, 
Cohort 1 have been immunized, completed 28 days of follow-up, 
and passed a safety and PK assessment. 
 
There will be formal safety reviews of data from adult and pediatric 
protocols of VRC01LS and VRC07-523LS (from the P1112 
database and most recent safety reports available from other 
protocols) approximately every six months to coincide with the 
already occurring reviews described above.  
 

 
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TREATMENT  
DURATION:  
VRC01: One day for Dose Groups 1 and 2.   
 
VRC01: For Dose Group 3, all have received monthly doses for at 
least 6 months.  Infants who continue to receive breastmilk will 
receive monthly doses through the complete cessation of 
breastfeeding up to a maximum of 72 weeks (19 doses). 
 
VRC01LS: All infants in Dose Group 4 received a single dose at 
birth.  Infants in Dose Group 4, Cohort 2 will receive a second dose 
at Week 12 if they have not achieved complete cessation of 
breastfeeding. 
 
VRC07-523LS: All infants in Dose Group 5 will receive a single 
dose at birth.  Infants in Dose Group 5, Cohort 2 will receive a 
second dose at Week 12 if they have not achieved complete 
cessation of breastfeeding. 
 
NOTE:  It is expected that serum levels will remain detectable for > 
1 month after the final dose of VRC01 and at least 6 months after the 
final dose of VRC01LS or VRC07-523LS. 
 
STUDY  
DURATION:  
Dose Groups 1 and 2: minimum of 48 weeks 
Dose Group 3: 96 weeks 
Dose Group 4: 96 weeks 
Dose Group 5: 96 weeks 
 
OBJECTIVES: 
 
Primary:  In HIV exposed infants at increased risk for peripartum or breastfeeding HIV 
transmission: 
 
1. To assess safety of single subcutaneous dose (20 mg/kg or 40 mg/kg) of VRC01 
(Dose Groups 1 and 2).  
2. To determine pharmacokinetic profile of single dose, subcutaneous VRC01 (Dose 
Groups 1 and 2). 
3. To assess safety of monthly subcutaneous doses of VRC01 (Dose Group 3).  
4. To determine pharmacokinetic profile of monthly subcutaneous doses of VRC01 
(Dose Group 3). 
5. To assess safety of one and two subcutaneous doses of VRC01LS (Dose Group 4, 
Cohorts 1 and 2).  
6. To determine pharmacokinetic profile of one and two subcutaneous doses of 
VRC01LS (Dose Group 4, Cohorts 1 and 2). 
7. To assess safety of one and two subcutaneous doses of VRC07-523LS (Dose 
Group 5, Cohorts 1 and 2).  

 
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06 November 2018 
8. To determine pharmacokinetic profile of one and two subcutaneous doses of 
VRC07-523LS (Dose Group 5, Cohorts 1 and 2). 
 
Secondary: 
 
1. To examine the anti-VRC01 antibody production following immunization. 
2. To examine the anti-VRC01LS antibody production following immunization. 
3. To examine the anti-VRC07-523LS antibody production following immunization. 
 
Exploratory:  
 
1. To assess the amount of VRC01/ VRC01LS/ VRC07-523LS in oral secretions. 
2. If one or more infants are determined to be HIV-infected, to describe the 
neutralization sensitivity of the infant and maternal virus and the amount of HIV-
1 provirus and plasma HIV-1 RNA (measured in copies/mL), after receipt of 
VRC01, VRC01LS, or VRC07-523LS. 
3. To assess neutralizing ability of serum before and after receipt of the antibody. 

 
IMPAACT P1112 Version 4.0 
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06 November 2018 
  
 
 
 
If review of interim safety data reveals 
signal: consult SMC. 
Upon release of Version 3.0, protocol team reviewed safety data from all adult and pediatric protocols of VRC01 and VRC01LS 
(from P1112 database and most recent safety reports available from other protocols) as well as accrual status of Dose Group 3. 
There was no pause during the review of these data. 
Upon release of Version 4.0, protocol team reviews interim safety data from all adult and pediatric protocols of VRC01, 
VRC01LS, and VRC07-523LS (from P1112 database and most recent safety reports available from other protocols).  
There will be no pause during the review of these data. 
If review of interim safety data reveals no signal: open 
enrollment into Dose Group 5, Cohort 1.  
Review of safety data revealed no signal: enrollment into Dose Group 4, Cohort 1 opened on 21 June 2017.  
There have been and will be formal safety reviews of data from adult and pediatric protocols of VRC01, 
VRC01LS, VRC01LS and VRC07-523LS (from P1112 database and most recent safety reports available from 
other protocols) approximately every 6 months beginning after the first participant in Dose Group 5 reaches the 
Week 16 milestone, concurrently with the reviews described above for Dose Groups 3 and 4.   
After six infants in Dose Group 2 had completed Day 28 safety assessments,  
protocol team reviewed all available safety data.
After six infants in Dose Group 3 completed Week 8 safety assessments, protocol team reviewed all available safety (P1112) data.  
There was no pause in enrollment or immunization during this review
Protocol team reviewed 14 days of safety data on last infant 
enrolled and all available safety data on other participants.
Review of safety data revealed no signal: enrollment to Dose Group 2 resumed. 
Dose Group 1 reached target accrual on 28 January 2016.  Following review of data from all infants 
who had completed Day 28, Dose Group 2 was opened to accrual on 2 February 2016. 
Review of safety data revealed no signal: enrollment into 
Dose Group 3 opened 24 August 2016. 
After six infants in Dose Group 4, Cohort 1 completed Day 28 safety assessment, the protocol team reviewed all available safety 
data. There was no pause in Dose Group 4, Cohort 1 enrollment or immunization during this review. 
Review of safety data revealed no signal; enrollment into Dose Group 4, Cohort 2 opened on 7 December 2017.  
Enrollment into Dose Group 2 was paused on 18 May 2016 after first 3 mother-infant (MI) pairs had been enrolled.   
Review of safety data revealed no signal: enrollment into Dose Group 3 continued. 
After six infants in Dose Group 5, Cohort 1 complete Day 28 safety assessment, the protocol team will review interim safety and 
PK data. There will be no pause in Dose Group 5, Cohort 1 enrollment or immunization during this review. 
If review of safety and PK data reveals 
signal: consult SMC. 
If review of safety and PK data reveals no signal: open 
enrollment into Dose Group 5, Cohort 2.  
Figure 1: Overview of Study Design 

 
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1 
INTRODUCTION 
1.1 
Background 
In the United States and other resource rich countries, the risk of Mother to Child Transmission 
(MTCT) of Human Immunodeficiency Virus-1 (HIV) has been dramatically reduced through the 
combination of wide scale testing for HIV during pregnancy, treatment of all pregnant HIV-
infected women with highly active antiretroviral therapy (HAART), provision of cesarean 
section if the pregnant woman has active viral replication, administration of antiretroviral 
therapy to the infant for the first six weeks of life, and formula feeding.  With all these measures, 
1% or less of HIV-exposed infants will become HIV-infected.  However, in resource poor 
countries prevention of transmission is not so successful, resulting in continued MTCT of HIV to 
260,000 infants each year [1].  A partial list of factors that contribute to ongoing transmission in 
this setting include late diagnosis of maternal HIV infection, sometimes as late as the intrapartum 
period; lack of universal access to HAART during pregnancy; continued need to breast feed at 
least through the first year of life in most of the developing world; and limited access to maternal 
HAART or nevirapine (NVP) for the breastfeeding infant. 
 
In the United States, while transmission has been significantly reduced, HIV MTCT continues to 
occur.  Review of these transmission events allows identification of infants at highest risk of 
perinatal transmission and, therefore, the most likely to benefit from additional interventions that 
might further reduce the risk of intrapartum transmission of HIV.  Data on ongoing transmission 
in the US comes in part from the US Centers for Disease Control and Prevention Enhanced 
Perinatal Surveillance in 15 U.S. jurisdictions.  In a study evaluating transmission risk in 2005-
2008 in 8,054 births to HIV-infected mothers, 179 infants (2.2%) were diagnosed with HIV 
infection [2].  The odds of having an HIV-infected infant were higher among HIV-infected 
women who were tested late, had no antiretroviral (ARV) medications, abused illicit substances, 
breastfed, or had lower CD4 cell counts.  In another report of nearly 8,600 births to HIV-infected 
women reported to the CDC, 8% of women did not receive prenatal care; of those with prenatal 
care, 3% did not receive HIV testing during pregnancy; of those with HIV testing, 6% did not 
receive ARV prophylaxis or treatment during pregnancy; of those who received antenatal 
therapy, 5% did not receive ARV drugs during labor and delivery [3].  In a study of 707 women 
receiving HAART during pregnancy, overall transmission was 1.6%; MTCT was directly 
correlated with HIV viral load nearest delivery and duration of HAART during pregnancy and 
CD4 count near delivery were correlated with viral load [4].  A number of studies have 
demonstrated that duration of ARV prophylaxis during pregnancy is significantly associated with 
the risk of MTCT [4, 5]; in the European Collaborative Study, MTCT was significantly related to 
insufficient antenatal HAART, defined as no or <13 days of HAART [4].  An additional 
important risk factor for transmission in the U.S. is acute HIV infection during pregnancy in 
women with initially negative HIV tests [6].  Finally, the number of women with HIV infection 
giving birth in the U.S. has increased by approximately 30% since the year 2000 to 
approximately 9,000 annually, which can result in increased perinatal transmission secondary to 
these missed opportunities for prevention [3]. Thus, infants born to mothers with late diagnosis 
of HIV, receiving no antiretroviral drugs or short duration of HAART, or detectable viral load at 
delivery, are at particularly high risk of HIV transmission in the U.S. as well as in developing 
countries. 
 

 
IMPAACT P1112 Version 4.0 
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06 November 2018 
Globally, transmission resulting from breastfeeding is a major challenge to reducing rates of 
MTCT.  Breastfeeding carries a significant risk of HIV transmission: without antiretroviral 
therapy to mother or infant, transmission risk over the first year of life is between 5 and 15% [7-
9].  The risk can be reduced by exclusive breastfeeding, rather than mixed feeding, in the first six 
months and provision of antiretroviral therapy during the time of breastfeeding to either mother 
or infant.  Recommended therapy to prevent breast milk transmission includes either HAART to 
the mother or NVP to the infant during the period of breastfeeding.  However, even with 
treatment, breast milk transmission occurs in approximately 2 to 3% of infants [7, 8].   
 
Breastfeeding continues in spite of the transmission risk primarily because breast milk provides a 
substantial survival advantage in low resource settings.  In a meta-analysis conducted by the 
World Health Organization (WHO) collaborative study team, breastfeeding in the first two 
months of life provided a 6-fold reduction in infectious disease mortality [10].  This benefit 
diminished over time but remained significant throughout the first year of life with a 1.4-fold 
decrease in mortality due to infectious diseases attributable to breastfeeding in months 9-11.  
Thus, even with the risk of HIV transmission, in many low resource settings, breastfeeding still 
provides the best opportunity for a child to remain alive and HIV-infection free.  Therefore, it 
remains critically important to identify means whereby infants may be further protected from 
HIV during the time of breastfeeding. 
 
Administration of pre-formed antibodies, also known as passive immunization, can provide 
protection from infection or disease if protection is mediated through antibodies.  Evidence 
increasingly suggests that antibody, in particular neutralizing antibody, has the potential to 
prevent infection with HIV [11-15].  Further, passive antibody has been successfully used to 
prevent disease caused by other viral infections in children.  Infants born to women with hepatitis 
B who receive a single dose of hepatitis B immune globulin (HBIG) are protected against 
transmission in the intrapartum period [16] and infants at risk for serious respiratory syncytial 
virus (RSV) who receive monthly doses of the monoclonal antibody (mAb), palivizumab 
(Synagis®), have a reduced risk of serious RSV illness during the first few months of life [17]. 
These two examples highlight viral infections that can be prevented with administration of 
polyclonal and monoclonal antibody and suggest the possibility that passive antibody might 
prevent mother to child transmission of HIV. 
 
While previous studies of monoclonal antibodies (mAb) to prevent MTCT of HIV have been 
proposed, the studies were not implemented because there was no antibody product with broad, 
cross clade neutralization ability that also lacked anti-self-reactivity.  Recently, investigators in 
the Vaccine Research Center (VRC) at the National Institutes of Health (NIH) have described a 
broadly neutralizing mAb, VRC01 [18, 19].  VRC01 is a recombinant human immunoglobulin 
G1 (IgG1) monoclonal antibody produced in a Chinese Hamster Ovary (CHO) cell line that 
binds to the CD4 binding site of gp120 and neutralizes more than 90% of a diverse panel of tier 2 
viruses (Table 1).  Antibody levels of 50 µg/mL neutralize (IC50) 91% of isolates tested and more 
than 70% are neutralized by 1 µg/mL.  In comparison, the mAb b12, [19-21]  which was the 
prior gold standard for broad neutralization, achieved an IC50 at 50 µg/mL against <50% of tier 2 
isolates.  Potency breadth curves ( 
 

 
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06 November 2018 
Figure 2) demonstrate broad and potent neutralization against a panel of 179 viruses.  Further, 
there is no evidence that VRC01 is auto- or poly-reactive as demonstrated by antinuclear 
antibody (ANA) reactivity, anticardiolipin assay, or prolongation of the activated partial 
thromboplastin time (aPTT) [22].  Additional experiments, outlined in the Investigator’s 
Brochure (IB), detail extensive immunohistochemical studies performed on 38 types of tissue for 
adults and 21 types of tissue from neonates demonstrating no cross reactivity with any tissue 
type (IB).  Anti-self properties limited the development of earlier “broadly” neutralizing anti-
HIV monoclonal antibodies such as 2F5 and 4E10 [23].  Based on the potent and broad 
neutralizing activity as well as the in vitro safety profile, VRC01 holds tremendous promise as a 
therapeutic agent to further reduce HIV transmission in infants.   
 
Two groups have evaluated the ability of monoclonal antibodies to neutralize early infant virus 
and both showed that VRC01 was a potent inhibitor, neutralizing 18/23 infant isolates in one 
study [24] and six of seven early infant isolates in a second study [25], demonstrating that 
VRC01 is capable of neutralizing early, transmitted virus.   
 
 
Table 1: Breadth and Potency of VRC01 neutralization of tier 2 virus 
 
Clade B (N=25) 
 
 Clade A (N=24) 
 
         Clade C (N=32) 
 
 

 
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Figure 2: Breadth Potency Curves for VRC01 Data. 
 
Left curve: IC50 
 
 
Right curve: IC80 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.1.1 Pre-clinical in vivo data supporting product and dose selection 
A series of experiments were conducted in male and female rhesus macaques to determine 
VRC01 levels in serum and secretions after IV and SC dosing and the ability of VRC01 to 
protect animals from simian-human immunodeficiency virus (SHIV) challenge.  The first study 
determined plasma concentrations up to 28 days after IV or SC administration of 40mg/kg of 
pre-GMP VRC01 in female rhesus macaques.  The plasma concentration of VRC01 at day 14 
exceeded 50 µg/mL in 7/8 animals and 10 µg/mL in 7/8 animals (IB).  In addition, detectable 
concentrations were measured in rectal, vaginal, and nasal secretions.  The challenge-protection 
experiments were then completed in rhesus macaques using virulent chimeric SHIV which 
contains the HIV envelope in an SIV background.  The first experiment included groups of male 
rhesus macaques infused IV with research-grade VRC01 5 or 20 mg/kg or control human IgG.  
At 2 days post-infusion animals were challenged intrarectally with 300 tissue culture infectious 
doses (TCID) 50 of SHIV SF162P3.  All four animals infused with 20 mg/kg remained 
uninfected whereas two of four infused with 5 mg/kg had confirmed infection and three of four 
animals in the control group became infected.   
 
A similar study was conducted in female macaques but for this experiment all animals received 
IV VRC01 20mg/kg or control human IgG and the challenge was performed via the intravaginal 
route.  Again, all four animals infused with VRC01 remained uninfected, whereas three of four 
animals infused with control human IgG were infected.  
 
To extend these findings another challenge-protection study was conducted using a different 
SHIV and a larger number of animals.  Groups of at least 4 male rhesus macaques were 
administered a single dose of research-gradeVRC01 IV at 20 (n=6), 5 (n=6), 1.25 (n=4) or 0.3 
(n=16) mg/kg.  Fourteen controlled animals received human IgG.  At day 2 post infusion, all 
animals were challenged intrarectally with 1mLof SHIV-Ba-L virus that had a TCID50 titer of 
12,800/ml in Tzm-bl cells.  All animals infused with 20, 5 and 1.25 mg/kg VRC01 were 
protected from infection with SHIV-Ba-L; 7 out of 16 animals infused with 0.3 mg/kg were 
0.001
0.01
0.1
1
10
100
0.0
0.2
0.4
0.6
0.8
1.0
ug/ml
Fraction vs neutralized
0.001
0.01
0.1
1
10
100
0.0
0.2
0.4
0.6
0.8
1.0
ug/ml
Fraction vs neutralized

 
IMPAACT P1112 Version 4.0 
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protected; in contrast, all 14 animals that received a control human IgG were infected after the 
challenge with SHIV-Ba-L.  One hundred percent protection from SHIV-Ba-L challenge was 
demonstrated at 20, 5 and 1.25 mg/kg dose of VRC01 administered IV.   
 
In the final challenge-protection experiment conducted by Nancy Haigwood, seven newborn M. 
mulatta received a single SC dose of VRC01 followed by a single high dose oral challenge with 
SHIV SF162P3 24 hours later.  This animal model was previously shown to result in acquisition 
of infection in 100% of challenged animals.  In this experiment, one of five animals that received 
5 mg/kg had breakthrough infection and zero of two animals that received 20 mg/kg were 
infected.    
 
Although there has been a great increase in the understanding of the biological events occurring 
during HIV transmission in humans, there is much that is not yet known.  Non-human primate 
(NHP) models using various strains of SIV and SHIV have been developed, refined, and 
improved over years to more closely mimic the known events of HIV transmission [26]. The 
NHP models provide important data about transmission and potential efficacy of prevention 
interventions.  However, a fully predictive animal model is not available and animal data have 
sometimes failed to predict the results of human trial [27].  On the other hand, careful design of 
animal models recapitulated the result of a failed HIV candidate vaccine in a human trial 
indicating the potential to provide predictive results [28, 29].  NHP transmission studies are the 
best available pre-clinical model but proof of efficacy must be determined in human trials [26, 
27].   
 
VRC01LS was produced from VRC01 through modification by site-directed mutagenesis to 
increase its binding affinity for the neonatal Fc receptor (FcRn), and the resulting antibody was 
designated VRC01LS. 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]. Other than the two amino acid 
difference, VRC01LS is structurally identical to VRC01. As a result of its enhanced FcRn 
function, VRC01LS has an extended half-life in both serum and mucosal tissue compared to 
VRC01 and improved protection against primate SHIV infection [31]. 
 
VRC07-523LS was derived from VRC-01 through cloning and structure-guided optimization 
techniques designed to produce an antibody with greater potency, breadth and half-life. The 
increased neutralization potency in vitro and prolonged half-life of VRC07-523LS correlate with 
improved protection against SHIV infection in vivo in animal studies, suggesting a potential 
clinical advantage in humans for preventive and/or treatment of HIV. Like VRC01 and VRC01-
LS, VRC07-523LS is targeted against the HIV-1 CD4 binding site. The mutations that together 
define the 523 designation are a glycine to histidine mutation at residue 54 of the heavy chain, a 
deletion of the first two amino acids, glutamate and isoleucine, from the light chain, and a valine 
to serine mutation at the third amino acid residue of the light chain. The LS designation specifies 
methionine to leucine (L) and asparagine to serine (S) (M428L/N434S, referred to as LS) 
changes within the C-terminus of the heavy chain constant region. The LS mutation was 
introduced by site-directed mutagenesis to increase the binding affinity for the neonatal Fc-
receptor (FcRn), resulting in increased recirculation of functional IgG, thus increasing plasma 

 
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06 November 2018 
half-life. The resulting product has significantly increased potency and breadth compared to 
VRC01 or VRC01LS (Table 2).    
 
VRC07-523LS is 5- to 8-fold more potent than VRC01, with an inhibitory concentration IC50 
<50 mcg/mL against 96% of HIV-1 pseudoviruses representing the major circulating HIV-1 
clades and IC50 <1 mcg/mL against 92% of HIV-1 viruses tested and displays minimal levels of 
autoreactivity. VRC07-523LS was shown to have a prolonged half-life over VRC07 by about 2-
fold. In vivo proof-of-concept studies showed that VRC07-523LS is about 5-fold more potent 
than VRC01-LS in rhesus macaques [32].  
 
Table 2: Potency and Breadth of HIV-1 Neutralization of VRC01 and VRC07-523LS (Development-Grade 
Material) 
 
  
 
 
 

 
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06 November 2018 
 
1.1.2 Study Product 
Detailed descriptions of the products are contained in their respective IBs, which will be 
provided to all registered sites. 
 
1.1.3 Product Development 
The present study is one in a series of planned studies that will ultimately result in sufficient 
clinical data to allow a larger efficacy trial to occur in infants exposed to HIV at delivery and 
through breastfeeding. The first studies to be conducted have occurred in adults in the US. The 
studies are summarized in Table 3 below. Two Phase I studies of VRC01 occurred in HIV 
positive and HIV negative adults, respectively, to confirm safety and PK in both populations [33, 
34]. These were dose-escalating up to 40mg/kg. Similarly, safety and PK studies of VRC01LS 
[35] and VRC07-523LS have been completed in adults. The studies were conducted at the NIH 
VRC and had data available prior to enrollment of infants into IMPAACT P1112. Additional 
studies are now enrolling large numbers of adult subjects into studies of each of these 
monoclonals in adults for prevention and treatment of HIV (Table 3). 
 
The present study is the initial infant study and it will be conducted at sites in the US and in 
Africa. Further infant studies will be conducted through IMPAACT in settings where 
breastfeeding of infants remains the best option for infants born to HIV-infected women.  This is 
a Phase I safety study that may position IMPAACT to conduct a large efficacy study depending 
on the results of an ongoing study in adults.  
 
 

 
IMPAACT P1112 Version 4.0 
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06 November 2018 
Table 3: Planned or completed studies of VRC01, VRC01LS and VRC07-523LS 
Study 
Study Design 
Participant 
Population 
Dosage (mg/kg) route x numbers of administrations 
Target Accrual 
VRC01 or VRC01LS/placebo 
VRC 601 
(Completed) 
Phase 1, open label, dose 
escalation of VRC01 
HIV-infected adults 
1 mg/kg IV x 2 doses 
5 mg/kg IV x 2 doses 
5 mg/kg SC x 2 doses 
20 mg/kg IV x 2 doses 
40 mg/kg IV x 2 doses 
Pharmacokinetics (PK) and viral phenotype 
23 
(up to 5 per dose group;  
11 in 40 mg/kg) 
VRC 602 
(Completed) 
Phase 1, open label, dose 
escalation of VRC01 
Healthy Adults 
5 mg/kg IV x 2 doses 
5 mg/kg SC x 2 doses 
Placebo SC x 2 doses 
20 mg/kg IV x 2 doses 
40 mg/kg IV x 2 doses 
PK  
23/5 
(5 per dose group) 
IMPAACT P1112  
(the present study) 
Phase 1, open label, dose 
escalation of VRC01 and 
VRC01LS 
Newborn infants of 
HIV-infected 
mothers 
(US and African 
sites) 
Dose Group 1: 20 mg/kg SC x 1 dose 
Dose Group 2: 40 mg/kg SC x 1 dose 
Dose Group 3: 40 mg/kg SC at ≤ 5 days of life 
then, 20 mg/kg SC q 4 wks for minimum of 24 weeks and no more than 72 
weeks while breastfeeding 
Dose Group 4: VRC01LS SC at ≤ 5 days of life and then at Week 12 if still 
breastfeeding.  80mg < 4.5kg; 100mg ≥ 4.5kg 
(in addition to standard perinatal ARV prophylaxis for all arms) 
Safety assessed and PK done to assess target trough.  
59/0 
(13 per dose group) 
 
 
HVTN 104 
(Completed) 
Phase 1, multicenter 
randomized trial, Group 1 
and Group 2 are open-
label VRC01 and Group 
3 is double-blind, placebo 
controlled. 
HIV-uninfected 
volunteers aged 18 to 
50 years  
Group 1 (open-label): 40 mg/kg, IV at Month 0 then 20 mg/kg IV at Month 1, 
2, 3, 4, 5 
Group 2 (open-label): 40 mg/kg IV at month 0 then 40 mg/kg IV at month 2, 4 
Group 3 (double-blind): 40 mg/kg IV at month 0 then 5 mg/kg SC at month 
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 
Group 3 (placebo controlled) IV placebo at month 0 then SC placebo at month 
0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5  
Group 1: 20/0 
Group 2: 20/0 
Group 3 (double blind): 20/0 
Group 3 (placebo controlled): 0/4  
HVTN 703/ 
HPTN 081 
(Ongoing) 
Phase 2b, multicenter 
randomized trial, double-
blind, placebo controlled 
VRC01 
HIV-uninfected  
sub-Saharan African 
women aged  
18-40 years 
Group 1: 10 mg/kg IV at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72 
Group 2: 30 mg/kg IV at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72 
Group 3: IV placebo at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72 
1268/634 
HVTN 704/HPTN 085 
(Ongoing) 
Phase 2b, multicenter 
randomized trial, double-
blind, placebo controlled 
VRC01 
HIV-uninfected 
adults 
Group 1: 10 mg/kg IV at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72 
Group 2: 30 mg/kg IV at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72 
Group 3: IV placebo at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72 
1800/900 
A5342 
 (Participants off study 
and primary analysis 
completed) 
Phase 1, multicenter 
randomized trial, double-
blind, placebo controlled 
VRC01 
HIV-infected adults 
Arm A:  Two infusions of VRC01 (40 mg/kg) IV at weeks 0 and 3 and two 
infusions of placebo IV at weeks 6 and 9 
Arm B: Two infusions of placebo IV at weeks 0 and 3 and two infusions of 
VRC01 (40 mg/kg) IV at weeks 6 and 9 
20/20 

 
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06 November 2018 
A5340 
(Closed to follow-up) 
Phase 1, open label 
VRC01 
HIV-infected adults 
40 mg/kg IV x 3 doses; One each on days 0, 21, and 42 
15/0 
 
IMPAACT 2008  
(Ongoing) 
Phase I/II, multicenter 
randomized trial, open 
label VRC01 
HIV-infected infants 
age 0-120 days 
Arm 1: 40mg/kg/dose SC at Weeks 0, 2, 6, 10 with cART provided outside 
the study 
Arm 2: cART with cART provided outside the study 
34/34 
 
15-I-01040 
(Completed) 
Phase I/II, open label 
VRC01 
HIV-infected adults 
40mg/kg IV x 3-8 doses, given on days -3, 14, 28, and monthly up to 6 
months. 
10/0 
RV397 
(Completed) 
Phase II single center 
randomized placebo 
controlled trial of VRC01 
HIV-infected adults, 
acutely treated  
Arm 1: 40mg/kg/dose VRC01 IV at Weeks 0, 3, 6, 9, 12, 15, 18, 21 and 24 
Arm 2: Placebo IV at the same time points 
ART interruption will occur at week 0 
Arm 1: 18 
Arm 2: 6 
RV398 
(Ongoing) 
Phase I multicenter 
randomized placebo 
controlled trial of VRC01 
HIV-infected adults 
with acute HIV 
infection 
Arm 1: Immediate ART and placebo infusion at Week 0 
Arm 2: Immediate ART and single infusion of 40mg/kg VRC01 IV at Week 0 
Arm 3: Single infusion of 40mg/kg VRC01 IV at Week 0 and ART at Week 1 
24 (8 per arm) 
HVTN 116  
(Ongoing) 
Phase I, open label 
(VRC01 and VRC01LS)  
HIV-uninfected 
adults 
Group 1: 10 mg/kg VRC01 IV at Month 0, 2, 4 and 6 
Group 2: 30 mg/kg VRC01 IV at Month 0, 2, 4 and 6 
Group 3: 30 mg/kg VRC01LS IV at Month 0, 3 and 6 
Group 4: 30 mg/kg VRC01 IV at Month 0 
Group 5: 30 mg/kg VRC01LS IV at Month 0 
101/0 
VRC 606 
(Closed to follow-up) 
Phase 1, open label, dose 
escalation of VRC01LS 
HIV-uninfected 
adults 
Group 1: 5 mg/kg VRC01LS IV on Day 0 
Group 2: 5 mg/kg VRC01 SC on Day 0 
Group 3: 20 mg/kg VRC01LS IV on Day 0 
Group 4: 40 mg/kg VRC01 IV on Day 0 
Group 5: 5 mg/kg VRC01LS SC on Day 0, Week 12 and Week 24 
Group 6: 20 mg/kg VRC01LS IV on Day 0, Week 12 and Week 24 
40/0 
VRC 607/A5378 
(Ongoing) 
Phase 1, open label, 
single dose VRC01LS 
and VRC07-523LS 
HIV-1-infected 
adults 
40 mg/kg IV x 1 dose 
10-20/0 
VRC 605 
(Ongoing, closed to 
accrual) 
Phase 1, open label, dose 
escalating VRC07-523LS 
HIV-uninfected 
adults 
Group 1 1mg/kg IV 
Group 2 5mg/kg IV 
Group 3 5mg/kg SC 
Group 4 20mg/kg IV 
Group 5 40mg/kg IV 
Group 6 5mg/kg SC on Month 0, 3, and 6 
Group 7 20mg/kg IV on Month 0, 3, and 6 
Groups 1-5:  3/0 
Groups 6-7:  5/0 
HVTN127/HPTN087 
(Ongoing) 
Randomized Phase 1 Trial 
to Evaluate the Safety and 
PK of VRC07-523LS, 
Multiple Doses, Routes, 
and Dosing Schedules 
HIV-uninfected 
adults 
Group 1 2.5mg/kg IV at weeks 0, 16, 32, 48, 64 
Group 2 5 mg/kg IV at weeks 0, 16, 32, 48, 64   
Group 3 20mg/kg IV at weeks 0, 16, 32, 48, 64  
Group 4 2.5mg/kg SC 0, 16, 32, 48, 64 
Group 5 5mg/kg SC at 0, 16, 32, 48, 64  
Group 6 2.5 mg/kg IM at weeks 0, 16, 32, 48, 64 
20/0 per group 
Group 6: 20/4 

 
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1.1.4 Product Safety 
Preclinical: 
A series of experiments have been conducted to assess anti-self properties and toxicities 
in laboratory animals of both study products.  These studies are described in detail in the 
respective IBs.  To briefly summarize; antiphospholipid characteristics were assessed by 
two different methods.  The first method utilized a luminescent assay to measure binding 
of VRC01 to cardiolipin.  While another anti-HIV mAb demonstrated strong binding to 
cardiolipin, neither Synagis (an FDA-approved mAb), nor VRC01 reacted with 
cardiolipin.  In a separate experiment, anti-Phospholipid characteristics were evaluated by 
measuring impact on activated partial thromboplastin time (aPTT).  Again, VRC01 was 
compared to 4E10 and Synagis and again, antiphospholipid activity was seen for 4E10 
but not for Synagis or VRC01.   
 
Anti-nuclear antigen reactivity was assessed with a commercial lupus kit (anti-ANA).  
Unlike other anti-HIV neutralizing mAb, VRC01 does not react with nuclear antigens.   
 
In an additional experiment, binding to a human cell line was assessed via 
immunohistochemistry.  In this experiment, fluorescently-labeled VRC01 does not bind 
Hep-2 cells.   
 
In experiments to evaluate the potential for human autoreactivity, VRC01LS was 
assessed for anti-phospholipid reactivity, anti-nuclear antigen reactivity, binding to a 
human epithelial cell line (HEp-2) by immunohistochemistry, and potential “off target” 
binding to protein arrays microchips precoated with 9400 full-length human proteins: all 
experiments showed no clinically significant autoreactivity.  In an assessment of potential 
“off target” binding in a human Tissue Cross-Reactivity study VRC01LS and VRC01 
variably stained cytoplasm and cytoplasmic granules in epithelial and/or decidual cells in 
several human tissues. The findings were judged of no toxicologic significance for mAb 
as the cytoplasmic compartment is not available to mAb in vivo [36, 37].     
 
As previously noted, VRC01 and VRC01LS differ by only two amino acids. As a result 
of these changes, binding to the neonatal Fc receptor (FcRn) is increased resulting in an 
extended half-life in both serum and mucosal tissue compared to VRC01 and improved 
protection against primate SHIV infection [31]. VRC01LS has similar in vitro 
neutralization potency and breadth when compared to VRC01 (wild type). VRC01LS is 
found at higher concentrations in macaque rectal secretions, as well as rectal and vaginal 
tissues. When administered IV at a single dose of 10 mg/kg to rhesus macaques, 
VRC01LS persisted up to 70 days in rectal tissues, while VRC01 was no longer 
detectable after 28 days. 
 
In preclinical experiments in macaques, after a single dose of VRC01LS was 
administered intravenously (IV) at doses from 0.02 to 20 mg/kg (n=26), or 
subcutaneously (SC) at a dose of 10 mg/mL (n=6), there was no indication of local 
reactogenicity, anaphylactoid reaction, or any systemic disease (based on clinical 
symptoms).  In a series of experiments, VRC01LS was compared to VRC01 in ability to 

 
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06 November 2018 
protect from challenge in male and female macaques.  In all experiments, VRC01LS 
demonstrated a longer half-life (increased about 3-fold), persistent levels in GI tract and 
other mucosal surfaces, and improved ability to protect from infection.   
 
To summarize the VRC01LS preclinical data, VRC01 and VRC01LS are similar with 
VRC01LS displaying improved pharmacokinetics, identical or improved antiviral effects, 
and no unexpected cross reactivity in any of the neonatal human tissues examined 
(VRC01LS IB, Version 3.0, dated 21 August 2017). 
 
In other pre-clinical safety studies, VRC07-523LS demonstrated slight reactivity to 
phospholipids and a small subset of nuclear antigens, minimal reactivity with HEp-2 
cells, and no impact on aPTT by binding phospholipids. In studies of potential “off 
target” binding in a GLP tissue cross-reactivity study with normal adult human and rat 
tissue, VRC07-523LS staining of cytoplasmic and extracellular elements was similar 
between the human and Sprague-Dawley rat tissues examined. According to ICH S6(R1), 
monoclonal antibody binding to cytoplasmic sites generally is considered of little to no 
toxicologic significance. In further “off target” binding studies in human tissue, VRC07-
523LS staining was observed in cytoplasm, cytoplasmic granules, and/or perinuclear 
cytoplasm of various neonatal human tissues. No membrane specific binding was 
observed suggesting that there is no cross-reactivity of toxicologic concern.  
 
Pharmacokinetics Study in Sprague-Dawley Rats:  
A single-dose IV and SC PK study (SRI Study No. M896-11) was performed by SRI 
International (Menlo Park, CA) with VRC-HIVMAB060-00-AB (VRC01) in male and 
female Sprague-Dawley rats in accordance with U.S. FDA “Good Laboratory Practice 
(GLP) for Nonclinical Laboratory Studies.” This study was conducted with a pre-GMP 
pilot lot of VRC01 using a purification process similar to that of the GMP clinical-grade 
drug product.  For the PK study, a cohort of rats received VRC01 on day 1 at 4 mg/kg 
and 40 mg/kg by the IV route of administration and at 40 mg/kg by the SC route of 
administration. Each of these 3 groups contained 9 male and 9 female rats. VRC01 levels 
in serum were determined using an enzyme-linked immunosorbant assay (ELISA) with 
samples collected pre-dose from each animal and from an additional 3 males and 3 
females to provide untreated control serum. Blood was collected from 3 rats/sex/PK 
group for a total of 4–5 collections per PK animal at each of the following time points: 1, 
4, 8, 24, 48, and 72 hours and 7, 14, 21, and 29 days.   
 
VRC01 administration by the IV route resulted in a dose-proportional exposure. The 
terminal elimination phase half-life (t1/2) was about 10 days, with clearance (Cl) of 
approximately 20 ml/day/kg and volume of distribution (Vd) that was about 0.28 L/kg, 
indicating that the drug was distributed primarily in the serum and eliminated slowly. 
VRC01 administration by the SC route resulted in mean peak serum levels at 7 days for 
males or 3 days for female animals. The maximum serum concentration (Cmax), and area 
under the concentration-time curve to the last time point (AUClast) values were lower 
when 40 mg/kg was administered by the SC route compared with the IV route. The 
bioavailability of 40 mg/kg VRC01 administered by the SC route was estimated to be 
31.4% (males) and 42.3% (females). After the peak concentration of VRC01 was 

 
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06 November 2018 
achieved in the SC group, the serum levels decreased much more rapidly from 7 to 14 
days than they did in the IV groups, and VRC01 concentrations in the SC group were not 
quantifiable at time points after 14 days. These data indicate that clearance of VRC01 in 
rats was markedly enhanced when it was administered by the SC route. The development 
of antidrug antibodies that contribute to an increased rate of clearance is often observed 
in preclinical safety studies of protein-based test articles when they are not tested in the 
species of origin. Although immunogenicity was not examined in this study, the presence 
of such antibodies might have possibly contributed to the increased rate of clearance of 
VRC01 after SC administration that was observed in this study [10, 11].   
 
Repeat Dose Toxicity Study: 
A repeat dose IV and SC toxicity study (SRI Study No. M896-11) was performed by SRI 
International (Menlo Park, CA) with VRC-HIVMAB060-00-AB (VRC01) in male and 
female Sprague-Dawley rats in accordance with U.S. FDA “Good Laboratory Practice 
(GLP) for Nonclinical Laboratory Studies.” This study was conducted with a pre-GMP 
pilot lot of VRC01 using a purification process similar to that of the GMP clinical-grade 
drug product.   
 
For the safety assessment, vehicle or 4 mg/kg, 40 mg/kg, or 400 mg/kg VRC01 was 
administered by tail vein injection on days 1 and 8 to Groups 1 through 4, respectively.  
An additional group (Group 5) received 40 mg/kg VRC01 via SC administration to the 
dorsal scapular region on days 1 and 8.   
 
Results obtained showed that both IV and SC routes of administration were well tolerated 
in the rats. All animals survived until their scheduled necropsy. No findings or changes 
were seen in clinical observation, body weight, food consumption, body temperature, 
injection site irritation, hematology, coagulation, or organ weight evaluations that are 
attributed to administration of VRC01. VRC01 administration resulted in small, transient, 
dose-dependent increases in aspartate aminotransferase (AST) and alkaline phosphatase 
(ALP) on day 9, one day after the second dose. The increase in AST was up to 1.5-fold 
when compared with prestudy levels; the increase in ALP was up to 2.3-fold. By day 30, 
AST values had returned to normal, and ALP values were returning to normal. The small 
and transient elevations in AST and ALP are of minimal toxicological significance 
because of the following: (1) the animals had recovered or were recovering by Day 30; 
(2) there were no corresponding histopathology findings in the organs typically 
associated with AST and/or ALP increases (liver, kidney, muscle, bone, or intestines); 
and (3) other biomarkers of liver or kidney damage such as alanine aminotransferase, 
creatinine, blood urea nitrogen, and electrolytes were not meaningfully affected after 
administration of VRC01. 
 
Other than erythema red discoloration of the administration site in one male in the SC 
group on day 9, there were no other gross necropsy observations attributable to VRC01 
administration. There were no histopathology findings considered related to IV 
administration of VRC01. However, histopathology evaluation revealed subacute 
inflammation at the SC injection site on day 9, one day after injection, in all 10 SC 
administered rats; dermal inflammation was usually minimal or mild while SC 

 
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inflammation was usually mild, moderate, or marked. By day 30, this inflammation had 
completely resolved, and the SC dose site was normal in all rats.   
 
This GLP repeat dose toxicology study, which included an IV dose 10 times higher than 
the intended dose in humans, supports both the IV and SC administration of VRC01 in 
the proposed human studies. 
 
To bridge the preclinical proof-of-concept studies performed with research-grade VRC01 
to the clinical product, the neutralization profiles of all materials used in the preclinical 
studies were generated against a panel of up to five strains of HIV-1. The virus panel 
included the four strains (3 HIV isolates and 1 murine leukemia virus variant isolate 
(SVA.MLV) negative control) tested in the viral neutralization assay used for release 
testing of the clinical product. All clinical drug substance and drug product lots of 
VRC01 were found to have equivalent or better neutralizing potency when compared to 
the research-grade materials. 
 
Administration of VRC07-523 LS at repeat doses up to 400 mg/kg/dose IV or SC was 
well tolerated in Sprague-Dawley Rats and most findings were reversible and no longer 
seen at the end of the recovery period. 
 
Clinical Studies: 
Phase I clinical trials of VRC01 and VRC01LS are currently underway. Completed 
studies include first-in-humans dose escalation studies for safety, tolerability, and PK of 
VRC01 in HIV-1-infected (VRC 601) [33] and HIV-1-uninfected (VRC 602) adults [34]. 
Both the IV and SC routes of administration have been evaluated. A clinical trial (HVTN 
104) evaluating serial dosing using several different IV or SC doses with different dosing 
schedules, for prevention of HIV-1 is completed [38, 39]. Studies of multiple doses of 
VRC01 to reduce markers of HIV-1 persistence in chronically infected, cART-treated 
HIV-1-infected adults are underway or completed (A5340, NIH 15-I-0140, A5342) [40], 
as is a study of the efficacy of VRC01 administration during ART interruption in adults 
(RV 397) [41] and another study of VRC01 for treatment during acute HIV-1 infection in 
adults is underway (RV 398).  
 
VRC 601 was the first study of the VRC01 mAb in HIV-1-infected participants [33]. It 
was a dose-escalation study to examine safety, tolerability, dose, PK, and anti-antibody 
immune responses. VRC 601 opened in September 2013 as a single-site study at the NIH 
Clinical Center, Bethesda, Maryland, and in total, 23 HIV-1-infected participants, 
including 15 aviremic ARV-treated participants and eight viremic non-ARV treated 
participants received one or two doses of VRC01 IV or SC at doses ranging from 1 
mg/kg to up to 40 mg/kg. The eight viremic patients received a single dose of study 
product IV and at 40 mg/kg. The first infusion at 1 mg/kg IV was administered in the 
VRC 601 study on September 30, 2013. Beginning on March 28, 2014, the dose 
escalation proceeded according to the schema. The first 40 mg/kg IV administration in 
this study occurred May 12, 2014, and the last infusion in VRC 601 occurred on April 6, 
2015. There were a total of 36 infusions in 23 participants. All IV and/or SC infusions 
were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicity.  

 
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There were no moderate or severe local or systemic reactions. One participant had mild 
tenderness at the injection site. Systemic events reported in the three days post-infusion 
included headache (7), myalgia (6), malaise (4), nausea (4), joint pain (3), and fever (1); 
all were mild [33].   
 
VRC 601 demonstrated antiviral effect. A single 40 mg/kg IV dose led to a 1.1 to 1.8-
log10 drop in plasma viral load in 6 of the 8 viremic participants not on ART [33]. Two 
viremic participants had only a marginal drop in plasma viral loads of 0.26 and 0.18 log10 
copies/mL, respectively; however, these two individuals were found to have baseline 
virus that was relatively neutralization resistant. Two adults, who had baseline plasma 
viremia <1000 copies/mL, had sustained suppression of viremia for over 20 days, until 
the plasma level of VRC01 decreased. The adults with higher baseline plasma viremia 
had evidence of outgrowth of escape variants in rebound viremia. These data indicate that 
a single dose of VRC01 at 40 mg/kg IV given as monotherapy resulted in an average 
virus load significantly decreased between days 3 and 21 after infusion compared to 
baseline, with the nadir at day 9. A 0.5 log10 copies/mL or greater decrease in plasma 
viral load is considered a positive antiviral response to a single antiretroviral drug. 
Among the ART-treated, virally suppressed adults, no change in proviral DNA load was 
observed after receiving two infusions of VRC01. However, the study demonstrated a 
VRC01-mediated anti-viral effect, with preferential suppression of neutralization-
sensitive strains [33].   
 
VRC 602 was the first study of the VRC01 mAb in HIV-1-uninfected adults [34]. It was 
a dose-escalation study to examine safety, tolerability, dose, and PK of VRC01. VRC 602 
opened in December 2013 as a single-site study at the NIH Clinical Center, Bethesda, 
Maryland, and the final infusion was administered in August 2014. There were three 
open-label, dose-escalation groups receiving intravenous doses at Week 0 and Week 4 
(5mg/kg, 20mg/kg, 40 mg/kg) and one double-blinded, placebo-controlled group for SC 
administration (5mg/kg). Cumulatively, 23 participants received 43 doses of VRC01, 
including five participants who each received two SC 5mg/kg doses. As observed in VRC 
601, the IV and/or SC infusions were well tolerated with no SAEs or dose-limiting 
toxicity [34]. There were only mild local reactions (5/23 participants) limited to redness 
and tenderness which were more common for the SC dose recipients. Similarly, only 
mild systemic reactions (nausea, headache, myalgia, malaise) were observed in a 
minority of participants. Anti-VRC01 antibody responses were not detected, and the mAb 
retained its expected neutralizing activity in serum.   
 
Data from ACTG A5340 demonstrated maintenance of viral suppression for 4 weeks in 
HIV-infected VRC01 recipients following ART interruption. There was a modest delay, 
overall, in the return of viremia compared to historical controls [40]. 
 
Further study of 88 adults at low risk for HIV infection (50% female) demonstrated 
favorable safety and PK profiles when the antibody was administered at varying doses 
over a prolonged period of time in study HVTN 104 [42]. Participants were followed for 
32 weeks after their first VRC01 administration and received a total of 249 IV infusions 

 
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and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor 
evidence for anti-VRC01 antibodies observed.  
 
As of February 2018, studies of VRC01 have now enrolled more than 800 adult 
volunteers with over 2500 doses. There have been no SAEs related to VRC01 that 
required expedited reporting to the FDA or other regulatory authorities and no study 
safety pauses for adverse events. In Phase 2 trials (still blinded), there have been 22 
related AEs of mild or moderate severity in 15 participants (two AEs of change in sleep 
pattern, two AEs of hypogeusia (decreased ability to taste), five AEs of urticaria, and one 
event each of wheals and erythema-left upper arm/right calf/under right breast, urticaria 
of upper limbs, urticaria of the face, infusion site pruritus, generalized body itchiness, 
low neutrophil count, dizziness during infusion, lightheadedness, loose stools, dermatitis, 
headache, nausea and malaise). There has been one related severe (Grade 3) AE of 
urticaria in one participant (VRC01 IB, Version 8.0, dated 21 August 2017).   
  
Given the potential for urticarial and/or allergic reactions after injections that may present 
with non-specific findings such as GI symptoms, clinicians should observe infants 
carefully following each injection and should manage any post-injection 
allergic/hypersensitivity reactions per site standard of care. In particular, clinicians should 
pay special attention to gastrointestinal symptoms (e.g., as part of post-injection 
observations and during contacts). 
 
VRC 606 was the first in human dose-escalation study to examine safety, tolerability, 
dose, and pharmacokinetics of VRC-HIVMAB080-00-AB (VRC01LS) monoclonal 
antibody in healthy adults [35]. The first 37 volunteers who received administrations of 
VRC01LS had no serious adverse events (SAEs) or dose-limiting toxicities. Mild malaise 
and myalgia were the most common adverse events (AEs). There were six AEs assessed 
as possibly related to VRC01LS administration, and all were mild in severity and 
resolved during the study.  
 
Regarding local reactions, VRC01LS administrations have been generally well tolerated. 
There was one instance of Grade 1 injection site reaction with persistent 
hyperpigmentation ongoing but improving at Day 28. Overall, three of 21 participants 
(14.3 %) who received VRC01LS IV and 14 of 18 participants (77.8%) who received 
VRC01LS SC and completed diary cards reported solicited local reactions in the week 
after product administration. These include 14 reports of mild local pain/tenderness. One 
participant in Group 5 (5 mg/kg SC) reported moderate pain, two participants (Group 5, 5 
mg/kg SC and Group 6, 20 mg/kg IV) reported mild bruising, two participants in Group 5 
(5 mg/kg SC) reported mild swelling, and two participants (Group 2 and Group 5, 5 
mg/kg SC) reported mild redness.  
 
Preliminary pharmacokinetic data from an ongoing clinical trial of VRC01LS in healthy 
adults shows increased persistence of antibody in participant sera with an elimination 
half-life of 71 +/- 18 days. The mean (+/-SD) serum concentration 12 weeks after one IV 
administration of 20 mg/kg or 40 mg/kg were 180 +/- 43 mug/mL (n = 7) and 326 +/- 35 
mug/mL (n = 5), respectively, which supports the planned dosing interval of 12 weeks in 

 
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Dose Group 4, breastfed infants. See Section 1.2 and Section 9 of this protocol for 
rationale used in dose selection. 
 
There is an ongoing study (VRC605) in adult participants to determine safety and PK of 
VRC07-523LS when administered intravenously or subcutaneously. To date, 26 
participants have been enrolled and received one or more doses of between 1 mg/kg and 
40 mg/kg. The preliminary PK results confirm the slower elimination and a longer half-
life than “non-LS” bNAbs, but the half-life of VRC07-523LS is not as long as has been 
described for VRC01LS. However, due to the increased potency, the resulting ability of 
plasma to neutralize virus is similar or even slightly better with VRC07-523LS even at 
trough concentrations. The net result may be an antibody that can still be given very 
infrequently that has enhanced breadth compared to VRC01LS.   
 
Twenty-five (25) of 26 subjects enrolled in VRC605 received at least 1 dose of VRC07-
523LS (12 SC and 25 IV administrations). One participant withdrew prior to receiving 
the study product. There have been no SAEs and no safety pauses for AEs. Overall, 15 of 
25 participants who received the product (60%) have had at least one AE with the 
maximum severity being Grade 1 for 7 participants, Grade 2 for six, Grade 3 for one and 
Grade 4 for one. The Grade 3 AE was for an elevated creatinine 56 days after the last 
product administration, most likely related to dehydration following exercise. The Grade 
4 AE was for elevated liver enzymes likely related to starting a concomitant medication, 
fluoxetine, known to cause hepatoxicity, and was not related to VRC07-523LS. In 
summary, AEs were generally mild, and the few severe AEs were not likely related to 
study drug.  
 
Two participants developed infusion reactions shortly after IV product administration. 
Specifically, one participant enrolled in the 40 mg/kg IV group experienced a moderate 
infusion reaction with chills, rigors, fever, myalgia, and headache beginning 15 minutes 
after completion of the infusion. All symptoms resolved within 12 hours. Another 
participant in the 20 mg/kg IV group experienced three separate infusion reactions (n=2 
moderate, n=1 mild) after each product infusion. The participant experienced nausea, 
chills, rigors, malaise, tachycardia, headache, myalgia, and arthralgia.  
 
Four (25%) participants reported mild or moderate systemic reactogenicity symptoms 
three days after product administration. The reported symptoms were malaise (n=2 mild, 
n=1 moderate), myalgia (n=2 mild, n=1 moderate), mild headache (n=2), and moderate 
chills (n=2). Five of 8 subjects (62.5%) receiving VRC07-523LS SC reported mild 
systemic reactogenicity symptoms: malaise (n=3), myalgia (n=2), headache (n=3), chills 
(n=1), nausea (n=1), and joint pain (n=2).   
 
Based on the PK and safety data available to date, the dose to be used in the present study 
is 80 mg (birthweight ≥ 2.0 to < 4.5 kg) and 100 mg (birthweight ≥ 4.5 kg), or 
approximately 18-40 mg/kg, administered subcutaneously (SC) as a single injection as 
close to birth as possible. This will be followed by a second 100 mg SC dose 
administered at Week 12 for infants still being breastfed.   
 

 
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1.1.5 Passive antibody safety in infants 
Use of monoclonal antibodies to prevent infectious disease is a relatively recent 
development; however, passive polyclonal antibody products have been used for decades 
with excellent safety profiles. The following paragraphs will first outline data on 
polyclonal antibody products followed by monoclonal data.   
 
Polyclonal products have been delivered to infants via the intravenous (IV), 
intramuscular (IM) and subcutaneous routes (SC) to prevent transmission of infections. 
Perhaps the best established and most frequently used product is hepatitis B 
immunoglobulin (HBIG) which is recommended as a single IM dose for all infants born 
to Hepatitis B antigen positive women in the US (and many other countries) [43]. This 
has been administered to thousands of infants as part of studies and as part of clinical care 
with few reported side effects. There is only one case report of an anaphylactic reaction 
in the literature [44]. In one study, HBIG was given by the SC route and found to also be 
safe and well tolerated [45]. Other polyclonal antibodies used in infants include 
Respigam®, Cytogam®, HIVIg, and IVIG. In a trial in which 500 women and their 
newborns received either HIVIg or IVIG, side effects in the women were uncommon and 
when they did occur, they were generally mild or moderate; only two women had severe 
side effects. In that trial, only two infants had toxicity thought to be related to study drug 
infusion, all graded as mild [46]. In a very large study of IVIG to prevent infection in 
preterm infants, the product was found to not decrease the risk of death or serious 
disability; however, product related adverse events were rare and no different in the IVIG 
group compared to placebo [47].   
 
There is considerably less experience in the use of monoclonal antibodies in neonates and 
infants; however, the data that do exist support the safety of monoclonal antibody 
products and provide some information that helps to guide initial dosing. Currently, there 
are only two monoclonal antibody products FDA-approved to prevent an infectious 
disease: Palivizumab (Synagis®), an anti-RSV monoclonal antibody; and Raxibacumab, 
an anti anthracis toxin. While the latter is FDA-approved for children, there are no 
pediatric data available. The most extensive safety data come from use of Palivizumab 
and several other products which are not FDA-approved, outlined below.   
   
Palivizumab is a humanized murine mAb directed against the F glycoprotein of RSV. 
This product is administered as a monthly 15 mg/kg intramuscular (IM) dose to infants at 
high risk of serious RSV disease during the RSV season. During the time of peak RSV 
activity (October through March) premature infants and others at high risk of severe 
disease may receive up to 6 doses of Palivizumab. In general, the series of Palivizumab 
doses are safe and well tolerated. The most frequently reported adverse events listed in 
the package insert are noted in Table 4; none occur more frequently in the Palivizumab 
recipients compared to placebo.   
 
 

 
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Table 4: Adverse Events Occurring at a Rate of 1% or Greater in Infantsϯ 
Receiving Palivizumab or Placebo 
Event 
Palivizumab (n=1641) 
n (%) 
Placebo (n=1148) 
n (%) 
Upper respiratory infection 
830 (50.6) 
544 (47.4) 
Otitis media 
597 (36.4) 
397 (34.6) 
Fever 
446 (27.1) 
289 (25.2) 
Rhinitis 
439 (26.8) 
282 (24.6) 
Hernia 
68 (4.1) 
30 (2.6) 
SGOT Increase 
49 (3.0) 
20 (1.7) 
ϯCyanosis (Synagis [9.1%]/placebo [6.9%]) and arrhythmia (Synagis [3.1%]/placebo [1.7%]) were 
reported during Trial 2 in CHD patients 
 
During the Palivizumab post-marketing period, severe thrombocytopenia, injection site 
reactions, and severe hypersensitivity reactions have been rarely reported. Because the 
reporting systems are voluntary, the actual incidence of such reactions cannot be 
determined. None of the reactions were fatal. It is not known whether the chimeric nature 
of Palivizumab (CDR3 region retained from original murine mAb on human IgG1 
backbone) plays a role in these rare hypersensitivity reactions and whether treatment with 
a fully human mAb like VRC01 would result in similar reactions.   
 
One theoretical concern with use of monoclonal antibodies is that the patient could 
develop their own antibody directed against the monoclonal and then either clear the 
monoclonal more rapidly over time (resulting in decreasing serum levels) or develop 
immune complex disease as the patient’s antibody and the administered monoclonal 
antibody formed complexes. This possibility was previously evaluated when Palivizumab 
was administered and found not to occur. Similarly, this has been evaluated for the 
products described below and not found to occur.   
 
Other monoclonal antibodies that have been administered to neonates or infants include 
pagibaximab (a human chimeric anti-staphylococcal mAb) [48, 49]; SB 209763 (a mouse 
humanized anti-RSV fusion protein) [50]; and motavizumab (a maturation variant of 
palivizumab) [51]. The above agents have been studied in preterm and term infants.  In 
all cases, the mAb was generally well tolerated. The one safety concern that was raised 
was for the motavizumab which was administered to over 5,000 children. Nine of 3,000 
(0.3%) children in one study of this product required treatment discontinuation due to a 
skin reaction; all in the treatment group (0 in placebo) and there was overall a higher 
incidence of skin AE in the treated group. A partial list of anti-infective monoclonal 
antibodies studied in adults includes KPBA-101 (anti Pseudomonas), CDA1, CDB1 (anti 
C. difficile) and others. The efficacy to prevent disease varies between the products but 
the safety profile is consistently good.   
 

 
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The excellent safety profile seen with anti-infective monoclonal antibodies is in direct 
contrast to the safety profile of monoclonal antibodies that have been developed to treat 
cancer and/or autoimmune disease. A review of the currently FDA-approved monoclonal 
antibodies (http://www.fda.gov/BiologicsBloodVaccines) lists 39 total products; 33 of 
which are used to treat cancer and or autoimmune disease. These agents carry a long list 
of side effects due to their anti-self-properties. In contrast, monoclonal antibodies that 
react with an infecting agent, rather than components of human tissue are consistently 
well tolerated and safe even when used in neonates. Given VRC01 documented lack of 
reactivity to human tissue, it is likely to be safe and well tolerated.    
 
1.1.6 Monoclonal antibody dosing 
The half-life (T1/2) of antibodies depends on a variety of factors including the isotype 
(IgG vs IgM or IgA), the subclass (IgG1), the ongoing transudative losses in a patient, 
and patient age. In general, IgG antibodies have a half-life (T1/2) in the range of 14 to 28 
days. In a primate model, VRC01 has a T1/2 of 10 days, and VRC01LS has a T1/2 of about 
30 days; however, clearance of a human mAb is expected to be increased in another 
animal species, therefore, it is anticipated that the T1/2 will be substantially longer in 
humans. The T1/2 of the human monoclonal Palivizumab in infants is 20 days. An initial 
pharmacokinetic study to determine T1/2 of VRC01 in adults was completed prior to the 
initiation of the infant study. While the adult study will be useful in predicting half-life in 
infants, the absolute level of antibody needed for protection cannot be determined from 
those adult studies. Further, the half-life of VRC01 in infants may be somewhat different 
than that seen in adults. Therefore, the proposed trial is necessary to confirm the 
appropriate dosing interval to use in future multi-dose trials with this agent.  
 
The PK results in HIV-infected and uninfected adults for VRC 601 and 602 have been 
published [33, 34] and are detailed in the IB. These results indicate that PK parameters 
are comparable in these two adult populations. The participants received one or two IV or 
SC doses at 28-day intervals.  
 
In healthy adults receiving VRC01 20 and 40 mg/kg IV, maximum serum concentrations 
were 940±320 (n=8) and 1600±230 (n=5) mcg/ml, respectively, after the first infusion, 
and 1100±360 (n=5) and 1500±400 (n=5) mcg/ml after the second dose, respectively. At 
20 and 40mg/kg, mean 28-day trough serum concentrations were 35±6.5 (n=8) and 
57±19 (n=5), and 56±19 (n=5) and 80±40 (n=5) mcg/ml after the second dose, 
respectively. The overall clearance for all IV groups (n=18) was 0.016±0.0033L/h. In the 
HIV-infected participants at 20 and 40 mg/kg IV, maximum serum concentrations were 
1000±340 (n=3) and 1500±340 (n=11), respectively, after the first infusion, and 
1000±510 (n=3) and 1700±460 (n=2) mcg/ml after the second dose, respectively. At 20 
and 40mg/kg, mean 28-day trough serum concentrations were 33±15 (n=3) and 30±16 
(n=11) after the first dose, and 46±27 (n=3) and 65±57 (n=2) mcg/ml after the second 
dose, respectively. The overall clearance for the IV groups (n=20) was 0.024±0.006 L/h. 
There were not significant differences in the PK parameters for the viremic and non-
viremic infected adults.    
 

 
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Evaluation of the SC route of administration in adults has been limited to the 5 mg/kg 
dose due to limitation on the volume that can be administered SC to adults.  As expected, 
the peak concentrations are achieved later than IV, at 67 and 62 hours for the uninfected 
and infected adults, respectively. The Cmax in plasma is higher for IV than SC dose 
(240±42 vs. 34±5 mcg/ml at a dose of 5mg/kg in the infected adults). However, the 
clearance and terminal half-life are similar between IV and SC. For the uninfected and 
infected participants, the terminal half-life was 15±3.9 and 12±4.5 days for IV dosing and 
17±2.9 and 11±5 days for SC dosing, respectively. Clearance (CL) following IV 
administration and apparent clearance (CL/F) following SC administration were similar 
suggesting good bioavailability (F) following SC administration. 
 
For VRC01LS, the maximum serum concentrations in adults in VRC606 following IV 
administration of 20mg/kg and 40mg/kg were 1221±398 mcg/mL (n=8) and 2451+626 
mcg/mL (n=3), respectively, with an overall half-life over 2 months. Following the single 
dose SC administration of VRC01LS 5 mg/kg, the Cmax is reduced to levels about 25% of 
those seen following IV administration but the SC AUC is only reduced by about 20% 
compared to IV.    
 
In preliminary PK studies of VRC07-523LS, adults who received 20 mg/kg (N=8) had a 
mean (± SD) day 28 concentration of 195 mcg/mL (+63) and a mean day 84 
concentration of 37 mcg/mL (+5.5). While the levels at day 28 and 84 are lower than that 
seen with VRC01LS, due to the increased potency, it is expected that the ability of 
VRC07-523LS to neutralize virus will be similar or better than that of VRC01LS at these 
timepoints. 
 
1.2 
Rationale  
UNAIDS estimates that almost 300,000 infants are newly HIV-infected each year, the 
vast majority due to mother to child transmission (MTCT). Measures to prevent 
transmission of HIV infection have improved dramatically leading to calls by UNAIDS 
and other organizations to eliminate new pediatric HIV infections by 2015. In spite of the 
successes, perinatal and breast milk transmission continues to occur. A substantial 
number of women are diagnosed and treated late in pregnancy resulting in higher rates of 
peripartum and early post-natal transmission even with maternal and/or infant 
antiretroviral therapy. Even with effective treatments for infants born to women with 
known infection, in high seroincidence regions, women will continue to transmit due to 
new maternal infections that occur after delivery. Studies show that acute maternal 
infection can occur in as many as 3% of women in high prevalence regions and the risk 
of transmission in the setting of acute infection is dramatically increased [52-56]. 
Protection of all infants will only be provided by vaccine that can be administered 
universally; however, a safe and effective vaccine capable of providing long-lasting 
protection is still not available. Recently, investigators at the United States National 
Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC) at 
NIH have discovered monoclonal antibodies (mAbs) that have potent and broad 
neutralizing activity (<50 µg/ml) against over 90% of tier 2 (difficult to neutralize) 
viruses from a multiclade panel. This broad and potent neutralizing ability has the 
potential to prevent HIV transmission in a variety of settings but in particular, holds 

 
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tremendous promise in the prevention of MTCT of HIV. Therefore, the following study 
is proposed to provide initial safety and pharmacokinetic information on single and 
multiple dose mAb VRC01, VRC01LS, and VRC07-523LS when administered to infants 
at increased risk of peripartum and post-partum HIV transmission.   
 
Single and multiple dose pharmacokinetic data from the present study will be used to 
select a dose regimen for repeated dosing that will be needed for protection during 
ongoing breast milk exposure. Protective efficacy will be determined in a future study 
which cannot begin until the present study determines a safe dose that provides a 
sufficient trough level. Demonstration that a neutralizing antibody prevents HIV 
transmission in humans would be a major milestone in the field of HIV prevention. 
Although ample data in animal models demonstrate protection with neutralizing 
antibody, this has yet to be studied in humans. Demonstration of efficacy will lead toward 
further development of mAb for use in prevention of MTCT and potentially for other 
post-exposure prophylaxis. It will also provide proof-of-concept for neutralizing antibody 
protection that will be important for design of active vaccines to induce immunity. 
 
While VRC01LS is a very promising product with excellent breadth, potency and a very 
long half-life, the newer product VRC07-523LS has increased potency and increased 
breadth compared with either VRC01 product. Thus, if VRC07-523LS has a similar 
safety profile and a half-life that approaches that of VRC01LS, then it would be the 
preferred product to take into subsequent trials. 
 
Product availability 
Monoclonal antibody products currently available in the US are extremely expensive. 
Lower prices and ability to deliver in resource poor settings are made feasible by recent 
advances in technology which allow production of clinical grade monoclonal antibody 
products for dramatically reduced prices; as low as $200 per gram for cost-of-goods 
depending on the scale of production. Thus, if the appropriate dose of VRC01 is 40 
mg/kg initially followed by 20 mg/kg monthly, total cost-of-goods for 6 months’ therapy 
is <$100. If 30 infants need to be treated to prevent one infection, then the cost would be 
about $3,000 for each infection prevented, far lower than the estimated cost for 20 years 
of HAART. Estimated costs would be lower for a long-acting monoclonal, such as 
VRC01LS, for which fewer doses would be required for protection. It is often difficult to 
predict how products will be made feasibly available in resource-constrained settings; 
however, it is clear that the technology can be adapted to low cost production and that a 
product which is sufficiently effective could be made available to populations that need 
it. These arrangements cannot be guaranteed or even planned until further evidence of 
product efficacy is in hand. 
 
Rationale for study population 
The greatest risk for MTCT of HIV occurs in Africa and India, among infants who are 
being breastfed; however, we are proposing this initial study to also include non-breast-
fed neonates in the US as well as at select international sites. In spite of the success in 
preventing most MTCT in the US and other countries where formula is a safe and 
affordable option and PMTCT regimens are available, there continue to be high risk 

 
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infants. The high-risk group includes infants born to women who seek care late in 
pregnancy, even as late as in labor, and who are, therefore, not treated until the 
intrapartum period.  Risk of transmission in this setting, even with combination therapy 
to the infant is >5% [57]. Further, there are women who are known to be infected and on 
therapy but with ongoing viral replication due to poor adherence or resistant virus. These 
high-risk infants have the potential to benefit from a neutralizing monoclonal antibody.   
 
The study product has the potential to decrease mother to child transmission of HIV in a 
variety of settings and this study is an initial step in the evaluation of the product. 
Ultimately, the target population that can benefit from a passive antibody would include 
infants both in the US and in resource poor countries. In the US, the target population 
would include high risk infants: that is, infants born to women who have replicating virus 
late in pregnancy, either due to late diagnosis, late presentation for care, poor medication 
adherence, or resistant virus. Worldwide, the target population would include infants with 
ongoing breast milk exposure who have a continued risk during the period of 
breastfeeding and around the time of weaning in spite of optimal ARV therapy. An added 
intervention such as this is necessary to eventually achieve a generation free of HIV. 
 
Risks and Benefits to Study Participants  
The potential benefit of the product is the potential for further reduction of MTCT of 
HIV, when given in addition to standard of care ARV therapy. This is particularly true 
for VRC01LS and VRC07-523LS, which – because of the long half-life – might be easier 
to implement as a public health measure in countries where risk of transmission from 
breastfeeding is common. The potential for this benefit is supported by in vitro data 
(ability to neutralize) and non-human primate experiments, both outlined in greater detail 
in the background section of the protocol.  
 
The potential risks of the product include risks of reactions at the local injection site or, in 
rare cases, systemic allergic reactions, such as urticaria observed in several adult study 
participants. Given the persistence of MTCT in the high-risk populations we are enrolling 
in the protocol, VRC01 offers a potential for benefit and, based on the available data 
from in vitro studies, animal studies, and studies of other monoclonal antibodies, appears 
to have an acceptable safety profile. VRC07-523 has a slight increase in auto-reactivity in 
in vitro studies, compared with VRC01. This auto-reactivity appears to be mild and did 
not result in adverse events in pre-clinical testing nor in initial clinical studies of adults. 
Further, the off-target binding assays displayed only intracytoplasmic binding and no 
membrane binding, suggesting that toxicity associated with that binding is unlikely.   
 
Research participation should always be carefully considered, but for some women it 
may be challenging to make a decision about participation if they are just learning their 
HIV status or were not previously engaged in HIV care. When P1112 was first 
conceived, there were concerns that, for women who have not been regularly engaged in 
care, there may be loss to follow-up in the course of research. However, because it is the 
infants born to such women who have the greatest potential for benefit – as this group has 
a significant ongoing transmission risk in spite of use of aggressive ARV therapy once in 
care – P1112 was opened. Under Version 1.0, the study did not enroll infants born to 

 
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HIV-infected women with well controlled virus in Dose Groups 1 and 2 because such 
infants have a very low risk of HIV-transmission, thus less potential for benefit from the 
investigational product. In Version 2.0, with evidence of safety, the criteria for risk were 
modified for Dose Group 2 (Dose Group 1 had been fully enrolled), and Dose Group 3 
was opened to infants with risk of transmission from breastfeeding. IMPAACT sites have 
successfully completed prior treatment trials requiring enrollment within 48 hours of 
birth of infants born to HIV-infected women who presented at near or at the time of 
delivery [57]. Conduct of P1112 has documented similar success with dosing within the 
protocol-specified timeframe for each dose group. Dose Group 4 and 5 Cohorts 1 enroll 
at both domestic and African sites to HIV-exposed non-breastfeeding infants; Cohorts 2 
enroll at African sites to HIV-exposed infants at risk of transmission from breastfeeding.   
 
There is a small risk of enrolling infants based on a maternal intrapartum rapid test results 
that is later determined to be a false positive test result. However, women who first test 
positive intrapartum are at extremely high risk for transmission and therefore, their 
infants are the most likely to benefit from aggressive intrapartum intervention including 
multidrug therapy. Most hospitals now offer, as standard of care, rapid intrapartum 
testing for women not tested during the current pregnancy or tested early in pregnancy 
but with other risk factors. Such products have good positive predictive value, especially 
when used in high risk populations. In a meta-analysis of Oraquick®, a popular rapid 
test, performed on blood samples that was reported recently in Lancet Infectious Diseases 
[58], specificity of the test was 99.91% and the positive predictive value in high 
prevalence populations was 98.5% and in low prevalence populations was 97.7%; 
therefore, we believe it is appropriate to allow sites to enroll women with positive rapid 
tests who are being approached to discuss strategies to reduce mother to child HIV 
transmission. However, in the Manual of Procedures (MOP), we will request that all sites 
work with their clinical and research labs to identify strategies to obtain confirmatory 
testing as rapidly as possible and if that confirmatory testing can be obtained rapidly, the 
sites are encouraged to review that test result before enrolling. However, requiring that 
second test result to be documented in all cases before enrollment will make it very 
difficult for the babies who are most likely to benefit to receive the drug rapidly; at the 
time it is most likely to help. 
 
The women enrolled will likely have challenges with the burden of clinical care and 
study participation. The study sites are experienced in assisting these women with access 
to care for both themselves and their infants. Further, since the infants are by definition 
high risk, the infants will require very frequent medical evaluation for clinical care alone; 
therefore, the added burden of study participation is relatively small. The sites will be 
required to coordinate research visits with clinical care visits and whenever possible 
facilitate transportation or even complete some study visits in the patient’s home, if the 
woman finds such home visits to be desirable. Women will be enrolled in the study as 
some of the history data needed to confirm infant eligibility will be gathered from 
maternal medical records (viral load, viral resistance for example) and maternal serum 
and PBMC will be collected and stored so that, if a transmission event occurs, we will be 
able to evaluate maternal virus transmitted and not transmitted with the infant isolate.  
However, women will not receive VRC01/VRC01LS/VRC07-523LS. 

 
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Consent  
Asking for consent during labor and reconfirmation of consent (and the right to 
withdraw) after labor is not without precedent, nor is it ethically necessarily problematic.  
However, the protocol team and investigators will take further steps (detailed in MOP) to 
bolster participants' ability to give informed consent during a particularly difficult period.  
We will include the following steps: 
1. The MOP will detail when and how women will be approached for consent 
antepartum and postpartum. Women who appear overly fatigued, in severe pain, 
or too inwardly focused to converse about the details of study participation will 
not be approached during labor.  
2. Gatekeepers including the woman’s primary OB provider and/or family members 
may be approached to ask if it is appropriate to approach a woman at that time; 
however, as family members may not be aware of the woman’s HIV diagnosis, 
this strategy will only be employed if family members are aware of the diagnosis.   
 
Whenever possible, women will be approached prior to onset of labor. For women who 
cannot be approached prior to labor (for whatever reason), consent will be obtained with 
great care and attention to the woman’s ability to understand and consent. Further, she 
will be provided an opportunity to withdraw consent after she delivers the infant and 
before the dose of study medication is administered, if she chooses. There is a 72-hour 
window after delivery for Dose Groups 1, 2 and Cohort 1 of Dose Groups 4 and 5 and a 
five-day window for Dose Group 3 and Cohort 2 of Dose Groups 4 and 5 for women who 
would like more time to consider the study before consenting. This option must be 
balanced by the knowledge that the product is more likely to work the sooner it is 
administered after exposure (delivery).   
 
Sites that intend to conduct home visits in lieu of clinic visits are expected to add detail 
about this to the site-specific informed consents. 
 
Rationale for VRC01 dose selection in multi-dose groups 
Doses up to 40 mg/kg have been tested in adults prior to the initiation of this study.  
Based on data from the adult studies (as described in “Clinical Studies”), from 
Palivizumab and other mAb, IC50 of tier 2 isolates, and the challenge-protection 
experiments conducted in primates we are projecting VRC01 doses of 20 and 40 mg/kg 
as sufficient to achieve a target trough (day 28) concentration of 50 µg/mL. For the multi-
dose cohort (Dose Group 3), we have selected an initial (loading) dose of 40 mg/kg 
followed by monthly doses of 20mg/kg. Assessment of the PK of the initial infants 
receiving 20 mg/kg supports this approach. The team also considered available data from 
adults (ACTG A5340; 40/mg/kg IV first dose) [40]). Figure 3 shows VRC01 
concentrations seen in P1112 infants (20mg/kg SC) and those seen in adults following 
40mg/kg IV. In A5340, the 40mg/kg IV dose was well tolerated and achieved VRC01 
concentrations approximately double those seen thus far in P1112 with the 20mg/kg SC 
dose. Thus, the team expects the Day 28 concentrations from P1112 Dose Group 2 
(40mg/kg SC) to be in the range seen in current adult trials of intravenous VRC01 
(40mg/kg) and, therefore, to the be appropriate starting dose for Dose Group 3.   

 
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06 November 2018 
 
Rationale for VRC01LS dose selection 
VRC01LS offers some clear advantages over VRC01.  Based on structural similarities, 
preclinical data, and initial adult data, VRC01LS is expected to have identical or 
improved antiviral effect and a safety profile similar to VRC01; however, given its 
dramatically improved half-life and preferential concentration at mucosal surfaces, it has 
the potential to improve delivery of the monoclonal antibody. Based on the adult PK data, 
modeling demonstrated that two doses (at birth and age 3 months) in an infant should 
result in serum levels above target (50 µg/mL) for six months or more. Because VRC01 
and VRC01LS are structurally so similar, the PK and safety data from studies of VRC01 
as well as studies ofVRC01LS (study VRC 606) have been considered in determining the 
dose for Dose Group 4. Based on the data available to date, weight-based dosing is 
planned: 80mg SC for infants weighing < 4.5kg at birth; 100 mg SC for infants weighing 
≥ 4.5kg at birth. If the infant is still breastfeeding at Week 12, a second dose will be 
administered. Figure 4 below shows that, when VRC01LS is administered as a single 
20mg/kg IV dose to healthy adults, average levels at day 84 are approximately > 
180mcg/mL, well above the 30-day trough target used for VRC01.   
 
Rationale for VRC07-523LS dose selection 
VRC07-523LS demonstrates a shorter half-life than VRC01LS; however, much longer 
than that of VRC01 (Figure 5). The shorter duration is balanced by the greater potency; 
therefore, we anticipate that by administering the same dose as used for VRC01LS, we 
will have similar ability of serum to neutralize susceptible virus at these later time points.  
Since VRC07-523LS has greater breadth, then more viruses that the child is potentially 
exposed to should be neutralized.   
 
It should be noted, however, that the dose needed to prevent infection is unknown, levels 
as low as 1 µg/mL neutralize more than 70% of tier 2 isolates, and the gradient between 
serum and relevant mucosal secretions is not known. Therefore, lower levels may be 
acceptable for moving these products into larger clinical trials.   
 
PK modeling, described in more detail in Section 9, demonstrates how the doses selected 
for the present study are anticipated to achieve target concentrations.  Briefly, based on 
preliminary adult data and data on VRC01LS PK in infants, modeling projects a median 
day 84 level in infants of 25 mcg/mL, assuming linear PK and no dose effect.  This 
suggests that all infants will achieve or surpass our target level of 10 mcg/mL on day 84 
(Figure 6). 
 
 

 
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Figure 3: Comparison of Infant SC 20mg/kg and Adult IV 40mg/kg of VRC 01 
 
 
 
Figure 4: VRC01 and VRC01LS levels following IV administration in adults 
 
 
 
0
7
14
21
28
35
Time Days
0
50
100
150
200
250
300
VRC01 Conc (mcg/mL)
VRC01 P1112 PK - MAR 2016 (n=8)
Infant (P1112 - SC) vs Adults (A5340 - IV)
Infant P1112
20mg/kg SC
Adult - A5340
40mg/kg IV
Two outlier A5340 >300mcg/mL shown as 300 mcg/mL
0
10
20
30
40
50
60
70
80
90
100
110
120
10
100
1000
10000
Time (days)
VRC01LS VRC01 (mcg/mL)
20 mg/kg IV
VRC01LS day 0 and 84
VRC01LS day 0 
VRC01 days 0 and 28
0
10
20
30
40
50
60
70
80
90
100
110
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10
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VRC01LS VRC01 (mcg/mL)
20 mg/kg IV
VRC01 day 0 
VRC01LS day 0 

 
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Figure 5: VRC01, VRC01LS and VRC07-523LS levels following IV administration 
of 20 mg/kg in adults 
 
 
 
 
Figure 6: Modeling of VRC07-523LS levels  
 
 
0
28
56
84
112
140
168
196
Days
0
25
50
75
100
125
150
175
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VRC07-523LS Conc (mcg/mL)
P1112 ARM 5 - VRC07-523LS 80-100 THEN 100MG (90% CI)
 
 
Study duration 
The study duration of 48 weeks for Dose Groups 1 and 2 is warranted for the following 
reasons. First, in other intervention studies in which the infants receive HAART (instead 
of just ZDV monotherapy), detection of a positive HIV DNA or RNA may be delayed. 
While most infected children have an initial positive test result by 6 weeks of age, in the 
setting of HAART, the first positive may not be apparent until 10-12 weeks or even 
later. As children in the present study are by definition, high risk, it is likely that many 
will be receiving combination ARV. Further, we do not know what impact VRC01 
VRC01LS, or VRC07-523LS will have on time to diagnosis; it may be that first infant 
positive test may not be apparent until weeks after the antibody is gone. In addition, we 

 
IMPAACT P1112 Version 4.0 
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06 November 2018 
know that maternal antibodies to HIV may be present in exposed infants for as long as 
15 months and, in the international setting, it is common to use EIA or rapid antibody 
testing to confirm an infant is HIV negative. It is possible, even likely that some 
antibody will remain and may interfere with the infants’ HIV antibody tests. Therefore, 
to confirm that infants who receive VRC01 become EIA and Western Blot negative by 
12 months of age and to be certain that any infant infections are detected, the protocol 
team believes that 48 weeks of follow up is important for the children receiving a single 
dose of VRC01. If a child remains antibody positive on laboratory testing at 48 weeks, 
he/she will continue every 3 month follow up until antibody tests are negative. This is 
important to confirm that receipt of monoclonal antibody does not delay the time until 
when infants test negative on routine HIV antibody testing.  Infants in Dose Groups 3 
(multi-dose), 4 and 5 will be followed for 96 weeks. 
 
Follow-up of infected infants 
Two recent studies [59, 60] have demonstrated rapid and prolonged viral suppression of 
SHIV in primates after receipt of single or multiple monoclonal antibodies, prompting 
interest in evaluating monoclonal antibodies as a potential “cure” strategy. A third study 
demonstrated eradication of SHIV with administration of two antibodies within 24 hours 
of oral inoculation of infant macaques [61]. While the present study is not designed to 
test this potential, there is a possibility that one or more of the high-risk infants enrolled 
in this study may be HIV-infected either in utero or intrapartum. Therefore, it will be 
important to describe changes in replicating and integrated virus in such infants after 
receipt of VRC01. All such infants will receive ARV therapy as part of standard of care 
as determined by their treating physicians but will have additional virologic and 
immunologic evaluations and follow up as described in Section 6.6 and APPENDIX IC: 
HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1.   
 
2 
STUDY OBJECTIVES 
2.1 
Primary Objectives 
In HIV-exposed infants at increased risk for peripartum or breastfeeding HIV 
transmission: 
 
2.1.1 To assess safety of single subcutaneous dose (20 mg/kg or 40 mg/kg) of VRC01 
(Dose Groups 1 and 2). 
2.1.2 To determine pharmacokinetic profile of single dose, subcutaneous VRC01 (Dose 
Groups 1 and 2). 
2.1.3 To assess safety of monthly subcutaneous doses of VRC01 (Dose Group 3)  
2.1.4 To determine pharmacokinetic profile of monthly subcutaneous doses of VRC01 
(Dose Group 3). 
2.1.5 To assess safety of one and two subcutaneous doses of VRC01LS (Dose Group 4, 
Cohorts 1 and 2). 
2.1.6 To determine pharmacokinetic profile of one and two subcutaneous doses of 
VRC01LS (Dose Group 4, Cohorts 1 and 2). 
2.1.7 To assess safety of one and two subcutaneous doses of VRC07-523LS (Dose 
Group 5, Cohorts 1 and 2).  

 
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2.1.8 To determine pharmacokinetic profile of one and two subcutaneous doses of 
VRC07-523LS (Dose Group 5, Cohorts 1 and 2). 
2.2 
Secondary Objectives 
2.2.1 To examine the anti-VRC01 antibody production following immunization.  
2.2.2 To examine the anti-VRC01LS antibody production following immunization. 
2.2.3 To examine the anti-VRC07-523LS antibody production following immunization. 
2.3 
Exploratory 
2.3.1 To assess the amount of VRC01/ VRC01LS/ VRC07-523LS in oral secretions 
2.3.2 If one or more infants are determined to be HIV-infected, to describe the 
neutralization sensitivity of the infant and maternal virus and the amount of HIV-
1 provirus and plasma HIV-1 RNA (measured in copies/mL), after receipt of 
VRC01, VRC01LS or VRC07-523LS. 
2.3.3 To assess neutralizing ability of serum before and after receipt of the antibody. 
 
3 
STUDY DESIGN 
This is an open-label, dose-escalating, Phase 1, multicenter study to determine the safety 
and pharmacokinetic parameters of subcutaneous VRC01, VRC01LS, and VRC07-
523LS, three potent anti-HIV neutralizing monoclonal antibodies.  VRC01 is 
administered in a single dose in 26 HIV-1-exposed infants (between birth and 72 hours of 
life in Dose Groups 1 and 2 and between birth and 5 days of life in Dose Group 3) and as 
monthly doses in 13 HIV-1-exposed breastfed infants. VRC01LS is administered in a 
single dose in 10 HIV-exposed non-breastfed infants at risk of infection between birth 
and 72 hours of life (Dose Group 4, Cohort 1) and in a single dose in 10 HIV-exposed 
breastfeeding infants between birth and five days of life (Dose Group 4, Cohort 2). A 
second dose of VRC01LS is given at 12 weeks of life in Dose Group 4, Cohort 2 if the 
infant has not achieved complete cessation of breastfeeding. VRC07-523LS is similarly 
administered in a single dose in 10 HIV-exposed non-breastfed infants at risk of infection 
between birth and 72 hours of life (Dose Group 5, Cohort 1) and in a single dose in 10 
HIV-exposed breastfeeding infants between birth and five days of life (Dose Group 5, 
Cohort 2). A second dose of VRC07-523LS will be given at 12 weeks of life in Dose 
Group 5, Cohort 2 if the infant has not achieved complete cessation of breastfeeding.   
 
Based on what is currently known about the pharmacokinetics of VRC01, the expectation 
is that this drug will be well tolerated in these infants and that a dose of 20 mg/kg will 
meet or exceed the target 28-day trough of 50 µg/mL in 50% of infants, while 40mg/kg 
will result in 90% of infants surpassing that trough level. The percentages of infants who 
meet these criteria will be estimated with considerable uncertainty given the small sample 
size. Table 7 in Section 8.6 provides CI around all potential results. For VRC01LS, it is 
expected that most infants who receive the initial dose will have levels of 50-100 µg/mL 
at Week 12. Based on the its shorter half-life in adults, levels of VRC07-523LS at 12 
weeks in infants in Cohort 5 are expected to be lower than those of Cohort 4, in the range 
of 10-50 µg/mL. 

 
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06 November 2018 
 
The study is being conducted domestically in sites with a perinatal program and at select 
international sites and is open to a population of infants born to HIV-infected women at 
risk for intrapartum or postpartum HIV transmission. Factors that put the child at 
increased risk for mother-to-child HIV transmission include lack of or late maternal 
antiretroviral (ARV) drug administration during pregnancy or inadequate antepartum 
ARV drug administration (see inclusion criteria), active viral replication near the time of 
delivery, an intrapartum event that might increase risk of transmission such as prolonged 
or premature rupture of membranes (PROM) or exposure to breast milk (for Dose Group 
3 and Cohort 2 of Dose Groups 4 and 5). Participation in Dose Group 3 and Cohort 2 of 
Dose Groups 4 and 5 will be limited to select sites in Africa, where breastfeeding is 
recommended for mothers living with HIV. Specific requirements are listed in 
inclusion/exclusion criteria (see Section 4). Mothers may be consented prior to delivery 
or shortly after delivery of their infants, but enrollment of the mother-infant pair will not 
proceed until the infant eligibility criteria have been confirmed. The first dose of the 
study product must be administered less than 72 hours after birth to infants in Dose 
Group 1, 2, 4 (Cohort 1) and 5 (Cohort 1) and before the end of Day 5 of life for Dose 
Groups 3, 4 (Cohort 2) and 5 (Cohort 2).  
 
The approximate sample size of the study is 79 mother-infant pairs, 13 per Dose Groups 
1, 2 and 3 and 10 per each of the cohorts in Dose Groups 4 and 5, to assure both that 30 
infants receive VRC01 and 8 infants per cohort in Dose Group 4 receive VRC01LS and 8 
infants per cohort in Dose Group 5 receive VRC07-523LS and that these infants 
complete: 
• Day 28 evaluations for Dose Groups 1 and 2 and Cohort 1 of Dose Groups 4 and 5 
• Week 24 for Dose Group 3 
• Week 16 for Cohort 2 of Dose Groups 4 and 5   
 
The mothers are enrolled as well, but only the infants receive the 
VRC01/VRC01LS/VRC07-523LS immunization and are followed on the study.  All 
infants receive prophylactic ARV treatment per local standard of care, as prescribed by 
their clinician. Mothers are counseled on the importance of their own adherence to 
antiretroviral therapy for the entire duration of treatment to reduce the risk of mother-to-
child transmission of HIV and on the importance of their infants receiving all standard 
prophylactic ARV regimens. In particular, they are informed that the study drug is not 
known to reduce risk of transmission.  See Error! Reference source not found. for an 
overview of the study design. 
 
The treatment regimen will be the following: 
 
Dose Group 1 
VRC01 (human monoclonal antibody) 20 mg/kg was given by subcutaneous (SC) 
injection one time to infants ideally within 24 hours but always less than 72 hours after 
birth.  After 13 infants were accrued and 6 of those infants were immunized and 
completed the Day 28 evaluations and safety criteria described in section 8.5.1 have been 
passed; then 

 
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06 November 2018 
 
Dose Group 2 
An additional 13 infants were enrolled and received a single 40 mg/kg SC dose of the 
same monoclonal antibody ideally within 24 hours but always less than 72 hours after 
birth.    
 
Dose Group 3 
After six infants in Dose Group 2 completed Day 28 safety assessments and safety 
criteria described in Section 8.5.1 had been passed, Dose Group 3 opened and enrolled 
concurrently with the remaining Group 2 participants. The 13 infants in this Dose Group 
received 40 mg/kg SC for the initial dose, then 20 mg/kg SC monthly for at least 24 
weeks and no more than 72 weeks while breastfeeding. In Dose Group 3, while it is 
desirable for infants to receive the first dose ideally within 24 hours and less than 72 
hours after birth, enrollment was allowed through Day 5 of life as these infants have an 
ongoing breastmilk transmission risk.   
 
In all cases, the earlier the treatment is provided, the better; therefore, ideally enrollment 
would have been completed and study drug administered prior to 24 hours of life. 
However, given the challenges of obtaining informed consent and appropriate screening, 
enrollment and dosing up to 72 hours of life was and will be allowed for Dose Groups 1, 
2, 4 (Cohort 1), and 5 (Cohort 1) and through Day 5 of life for Dose Groups 3, 4 (Cohort 
2), and 5 (Cohort 2). (In all dose groups, if the dose is not administered within this stated 
window, the child may not receive the dose.)   
 
Under Version 1.0, Dose Group 1 closed to enrollment on January 28th 2016. On 
February 2nd, Dose Group 2 was opened to enrollment and the dose escalated after 13 
Group 1 infants had been randomized, all had completed 48-hour post immunization 
evaluations, and 10 had completed Day 28 evaluations. The protocol opened to Group 3 
after at least 6 infants in Group 2 received the 40mg/kg dose, completed Day 28 
evaluations and passed safety review.  Dose Groups 2 and 3 have completed enrollment. 
We believed this sequential enrollment would be safe for the following reasons: 1) in 
adult studies to date, there have been no dose limiting toxicities even up to 40 mg/kg and 
2) all infants will have received the 20 mg/kg dose and will have undergone initial post 
immunization monitoring; therefore, any acute severe reactions will have been identified. 
While adults will not have received 40mg/kg via the subcutaneous route, adults have 
received larger SC volumes (2-3 mL) and repeated doses without significant local 
reactions. In addition, we expected that if the SC dosing in the infants were to produce 
reactions not seen in adults, the events would most likely be acute reactions rather than 
long term (28-day events). Finally, in addition to an initial review of data through Week 8 
on the first 6 infants to be enrolled in Dose Group 3, six-month reviews of all safety data 
from adult and pediatric protocols of VRC01 (from P1112 database and most recent 
safety reports available from the other protocols) commenced after the first infant 
enrolled into Dose Group 3 reached the 6-month milestone. 
 
Dose Group 4 

 
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Upon release of Version 3.0, the protocol team reviewed all available safety and PK data 
as well as accrual data of Dose Group 3 on April 19, 2017. The safety data revealed no 
signal, and the team determined that Dose Group 4, Cohort 1 enrollment could begin as 
soon as study documents were updated per protocol V3.0 and site approvals were 
obtained. When the first six infants in Dose Group 4, Cohort 1 were immunized and 
completed 28 days of follow-up, the team reviewed all available safety data. There was 
no pause in Dose Group 4, Cohort 1 enrollment or immunization during this review. As 
the review of safety data revealed no signal, enrollment into Dose Group 4, Cohort 2 was 
opened.   
 
All 20 (10 per cohort) of the infants in Dose Group 4 received an initial dose of 
VRC01LS SC at birth (within 72 hours for Cohort 1; within 5 days of life for Cohort 2).  
Infants in Dose Group 4, Cohort 2 will receive a second dose at 12 weeks if they have not 
achieved complete cessation of breastfeeding. In Cohort 2, while it is desirable for infants 
to receive the first dose within 24 hours or as soon as possible, enrollment will be 
allowed through Day 5 of life. 
 
Dose Group 5 
Upon release of Version 4.0, the protocol team will review interim safety and PK data 
(accrual data will not need to be reviewed, as Dose Group 4 was fully accrued as of 
February 1, 2018). If the safety data reveal no signal, Dose Group 5, Cohort 1 enrollment 
may begin as soon as study documents are updated per protocol V4.0 and site approvals 
are obtained. When the first six infants in Dose Group 5, Cohort 1 have been immunized 
and completed 28 days of follow-up, the team will review interim safety and PK data. 
There will be no pause in Dose Group 5, Cohort 1 enrollment or immunization during 
this review. If review of safety and PK data reveals no signal, enrollment into Dose 
Group 5, Cohort 2 will be opened.   
 
All 20 (10 per cohort) of the infants in Dose Group 5 will receive an initial dose of 
VRC07-523LS SC at birth (within 72 hours for Cohort 1; within 5 days of life for Cohort 
2). Infants in Dose Group 5, Cohort 2 will receive a second dose at 12 weeks if they have 
not achieved complete cessation of breastfeeding. In Cohort 2, while it is desirable for 
infants to receive the first dose within 24 hours or as soon as possible, enrollment will be 
allowed through Day 5 of life. 
 
The description of the dose groups is presented in the table that follows, (Table 5). 
 

 
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Table 5: Description of Dose Groups  
 
N 
Dose of VRC01/VRC01LS/VRC07-523LS 
Dose Group 1 
13 
20 mg/kg VRC01 SC X1 
Dose Group 2 
13 
40 mg/kg VRC01 SC X1 
Dose Group 3 
13 
40 mg/kg VRC01 SC for initial dose 
20 mg/kg VRC01 SC monthly for at least 24 weeks and no more than 72 
weeks while breastfeeding 
Dose Group 4 
10 
 
 
 
 
 
10 
Cohort 1: Non-breastfeeding 
Single dose VRC01LS at birth administered SC; dose is based on weight: 
< 4.5 kg: 80 mg 
≥ 4.5 kg: 100 mg 
 
Cohort 2: Breastfeeding 
Initial dose VRC01LS at birth administered SC; dose is based on weight: 
< 4.5 kg: 80 mg 
≥ 4.5 kg: 100 mg 
 
Second dose of 100mg VRC01LS at Week 12 administered SC if complete 
cessation of breastfeeding not achieved. 
Dose Group 5 
10 
 
 
 
 
 
10 
Cohort 1: Non-breastfeeding 
Single dose at birth of VRC07-523LS to be administered SC; dose is based 
on weight: 
< 4.5 kg: 80 mg 
≥ 4.5 kg: 100 mg 
 
Cohort 2: Breastfeeding 
Initial dose at birth of VRC07-523LS to be administered SC; dose is based 
on weight: 
< 4.5 kg: 80 mg 
≥ 4.5 kg: 100 mg 
 
Second dose of 100 mg VRC07-523LS at Week 12 to be administered SC 
if the infant has not achieved complete cessation of breastfeeding 
 
The product vials of VRC01 are formulated at 100 mg/mL.  Thus, an average 3.5 kg 
infant would receive a 0.7 mL dose if in the 20 mg/kg dose group or a 1.4 mL dose if in 
the 40 mg/kg dose group. Doses > 1.0 mL may be administered as 1 or 2 separate 
injections, based on site preference. In Dose Group 4, VRC01LS is administered as an 80 
mg (or 0.8 mL) dose to all infants < 4.5 kg birth weight, which is expected to be most 
children. The small number of children with birth weight ≥ 4.5 kg receive 100 mg (1.0 
mL).  Modeling suggests that using this dosing approach will achieve target plasma levels 
in 95% of infants. Infants in Cohort 2 of Dose Group 4 will receive a second dose of 100 
mg at Week 12 if complete cessation of breastfeeding has not been achieved.  
 
Likewise, in Dose Group 5, VRC07-523LS will be administered as an 80 mg (or 0.8 mL) 
dose to all infants < 4.5 kg birth weight, which is expected to be most children. The small 
number of children with birth weight ≥ 4.5 kg will receive 100 mg (1.0 mL).  Modeling 
suggests that using this dosing approach will achieve target plasma levels in 95% of 

 
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infants. For VRC07-523LS, the target level at 12 weeks is 10 µg/mL or higher in most 
infants; 5-fold lower than that of VRC01LS. The lower target is appropriate considering 
the significant increased potency of the VRC07-523LS product.  Infants in Cohort 2 of 
Dose Group 5 will receive a second dose of 100 mg at Week 12 if complete cessation of 
breastfeeding has not been achieved. 
 
Maternal participants are evaluated at screening and enrollment. Infant participants in 
Groups 1 and 2 are followed for 48 weeks; infants in Group 3 are followed for 96 weeks; 
and infants in Groups 4 and 5 for 96 weeks. PK sampling, anti-VRC01Ab, and oral 
secretions are collected over the entire study period.  Refer to Schedules of Evaluations in 
Appendices as follows: APPENDIX IA: Maternal Schedule of Evaluations (all dose 
groups) (Maternal); APPENDIX IB: Infant Schedule of Evaluations (Dose Groups 1 and 
2) (Infant: Dose Groups 1 and 2); APPENDIX IC: HIV-1 Infected Infant Schedule of 
Evaluations (all dose groups)1 (HIV infected infants, all dose groups); APPENDIX ID: 
Schedule of Evaluations (Dose Group 3) (Infant; Dose Group 3); APPENDIX IE: 
Schedule of Evaluations (Dose Group 4, Cohort 1: non-breastfeeding); APPENDIX IF: 
Schedule of Evaluations (Dose Group 4, Cohort 2: breastfeeding); APPENDIX IG: 
Schedule of Evaluations (Dose Group 5, Cohort 1: non-breastfeeding) (Infant: Dose 
Group 5, non-breastfeeding); and APPENDIX IH: Schedule of Evaluations (Dose Group 
5, Cohort 2: breastfeeding)(Infant: Dose Group 5, breastfeeding) for a complete 
description of the clinical and laboratory evaluations to be performed. 
 
4 
SELECTION AND ENROLLMENT OF PARTICIPANTS 
4.1 
Maternal Inclusion Criteria 
 
4.1.1 Documentation of HIV infection. 
Documentation of HIV-1 infection is defined as positive results from two samples 
collected at different time points. All samples tested must be whole blood, serum or 
plasma. For this protocol, the results for sample #2 may be pending at the time of 
enrollment. Results documented in the clinical record from past testing may be used to 
satisfy the criteria for documentation of HIV-1 infection. 
 
• Sample #1 may be tested by non-study clinical or PEPFAR programs. However, 
both the result and the assay date must be recorded in participant’s charts. Source 
documentation (patient’s medical record/chart, Ministry of Health (MOH) 
registers, laboratory results, etc.) must be available.   
• Sample #2 must be performed in a CAP/CLIA-approved laboratory (for US sites) 
or in a laboratory that operates according to GCLP guidelines and participates in 
appropriate external quality assurance program (for international sites).  
 
Acceptable Tests 
 
Sample #1 must be tested using any of the following: 
• Two rapid antibody tests from different manufacturers or based on different 
principles and epitopes.  

 
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• One EIA OR Western Blot OR immunofluorescence OR chemiluminescence  
• One HIV nucleic acid amplification test specified in the MOP 
• One quantitative HIV RNA PCR (above the limit of detection) 
• One qualitative HIV RNA PCR  
• One HIV culture (prior to August 2009) 
• One total HIV nucleic acid test 
 
Note: Confirmatory testing (Sample #2) may be pending at the time of enrollment of the 
mother-infant pair. If maternal confirmatory testing is negative and the infant has 
received the VRC01, VRC01LS, or VRC07-523LS immunization, the infant will be 
followed for safety as part of the study. If the infant has not received the VRC01, 
VRC01LS, or VRC07-523LS immunization, then the mother and infant will be removed 
from the study.   
 
Sample #2 may be tested using any of the following:   
• Rapid antibody test. If this option is used in combination with two rapid tests for 
Sample #1, at least one of the three rapid tests must be FDA-approved and the third 
rapid test must be from a third manufacturer or based on a third principle or epitope. 
• One EIA confirmed by Western Blot OR immunofluorescence OR 
chemiluminescence  
• One HIV nucleic acid amplification test specified in the MOP  
• One quantitative HIV RNA PCR (above the limit of detection) 
• One qualitative HIV RNA PCR 
• One HIV culture (prior to August 2009) 
• One total HIV nucleic acid test 
 
4.1.2 Greater than or equal to 18 years of age. 
4.1.3 Able and willing to provide signed informed consent for herself and her infant.  
 
4.2 
Maternal Exclusion Criteria 
4.2.1 Prior participation in any HIV-1 vaccine trial. 
4.2.2 Receipt of any other active or passive HIV immunotherapy or investigational 
product during this pregnancy. (Note that administration of FDA-approved 
antiretroviral drugs when used to treat disease or prevent mother to child 
transmission are not considered investigational). 
4.2.3 Documented or suspected serious medical illness or immediate life-threatening 
condition (other than HIV infection) in the mother that may interfere with the 
ability to complete study requirements, as judged by the examining clinician. 
 
4.3 
Infant Inclusion Criteria 

 
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06 November 2018 
4.3.1 Born to an HIV-1-infected woman who meets all maternal inclusion/exclusion 
criteria listed above. 
4.3.2 Gestational age, by best obstetrical, ultrasound, or infant exam, ≥36 weeks  
4.3.3 Birth weight ≥ 2.0 kg. 
 
4.3.4 Allowable infant age at the time of enrollment is dependent on the Dose Group 
and Cohort: 
• 
Dose Groups 4 and 5 (Cohort 1): <72 hours of age, and anticipated 
availability to receive VRC01LS or VRC07-523LS immunization at less than 
72 hours after birth. 
• 
Dose Groups 4 and 5 (Cohort 2): < 5 days of age, and anticipated availability 
to receive VRC01LS or VRC07-523LS immunization no more than 5 days 
after birth. 
 
4.3.5 At increased risk of HIV acquisition defined as documentation of one or more of 
the following risk factors: 
 
Dose Groups 4 and 5 (Cohort 1), only: 
• Mother received no ART during pregnancy or mother began or reinitiated ART 
(after an interruption of >14 days), during the third trimester of pregnancy; or 
• Mother with any detectable viral replication (HIV RNA above the limit of 
detection) at last measurement prior to delivery determined within 30 days of 
delivery; or 
• Prolonged rupture of membranes (> 12 hours); or  
• Mother with documented* 2-class resistant HIV infection, which may include 
historical documentation of lack of response 
 
*Women who have a documented history of virologic failure while on 
NNRTIs but who had no resistance testing at the time of viral failure will be 
considered to have NNRTI documented resistance. 
 
Dose Groups 4 and 5 (Cohort 2), only (African sites): 
• Mother intends to breastfeed   
 
4.4 
Infant Exclusion Criteria 
4.4.1 Receipt of any other active or passive HIV immunotherapy or investigational 
product other than the study vaccine (Note: Infant prophylaxis with any licensed 
ARV drugs clinically prescribed to prevent mother to child HIV transmission are 
not considered investigational). 
4.4.2 Receipt of or anticipated need for blood products, immunoglobulin, or 
immunosuppressive therapy. This includes infants who require Hepatitis B 

 
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Immunoglobulin (HBIG) but does not require exclusion of infants who receive 
Hepatitis B vaccine in the newborn period.  
 
4.4.3 Documented or suspected serious medical illness, serious congenital anomaly, or 
immediate life-threatening condition in the infant that may interfere with the 
ability to complete study requirements, as judged by the examining clinician. 
4.4.4 Any requirement for supplemental oxygen beyond 24 hours of life or requiring 
supplemental oxygen at the time of the VRC01, VRC01LS, or VRC07-523LS 
dose. 
4.4.5 Baseline laboratory results 
• Hemoglobin < 12.0 g/dL 
• Platelet count < 100,000 cells/mm3 
• Absolute neutrophil count: for infants < 24 hours old, < 4000 cells/mm3; for 
infants >24 hours old, < 1250 cells/mm3 
• SGPT (ALT) ≥ 1.25 times upper limit of age adjusted normal 
 
4.4.6 Dose Groups 4 and 5 (Cohort 1), only: Infant is breastfeeding at time of 
enrollment or mother has indicated an intention to initiate breastfeeding.  Note, if 
a child breastfed prior to known maternal diagnosis (in the case of a woman 
diagnosed in the intrapartum period), the child is still eligible as long as 
breastfeeding is stopped by the time the child is enrolled and there is no plan to 
resume breast milk feeding.   
 
4.5 
Concomitant Medication Guidelines 
There are no prohibited medications; however, all concomitant medications must be 
recorded on the appropriate CRFs.  
 
4.6 
Enrollment Procedures 
Prior to implementation of this protocol, and any subsequent full version amendments, 
each site must have the protocol document and the consent form(s) approved, as 
appropriate, by their local Institutional Review Board (IRB) /Ethics Committee (EC), and 
any other applicable regulatory entity (RE). A Site Implementation Plan (SIP) will be 
required from each site participating in the study and the plan must be submitted to the 
Protocol Team for review and approval before protocol registration can occur. 
 
Upon receiving final approval, sites will submit all required protocol registration 
documents to the DAIDS Protocol Registration Office (DAIDS PRO) at the Regulatory 
Support Center (RSC). The DAIDS PRO will review the submitted protocol registration 
packet to ensure that all the required documents have been received. Site-specific 

 
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06 November 2018 
informed consent forms (ICFs) WILL be reviewed and approved by the DAIDS PRO and 
sites will receive an Initial Registration Notification from the DAIDS PRO that indicates 
successful completion of the protocol registration process. A copy of the Initial 
Registration Notification should be retained in the site's regulatory files. 
 
IMPAACT Operations Center notification of approval to begin enrollment is required 
before participants can be enrolled in this study. Participants meeting the study eligibility 
criteria will be enrolled through the Data Management Center Subject Enrollment 
System. Written informed consent for study participation must be obtained before any 
study related procedures are performed. 
 
Upon receiving final IRB/EC and any other applicable RE approval(s) for an amendment, 
sites should implement the amendment immediately. Sites are required to submit an 
amendment registration packet to the DAIDS PRO at the RSC. The DAIDS PRO will 
review the submitted protocol registration packet to ensure that all the required 
documents have been received. Site-specific ICF(s) WILL NOT be reviewed and 
approved by the DAIDS PRO and sites will receive an Amendment Registration 
Notification when the DAIDS PRO receives a complete registration packet.  A copy of 
the Amendment Registration Notification should be retained in the site's regulatory files. 
 
For additional information on the protocol registration process and specific documents 
required for initial and amendment registrations, refer to the current version of the 
DAIDS Protocol Registration Manual. 
 
Written informed consent for study participation must be obtained before any study 
related procedures are performed.  Mothers may be consented prior to delivery or shortly 
after delivery of their infants, but enrollment of the mother-infant pair will not proceed 
until the infant eligibility criteria have been confirmed.   
Enrollment of participants onto the study will be done through the Subject Enrollment 
System (SES) on the Data Management Center website (at https://www. 
Frontierscience.org) under the Systems heading. 
 
4.7 
Co-enrollment Procedures 
Co-enrollment into other observational studies is permitted but requires notification of 
the IMPAACT P1112 protocol team and appropriate maximum blood draw 
considerations.  The NIH Clinical Center blood guidelines allow a maximum of 5ml/kg 
within 24 hours and 9.5 ml/kg drawn over an 8-week period.    
 
Co-enrollment into IMPAACT P1110 and P1115 will not be permitted.  Co-enrollment 
into other interventional studies will be considered on a case-by-case basis but will 
require written permission from both protocol teams. 
 
 

 
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5 
STUDY TREATMENT 
 
5.1 
Drug Regimens, Administration and Duration 
 
5.1.1 Dose Group 1 
VRC01 20 mg/kg subcutaneous injection ideally within 24 hours and less than 72 
hours after birth.  
 
5.1.2 Dose Group 2 
VRC01 40 mg/kg subcutaneous injection ideally within 24 hours and less than 72 
hours after birth.  
 
5.1.3 Dose Group 3 
VRC01 40 mg/kg subcutaneous injection for the initial dose, then 20 mg/kg 
subcutaneous injection monthly for at least 24 weeks and no more than 72 weeks 
while breastfeeding.  Initial dose ideally within 24 hours and no more than 5 days 
of life.   
 
5.1.4 Dose Group 4 
• Cohort 1: VRC01LS subcutaneous injection, ideally within 24 hours and less 
than 72 hours of life.  Dosing is weight-based: 80mg if birth weight < 4.5kg; 
100mg if birth weight is ≥ 4.5kg. If birth weight is not available, may use 
weight at time of screening.   
• Cohort 2: VRC01LS subcutaneous injection at entry (all participants) and at 
Week 12 if infant is still breastfeeding. Initial dose ideally within 24 hours and 
less than 5 days of life.  Dosing will be weight based: 80mg if birth weight < 
4.5kg; 100mg if birth weight is ≥ 4.5kg. If birth weight is not available, can use 
weight at time of screening.  The second dose at Week 12 will be 100mg. 
 
5.1.5 Dose Group 5 
• Cohort 1: VRC07-523LS subcutaneous injection, ideally within 24 hours and 
less than 72 hours of life.  Dosing will be weight-based: 80mg if birth weight < 
4.5kg; 100mg if birth weight is ≥ 4.5kg. If birth weight is not available, may use 
weight at time of screening.   
• Cohort 2: VRC07-523LS subcutaneous injection at entry (all participants) and 
at Week 12 if infant is still breastfeeding. Initial dose ideally within 24 hours 
and less than 5 days of life.  Dosing will be weight-based: 80mg if birth weight 
< 4.5kg; 100mg if birth weight is ≥ 4.5kg. If birth weight is not available, can 
use weight at time of screening.  The second dose at Week 12 will be 100mg. 
 
Refer to the P1112 MOP for the weight band tables. Please note that these tables only 
apply to Dose Groups 1-3. Infants in Dose Group 4 and 5 receive either 80 or 100 mg as 
described above and in the MOP.   

 
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• Table 7-1:  Product Volume by Weight Band to Achieve a 20 mg/kg Dose with 
Additional Volume to Add to Syringe to Fill Tubing Dead Space in Study-Supplied 
Infusion Set 
• Table 7-2:  Product Volume by Weight Band to Achieve a 40 mg/kg dose with 
Additional Volume to Add to the Syringe to Fill Tubing Dead Space. 
• Table 7-3: Product Volume by Weight Band to Achieve a 20 mg/kg Dose with 
Additional Volume to Add to Each of Two Syringes to Fill Tubing Dead Space: 
Administration with Two Syringes 
 
Dose volumes greater than 1 ml may be separated into two injections to be given 
successively depending on site policy or preference.  In order to evaluate any potential 
site reaction, product should not be administered in the same thigh where the infant 
received hepatitis B or any other vaccination.     
 
VRC01, VRC01LS, and VRC07-523LS are administered subcutaneously, by slow push 
in the thigh using a BD Safety-Lok™ infusion set with a 25 G x 0.75-inch needle with 7 
inches of tubing and a luer lock adapter.  After the administration is completed, the 
sliding safety shield is to be manually activated. 
 
5.2 
Drug Formulation 
5.2.1 VRC01: VRC-HIVMAB-060-00-AB 
VRC01 is a recombinant human immunoglobulin G1 (IgG1) antibody produced in a 
Chinese Hamster Ovary (CHO) cell line in accordance with the current Good 
Manufacturing Practice (cGMP) regulations.  VRC01 is manufactured for the VRC at the 
Vaccine Pilot Plant (VPP) operated by Leidos Biomedical Research, Inc. (formerly 
SAIC-Frederick, Inc.), Frederick, MD.  VRC01 human monoclonal antibody is 
manufactured as a 100 mg/ml solution and provided in single-dose vials.  VRC01 is 
supplied at a concentration of 100 ± 10 mg/mL in an isotonic, sterile solution; the fill 
volume used for P1112 is 2.25 ± 0.10 mL in a 3-mL glass vial.  The formulation buffer is 
composed of 25 mM sodium citrate, 50 mM sodium chloride, and 150 mM L-arginine 
hydrochloride at pH 5.8.  At the CRPMC, VRC01 is to be stored in a freezer at -35⁰C to -
15⁰C.  In clinical site pharmacies, VRC01 is to be stored in a freezer with a temperature 
range of -45⁰C to -10⁰C (-49⁰F-14⁰F).  Dispense one BD Safety-Lok™ infusion set with 
a 25 G x 0.75-inch needle with 7 inches of tubing and a luer lock adapter item number 
367294 for each syringe dispensed. 
 
5.2.2 VRC01LS: VRC-HIVMAB080-00-AB 
VRC01LS is an IgG1, and the glycosylation pattern is derived from its production in a 
Chinese Hamster Ovary (CHO) mammalian cell line. The bulk lot of the drug substance 
was manufactured under cGMP using a stably transfected CHO cell line, purified, and the 
drug product vials were filled and labeled at the VRC, Vaccine Clinical Material Program 
operated by Leidos Biomedical Research, Inc., Frederick, MD. Each product vial 
contains 6.25 mL volume at a concentration of 100 mg/mL VRC01LS in formulation 

 
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buffer containing 25 mM Sodium Citrate, 50 mM Sodium Chloride, and 150 mM L-
Arginine Hydrochloride at pH 5.8. At the CRPMC, VRC01LS is to be stored in a freezer 
at -35⁰C to -15⁰C.  In clinical site pharmacies, VRC01LS is to be stored in a freezer with 
a temperature range of -45⁰C to -10⁰C (-49⁰F to 14⁰F).  Dispense one BD Safety-Lok™ 
infusion set with a 25 G x 0.75-inch needle with 7 inches of tubing and a luer lock 
adapter item number 367294 for each syringe dispensed. 
 
5.2.3 VRC07-523LS: VRC-HIVMAB075-00-AB 
VRC07-523LS is a broadly neutralizing human MAb targeted against the HIV-1 CD4 
binding site.  It was developed by VRC/NIAID/NIH and produced in a Chinese Hamster 
Ovary (CHO) DG44 cell line in accordance with the cGMP regulations at the VRC Pilot 
Plant operated under contract by the Vaccine Clinical Materials Program, Leidos 
Biomedical Research, Frederick, MD.  VRC07-523LS is a sterile, aqueous buffered 
solution filled into 10 mL or 3 mL single-dose glass vials.  Each vial contains a volume 
of 6.25 ± 0.1 mL or 2.25 ± 0.1 mL at a concentration of 100 ± 10 mg/mL in formulation 
buffer composed of 50 mM histidine, 50 mM sodium chloride, 5% sucrose, and 2.5% 
sorbitol at pH 6.8. At the CRPMC, VRC07-523LS is to be stored in a freezer at -35⁰C to 
-15⁰C.  In clinical site pharmacies, VRC07-523LS is to be stored in a freezer with a 
temperature range of -45⁰C to -10⁰C (-49⁰F to 14⁰F).  Dispense one BD Safety-Lok™ 
infusion set with a 25 G x 0.75-inch needle with 7 inches of tubing and a luer lock 
adapter item number 367294 for each syringe dispensed. 
 
5.3 
Thawing Instructions 
Refer to the P1112 MOP for thawing instructions.   
 
5.4 
Study Product Preparation 
Each dose of VRC01, VRC01LS, and VRC07-523LS must be ordered by prescription, 
and each prescription must include the infant’s current weight.  Upon receipt of each 
prescription, the site pharmacist prepares the 20 mg/kg dose or 40 mg/kg dose of VRC01 
and 80mg or 100mg of VRC01LS or VRC07-523LS.  Refer to the P1112 MOP for 
detailed instructions for preparation of VRC01, VRC01LS or VRC07-523LS.  
 
5.5 
Study Product Administration 
 
VRC01, VRC01LS, and VRC07-523LS are administered subcutaneously, by slow push 
in the thigh using a BD Safety-Lok™ infusion set with a 25 G x 0.75-inch needle with 7 
inches of tubing and a luer lock adapter.  After administration is completed, the sliding 
safety shield should be manually activated.  
 
When administering VRC01, VRC01LS, or VRC07-523LS, the thigh where infant 
vaccines were administered within the preceding two weeks should be avoided, if 
possible, as should any site where the skin or tissue is irritated.  For each subsequent dose 

 
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06 November 2018 
of VRC01, VRC01LS, or VRC07-523LS, alternate administration to the opposite thigh 
from the preceding dose, when feasible, and document whether the injection was given in 
the right or the left thigh on each occasion.   
Refer to MOP Section 5.4 for more information on post-administration monitoring for 
injection site reactions.  
 
5.6 
Drug Supply, Distribution and Pharmacy 
VRC01, VRC01LS, and VRC07-523LS are provided by the NIH VRC and available 
through the NIAID CRPMC.  BD infusion 367294 BD Safety-Lok™ infusion set with a 
25 G x 0.75-inch needle with 7 inches of tubing and a luer lock adapter is also available 
through the CRPMC.  The site pharmacist can obtain the study products for this protocol 
by following the instructions in the manual Pharmacy Guidelines and Instructions for 
DAIDS Clinical Trials Networks in the section titled Study Product Management 
Responsibilities. 
 
The site pharmacists are required to maintain complete records of all study products 
received from the CRPMC and dispensed.  All unused unopened vials of VRC01, 
VRC01LS, and VRC07-523LS must be returned to the NIAID CRPMC after the study is 
completed or terminated.  The procedures to be followed are provided in the manual, 
Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks, in the section 
Study Product Control. 
 
Partially used vials will not be administered to other participants or used for in vitro 
experimental studies.  Any unused portion of entered vials, any BD infusions set, any 
used syringes and/or unused filled syringes should be disposed of in a biohazard bag and 
incinerated or autoclaved or as per approved local site policy.  The site pharmacist at non-
U.S. clinical research sites must follow the instructions in the Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks DAIDS Pharmaceutical Affairs for the 
destruction of unused study products. 
 
6 
PARTICIPANT MANAGEMENT 
 
6.1 
Toxicity Management 
The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, 
(DAIDS AE Grading Table), Corrected Version 2.1, July 2017, must be used and is 
available on the RSC website at https://rsc.niaid.nih.gov/clinical-research-sites/daids-
adverse-event-grading-tables 
 
Management of adverse experiences is done according to the best clinical practice and the 
judgment of the site investigator.  Alternate explanations for clinical and laboratory 
abnormalities must be sought.  Laboratory normals will be the institutional values.  However, if 
a site does not have an age-specific normal range/value for a particular lab, the site should use 
the latest edition of the Harriet Lane Handbook for normal ranges/values and document this for 

 
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monitoring purposes.  Abnormal clinical and laboratory findings should be followed until 
resolution to < Grade 2, or no further change expected.   
 
This study involves a single or multiple dose(s) of VRC01, VRC01LS, or VRC07-523LS 
antibody.  Safety data will be collected and reviewed by the study team on regular (twice 
a month) study conference calls.   
 
Sites record and submit CRFs to the Data Management Center on all AEs from the time 
of the initial immunization as follows: 
 
For Dose Groups 4 and 5 (both cohorts), all laboratory events required by the Schedules 
of Evaluations should be recorded on CRFs regardless of grade. See the CRF instructions 
for further details. For all other events: 
 
• For Grade 1 reactogenicity AEs, and all Grade 2 AEs that study sites assess as 
possibly, probably or definitely related to the study product, and all AEs grade 3 or 
higher (regardless of their relationship to study product): CRFs should be submitted 
through the entire course of study. 
• For all Grade 1 AEs (other than reactogenicity AEs), and Grade 2 AEs that sites 
assess as definitely not or probably not related to the study product: CRFs should only 
be submitted for these AEs occurring up to 30 days after the single immunization for 
Dose Groups 1 and 2 and Dose Groups 4 and 5 (Cohort 1) or 30 days after the final 
immunization for Dose Group 3 and Dose Groups 4 and 5 (Cohort 2).  After that, 
sites will not be required to record/submit these AEs on CRFs.  Note that sites should 
continue to report – beyond the time periods specified above – unresolved AEs that 
began during the reporting period.   
 
The study Data Management Center report the data described above on a monthly basis for 
safety monitoring/review by the IMPAACT P1112 study team.  All infants who receive an 
immunization will be followed for safety assessment for the full length of the study. 
 
6.1.1 Toxicity Management Multiple Doses - Dose Groups 3, 4 (Cohort 2), and 5 
(Cohort 2) 
• After Grade 3 toxicities, subsequent doses should not be administered until after 
consultation with the protocol team AND improvement of the event to < Grade 3.  
After approval by the protocol team, subsequent doses may be administered.  If the 
event recurs and is deemed related to study product, no further doses may be 
administered.   
• After Grade 4 toxicities considered not related or probably not related, subsequent 
doses may be administered after improvement to < Grade 3 and consultation with the 
protocol team.  If the event recurs, no further doses may be administered. 
• After any Grade 4 toxicities considered possibly, probably, or definitely related to 
immunization, subsequent doses should not be administered.  
Sites should evaluate all AEs to determine if the AE meets criteria for expedited AE 
reporting to DAIDS (Section 7). 
 

 
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6.2 
Study Management Plan  
Mothers may be consented prior to delivery or shortly after delivery of their infants, but 
enrollment of the mother-infant pair will not proceed until the infant eligibility criteria 
have been confirmed. 
 
The Data Management Center will maintain a web page informing sites as to the 
availability of enrollment slots per dose group.  
 
It is a study requirement that all enrolled infants receive the first immunization at less 
than 72 hours after birth (Dose Groups 1, 2, 4 [Cohort 1] and 5 [Cohort 1]) and by the 
end of Day 5 of life for Dose Group 3, 4 [Cohort 2] and 5 [Cohort 2]). If an infant is 
enrolled but there is a delay in administering the dose such that the infant is beyond the 
age cutoff, then the study immunization should not be administered and the infant should 
be withdrawn from the study.  If an infant receives the dose after the designated age, it 
will be considered a protocol violation and the site must notify the team by email as soon 
as possible.  These infants will still be followed for the length of the study (up to 48 
weeks for Dose Groups 1 and 2 and 96 weeks for Dose Groups 3, 4 and 5). 
 
If maternal sample #2 testing is negative and the infant has received any VRC01, 
VRC01LS, or VRC07-523LS immunizations, there will be no subsequent immunizations 
and the infant will be followed for safety as part of the study.  If the infant has not 
received the VRC01, VRC01LS, or VRC07-523LS immunization, then the mother and 
infant will be removed from the study.   
 
6.2.1 Dose Group Management 
Dose Group 1 
Under Version 1.0, Dose Group 1 closed to enrollment on 28 January 2016 after meeting 
full accrual. 
 
Dose Group 2 
On 2 February 2016, upon review of available date and documentation that all infants 
who had reached Day 28 (N=10) had passed the safety criteria, Dose Group 2 was opened 
to enrollment.  On 2 November2016, Dose Group 2 was closed to enrollment after 14 
mother-infant pairs had been enrolled. 
 
Note.  If 10 infants in Dose Groups 1 or 2 had completed Day 28 safety and PK 
assessments before all 13 had been enrolled in that dose group, the dose group could have 
been closed early (since assessments on 10 evaluable infants had been completed). 
However, as noted above, neither group closed early. 
 
Dose Group 3 
After the mini cohort of six infants in Dose Group 2 passed the Day 28 safety criteria, 
enrollment in Dose Group 3 began on 24 August 2016.  On 1 February 2017, Dose Group 
3 was closed to enrollment after 13 mother-infant pairs had been enrolled.  After the first 

 
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infant enrolled into Dose Group 3 reaches the Week 24 milestone, the protocol team will 
review available safety data from adult and pediatric protocols of VRC01 (from P1112 
database and safety reviews from other protocols); there will be no pause in either 
enrollment or administration of VRC01 during this review.  Thereafter, all safety data 
will be reviewed every 6 months.     
 
Dose Group 4 
Upon release of Version 3.0, the protocol team reviewed available safety data from adult 
and pediatric protocols of VRC01 and VRC01LS (from P1112 database and safety 
reviews from other protocols) and Dose Group 3 accrual data.  There was no safety 
signal, and the team determined that Dose Group 4, Cohort 1 could open to enrollment 
as soon as study documents were updated per protocol V3.0 and site approvals were 
obtained; see Error! Reference source not found.. This occurred on 21 June 2017. 
When the first six infants in Dose Group 4, Cohort 1 were immunized and completed 28 
days of follow-up, the team reviewed all available safety data. This review of safety data 
revealed no signal, and enrollment into Dose Group 4, Cohort 2 was opened on 7 
December 2017. 
 
Dose Group 5 
Upon release of Version 4.0, the protocol team will review available interim safety data 
from adult and pediatric protocols of VRC01, VRC01LS and VRC07-523LS (from 
P1112 database and safety reviews from other protocols). If there is no safety signal, the 
team will determine Dose Group 5, Cohort 1 may open to enrollment as soon as study 
documents are updated per protocol V4.0 and site approvals are obtained; see Error! 
Reference source not found.. When the first six infants in Dose Group 5, Cohort 1 have 
been immunized and completed 28 days of follow-up, the team will review interim safety 
and PK data. There will be no pause in Dose Group 5, Cohort 1 enrollment or 
immunization during this review. If review of safety and PK data reveals signal, the team 
will consult with the SMC. If review of safety and PK data reveals no signal, enrollment 
into Dose Group 5, Cohort 2 will be opened. 
 
6.2.2 Study Pauses 
Safety assessments are a continuous, real-time process.  That is, the team reviews all AEs 
on conference calls twice a month while the study is enrolling.  If study pause criteria as 
defined in Section 8.5.1 are met, enrollment and immunizations will be paused for SMC 
review.  If the SMC decides that further enrollment and immunizations cannot be 
continued, the study will stop accrual but continue safety follow-up of all enrolled 
infants. 
 

 
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6.3 
Criteria for Treatment Pause for Individual Participants 
For Dose Groups 1 and 2, who received a single dose of VRC01, there were no criteria to 
pause the treatment for individual participants.  For Dose Group 3 and Cohort 2 of Dose 
Groups 4 and 5, the decision to hold administration of subsequent doses may be at the 
discretion of the site clinician in consultation with the P1112 study team. 
 
 

 
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6.4 
Criteria for Treatment Discontinuation 
For Dose Groups 1 and 2, who received a single dose of VRC01, there were no criteria to 
discontinue the treatment for individual participants.  For Dose Group 3 and Cohort 2 of 
Dose Groups 4 and 5, refer to Toxicity Management (Section 6.1.1) for criteria for 
treatment discontinuation.  In addition, treatment discontinuation will occur if an infant is 
determined to be HIV-infected before he or she is 12 weeks old (see Section 6.6). 
 
6.5 
Criteria for Study Discontinuation 
• Infant does not receive the first VRC01, VRC01LS, or VRC07-523LS immunization. 
• The mother or legal guardian refuses infant follow-up evaluations. 
• The investigator determines that further participation would be detrimental to the 
participant’s health or well-being. 
• The participant fails to comply with the study requirements so as to cause harm to 
him/herself or seriously interfere with the validity of the study results. 
• The study may be discontinued by the NIH, Office of Human Research Protection 
(OHRP), U.S. Food, and Drug Administration (FDA), the IMPAACT Network, 
IRB/EC or local government regulatory agency. 
 
6.6 
If an Infant is Determined to be HIV-Infected 
If an infant enrolled in P1112 has a positive HIV-1 NAT result at any time point, sites 
should notify the Protocol Team at impaact.teamP1112@fstrf.org as soon as possible.  
Infants in Dose Group 3 with a positive HIV-1 NAT will not continue to receive VRC01 
and will continue to be followed as per APPENDIX ID: Schedule of Evaluations (Dose 
Group 3) per the columns “Observation Period: Every 12 weeks after BF Cessation, HIV 
Diagnosis, and/or at Weeks 84 and 96.”  Likewise, an infant identified as HIV-infected 
before he or she is 12 weeks old in Dose Groups 4 and 5 Cohort 2 would not receive a 
second dose of VRC01LS or VRC07-523LS and would continue to be followed per 
APPENDIX IF: Schedule of Evaluations (Dose Group 4, Cohort 2: breastfeeding) or 
APPENDIX IH: Schedule of Evaluations (Dose Group 5, Cohort 2: breastfeeding), 
respectively, per the column “Observation Following Dosing Period.” In addition, an 
infant with a positive HIV-1 NAT result in any Dose Group will undergo additional 
testing to confirm the infection and to collect blood samples for viral quantification and 
evaluation.  The additional evaluations are listed in APPENDIX IC: HIV-1 Infected 
Infant Schedule of Evaluations (all dose groups)1 
 
7 
EXPEDITED ADVERSE EVENT REPORTING  
 
7.1 
Adverse Event Reporting to DAIDS 
Requirements, definitions and methods for expedited reporting of Adverse Events (AEs) 
are outlined in Version 2.0 of the DAIDS Expedited Adverse Event (EAE) Manual, 

 
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which is available on the Regulatory Support Center (RSC) website at 
https://rsc.niaid.nih.gov/clinical-research-sites/manual-expedited-reporting-adverse-
events-daids  
 
The DAIDS Adverse Experience Reporting System (DAERS), an internet-based 
reporting system, must be used for expedited AE reporting to DAIDS.  In the event of 
system outages or technical difficulties, expedited AEs 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 NIAID CRMS Support at 
CRMSSupport@niaid.nih.gov.  Site queries may also be sent from within the DAERS 
application itself. 
For questions about expedited reporting, please contact the DAIDS RSC Safety Office at 
DAIDSRSCSafetyOffice@tech-res.com. 
 
7.2 
Reporting Requirements for this Study 
The SAE Reporting Category, as defined in Version 2.0 of the DAIDS EAE Manual, are 
used for this study. 
 
The study agent for which expedited reporting is required are: VRC01, VRC01LS, and 
VRC07-523LS. 
 
In addition to the EAE Reporting Category identified above, other AEs that must be 
reported in an expedited manner are: immune complex disease. 
 
7.3 
Grading Severity of Events 
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (DAIDS AE Grading Table), Corrected Version 2.1, July 2017, must be used with 
the exception of infant pain assessment.  For pain assessment, a description of the pain 
grading to be used for IMPAACT P1112 may be found in the MOP.  The DAIDS AE 
Grading Table is available on the RSC website at. https://rsc.niaid.nih.gov/clinical-
research-sites/daids-adverse-event-grading-tables 
 
7.4 
Expedited AE Reporting Period 
The expedited AE reporting period for this study is as per the EAE manual, i.e., from 
enrollment of a trial participant to the end of trial follow-up for that participant. 
 
After the protocol-defined AE reporting period, unless otherwise noted, only SUSARs as 
defined in Version 2.0 of the EAE Manual will be reported to DAIDS if the study staff 
become aware of the events on a passive basis (from publicly available information). 

 
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8 
STATISTICAL CONSIDERATIONS 
 
8.1 
General Design Issues 
This is an open label, multicenter, Phase 1 study to determine the safety and 
pharmacokinetic parameters of three subcutaneous, potent anti-HIV neutralizing 
monoclonal antibodies, VRC01, VRC01LS, and VRC07-523LS, in order to select a safe 
and PK-acceptable dose to be used in future efficacy clinical trials. 
 
The study population is the newborns of HIV-1-infected women, who are ≥ 36 weeks 
gestation and are at increased risk for perinatal or post-natal HIV transmission (see 
Section 4.3.5 for definition of increased risk).  The women do not receive study 
immunizations.  After delivery, the mothers and their exposed neonates are checked for 
eligibility (see Section 4 for eligibility requirements for both mother and baby).  If 
eligible, both the mothers and infants are enrolled.  Only the infant is immunized with a 
subcutaneous injection(s) of VRC01, VRC01LS, or VRC07-523LS.  Only the infants are 
assessed for safety and followed on the study.   
 
The study will enroll 79 infants, with the aim of having approximately 62 evaluable 
infants: 10 of 13 (77%) each in Dose Groups 1-3 and 8 of 10 (80%) per cohort in Dose 
Groups 4 and 5. Evaluable infants must have received the required immunization(s) and 
have completed the required follow-up for the primary safety outcome measure for the 
relevant group (Day 28 evaluations for Dose Groups 1 and 2 and Cohort 1 in Dose 
Groups 4 and 5; Week 24 evaluations for Dose Group 3; and Week 16 evaluations for 
Cohort 2 in Dose Groups 4 and 5).  .   
 
Safety will be monitored in real time throughout the study.  If none of the triggers listed 
in section 8.5.1 are met, the accrual and immunizations will proceed continuously, with 
no pause, until enrollment in the dose group has been completed.  This will ensure that 
the study will remain open and all eligible infants will be enrolled and immunized in a 
timely manner.   
 
If any safety triggers are met, subsequent enrollment and immunizations will be paused 
until the safety data are reviewed by the Study Monitoring Committee (SMC) (see 
Section 8.5.1) and they will advise the team on how to proceed.   
 
Dose Groups 1-4 (Protocol Versions 1.0 - 3.0): 
 
1) Initially, only Dose Group 1 was open to enrollment.  Dose Group 1 accrued 13 
women and their infants to provide at least 10 infants who received the immunization and 
completed study evaluations.   
 
The infants received a single SC dose of 20 mg/kg of VRC01, as soon as possible after 
birth, and in all cases, less than 72 hours after birth.  
 

 
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Prior to opening Dose Group 2, the safety data through Day 28 after immunization for the 
first 10 infants immunized in Dose Group 1 were evaluated (see Section 8.5.1).  After 
these infants had completed 28 days of follow up and had passed the safety criteria 
described in Section 8.5.1, AND after the enrollment in Dose Group 1 has been 
completed, AND the adult cohort using the dose of 40 mg/kg of VRC01 had been fully 
enrolled and all participants in it had completed day 28 evaluation, then 
  
2) Dose Group 2 was opened and began accrual of a new set of 13 women and their 
infants, to provide at least 10 infants who received the immunization and study 
evaluations. 
 
The infants in Dose Group 2 received a single SC dose of 40 mg/kg of VRC01, ideally as 
soon as possible after birth, but in all cases, less than 72 hours after birth. 
 
Prior to opening Dose Group 3, the safety data through Day 28 after immunization for the 
first 6 infants immunized in Dose Group 2 were evaluated (see Section 8.5.1), After six 
Dose Group 2 infants completed 28 days of follow up and passed the safety criteria 
described in section 8.5.1, then 
  
3) Dose Group 3 began accruing, concurrently with the remaining Dose Group 2 
participants, a new set of 13 women and their infants, to provide at least 10 infants who 
received the immunizations and study evaluations. 
 
The infants in Dose Group 3 received a SC dose of 40 mg/kg of VRC01, ideally as soon 
as possible after birth, but in all cases, not later than the 5th day of life, then doses of 20 
mg/kg SC monthly for at least 24 weeks and no more than 72 weeks while breastfeeding. 
 
Prior to opening Dose Group 4, all available safety data were evaluated (see Section 
8.5.1).   
 
4) Dose Group 4 accrued 21 women and their infants to two cohorts, to provide at least 8 
infants in each cohort who will receive the immunizations and study evaluations. 
Enrollment into the two Dose Group 4 cohorts occurred sequentially (see Error! 
Reference source not found., Section 3, and Section 6.2.1). An additional mother-
infant pair was allowed to enroll because they had completed the screening when accrual 
limit was reached.  
 
Infants in Dose Group 4 received a SC dose of VRC01LS as follows: 
• Cohort 1 (non-breastfeeding): a single dose ideally as soon as possible after birth 
and within the first 72 hours of life. 
• Cohort 2 (breastfeeding): a single dose ideally as soon as possible after birth, but 
in all cases, not later than the 5th day of life.  A second dose of VRC01LS was 
administered at Week 12 if the infant has not achieved complete cessation of 
breastfeeding. 
 
 

 
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5) Dose Group 5 will accrue 20 women and their infants to two cohorts, to provide at 
least 8 infants in each cohort who will receive the immunizations and study evaluations. 
Enrollment into the two Dose Group 5 cohorts will occur sequentially (see Error! 
Reference source not found., Section 3, and Section 6.2.1). 
 
The infants in Dose Group 5 will receive a SC dose of VRC07-523LS as follows: 
• Cohort 1 (non-breastfeeding): a single dose ideally as soon as possible after birth 
and within the first 72 hours of life. 
• Cohort 2 (breastfeeding): a single dose ideally as soon as possible after birth, but 
in all cases, not later than the 5th day of life.  A second dose of VRC07-523LS 
will be administered at Week 12 if the infant has not achieved complete cessation 
of breastfeeding. 
 
Serious toxicity is not anticipated.  However, safety will be monitored carefully, given 
that: a) study participants are newborns, b) they are born to women at increased risk for 
intrapartum HIV transmission and c) safety must be assessed before opening new 
cohorts. 
 
8.2 
Outcome Measures 
All outcome measures apply to infants only. 
 
8.2.1 Primary Outcome Measures  
8.2.1.1 Safety  
Through Day 28 for Dose Groups 1, 2, Cohort 1 in Dose Groups 4 and 5; Week 24 for 
Dose Group 3; and Week 16 for Cohort 2 in Dose Groups 4 and 5: 
• 
Death 
• 
Grade 3 or higher adverse events  
• 
Vaccine-related Grade 3 or higher adverse events 
• 
HIV infection 
8.2.1.2 Pharmacologic  
(See Section 9 for PK targets and parameters) 
8.2.2 Secondary Outcome Measures  
From the end of the observation period in the primary outcome measure through the end 
of follow-up: 
• 
Death 
• 
Grade 3 or higher adverse events  
• 
Vaccine-related Grade 3 or higher adverse events 
• 
HIV infection 
From vaccine administration to end of follow-up: 
• 
Development of anti-VRC01 antibodies (yes/no) 
• 
Development of anti-VRC01LS antibodies (yes/no) 
• 
Development of anti-VRC07-523LS antibodies (yes/no) 

 
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8.2.3 Other Outcome Measures  
From vaccine administration to end of follow-up: 
• 
The amount of VRC01/ VRC01LS/ VRC07-523LS in oral secretions. 
 
Measured in infants determined to be HIV-infected from vaccine administration to end of 
follow-up: 
• 
The neutralization sensitivity of the infant and maternal virus 
• 
The amount of HIV-1 provirus in PBMC and plasma HIV-1 RNA (measured in 
copies/mL) 
• 
Serum neutralizing titer   
 
8.3 
Randomization and Stratification 
There will be no randomization or stratification of participants. 
 
8.4 
Sample Size and Accrual 
Both mothers and infants are enrolled in the study, but only infants receive the VRC01, 
VRC01LS, or VRC07-523LS immunization(s) and are followed on the study.  The study 
will enroll 79 mother-infant pairs: 13 in each of Dose Groups 1-3 and 10 in each cohort 
in Dose Groups 4 and 5, with the aim of having 10 evaluable infants in each Dose Group 
1-3 and 8 in each cohort in Dose Groups 4 and 5. Evaluable infants must have received 
the required study immunization(s) and have completed follow-up for the primary safety 
outcome measure (Day 28 evaluations for Dose Groups 1, 2 and Cohort 1 from Dose 
Groups 4 and 5; Week 24 evaluations for Dose Group 3; and Week  16 evaluations for 
Cohort 2 in Dose Groups 4 and 5).  This assumes a maximum missing data rate of 23% in 
Dose Groups 1-3 and 20% in Dose Groups 4 and 5. Non-evaluability could be due to 
losses to follow-up, missed visits or problems with laboratory samples.  Note that infants 
who do not receive the first immunization will be replaced.   
 
Safety data will be assessed as described in Section 8.5.1. If any of the safety criteria are 
triggered, enrollment and further immunizations will be temporarily stopped until the 
SMC reviews the data and advises the protocol team on how to proceed. Section 8.5.1 
discusses the error probabilities associated with the safety criteria and Section 8.6.1.2 
discusses the precision that the sample size will provide for estimating AE rates and PK 
success rates. The sample size is based on target precision for the estimation of key safety 
and PK parameters. The calculations are located in Section 8.6.1.2 for ease of discussion.   
 
We had anticipated that all participants in Dose Groups 1 and 2 would be enrolled within 
2 years after Version 1.0 was opened to accrual.  In fact, enrollment into both dose 
groups was more rapid than anticipated: taking less than 9 months to reach full accrual of 
each dose group.  Likewise, Dose Group 3 reached full accrual within approximately 4 
months. We had anticipated that Dose Group 4 would be fully enrolled within 1 year of 
that dose group being opened to accrual. However, this group also reached full accrual 
much faster than expected, within 6 months. It is anticipated that both cohorts in Dose 
Group 5 will be enrolled within 1 year after Version 4.0 opens to accrual. 

 
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8.5 
Monitoring 
The safety and tolerability of the VRC01, VRC01LS, and VRC07-523LS monoclonal 
antibodies are monitored by means of adverse events and toxicity reports presenting 
laboratory and clinical data collected throughout follow-up for the infants enrolled.  It is 
required that these data be entered into the database within 48 hours of the time at which 
the results of the laboratory tests or clinical examinations become available.  The accrual 
and toxicity reports compiled by the Data Management Center are discussed by the 
protocol team, including the medical officers and the representatives of the VRC, on 
regularly scheduled conference calls.  After the first infant enrolled into Dose Group 3 
reached the Week 24 milestone, the team began reviews of available safety data of adult 
and pediatric protocols of VRC01 (from P1112 database and most recent safety reports 
available from the other protocols) every 6 months.  These reviews will continue and 
include infants in Dose Groups 4 and 5 and data on VRC01LS and VRC07-523LS. There 
will be no pause in either enrollment or in administration of immunizations during these 
reviews.   
 
The attribution of relationship of serious adverse events to study product is discussed on 
the team calls and the relationship determined by the study team, taking into account the 
site and the Medical Officer’s assessment of the event.  Interpretation of VRC01, 
VRC01LS, or VRC07-523LS relationship to adverse events is based on the type of event, 
the relationship of the event to the time of immunization, the known biology of the 
monoclonal antibody and the investigators’ medical judgment.  Gradation of relationship 
uses the following terminology: “not related,” “probably not related,” “possibly related,” 
“probably related,” or “definitely related.”   
 
In addition to regularly scheduled toxicity reviews by the protocol team, the study is 
monitored by an independent Study Monitoring Committee (SMC) according to 
IMPAACT Standard Operation Procedure (SOP) on Study Data and Safety Monitoring.  
The committee meets via conference call to review relevant data as described in the 
sections below.  
 
8.5.1 Stopping Rules for Safety  
Stopping rules have been and will be applied in order to protect the study participants 
from unnecessary exposure to the monoclonal antibody, should the safety profile prove 
unacceptable in this population. The evaluation of safety for the purpose of applying 
these guidelines will be based on data: 
• through the first 28 days after immunization for Dose Groups 1, 2, and Cohort 1 
of Dose Groups 4 and 5;  
• on data through the first 8 weeks after the first immunization for Dose Group 3, 
which reflects the time point when this group would have received more 
immunizations than Dose Groups 1 and 2;    
• on data through the first 28 days after the second immunization in Dose Groups 4 
and 5, Cohort 2 (Week 16). 

 
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Due to the fact that infant hyperbilirubinemia is common in the first four to five weeks of 
life, especially during breastfeeding, and that Grade 3 neutropenia and anemia are 
common in infants on ARVs, these toxicities will not be counted in the safety evaluation 
algorithm presented below. 
  
NOTE: If at any time during the study the triggers below are met, the study will be 
paused for evaluation, as described below and an SMC review performed within 7 days.  
The SMC will decide what additional data they would like to see and advise the study 
team on how to proceed.   
 
To assess the early safety of the initial doses of VRC01, VRC01LS, and VRC07-523LS 
monoclonal antibodies, data from the first 6 infants immunized and followed through day 
28 in Dose Groups 1, 2, and Cohort 1 of Dose Groups 4 and 5 will be examined. 
Similarly, the early safety of the multiple dose regimen of VRC01 monoclonal antibody 
in Dose Group 3 will be assessed based on data from the first 6 infants immunized and 
followed through Week 8.  The early safety of the multiple-dose regimen of VRC01LS in 
Dose Group 4 (Cohort 2) and of VRC07-523LS in Dose Group 5 (Cohort 2) will be 
assessed based on data from the first 6 infants who have reached 28 days after the second 
dose (Week 16).  
 
• If any of the infants dies or has a life-threatening adverse event or any Grade 4 event 
that is possibly, probably or definitely attributable to the VRC01, VRC01LS, or 
VRC07-523LS immunization, or 
• If two or more of the six infants have a Grade ≥ 3 adverse event at least possibly 
related to the VRC01, VRC01LS, or VRC07-523LS immunization (excluding Grade 
3 neutropenia and anemia, and hyperbilirubinemia), then future enrollment and 
immunizations will be stopped.   
 
If these triggers are met, the team will confer with the SMC, which will judge whether 
enrollment and immunizations can be continued.  Note: for deaths and grade 4 life-
threatening events that are assessed by the protocol team as probably not related, 
immunizations will continue.  However, an SMC review to determine if it is safe to 
continue immunizations must occur within 7 days of the team’s awareness of the event. 
 
If the ongoing monitoring process reveals that a dose group has already failed the safety 
criteria, then further enrollment and immunizations will be suspended, and an SMC 
review will be performed immediately (within seven days). 
 
If the SMC decides that further enrollment and immunizations cannot be continued, the 
study will stop accrual but continue safety follow-up of all enrolled infants. 
 
Subsequent to the initial safety evaluation of each dose group, if the toxicity among the 
additional infants who have been immunized while waiting for the first 6 to reach the 
evaluation time point would increase the rate of Grade ≥ 3 adverse events at least 
possibly related to the VRC01 VRC01LS, or VRC07-523LS immunization (excluding 

 
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Grade 3 neutropenia and anemia) to over 30%, then future enrollment and immunizations 
will be paused.  For example, if only one of the first 6 infants enrolled had a Grade ≥ 3 
adverse event at least possibly related to the VRC01, VRC01LS, or VRC07-523LS 
immunization, this is not enough to trigger the stopping rule.  But if the next two infants 
each have a Grade ≥ 3 adverse event at least possibly related to the VRC01, VRC01LS, 
or VRC07-523LS immunization, this would represent a 37.5% (3/8) rate of such events, 
and because this is higher than 30%, the study will be paused for safety.  The team will 
confer with the SMC, which will judge whether enrollment and immunizations can 
continue. 
 
Given the relatively small sample size, the information available for preliminary safety 
decisions will be imperfect.  Two types of sampling errors are possible:  
 
1) In a group where the true rate of toxicity is too high to warrant increased exposure to 
the current VRC01, VRC01LS, or VRC07-523LS dose, the sample data may pass the 
safety guidelines;  
2) In a group where the true rate of toxicity is low enough that further exposure to the 
current VRC01, VRC01LS, or VRC07-523LS dose is warranted, the sample data may 
fail the guidelines.    
 
The extent to which the safety guidelines protect against the errors described above can 
be assessed by examining various hypothetical rates of "true toxicity" which could occur, 
if the study medication were used extensively among the participant population at the 
dose levels under question.  The hypothetical situations presented in Table 6 range from 
conditions under which a given dosing regimen would cause a high incidence of severe 
and life-threatening adverse events to conditions under which severe adverse events 
would be relatively rare and would not be life-threatening.  For each of these hypothetical 
situations, we assume that a sample of six participants is drawn from the participant 
population and that the safety guidelines, summarized above, are followed.  
 
Please note that the probabilities presented below would not apply if data from more than 
six infants were used. 
 
 

 
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Table 6: Probability of Meeting Safety Review Trigger Under Potential Rates of 
True Toxicity (N=6) 
 
For example, Table 6 shows that there is a 94% chance of failing the safety guidelines 
under conditions in which the true rate of life-threatening toxicity is 5% and the rate of 
non-life-threatening toxicity is 50%.  Assuming that a dosing regimen associated with 
this extent of severe toxicity would be unacceptable, the 6% chance of passing the safety 
criteria under these conditions would represent sampling error.  Note that the true rate of 
Grade 3 events would have to be quite high to provide a strong probability of pausing the 
study at a dose where there is no life-threatening toxicity and no Grade 4 events at least 
probably attributable to VRC01, VRC01LS, or VRC07-523LS.  This is considered 
acceptable, since a larger sample size would be needed to increase the probability of 
pausing the study at lower rates of Grade 3 events, and this would entail exposing greater 
numbers of children to an experimental dose, which may be either toxic or 
subtherapeutic. 
 
8.5.2 Accrual Rate Evaluation 
Accrual to this study will be monitored by the IMPAACT leadership in accordance with 
standard operating procedures.  The team will monitor feasibility quarterly, first based on 
site registration and then on accrual.  Initially, the team will monitor site registration 
quarterly to ensure that an adequate number of sites have registered to complete the 
protocol.  If less than one-third of eligible sites have registered after the protocol has been 
approved for 6 months, the team will re-assess the feasibility of the protocol and the 
reasons why sites have not registered and may amend the protocol accordingly.  Once 
one third of eligible sites have registered, the team will assess accrual on a quarterly 
True Toxicity Rates 
Probability of 
Meeting 
Safety Review 
Trigger 
Grade ≥ 3 adverse events at least possibly related to 
the VRC01, VRC01LS, or VRC07-523LS 
immunization, excluding Grade 4 events probably 
or definitely attributable to the study 
immunizationVRC01 or VRC01LS immunization 
Life-Threatening adverse 
event or Grade 4 events 
probably or definitely 
attributable to the VRC01, 
VRC01LS or VRC07-523LS 
immunization 
.50 
.00 
.89 
.50 
.05 
.94 
.50 
.25 
1.00 
.25 
.00 
.47 
.25 
.05 
.63 
.25 
.25 
.83 
.05 
.00 
.03 
.05 
.05 
.29 
.05 
.25 
.83 
.00 
.05 
.26 
.00 
.25 
.82 

 
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basis.  If the protocol has not accrued half its participants within 6 months of opening, the 
team will identify problems in accrual and possibly amend the protocol accordingly. 
 
A full monitoring plan was developed before the study opened to accrual. 
8.6 
Analyses 
 
8.6.1 Primary Analysis 
8.6.1.1 Safety 
 
Each participant’s safety data will be summarized as: the worst grade of adverse event 
experienced during the time period of observation for primary objectives and the worst 
grade of adverse event judged to be at least possibly related to the immunization(s) 
during the same time interval.  Descriptive analyses will consist of frequency 
distributions of these safety outcomes, broken down by dose group/Cohort.  All available 
safety data will be used.  All infants who receive an initial VRC01, VRC01LS, or 
VRC07-523LS immunization will be included in all analyses regardless of whether they 
receive ARV prophylaxis or are HIV-infected.   
 
With the small sample size used in this study, there will be insufficient statistical power 
for a formal test of differences between dose groups with respect to safety.  With 
insufficient power, a finding of no significant difference would not provide acceptable 
evidence of no adverse dose effect.  Thus, estimates of Grade 3 or higher toxicity rates 
will be computed separately for each dose group and bounded by 90% confidence 
intervals (CI), reflecting the precision of the estimates.  This will provide 95% assurance 
that the true rate of severe adverse events is not higher than the upper limits of the CI 
around the proportion of participants with grade 3 or higher events in the study sample.  
Because of the small sample sizes and the anticipated low toxicity rates, these intervals 
will be calculated using exact methods.    
8.6.1.2 Precision of Estimates  
 
The following table (Table 7) illustrates the confidence intervals for a range of 
hypothetical proportions of adverse events.  This table shows that a sample finding of no 
grade 3 or higher adverse events in a total sample of 10 participants would provide 95% 
confidence that the probability in the population from which the sample was drawn is no 
greater than 26%.   
 
 

 
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Table 7: Exact 90% Confidence Intervals around Potential Proportions of 
Participants Exhibiting Grade 3 or Higher Adverse Events (N=8, 10 and 13) 
 
Sample Toxicity Rates 
90% Confidence Limits 
Lower 
Upper 
0% (0/8) 
0% 
31% 
12.5% (1/8) 
0.6% 
47% 
25% (2/8) 
5% 
60% 
37.5% (3/8) 
11% 
71% 
50% (4/8) 
19% 
81% 
0% (0/10) 
0% 
26% 
10% (1/10) 
0.5% 
40% 
20% (2/10) 
4% 
51% 
30% (3/10) 
9% 
61% 
40% (4/10) 
15% 
70% 
0% (0/13) 
0% 
21% 
7.7%(1/13) 
0.4% 
32% 
15.4%(2/13) 
3% 
41% 
23.1%(3/13) 
7% 
49% 
30.8 (4/13) 
11% 
57% 
 
The proportions of infants in each dose group with adequate PK levels (see Section 9 for 
definition) and other PK results will be presented in a separate PK report,  
The table below (Table 8) presents exact 90% confidence intervals around various 
potential rates of PK success which might be observed in a total sample of 10 
participants.  This table shows that a sample finding of PK success in 6 of 10 participants 
would provide 95% confidence that the rate in the population from which the sample was 
drawn is no lower than 30%.   
 
 

 
IMPAACT P1112 Version 4.0 
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Table 8: Exact 90% Confidence Intervals around Potential Rates of PK Success 
(N=8, 10 and 13) 
 
Should this occur, the number of infants in each dose group who become HIV-infected 
will be reported.  The immunization is not expected to increase the rate of HIV infection.  
However, since these infants are born to women at increased risk of intrapartum HIV 
transmission, it is possible that a small percentage might become HIV-infected, and any 
infections will be brought to the attention of the SMC. 
 
8.7 
Secondary Analyses 
Adverse events occurring after the initial review period and throughout the remainder of 
follow-up will be summarized in the same way as for the primary safety objective.   
 
The number of infants in each dose group who develop anti-VRC01, VRC01LS, or 
VRC07-523LS antibodies will be summarized descriptively.    
 
 
Sample Rates of PK Success 
90% Confidence Limits 
Lower 
Upper 
62.5% (5/8) 
29% 
89% 
75% (6/8) 
40% 
95% 
87.5% (7/8) 
53% 
99% 
100% (8/8) 
69% 
100% 
50% (5/10) 
22% 
78% 
60% (6/10) 
30% 
85% 
70% (7/10) 
39% 
91% 
80% (8/10) 
49% 
96% 
90% (9/10) 
61% 
99.5% 
100% (10/10) 
74% 
100% 
38.5% (5/13) 
17% 
65% 
46.2% (6/13) 
22% 
71% 
53.8% (7/13) 
29% 
78% 
61.5% (8/13) 
35% 
83% 
69.2% (9/13) 
43% 
89% 
76.9% (10/13) 
51% 
93% 
84.6% (11/13) 
59% 
97% 
92.3% (12/13) 
68% 
99.6% 
100% (13/13) 
79% 
100% 
 
 
 

 
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8.8 
Exploratory Analyses 
 
The VRC01, VRC01LS, and VRC07-523LS antibody levels in oral secretions will be 
summarized at each time point by calculating 95% CI around the mean or median, 
depending on whether the data are normally distributed. 
 
Exploratory analyses will be performed in the infants who are determined to be HIV-
infected.  The neutralization sensitivity of the infant and maternal virus will be 
documented descriptively.  In addition, the changes from baseline to subsequent time 
points in the amount of HIV provirus in PBMC and plasma HIV-1 RNA (measured in 
copies/mL) over time will be presented. HIV serum neutralization titer before and after 
the study immunization will be compared.   
 
9 
CLINICAL PHARMACOLOGY PLAN 
 
9.1 
Pharmacology Objectives 
9.1.1 To determine pharmacokinetic profile of single dose, subcutaneous VRC01 in 
HIV-1-exposed infants (Dose Groups 1 and 2). 
9.1.2 To determine pharmacokinetic profile of monthly subcutaneous VRC01 in HIV-
1-exposed infants (Dose Group 3). 
9.1.3 To determine pharmacokinetic profile of one or two subcutaneous doses of 
VRC01LS (Dose Group 4) 
9.1.4 To determine pharmacokinetic profile of one or two subcutaneous doses of 
VRC07-523LS (Dose Group 5) 
 
9.2 
Primary and Secondary Data 
Demographic data (gender, ethnicity, weight, length, birth weight, gestational age at 
birth), dose group, VRC01, VRC01LS, or VRC07-523LS dose date, time, dose amount, 
administration location and sample collection times will be obtained.  Plasma VRC01 
(Dose Groups 1-3), VRC01LS (Dose Group 4), or VRC07-523LS (Dose Group 5) 
concentrations will be measured: 
 
• Dose Groups 1 and 2: before dosing and on days 1, 3, 7, 14 and 28; then at Weeks 8, 
16, 24, 48, and at HIV confirmation visits will be measured.  
• Dose Group 3: before dosing (on days 0 and 28 and weeks 16, 20, 24); for 
breastfeeding, HIV-exposed uninfected infants after Week 24: 36, 48, 60, 72, and 
early D/C visit.); on days 1 and 14; and during the observation period: at the first visit 
after complete cessation of breastfeeding or HIV diagnosis, every 12 weeks thereafter 
and then at Weeks 84 and 96. 
• Dose Group 4, Cohort 1: before dosing (Day 0) on Day 1, 14 and 28, and Week 8, 12, 
24, 36, 48, 60, 72, 84 and 96.  Cohort 2 infants will have these same visits and for 
those in Cohort 2 who receive a second VRC01LS dose at Week 12 due to continuing 

 
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to breastfeed, the Week 12 sample will be collected prior to their second dose and 
additional samples will be collected at Weeks 14 and 16. 
• Dose Group 5, Cohort 1: before dosing (Day 0) on Day 1, 3, 7, 14 and 28, and Week 
8, 12, 24, 36, 48, 60, 72, 84 and 96.   Cohort 2 infants will have these same visits and 
for those in Cohort 2, infants who receive a second VRC07-523LS dose at Week 12 
due to continuing to breastfeed, the Week 12 sample will be collected prior to their 
second dose and additional samples will be collected at Weeks 14 and 16. 
 
Assay Site: Plasma pharmacokinetic samples collected will be sent per the study-specific 
Laboratory Processing Chart (LPC) and will be assayed for serum/plasma concentration 
of VRC01, VRC01LS, or VRC07-523LS.  
 
Methods to be used: All assay methods will be standardized with a filed Methods Report, 
under Good Laboratory Practice (GLP) conditions.  The assays will be performed using 
immune based method. 
Reporting of Assay Data: At a minimum, assays will be conducted in batch after receipt 
of all samples through Week 8 for a particular participant in Dose Groups 1, 2, and 3 and 
through Week 12 for Dose Groups 4 and 5. Samples will be assayed within 60 days of the 
laboratory receiving the final Week 8 or Week 12 samples for Dose Groups 1-3 and 4-5, 
respectively.  Samples received during the conduct of the study may be assayed prior to 
the final shipment.  For Dose Group 5, Cohort 1, all samples collected to date will be 
assayed when the first six participants are enrolled.  The designated lab will run the 
assays for VRC01, VRC01LS, and VRC07-523LS levels once per week as the trial 
begins and anti-drug antibody assays once per month.  All PK samples will be registered 
in the Lab Data Management System (LDMS) database.   
For the purposes of reporting initial PK results to clinicaltrials.gov, the AUC0- and 
concentration at the end of the first dose interval, C time will be provided.  For Dose 
Groups 1-3 these are CD and AUC0-28D while for Dose Groups 4 and 5 they are CD 
and AUC0-84D. 
 
9.3 
Study Design, Modeling and Data Analysis 
Pharmacokinetic blood samples will be collected as noted in Section 9.2 and Schedule 
of Evaluation Appendices: APPENDIX IB: Infant Schedule of Evaluations (Dose 
Groups 1 and 2), APPENDIX ID: Schedule of Evaluations (Dose Group 3), 
APPENDIX IE: Schedule of Evaluations (Dose Group 4, Cohort 1: non-breastfeeding) 
APPENDIX IF: Schedule of Evaluations (Dose Group 4, Cohort 2: breastfeeding), 
APPENDIX IG: Schedule of Evaluations (Dose Group 5, Cohort 1: non-breastfeeding) 
and APPENDIX IH: Schedule of Evaluations (Dose Group 5, Cohort 2: breastfeeding). 
The samples will be 1-2 mL whole blood to yield 0.4-1.0 mL plasma.  Sample volume 
will be dependent on infant weight (See APPENDIX IB: Infant Schedule of Evaluations 
(Dose Groups 1 and 2)). 
 
VRC01, VRC01LS, and VRC07-523LS concentrations will be presented by study day, 
dose group and dose number.  The frequency of achieving Day 28 concentrations greater 

 
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than 50 µg/mL will be calculated.  For Dose Group 4, the frequency of maintaining 
VRC01LS concentrations >50 g/mL at Week 12 will be determined; likewise, for Dose 
Group 5, the frequency of maintaining VRC07-523LS concentrations >15 g/mL at 
Week 12 will be determined.  The median, mean and standard deviation of concentrations 
will be calculated from evaluable samples by each dose level.  Evaluable samples are 
defined as samples with volume and integrity to generate accurate concentration results 
and their associated accurate dosing and sample times data.  It is expected that VRC01 
pharmacokinetic parameters will have similar variability as those seen in infants with 
RSV monoclonal antibodies by Meissner et al [50]; CV=34% for apparent clearance 
(CL/F) and CV=33% for apparent volume (Vd/F).  With 10 completed participants 
planned from each dose group, it is expected that the 95% CIs for primary PK parameters 
for each dose group will be encompass a range of less than + 25% of the point estimate 
values.   
 
While it is expected that the CL/F for VRC01LS will be substantially lower than for 
VRC01, we expect the overall variability (CV) for PK parameters to be similar.  Thus, 
the proposed study will generate a similar confidence interval in the VRC01LS 
pharmacokinetic parameters.  Recent findings from VRC605 found the CV for VRC07-
523LS AUC to be < 25% for dosing groups receiving between 5-40 mg/kg and including 
following subcutaneous administration [62].  Based on these low variability values, the 
expected 95% CI will be tighter than those originally predicted for VRC01 based on RSV 
variability. 
 
The observed VRC01, VRC01LS and VRC07-523LS concentrations will be compared to 
those seen in adults.  Specifically, the geometric mean and 90% confidence interval for 
the Day 28 (VRC01) and Week 12 (VRC01LS and VRC07-523LS) concentrations will 
be generated.  Based on RSV mAb pharmacokinetics in infants, it is expected that 
VRC01 Day 28 concentrations will fall within the range of 20-70 g/mL for the 20mg/kg 
dose (Dose Group 1) and 65-115 g/mL for the 40mg/kg dose (Dose Group 2).  The 
predicted Week 12 VRC01LS and VRC07-523LS concentrations following 80-100mg 
SC are expected to be between 40-120 g/mL and 15-40 g/mL, respectively.  These are 
lower than the predicted levels in adults at Week 12 in part due to a "diluting" effect from 
the large increase in body weight expected in the infants during the first 12 weeks of life. 
The predicted concentrations of VRC01 at 40 mg/kg and 20 mg/kg, VRC01LS at 20 
mg/kg and VRC07-523LS at 80-100 mg are in Figure 7.   

 
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Figure 7: Predicted VRC01, VRC01LS, and VRC07-523LS Concentrations  
0
14
28
42
56
70
84
Time Days
0
50
100
150
200
250
300
350
400
VRC01 Conc (mcg/mL)
VRC01 40MG/KG SINGLE DOSE MEDIAN (90% CI)
0
14
28
42
56
70
84
Time Days
0
50
100
150
200
250
300
350
400
VRC01 Conc (mcg/mL)
VRC01 20MG/KG SINGLE DOSE MEDIAN (90% CI)
 
0
14
28
42
56
70
84
Days
0
100
200
300
400
500
600
700
800
VRC01LS Conc (mcg/mL)
VRC01LS 20MG/KG SINGLE DOSE MEDIAN (90% CI)
 
 

 
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0
14
28
42
56
70
84
Days
0
25
50
75
100
125
150
175
200
VRC07-523LS Conc (mcg/mL)
VRC07-523LS 80-100mg SINGLE DOSE MEDIAN (90% CI)
 
 
Individual Participant Pharmacokinetic Analysis 
 
A non-compartmental pharmacokinetic analysis will be performed using WinNonlin or a 
similar program on the VRC01, VRC01LS, and VRC07-523LS concentration data 
generated from each participant in Groups 1, 2, 4, and 5.  Calculated pharmacokinetic 
parameters will include: area-under-the-curve (AUC), maximum concentration (Cmax), 
time to Cmax (Tmax), apparent clearance (CL/F), apparent volume of distribution (Vdz/F) 
and terminal elimination rate constant (z) and the terminal half-life.  Cmax and Tmax will 
be taken directly from the observed concentration-time data.  The terminal slope, z, will 
be determined from log- linear portion of the curve and the half-life (T1/2) calculated as 
0.693/z. AUC0-last will be determined using the linear trapezoidal method.  If the final 
samples have measurable VRC01, VRC01LS, or VRC07-523LS concentrations, the 
remaining AUC after the final concentration will be estimated as Clast/z.  For the 
purposes of determining Vdz/F, it will be calculated as the ratio of (CL/F) / z.  Data will 
be summarized based by each dose group and overall for CL/F, Vdz/F and T1/2.  The 
potential for non-linearity pharmacokinetics between Dose Groups 1 and 2 will be 
determined by comparing the dose-adjusted ratios for Cmax and AUC between study dose 
groups.  Additional compartmental analysis will be performed as warranted by the data 
from Dose Groups 1, 2, 4, and 5.  For Dose Group 3, no intensive PK data is being 
collected; thus, the individual participant specific pharmacokinetic analysis will be 
limited to estimation of potential accumulation or decline in pre-dose concentrations with 
repeated dosing.  For these calculations, the Day 28 pre-dose VRC01 concentration will 
serve as the reference with the pre-dose concentrations collected at later weeks divided 
by the Day 28 pre-dose VRC01 concentration.  Both raw and dose adjusted (to 20mg/kg) 
concentration ratios will be calculated.   
 
Interim Pharmacokinetic Analyses 
 
Incremental pharmacokinetic analyses will be performed as data from Dose Groups 1-3 
through Week 8 and through Week 12 for Dose Groups 4-5 becomes available.  VRC01, 
VRC01LS and VRC07-523LS concentration data generated will be summarized and 
made available to the study team.  Given the long half-lives of VRC01LS and to a lesser 

 
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degree VRC07-523LS, a more limited pharmacokinetic analysis will be performed on 
preliminary data.  The focus of the Dose Groups 4 and 5 analyses will be on the Week 12 
VRC01LS and VRC07-523LS concentrations.  The purpose of these incremental 
analyses is to ensure that results are within the range of the expected targets.  If these 
interim results demonstrate significant inter-patient variability, the team will determine if 
protocol modifications are required.  
 
Population Pharmacokinetic Analysis 
 
Population pharmacokinetic analyses will be performed on the VRC01 pharmacokinetic 
data from P1112 Dose Groups 1-3 to determine compartmental PK parameters with the 
program NONMEM.  Based on VRC01 PK studies in adults and prior pharmacokinetic 
studies of antibodies in infants, a two-compartment model will be used to characterize the 
P1112 VRC01 PK data.  Both zero and first order absorption model will be assessed to 
determine the structural pharmacokinetic model.  Additional drug absorption models will 
be evaluated if dictated by the data.  The population analysis will generate estimates for 
initial and final apparent volumes of distribution (V1/F and V2/F), inter-compartmental 
clearance (Q/F), CL/F and absorption rate parameters either KA or the zero-order rate 
constant (R1).  Given the small participant numbers, the population pharmacokinetic 
analysis will not include an exploratory covariate analysis to assess clinical factors as 
fixed effects associated with VRC01 pharmacokinetic parameters with the exception of 
dose level (20mg/kg vs 40mg/kg) and repeat dosing as fixed effects on F, KA/R1, CL and 
V1/V2.   
 
This population analysis will be used to quantify the unexplained between participant 
pharmacokinetic variability.  Final model selection will be based on changes in the 
objective function and graphically by goodness of fit plots.  The final population model 
parameters will be assessed using bootstrapping to generate 95% CIs for parameter 
estimates and by visual posterior predictive check.  Post-hoc empiric Bayesian estimates 
of individual participant’s pharmacokinetic parameters will be generated.  The population 
parameters and their variability will be used as the input model to assess different dosing 
strategies.  Each VRC01 dosing strategy and its ability to achieve and maintain of target 
VRC01 concentrations will be performed using the final population pharmacokinetic 
model and Monte Carlo simulations with at least 5000 replicates.   
 
Similar population PK analyses will be performed on the VRC01LS and VRC07-523LS 
concentration data from Dose Groups 4 and 5.  These analyses will likely need to be 
nested with pharmacokinetic data from adults since the relatively sparse sampling and 
small number of P1112 participants receiving VRC01LS and VRC07-523LS will limit 
parameter estimate precision.  Monte Carlo simulations will be used to predict the 
expected VRC01LS and VRC07-523LS concentrations with the study dose and 
distribution of Week 12 concentrations. 
 
 

 
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9.4 
Anticipated Outcomes 
VRC01 exposure (Day 28 concentrations) will be consistently above 50 mcg/mL for 
40mg/kg but a significant portion of participants receiving 20mg/kg will have Day 28 
concentrations < 50 mcg/mL (Figure 8).  In Group 3, there will be modest accumulation 
from Day 28 (pre-dose) concentration to later pre-dose concentrations following repeat 
monthly dosing of 20mg/kg.  Accordingly, the ratio of pre-dose (repeat dosing)/pre-dose 
(Day 28) will likely be between 1 and 1.5.  For Dose Group 4, it is expected that the vast 
majority of participants will maintain VRC01LS concentrations above 50 g/mL for at 
least 12 weeks, while Dose Group 5 concentrations will maintain VRC07-523LS 
concentrations above 15 mg/mL for 12 weeks in most subjects. 
 
Figure 8: Expected Day 28 VRC01 Concentrations 
0
25
50
75
100
125
IgG Conc (mcg/mL)
0.00
0.20
0.40
0.60
0.80
1.00
Proportion of Subjects
Threshold Conc - Single Dose (Day 28) and Multiple Dose (Pre-Dose)
20mg/kg x 1
40mg/kg x 1
40mg/kg x1 + 20mg/kg x1
20mg/kg steady-state
dosed every 28 days
 
The individual participant non-compartmental and population pharmacokinetics of 
VRC01 will be determined and we expect there to be no relationships between VRC01 
absorption (F or KA) and dose.  For future protocols using repeated dosing, a dosing 
strategy of 40mg/kg initially then 20mg/kg every 4 weeks is expected to achieve 
therapeutic concentrations better than 20mg/kg every 4 weeks (Figure 9). 
 

 
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06 November 2018 
Figure 9: Expected VRC01 Concentrations 
 
 
0
30
60
90
120
Time Days
0
50
100
150
200
250
300
350
400
VRC01 Conc (mcg/mL)
VRC01 40MG/KG THEN 20MG/KG - MEDIAN (90% CI)
 
Monte Carlo simulations will help determine the optimal VRC01 VRC01LS, and 
VRC07-523LS dosing strategies to move forward into future infant trials. 
 
10 HUMAN SUBJECTS 
 
10.1 Institutional Review Board and Informed Consent 
This protocol, the informed consent documents (APPENDIX IIA: IMPAACT P1112 
Sample Informed Consent Template: Dose Group 5, Cohort 1 (Non-breastfeeding) and 
APPENDIX IIB: IMPAACT P1112 Sample Informed Consent Template: Dose Group 5, 
Cohort 2 (breastfeeding)), and any subsequent modifications must be reviewed and 
approved by the IRB or EC responsible for oversight of the study.  Written informed 
consent must be obtained from the participant (or parents or legal guardians of 
participants who cannot consent for themselves, such as those below the legal age).  The 
informed consent will describe the purpose of the study, the procedures to be followed, 
and the risks and benefits of participation.  A copy of the consent form will be given to 
the participant (or parent or legal guardian). 
Note: in P1112 protocol V4.0, no changes were made to the sample informed 
consent templates for Dose Groups 1, 2, 3, and 4 (formerly Appendices IIA, IIB, 
IIC in previous versions of the protocol). These appendices are therefore not 
included in protocol V4.0; the sample informed consent templates for Dose Group 
5 are instead included as Appendices IIA and IIB. 
 
Each site which receives US HHS funding and follows the United States Code of Federal 
Regulations Title 45-Public Welfare, Part 46-Protection of Human Subjects (also known 
as the Common Rule) should have on record at the site a plan that detects and addresses 
any change in guardianship occurring in pediatric participants and determines when a 
study participant must have a consent process which involves a legally authorized 
representative (LAR) other than a family member with guardianship.  The plan will 

 
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include how the site determines when a LAR is initially or no longer needed and how 
frequently the LAR re-signs the consent.  The plan should follow all IRB/EC, local, state, 
national and/or host country guidelines.  Confirmation of such a plan at a site should be 
submitted with protocol registration materials. 
 
10.2 Participant Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified 
only by a coded number to maintain participant confidentiality.  All records will be kept 
in a secured area.  All computer entry and networking programs will be done with coded 
numbers only.  Clinical information will not be released without written permission of the 
participant, except as necessary for monitoring by study staff, study monitors, the U.S. 
Food and Drug Administration (FDA) or other national Drug Regulatory Authority, the 
Office for Human Research Protections (OHRP), the NIH, the IMPAACT Network, the 
local IRB or Ethics Committee, or their designees, and other local, U.S., or international 
regulatory authorities. 
 
10.3 Study Discontinuation 
The study may be discontinued at any time by the NIH, Office of Human Research 
Protection (OHRP), the FDA, the IMPAACT Network, the IRB or EC, or other 
governmental agencies as part of their duties to ensure that research participants are 
protected.  
 
11 PUBLICATION OF RESEARCH FINDINGS 
 
Publication of the results of this trial will be governed by IMPAACT policies.   
 
 
12 BIOHAZARD CONTAINMENT 
 
As the transmission of HIV and other blood borne pathogens can occur through contact 
with contaminated needles, blood, and blood products, appropriate blood and secretion 
precautions will be employed by all personnel in the drawing of blood and shipping and 
handling of all specimens for this study, as currently recommended by the Centers for 
Disease Control and Prevention. 
All infectious specimens will be sent in accordance with the International Air Transport 
Association Dangerous Goods Regulations-Packing Instruction 602.  Refer to individual 
carrier guidelines (e.g., Federal Express or Airborne) for specific instructions. 
 

 
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19. 
Zhou, T., et al., Structural basis for broad and potent neutralization of HIV-1 by 
antibody VRC01. Science, 2010. 329(5993): p. 811-7. 
20. 
Burton, D.R., et al., Efficient neutralization of primary isolates of HIV-1 by a 
recombinant human monoclonal antibody. Science, 1994. 266(5187): p. 1024-
1027. 
21. 
Burton, D.R., et al., A large array of human monoclonal antibodies to type 1 
human immunodeficiency virus from combinatorial libraries of asymptomatic 
seropositive individuals. Proc.Natl.Acad.Sci.U.S.A, 1991. 88(22): p. 10134-
10137. 
22. 
Li, Y., et al., Mechanism of neutralization by monoclonal antibody VRC01, a CD4 
binding site directed neutralizing antibody with extensive neutralization breadth. 
Oral Abstract Session 09: B Cell Immunology, 2012: p. 87-87. 
23. 
Haynes, B.F., et al., Cardiolipin polyspecific autoreactivity in two broadly 
neutralizing HIV-1 antibodies. Science, 2005. 308(5730): p. 1906-1908. 
24. 
Nakamura, K.J., et al., Coverage of primary mother-to-child HIV transmission 
isolates by second-generation broadly neutralizing antibodies. AIDS, 2013. 
27(3): p. 337-346. 
25. 
Fouda, G.G., et al., Postnatally-transmitted HIV-1 Envelope variants have similar 
neutralization-sensitivity and function to that of nontransmitted breast milk 
variants. Retrovirology., 2013. 10: p. 3. 
26. 
Fennessey, C.M. and B.F. Keele, Using nonhuman primates to model HIV 
transmission. Curr.Opin.HIV.AIDS, 2013. 8(4): p. 280-287. 
27. 
Girard, M.P. and S.A. Plotkin, HIV vaccine development at the turn of the 21st 
century. Curr.Opin.HIV.AIDS, 2012. 7(1): p. 4-9. 
28. 
Qureshi, H., et al., Low-dose penile SIVmac251 exposure of rhesus macaques 
infected with adenovirus type 5 (Ad5) and then immunized with a replication-
defective Ad5-based SIV gag/pol/nef vaccine recapitulates the results of the phase 
IIb step trial of a similar HIV-1 vaccine. J.Virol., 2012. 86(4): p. 2239-2250. 
29. 
Reynolds, M.R., et al., A trivalent recombinant Ad5 gag/pol/nef vaccine fails to 
protect rhesus macaques from infection or control virus replication after a 
limiting-dose heterologous SIV challenge. Vaccine, 2012. 30(30): p. 4465-4475. 
30. 
Zalevsky, J., et al., Enhanced antibody half-life improves in vivo activity. Nat 
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31. 
Ko, S.Y., et al., Enhanced neonatal Fc receptor function improves protection 
against primate SHIV infection. Nature, 2014. 514(7524): p. 642-5. 
32. 
Rudicell, R.S., et al., Enhanced potency of a broadly neutralizing HIV-1 antibody 
in vitro improves protection against lentiviral infection in vivo. J Virol, 2014. 
88(21): p. 12669-82. 

 
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33. 
Lynch, R.M., et al., Virologic effects of broadly neutralizing antibody VRC01 
administration during chronic HIV-1 infection. Sci Transl Med, 2015. 7(319): p. 
319ra206. 
34. 
Ledgerwood, J.E., et al., Safety, pharmacokinetics and neutralization of the 
broadly neutralizing HIV-1 human monoclonal antibody VRC01 in healthy adults. 
Clin Exp Immunol, 2015. 182(3): p. 289-301. 
35. 
Gaudinski, M.R., et al., Safety and pharmacokinetics of the Fc-modified HIV-1 
human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in 
healthy adults. PLoS Med, 2018. 15(1): p. e1002493. 
36. 
Hall, W.C., et al., Tissue Cross-Reactivity Studies for Monoclonal Antibodies: 
Predictive Value and Use for Selection of Relevant Animal Species for Toxicity 
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Approach to Facilitating Clinical Trials, J.A. Cavagnaro, Editor. 2008, John 
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37. 
Leach, M.W., et al., Use of tissue cross-reactivity studies in the development of 
antibody-based biopharmaceuticals: history, experience, methodology, and future 
directions. Toxicol Pathol, 2010. 38(7): p. 1138-66. 
38. 
Mayer, K.H., et al., Safety, pharmacokinetics, and immunological activities of 
multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, 
VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized 
trial. PLoS Med, 2017. 14(11): p. e1002435. 
39. 
Huang, Y., et al., Population pharmacokinetics analysis of VRC01, an HIV-1 
broadly neutralizing monoclonal antibody, in healthy adults. MAbs, 2017. 9(5): 
p. 792-800. 
40. 
Bar, K.J., et al., Effect of HIV Antibody VRC01 on Viral Rebound after Treatment 
Interruption. N Engl J Med, 2016. 375(21): p. 2037-2050. 
41. 
Crowell, T.A., et al. HIV-specific broadly-neutralizing monoclonal antibody, 
VRC01, minimally impacts time to viral rebound following treatment interruption 
in virologically-suppressed, HIV-infected participants who initiated antiretroviral 
therapy during acute HIV infection in 9th IAS Conference on HIV Science (IAS 
2017). 2017. Paris, France. 
42. 
Mayer, K.H., et al., Clinical Safety and Pharmacokinetics of IV and SC VRC01, a 
Broadly Neutralizing mAb, in Conference on Retroviruses and Opportunistic 
Infections (CROI). 2016: Boston, MA. 
43. 
Mast, E.E., et al., A comprehensive immunization strategy to eliminate 
transmission of hepatitis B virus infection in the United States: recommendations 
of the Advisory Committee on Immunization Practices (ACIP) part 1: 
immunization of infants, children, and adolescents. MMWR Recomm.Rep., 2005. 
54(RR-16): p. 1-31. 
44. 
Bulbul, A., et al., Anaphylactic shock due to hepatitis B immunoglobulin in a 
newborn. J.Matern.Fetal Neonatal Med., 2010. 23(10): p. 1257-1259. 
45. 
Buxmann, H., et al., An open-label, randomized efficacy and safety trial of 
subcutaneous and intramuscular BT088 (Fovepta) human hepatitis B immunoglobulin 
in neonates of HBV-carrier mothers. J.Perinat.Med., 2012. 40(4): p. 433-438. 
46. 
Stiehm, E.R., et al., Efficacy of zidovudine and human immunodeficiency virus 
(HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission 

 
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from HIV-infected women with advanced disease: results of Pediatric AIDS 
Clinical Trials Group protocol 185. J.Infect.Dis., 1999. 179(3): p. 567-575. 
47. 
Brocklehurst, P., et al., Treatment of neonatal sepsis with intravenous immune 
globulin. N.Engl.J.Med., 2011. 365(13): p. 1201-1211. 
48. 
Weisman, L.E., et al., Phase 1/2 double-blind, placebo-controlled, dose 
escalation, safety, and pharmacokinetic study of pagibaximab (BSYX-A110), an 
antistaphylococcal monoclonal antibody for the prevention of staphylococcal 
bloodstream infections, in very-low-birth-weight neonates. Antimicrob.Agents 
Chemother., 2009. 53(7): p. 2879-2886. 
49. 
Weisman, L.E., et al., A randomized study of a monoclonal antibody (pagibaximab) 
to prevent staphylococcal sepsis. Pediatrics, 2011. 128(2): p. 271-279. 
50. 
Meissner, H.C., Antimicrobial agents and chemotherapy. American Society for 
Microbiology, 1999: p. 1188-1193. 
51. 
Motavizumab, RSV Monoclonal Antibody, Antiviral Drugs Advisory Committee 
Meeting. 2010  [cited 2014 21 July]; Available from: 
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52. 
Kieffer, M.P., et al., Improved detection of incident HIV infection and uptake of 
PMTCT services in labor and delivery in a high HIV prevalence setting. J 
Acquir.Immune.Defic.Syndr., 2011. 57(4): p. e85-e91. 
53. 
Moodley, D., et al., High HIV incidence during pregnancy: compelling reason for 
repeat HIV testing. AIDS, 2009. 23(10): p. 1255-1259. 
54. 
Humphrey, J.H., et al., Mother to child transmission of HIV among Zimbabwean 
women who seroconverted postnatally: prospective cohort study. BMJ, 2010. 341: 
p. c6580. 
55. 
Moodley, D., et al., Incident HIV infection in pregnant and lactating women and 
its effect on mother-to-child transmission in South Africa. J Infect Dis, 2011. 
203(9): p. 1231-4. 
56. 
Lockman, S. and T. Creek, Acute maternal HIV infection during pregnancy and 
breast-feeding: substantial risk to infants. J Infect Dis., 2009. 200(5): p. 667-669. 
57. 
Nielsen-Saines, K., et al., Three postpartum antiretroviral regimens to prevent 
intrapartum HIV infection. N Engl J Med, 2012. 366(25): p. 2368-79. 
58. 
Pant Pai, N., et al., Head-to-head comparison of accuracy of a rapid point-of-care 
HIV test with oral versus whole-blood specimens: a systematic review and meta-
analysis. Lancent Infectious Diseases, 2012. 12(5): p. 373-380. 
59. 
Shingai, M., et al., Antibody-mediated immunotherapy of macaques chronically 
infected with SHIV suppresses viraemia. Nature, 2013. 503(7475): p. 277-80. 
60. 
Barouch, D.H., et al., Therapeutic efficacy of potent neutralizing HIV-1-specific 
monoclonal antibodies in SHIV-infected rhesus monkeys. Nature, 2013. 
503(7475): p. 224-8. 
61. 
Hessell, A.J., et al., Early short-term treatment with neutralizing human 
monoclonal antibodies halts SHIV infection in infant macaques. Nat Med, 2016. 
22(4): p. 362-8. 
62. 
Gaudinski, M.R., et al. A Phase I dose-escalation study of monoclonal antibody 
VRC07-523LS in healthy adults. in Conference on Retroviruses and Opportunistic 
Infections (CROI). 2018. Boston, Massachusetts. 

 
 
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APPENDIX IA: Maternal Schedule of Evaluations (all dose groups) 
 
 
Screening1 
Entry2 
CLINICAL 
 
 
Consent 
X 
 
History3 
X 
X 
LABORATORY 
 
 
HIV diagnostic testing if not in medical record 
5 ml 
5 ml 
PBMC and Plasma Store4 
 
10 ml 
Serum Store4 
 
10 ml 
Total Blood Volume Mother (mL) 
0 – 5 ml 
20 – 25 ml 
 
Footnotes 
1. Screening may be performed within 30 days prior to birth or may be performed after birth provided that the infant meets all 
inclusion/exclusion criteria.  Screening and entry can be performed on the same date. 
2. Entry visit occurs after the newborn is determined to be eligible for the study.  Note that the Entry Visit is also the end of study for the 
maternal participant. 
3. A complete history is required at Entry and includes date of birth; race; ethnicity; all quantitative HIV RNA tests, HIV genotypes, and 
CD4 T lymphocyte counts that are obtained during pregnancy and that are available to the site, all HIV-related diagnoses present during 
pregnancy, all antiretroviral medications received during pregnancy and delivery (doses not required), all diagnoses at labor and delivery.   
4. Samples will be processed and shipped per the LPC for characterization of maternal virus and HIV antibodies.  Left over serum, plasma, 
and PBMC will be stored per the LPC for future HIV-related studies (including possible genetic testing) overseen per the IMPAACT SOP.   
Maternal blood can be collected any time from Entry up until 14 days after Entry. 
 

 
 
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APPENDIX IB: Infant Schedule of Evaluations (Dose Groups 1 and 2) 
  
 
Screen1 
Entry/ 
Day 02 
0 Hour 
Day 1 
24 hr3 
± 6 hr 
Day 3 
72 hr 3 
± 24 hr 
Day 7 
168 hr 3 
±24 hr 
Day 144 
+3 days 
 
Day 284 
+3 days 
 
Wk 8 
±1 wk 
Wk 164 
+2 wk 
Wk 24 
±2 wks 
Wk 48 
±2 wks 
Early 
D/C post 
Day 145 
Q3 month f/u 
after Wk 48 if 
still HIV Ab+21 
± 2 wks 
History6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical exam7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
DOSE VRC018 
 
X8 
 
 
 
 
 
 
 
 
 
 
 
LABORATORY EVALUATIONS 
Hematology9 
1mL 
 
 
 
1mL 
 
 
 
 
 
 
 
 
Chemistries10,22 
1mL 
 
 
 
1mL 
1mL 
 
 
1mL 
 
 
 
 
HIV-1 NAT 
testing11 
1mL12 
 
 
 
 
1mL 
1mL 
 
1mL 
1mL 
 
 
 
HIV antibody test 
 
 
 
 
 
 
 
 
 
 
1mL21 
 
2mL21 
Lymphocyte subsets 
(CD3/CD4/CD8)13 
1mL 
 
 
 
1mL 
 
 
 
 
 
 
 
 
VRC01 Plasma 
levels14 
 
2mL 
1mL 
1mL 
1mL 
1-2mL14 
2mL 
1-
2mL14 
2mL 
2mL 
2mL 
2mL 
 
PBMC storage15 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
VRC01 serum16,17 
 
0-
1mL17 
 
 
 
 
0-1 mL17 
1 mL17 
0-1 
mL17 
2 mL 
2 mL 
2 mL 
2mL 
 
Anti-VRC01 Ab18 
 
X 
 
 
 
 
 
X 
 
X 
X 
 
 
Oral secretions19 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Total Blood 
Volume Infant (mL) 
4mL 
2-3mL 
1mL 
1mL 
4mL 
3-5mL 
3-4mL 
1-3mL 
6mL 
5mL 
5mL 
4mL 
2mL 
 
NOTE: 18-24mL in 8-week period20 
 
 
 
 
 
 
 
 
 

 
 
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Footnotes 
1. Screening evaluations should be completed as soon as possible after birth.  The laboratory testing needed for inclusion/exclusion (CBC, ALT) 
must be completed and eligibility confirmed in time so that the VRC01 is administered at less than 72 hours after birth.   
2. The Entry/Day 0 visit can take place on the same day as the Screening Visit.  Blood for the Entry/Day 0 evaluations may be drawn with the 
screening blood or at the time of entry but must be drawn before the VRC01 immunization is administered.   
3. Hours (hr) after dose administration.  
4. Window permits visit to be done only 3 days after (not before) Day 14 and 28, and only 2 weeks after Week 16 (not before) to assure the 
timing of HIV testing meets criteria for presumptive exclusion of infant HIV infection. 
5. An Early Discontinuation visit should be scheduled if participant comes off study after Day 14 and prior to Week 48. 
6. A complete history is required at birth and includes date of birth, Race, ethnicity, gender, maternal risk factor meeting the inclusion criteria, all 
diagnoses, all signs and symptoms, all antiretroviral medications (ARV) with start and stop dates and doses, all injected medications (i.e. 
vitamin K, Hepatitis B vaccine) including location of injection.  At subsequent visits the history should include ARV doses with start and stop 
dates, other medications, diagnoses, signs and symptoms, and vaccinations.  Results of HIV-1 testing done outside of the study should be 
abstracted. 
7. Complete physical exam including vitals, weight, length, and head circumference at Screening, Day 0, Day 28, and Weeks 8, 16, 24 and 48.  
Targeted physical exam including vitals and weight at Day 1, 3, 7, 14.  Examination of VRC01 injection site should occur at all visits through 
Week 24.   
8. The VRC01 immunization must be administered less than 72 hours after birth (see MOP for administration instructions). 
Dose Group 1: Single VRC01 20mg/kg subcutaneous injection less than 72 hours after birth. 
Dose Group 2: Single VRC01 40mg/kg subcutaneous injection less than 72 hours after birth. 
1. Infants should be monitored for a minimum of 4 hours after study treatment injection, with initial assessments at 15, 30 and 60 minutes 
post dose.  Clinic personnel must observe participant for any potential adverse reactions to the study immunization.  Equipment, supplies, 
and properly skilled medical personnel must be immediately available for emergency use in the event of an unexpected adverse reaction. 
2. Infants will also be evaluated for local reactions and pain 1 hour (+/- 30 minutes) after the injection and results recorded on a study CRF. 
9. Hematology should include CBC with differential and platelet count.  (Not required at screening if collected clinically at birth and results are 
available). 
10. Chemistries should include AST, ALT, total bilirubin, and creatinine.  (Not required at screening if collected clinically at birth and ALT 
results are available). 
11. HIV-1 NAT (nucleic acid testing) by a method that detects DNA is required for diagnostic testing since VRC01 might suppress HIV-1 RNA.  
For the screening NAT, see footnote 12.  For U.S. sites, HIV-1 NAT testing must be run in a CLIA-approved laboratory.  For non-U.S. sites, 
the HIV-1 NAT must be run at a VQA-certified laboratory.  If the infant has a positive HIV-1 NAT at any time, confirmation and additional 
samples should be obtained as per APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1; infant follow up 
on study should also continue to be as per APPENDIX IB: Infant Schedule of Evaluations (Dose Groups 1 and 2).  When possible 
APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 visits should be scheduled to coincide with 
APPENDIX IB: Infant Schedule of Evaluations (Dose Groups 1 and 2).  
12. Blood for HIV-1 NAT drawn at Screening must be obtained prior to 48 hours of life AND prior to VRC01 administration.  It may be drawn 
with the Entry blood.  Results may be pending at study entry.  If an HIV-1 NAT (DNA or RNA or combined) was collected clinically prior to 

 
 
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48 hours of life and tested in a laboratory with CLIA approval (U.S. sites) or VQA approval (Non-U.S. sites), the test does not need to be 
duplicated for the study; in this case, results will be abstracted for the study. 
13. Lymphocyte subsets include CD3/CD4/CD8 counts and percentages.  Results are not needed for study entry.  Draw with CBC.  Must be 
performed at CLIA-certified (or equivalent) laboratory. 
14. Samples for VRC01 plasma levels to be obtained prior to VRC01 administration.  For infants with birth weight <2.8kg use lower sample 
volume at Day 14 and Week 8.  Plasma for VRC01 levels and anti-VRC01 levels processed and batch shipped per the LPC.  Leftover plasma 
will be stored per the LPC for future HIV-related studies overseen per IMPAACT SOP.  See LPC for collection procedure, processing, 
storage, and shipping instructions. 
15. PBMC from the VRC01 plasma level sample will be isolated if site is capable of PBMC storage.  PBMC will be used for HIV characterization 
if there are infants with HIV infection.  Leftover PBMC will be stored per the LPC for future HIV-related studies (possibly including genetic 
testing) per IMPAACT SOP.  See LPC for collection procedure, processing, storage, and shipping instructions. 
16. Samples for VRC01 serum to be obtained prior to VRC01 administration.  Serum for VRC01 antibody levels and neutralization assays will be 
processed and batch shipped per the LPC.  Leftover serum will be stored per the LPC for future HIV-related studies per IMPAACT SOP.  See 
LPC for collection procedure, processing, storage, and shipping instructions.  
17. For infants with birth weight <2.8kg: do not collect VRC01 serum samples at Entry, Day 14, Day 28, or Week 8.   
18. Assay will be performed with plasma from VRC01 plasma level sample.   
19. Oral fluid is collected with Weck-cel Sponge oral fluid collection device.  Sample at Entry should be collected prior to VRC01 administration 
as baseline.  Assay will be performed to detect VRC01 antibody level sample.  Leftover oral fluid will be stored per the LPC for future HIV-
related studies per IMPAACT SOP.  See LPC for collection procedure, processing, storage, and shipping instructions. 
20. For infants with birth weight <2.8kg lower sample volume will be collected.  See also Footnotes 12 and 17.  Volumes equate to < 3ml/kg 
drawn within 24 hours and < 9.0 ml/kg drawn over 8 weeks.  These are below the NIH Clinical Center guidelines allowing a maximum of 
5ml/kg within 24 hours and 9.5ml/kg drawn over an 8-week period.    
21. HIV antibody testing will be performed at Week 48.  If the infant remains antibody positive, he/she will remain on study for repeat antibody 
testing every 3 months until negative.  U.S sites should perform testing according to CLIA requirements, including those sites utilizing CLIA-
waived HIV rapid testing.  For Non-U.S. sites, testing should be performed at the approved site-associated DAIDS-monitored laboratory.   
22. Obtain additional ALT and AST measurement upon evidence of hepatic-related clinical adverse events (jaundice, enlargement of the liver). 
 
Priority for blood samples at: 
 
 
 
Screening and Entry 
 
Day 7  
Subsequent visits 
1. 
HIV-1NAT  
2. 
CBC, chemistry  
3. 
VRC01 plasma levels 
4. 
Lymphocyte subsets 
5. 
VRC01 serum 
1. VRC01 Plasma levels 
2. CBC, chemistry 
3. Lymphocyte subsets 
 
1. HIV-1 NAT 
2. VRC01 Plasma levels 
3. VRC01 Serum  
4. HIV Antibody 
5. Chemistry 
 
 

 
 
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APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 
 
 
1st Visit: Infected 
Infant 
(Confirmatory)2 
2nd Visit: 
Infected Infant 3 
3rd Visit: 
Infected Infant4 
Subsequent visits prior 
to initiation of ARVs5 
(q28d ±7d) 
Follow up after 
initiation of 
ARVs6 
History7 
X 
X 
X 
X 
X 
Physical exam 
X 
X 
X 
X 
X 
HIV-1 NAT testing8 
1 mL9 
 
 
 
 
Quantitative HIV-1 RNA 
testing10 
3 mL 
3 mL 
3 mL 
3 mL 
0 to 3 mL 
mAb Plasma levels11 
1 mL11 
1 mL11 
1 mL11 
 
 
Lymphocytes: CD3/CD4/CD816 
0 to 2 mL 
 
 
0 to 2 mL 17 
0 to 2 mL17 
PBMC storage 
X12 
X12 
X12 
1 mL 
1 ml13 
Stored plasma14 
X 
X 
X 
X 
X 
Total Blood Volume Infant (mL) 
5-7 ml15 
4 ml15 
4 ml15 
4 – 6 mL15 
1 - 6 mL15 
 
Footnotes 
1. Visits for APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 should be scheduled to concur with visits 
for APPENDIX IB: Infant Schedule of Evaluations (Dose Groups 1 and 2), APPENDIX ID: Schedule of Evaluations (Dose Group 3), 
APPENDIX IE: Schedule of Evaluations (Dose Group 4, Cohort 1: non-breastfeeding), APPENDIX IF: Schedule of Evaluations 
(Dose Group 4, Cohort 2: breastfeeding), APPENDIX IG: Schedule of Evaluations (Dose Group 5, Cohort 1: non-breastfeeding), or 
APPENDIX IH: Schedule of Evaluations (Dose Group 5, Cohort 2: breastfeeding) whenever possible.  The protocol team will review 
advance requests for deviations from the specified visit windows on a case-by-case basis.   
2. The 1st Visit for an Infected Infant (Confirmatory visit) should be as soon as possible after site notification of the first positive result and not 
later than 14 days after the date of the blood draw of the first positive HIV-1 NAT test. 
3. The 2nd Visit for an Infected Infant should be 28 days (± 7 days) after the date of the blood draw of the first positive HIV-1 NAT test. 
4. The 3rd Visit for an Infected Infant Visit should be 56 days (+ 10 days) after the date of the blood draw of the first positive HIV-1 NAT test. 
5. Subsequent visits prior to initiation of ARVs should be every 28 days (+ 7 days).  Total duration of follow up after study entry should not 
exceed 48 weeks for Dose Groups 1 and 2 or 96 weeks for Dose Groups 3, 4, and 5. 

 
 
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6. After infant has been started on ARVs, history, physical exam, plasma HIV RNA and CD4 lymphocyte subsets will be abstracted from the 
medical records when obtained per standard of care.  At standard of care clinical visits when blood will be obtained for clinical care, an 
additional sample for plasma and PBMC storage will be obtained for the study (see LPC).  Total duration of follow up after study entry should 
not exceed 48 weeks for Dose Groups 1 and 2 or 96 weeks for Dose Groups 3, 4, and 5. 
7. History should include ARV with start and stop dates, other medications, diagnoses, signs and symptoms, and vaccinations.  Results of HIV-1 
testing and lymphocyte subset testing done outside of the study should be abstracted. 
8. Initial positive HIV-1 nucleic acid testing (NAT) should be confirmed with a repeat HIV-1 NAT.  Assay must detect HIV DNA.  For U.S. 
sites, HIV-1 NAT must be performed in a CLIA certified laboratory.  For Non-U.S. sites, HIV-1 NAT must be performed at a VQA-certified 
laboratory.  For infants with two positive HIV-1 NAT tests, no further HIV-1 tests detecting DNA are required for APPENDIX IB: Infant 
Schedule of Evaluations (Dose Groups 1 and 2), APPENDIX ID: Schedule of Evaluations (Dose Group 3), APPENDIX IE: Schedule 
of Evaluations (Dose Group 4, Cohort 1: non-breastfeeding), APPENDIX IF: Schedule of Evaluations (Dose Group 4, Cohort 2: 
breastfeeding), APPENDIX IG: Schedule of Evaluations (Dose Group 5, Cohort 1: non-breastfeeding), or APPENDIX IH: Schedule 
of Evaluations (Dose Group 5, Cohort 2: breastfeeding). 
9. If the confirmatory HIV-1 NAT is not positive, consult with the team within 72 hours of receiving the result and continue to follow infant on 
APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 and APPENDIX IB: Infant Schedule of 
Evaluations (Dose Groups 1 and 2), APPENDIX ID: Schedule of Evaluations (Dose Group 3), APPENDIX IE: Schedule of 
Evaluations (Dose Group 4, Cohort 1: non-breastfeeding), APPENDIX IF: Schedule of Evaluations (Dose Group 4, Cohort 2: 
breastfeeding), APPENDIX IG: Schedule of Evaluations (Dose Group 5, Cohort 1: non-breastfeeding), or APPENDIX IH: Schedule 
of Evaluations (Dose Group 5, Cohort 2: breastfeeding).  
10. Quantitative plasma HIV-1 RNA must be performed at a VQA-certified (for non-US) or CLIA –certified (or equivalent) (for US-based) 
laboratory.  Each site should identify a single laboratory for all study specified HIV-1 RNA testing. 
11. If the visit is concurrent with a visit for APPENDIX IB: Infant Schedule of Evaluations (Dose Groups 1 and 2), APPENDIX ID: 
Schedule of Evaluations (Dose Group 3), APPENDIX IE: Schedule of Evaluations (Dose Group 4, Cohort 1: non-breastfeeding), 
APPENDIX IF: Schedule of Evaluations (Dose Group 4, Cohort 2: breastfeeding), APPENDIX IG: Schedule of Evaluations (Dose 
Group 5, Cohort 1: non-breastfeeding)or APPENDIX IH: Schedule of Evaluations (Dose Group 5, Cohort 2: breastfeeding) that 
includes the mAb plasma level, do not obtain APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 mAb 
plasma levels.  Samples will be processed and batch shipped per the LPC.   
12. PBMC from the study product plasma level sample and HIV-1 RNA sample (if possible) will be collected.  Leftover PBMC will be stored per 
the LPC for future HIV-related studies (possibly including genetic testing) per IMPAACT SOP.  See LPC for processing instructions. 
13. At standard of care clinical visits when blood will be obtained, an additional sample for plasma and PBMC storage will be obtained for the 
study (see LPC).  If there will be more than a three-month interval between blood samples for clinical care, then a study sample should be 
obtained at least every 3 months. 
14. Leftover plasma remaining from study product plasma levels and quantitative HIV-1 RNA testing (if possible) and plasma from the PBMC 
storage sample will be stored per the LPC for future HIV-related studies per IMPAACT SOP. 
15. Total study blood volume must be under a maximum of 5ml/kg within 24 hours and 9.5ml/kg drawn over an 8-week period.  Use the priority 
schema in APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 to further reduce blood volume if necessary 
for the infant weight. 

 
 
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16. Abstract from clinical chart if available.  Obtain lymphocyte subsets if not done for clinical care within ± 2 weeks of 1st confirmatory visit.  
Draw with CBC if required for lymphocyte subset parameters.  Must be performed at CLIA-certified (or equivalent) laboratory or at the 
approved site-associated DAIDS-monitored laboratory.  
17. Abstract from clinical chart if available.  If not, obtain every 12 weeks ± 4 weeks.   
 
    Priority for blood samples at: 
1st Infected Infant Visit 
2nd, 3rd, and Subsequent Infected Visits 
1. HIV NAT 
2. HIV-1 RNA 
3. Study product Plasma levels 
4. CBC, chemistry  
5. Study product Serum storage  
6. Lymphocyte subsets  
1. HIV-1 RNA 
2. Study product Plasma levels 
3. CBC, chemistry  
4. Study product Serum storage  
5. Lymphocyte subsets  
 
 
 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
APPENDIX ID: Schedule of Evaluations (Dose Group 3) 
 
VRC01 DOSING PERIOD: BIRTH THROUGH WEEK 24 AND, THEREAFTER, THROUGH COMPLETE 
CESSATION OF BREASTFEEDING7, DIAGNOSIS OF HIV INFECTION 7,11 OR WEEK 72 (WHICHEVER COMES 
FIRST) 
OBSERVATION PERIOD: EVERY 12 WEEKS 
AFTER BF CESSATION7, HIV DIAGNOSIS 7,11 
AND/OR AT WEEKS 84 AND 96  
 
 
Screen1 
Entry/Day 02 
0 Hour 
Day 1/24 hr3 
± 6 hr 
Day 14 
+/-3 days 
 
Day 28 
+/-3 days 
Wk 8 
+1/-1 wks 
Wk 12 
+1/-1 wks 
Wk 16 
+1/-1 wks 
Wk 20 
+1/-1 wks 
Wk 24 
+1/-1 wks 
Q 4 weeks until 
complete cessation 
of breastfeeding or 
Wk 72  
+1/-1 wks 
First visit after 
complete cessation 
of breastfeeding or 
HIV diagnosis 
+/- 1 wk  
Every 12 wks after 
complete cessation 
of breastfeeding or 
HIV diagnosis 
+/-1wk 
Wk 84 
±2 wks 
Wk 96 
±2 wks 
Early D/C of VRC 
01 or of study4 
History5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DOSE VRC017 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
LABORATORY EVALUATIONS 
Hematology8 
1mL 
 
 
1mL 
1ml 
1ml 
 
1mL 
1ml 
1mL 
1mL9 
1mL 
1mL 
 
 
1mL 
Chemistries10 
1mL 
 
 
1mL 
1ml 
1ml 
 
1mL 
1ml 
1mL 
1mL9 
1mL 
1mL 
 
 
1mL 
HIV-1 NAT 
testing11 
1mL12 
 
 
1mL 
1mL 
 
 
1mL 
 
1mL 
1mL9 
1mL 
1mL 
1mL 
1mL 
1mL 
HIV antibody test 
 
 
 
 
 
 
 
 
 
 
 
 
2mL13 
2mL13 
 
 
Lymphocyte: 
CD3/CD4/CD814 
1mL 
 
 
1mL 
 
 
 
 
 
 
1mL9 
1mL 
 
 
 
1mL 
VRC01 Plasma 
levels15 
 
2mL 
1mL 
0.5-
2mL15 
1-2mL 
1-2mL15 
. 
2mL 
2mL 
2mL 
2mL9 
2mL 
2mL 
2mL 
2mL 
2mL 
PBMC storage16 
 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
VRC01 serum17 
 
0-1mL17 
 
0-1 mL17 
0-1 mL17 
0-1 mL17 
 
2mL 
 
2mL 
2mL9 
2mL 
2mL 
2mL 
2mL 
2mL 
Anti-VRC01 Ab18 
 
X 
 
 
 
X 
 
 
 
X 
X9 
X 
X 
X 
X 
X 
Oral secretions19 
 
X 
X 
X 
X 
X 
 
X 
 
X 
 X9 
X 
X 
X 
X 
X 
Total Blood 
Volume Infant 
(mL)20 
4mL 
2-3mL 
1mL 
4.5-7mL 
4-6mL 
3-5mL 
0mL 
7mL 
4mL 
7mL 
0-8mL 
8mL 
9mL 
7mL 
5mL 
8mL 
 
NOTE: 18.5-26mL in 8-week period20 
 
 
 
 
 
 
 
 
 
 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
Footnotes 
1. Screening evaluations should be completed as soon as possible after birth.  The laboratory testing needed for inclusion/exclusion (CBC, ALT) 
must be completed and eligibility confirmed in time so that the VRC01 is administered ideally within 24 hours to less than 72 hours after birth 
and not more than the 5th day of life.   
2. The Entry/Day 0 visit can take place on the same day as the Screening Visit.  Blood for the Entry/Day 0 evaluations may be drawn with the 
screening blood or at the time of entry but must be drawn before the VRC01 immunization is administered.   
3. Hours (hr) after dose administration.  
4. An Early Discontinuation visit should be scheduled if participant comes off study after receiving any doses of VRC01.  This visit should also 
take place if a participant discontinues VRC01 but continues on study.  Following the Early Discontinuation visit, that participant should 
follow the schedule of the Observation Period.  
5. A complete history is required at birth and includes date of birth, race, ethnicity, gender, maternal risk factor meeting the inclusion criteria, all 
diagnoses, all signs and symptoms, all antiretroviral medications (ARV) with start and stop dates and doses, all injected medications (i.e. 
vitamin K, Hepatitis B vaccine) including location of injection.  At subsequent visits the history should include ARV doses with start and stop 
dates, other medications and vaccinations (including sites of injections), diagnoses, and signs and symptoms.  Results of HIV-1 testing done 
outside of the study should be abstracted.  Feeding history to determine breast milk exposure will be obtained at each visit until complete 
cessation of breastfeeding.  
6. Complete physical exam including vitals, weight, length, and head circumference at all visits except Day 1 and 14.  Targeted physical exam 
including vitals and weight at Day 1 and 14.  Examination of VRC01 injection site should occur at all visits.    
7. The initial VRC01 immunization, 40mg/kg subcutaneous injection, must be administered no later than the 5th day of life (see MOP for 
administration instructions).  Subsequent immunizations of VRC01, 20mg/kg subcutaneous injections, will be administered monthly up to and 
including the Week 24 visit and, thereafter, until complete cessation of breastfeeding, HIV diagnosis or Week 72, whichever comes first.  
Complete cessation of breastfeeding is defined as having completely stopped all exposure to breast milk for > 28 days.  Administration of 
VRC01 should stop upon first positive HIV PCR test result. 
• 
Infants should be monitored for a minimum of 4 hours after initial study treatment injection, with assessments at 15, 30 and 60 minutes 
post dose.  Clinic personnel must observe participant for any potential adverse reactions to the study immunization.  Equipment, supplies, 
and properly skilled medical personnel must be immediately available for emergency use in the event of an unexpected adverse reaction.  
Subsequent injections should be monitored for a minimum of 60 minutes (+30 minutes), with assessments at 15, 30 and 60 minutes post 
dose. 
• 
Infants will also be evaluated for local reactions and pain at 1 hour (+30 minutes) after every injection and results recorded on a study 
CRF. 
• 
Caregivers of participants will be provided with a diary card on which to note any reactions at the injection site.  Study staff will contact 
caregivers between 3 to 5 days following the injection.   
8. Hematology should include CBC with differential and platelet count.  (Not required at screening if collected clinically at birth and results are 
available).  
9. For breastfeeding, HIV-exposed uninfected infants after Week 24, hematology, chemistries, HIV-1 NAT, lymphocyte subsets, VRC01 plasma 
levels (including anti-VRC01) and VRC01 serum and oral secretions should be collected only at Weeks 36, 48, 60, 72, and early D/C visit. 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
10. Chemistries should include AST, ALT, total bilirubin, and creatinine.  (Not required at screening if collected clinically at birth and ALT 
results are available).  Obtain additional ALT and AST measurements upon evidence of hepatic-related clinical adverse events (jaundice, 
enlargement of the liver). 
11. HIV-1 NAT (nucleic acid testing) by a method that detects DNA is required for diagnostic testing since VRC01 might suppress HIV-1 RNA.  
For the screening NAT, see footnote 12.  HIV-1 NAT testing must be run in a VQA-approved laboratory.  If the infant has a positive HIV-1 
NAT at any time, confirmation and additional HIV testing should be performed as per APPENDIX IC: HIV-1 Infected Infant Schedule of 
Evaluations (all dose groups)1.  With the exception of HIV testing, on study follow up of the HIV-infected infant continues as per 
APPENDIX ID: Schedule of Evaluations (Dose Group 3).  When possible, APPENDIX IC: HIV-1 Infected Infant Schedule of 
Evaluations (all dose groups)1 visits should be scheduled to coincide with APPENDIX ID: Schedule of Evaluations (Dose Group 3).  
12. Blood for HIV-1 NAT drawn at Screening must be obtained prior to 48 hours of life AND prior to VRC01 administration.  It may be drawn 
with the Entry blood.  Results may be pending at study entry.  If an HIV-1 NAT (DNA or RNA or combined) was collected clinically prior to 
48 hours of life and tested in a laboratory with VQA approval, the test does not need to be duplicated for the study; in this case, results will be 
abstracted for the study. 
13. For HIV-exposed-uninfected infants that have achieved complete cessation of breastfeeding, HIV antibody testing will be performed every 12 
weeks after complete cessation of breastfeeding and at Week 84.  Testing should be performed at the approved site-associated DAIDS-
monitored laboratory.  If the infant remains antibody positive at either of those time points, notify the protocol team. 
14. Lymphocyte subsets include CD3/CD4/CD8 counts and percentages.  Results are not needed for study entry.  Draw with CBC.  Testing should 
be performed at the approved site-associated DAIDS-monitored laboratory. 
15. Samples for VRC01 plasma levels should be obtained prior to VRC01 administration.  For infants with birth weight <2.9kg use lower sample 
volume at Day 14 and Week 8.  Plasma for VRC01 levels and anti-VRC01 levels will be processed and batch shipped per the LPC.  Leftover 
plasma will be stored per the LPC for future HIV-related studies overseen per IMPAACT SOP.  See LPC for collection procedure, processing, 
storage, and shipping instructions. 
16. PBMC from the VRC01 plasma level sample will be isolated if site is capable of PBMC isolation and storage.  PBMC will be used for HIV 
characterization if there are infants with HIV infection.  Leftover PBMC will be stored per the LPC for future HIV-related studies (possibly 
including genetic testing) per IMPAACT SOP.  See LPC for collection procedure, processing, storage, and shipping instructions. 
17. Samples for VRC01 serum should be obtained prior to VRC01 administration.  For infants with birth weight <2.9kg: do not collect VRC01 
serum samples at Entry, Day 14, Day 28, or Week 8.  Serum for VRC01 antibody levels and neutralization assays will be processed and batch 
shipped per the LPC.  Leftover serum will be stored per the LPC for future HIV-related studies per IMPAACT SOP.  See LPC for collection 
procedure, processing, storage, and shipping instructions.   
18. Anti-VRC01 Ab will be tested using plasma collected for VRC01 levels.     
19. Oral fluid is collected with Weck-cel Sponge oral fluid collection device.  Sample at Entry should be collected prior to VRC01 administration 
as baseline.  Assay will be performed to detect VRC01 antibody level sample.  Leftover oral fluid will be stored per the LPC for future HIV-
related studies per IMPAACT SOP.  See LPC for collection procedure, processing, storage, and shipping instructions. 
20. For infants with birth weight <2.9kg lower sample volume will be collected.  See also Footnotes 15 and 17.  Volumes equate to < 3ml/kg 
drawn within 24 hours and < 9.0 ml/kg drawn over 8 weeks.  These are below the NIH Clinical Center guidelines allowing a maximum of 
5ml/kg within 24 hours and 9.5ml/kg drawn over an 8-week period.    
 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
Priority for blood samples: 1: HIV-1NAT; 2: CBC, chemistry; 3: VRC01 plasma levels; 4: VRC01 serum; 5: HIV-1 antibody; 6: 
Lymphocyte subsets 
 

 
 
IMPAACT P1112 Version 4.0 
Page 101 of 144 
06 November 2018 
APPENDIX IE: Schedule of Evaluations (Dose Group 4, Cohort 1: non-breastfeeding) 
  
 
 
 
Screen1 
Entry/Day 02 
0 Hour 
Day 1/24 hr3   
± 6 hr 
Day 14 
+/-3 days 
 
Day 28 
+/-3 days 
Wk 8 
+/-1 wks 
Wk 12; 
 +/-1 wk 
Wk 24 
+/- 1 wk 
 
Wk 36 
 +/- 1 wk  
Wks 48, 60, 72, 84 
+/-2 wk 
Wk 96: End of Study 
+/- 2 wk  
  
Early Study D/C4 
History5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PE6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VRC01LS7 
 
X 
 
 
 
 
 
 
 
 
 
 
LABORATORY EVALUATIONS 
Hematology8 
0-1mL 
 
 
1mL 
1mL 
 
1mL 
1mL 
 
 
 
1mL 
Chemistries9 
1mL 
 
 
1mL 
1mL 
 
1mL 
1mL 
 
 
 
1mL 
HIV-1 NAT10 
1mL11 
 
 
1mL 
1mL 
 
1mL 
1mL 
1mL 
 
 
1mL 
HIV Ab test12 
 
 
 
 
 
 
 
 
 
2mL 
2mL 
2mL 
Lymphocyte: CD3/CD4/CD813 
1mL 
 
 
 
 
 
 
 
 
 
 
1mL 
VRC01LS Plasma levels14 
 
2mL 
1mL 
1-2mL14 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
PBMC 15 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VRC01LS 
serum16 
 
0-1mL 
 
0-1mL16 
0-1mL 
0-1mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
Anti-VRC01LS Ab17 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Oral secretions18 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Total Blood Volume Infant 
(mL)19 
3-4mL 
2-3mL 
1mL 
4-6mL 
5-6mL 
2-3mL 
7mL 
7mL 
5mL 
6mL 
6mL 
10mL 
 
NOTE: 17-23mL from birth to 8 weeks19 
 
 
 
 
 
 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
Footnotes 
1. 
Screening evaluations should be completed as soon as possible after birth.  The laboratory testing needed for inclusion/exclusion (CBC, ALT) 
must be completed and eligibility confirmed in time so that the VRC01LS is administered ideally within 24 hours to less than 72 hours after 
birth.   
2. The Entry/Day 0 visit can take place on the same day as the Screening Visit.  Blood for the Entry/Day 0 evaluations may be drawn with the 
screening blood or at the time of entry but must be drawn before the VRC01LS immunization is administered.   
3. Hours (hr) after dose administration.  
4. An Early Discontinuation visit should be scheduled if participant comes off study after receiving any doses of VRC01LS.   
5. A complete history is required at birth and includes date of birth, race, ethnicity, gender, maternal risk factor meeting the inclusion criteria, all 
diagnoses, all signs and symptoms, all antiretroviral medications (ARV) with start and stop dates and doses, all injected medications (i.e. 
vitamin K, Hepatitis B vaccine) including location of injection.  At subsequent visits the history should include ARV doses with start and stop 
dates, other medications and vaccinations (including sites of injections), diagnoses, and signs and symptoms.  Results of HIV-1 testing done 
outside of the study should be abstracted.   
6. Complete physical exam including vitals (temperature, heart rate, respiratory rate, and, if possible, blood pressure), weight, length, and head 
circumference at all visits except Day 1 and 14.  Targeted physical exam including vitals (as above) and weight at Days 1 and 14 visits.  
Examination of VRC01LS injection site should occur at all visits, for good clinical care, but data will only be recorded on CRFs through the 
Day 28 visit, with the exception that if there are still signs of a reaction present at those visits or any reaction noted at a later visit, data will be 
recorded at scheduled visits until resolved or until no further resolution is expected.    
7. An initial VRC01LS immunization, 80 mg (if <4.5 kg) or 100 mg (if ≥ 4.5 kg) subcutaneous injection, must be administered less than 72 
hours of life (see MOP for administration instructions).   
• 
Infants should be monitored for a minimum of 4 hours after the study treatment injection, with assessments at 15, 30 and 60 minutes post 
dose.  Clinic personnel must observe participant for any potential adverse reactions to the study immunization.  Equipment, supplies, and 
properly skilled medical personnel must be immediately available for emergency use in the event of an unexpected adverse reaction.   
• 
Infants will also be evaluated for local reactions and pain at 1 hour (+30 minutes) after the injection and results recorded on a study CRF. 
• 
Caregivers of participants will be provided with a diary card on which to note any reactions at the injection site.  Study staff will contact 
caregivers between 3 to 5 days following the injection.   
8. Hematology should include CBC with differential and platelet count.  (Not required at screening if collected clinically at birth and results are 
available).  
9. Chemistries should include AST, ALT, total bilirubin, and creatinine.  (Not required at screening if collected clinically at birth and ALT 
results are available).  Obtain additional ALT and AST measurements upon evidence of hepatic-related clinical adverse events (jaundice, 
enlargement of the liver). 
10. HIV-1 NAT (nucleic acid testing) by a method that detects DNA is required for diagnostic testing since VRC01LS might suppress HIV-1 
RNA.  For the NAT at Screening, see footnote 11.  HIV-1 NAT testing must be run in a CLIA- or VQA-approved laboratory.  If the infant has 
a positive HIV-1 NAT at screening at any time, confirmation and additional HIV testing should be performed as per APPENDIX IC: HIV-1 
Infected Infant Schedule of Evaluations (all dose groups)1.  Infants confirmed to be HIV-1-infected should be evaluated according to both 
APPENDIX IE: Schedule of Evaluations (Dose Group 4, Cohort 1: non-breastfeeding) and APPENDIX IC: HIV-1 Infected Infant 
Schedule of Evaluations (all dose groups)1, but without duplication of specific blood tests if the study visit dates are concurrent.  When 
possible, APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 visits should be scheduled to coincide with 

 
 
IMPAACT P1112 Version 4.0 
Page 103 of 144 
06 November 2018 
APPENDIX IE: Schedule of Evaluations (Dose Group 4, Cohort 1: non-breastfeeding).  
11. Blood for HIV-1 NAT drawn at Screening must be obtained prior to 48 hours of life AND prior to VRC01LS administration.  It may be drawn 
with the Entry blood.  Results may be pending at study entry.  If an HIV-1 NAT (DNA or RNA or combined) was collected clinically prior to 
48 hours of life and tested in a laboratory with CLIA or VQA approval, the test does not need to be duplicated for the study; in this case, 
results will be abstracted for the study. 
12. HIV antibody testing should be performed at the approved site-associated DAIDS-monitored laboratory.  If the infant remains antibody 
positive at or after 72 weeks, notify the protocol team. If HIV antibody is negative at Week 48 or later, subsequent HIV antibody testing is not 
required. 
13. Lymphocyte subsets include CD3/CD4/CD8 counts and percentages.  Results are not needed for study entry.  Draw with CBC.  Testing should 
be performed at the approved site-associated DAIDS-monitored or CLIA-approved laboratory. 
14. Samples for VRC01LS plasma levels should be obtained prior to VRC01LS administration.  For infants with birth weight <2.6kg use lower 
sample volume at Day 14.  Plasma for VRC01LS levels and anti-VRC01LS levels will be processed and batch shipped per the LPC.  Leftover 
plasma will be stored per the LPC for future HIV-related studies overseen per IMPAACT SOP.  See LPC for collection procedure, processing, 
storage, and shipping instructions. 
15. PBMC from the VRC01LS plasma level sample will be isolated if site is capable of PBMC isolation and storage (see LPC for qualifications).  
PBMC will be used for HIV characterization if there are infants with HIV infection.  Leftover PBMC will be stored per the LPC for future 
HIV-related studies (possibly including genetic testing) per IMPAACT SOP.  See LPC for collection procedure, processing, storage, and 
shipping instructions. 
16. Samples for VRC01LS serum should be obtained prior to VRC01LS administration.  For infants with birth weight <2.6kg: do not collect 
VRC01LS serum samples at Entry, Day 14, Day 28, and Week 8.  Serum for VRC01LS antibody levels and neutralization assays will be 
processed and batch shipped to central testing laboratory.  Leftover serum may be stored per the LPC for future HIV-related studies per 
IMPAACT SOP.  See LPC for collection procedure, processing, storage, and shipping instructions.   
17. Anti-VRC01LS Ab will be tested using plasma collected for VRC01LS levels.     
18. Oral fluid is collected with Weck-cel Sponge oral fluid collection device.  Sample at Entry should be collected prior to VRC01LS 
administration as baseline.  Assay will be performed to detect VRC01LS antibody level sample.  Leftover oral fluid will be stored per the LPC 
for future HIV-related studies per IMPAACT SOP.  See LPC for collection procedure, processing, storage, and shipping instructions. 
19. For infants with birth weight <2.6kg lower sample volume will be collected.  See also Footnotes 14 and 16.  Volumes equate to < 3ml/kg 
drawn within 24 hours and < 9.0 ml/kg drawn over 8 weeks.  These are below the NIH Clinical Center guidelines allowing a maximum of 
5ml/kg within 24 hours and 9.5ml/kg drawn over an 8-week period.    
 
 
Priority for blood samples: 1: HIV-1NAT; 2: CBC, chemistry; 3: VRC01LS plasma levels; 4: VRC01LS serum; 5: HIV-1 antibody; 6: 
Lymphocyte subsets.  At Day 28, Week 12, and 24 VRC01LS plasma levels are first priority. 
 
 
 

 
 
IMPAACT P1112 Version 4.0 
Page 104 of 144 
06 November 2018 
APPENDIX IF: Schedule of Evaluations (Dose Group 4, Cohort 2: breastfeeding) 
 
 
 
VRC01LS DOSING PERIOD 
AFTER INITIAL DOSE: SCREENING TO WK 12 
 
 
VRC01LS DOSING PERIOD 
AFTER 2ND DOSE:  
WK 14 AND 16 
 
OBSERVATION FOLLOWING DOSING 
PERIOD(S) 
 
 
Screen1 
Entry/Day 02 
0 Hour 
Day 1/24 hr3   
± 6 hr 
Day 14 
+/-3 days 
 
Day 28 
+/-3 days 
Wk 8 
+/-1 wks 
Wk 12;  
+/-1 wk 
Wk 14 
+/-3 days 
 
Wk 16 
+/-3 days 
Wk 24 and 36 
+/-1 wk 
Wks 48, 60, 72, 84 
+/-2 wk  
 
Wk 96: End of Study 
+/- 2 wks 
 
Early Study D/C4 
History5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PE6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VRC01LS7 
 
X 
 
 
 
 
(X) 
 
 
 
 
 
 
LABORATORY EVALUATIONS 
Hematology8 
0-1mL 
 
 
1mL 
1mL 
 
1mL 
1mL 
 
1mL 
 
 
1mL 
Chemistries9 
1mL 
 
 
1mL 
1mL 
 
1mL 
1mL 
 
1mL 
 
 
1mL 
HIV-1 NAT10 
1mL11 
 
 
1mL 
1mL 
 
1mL 
 
 
1mL 
1mL 
1mL 
1mL 
HIV Ab test12 
 
 
 
 
 
 
 
 
 
 
2mL 
2mL 
2mL 
Lymphocyte: 
CD3/CD4/CD813 
1mL 
 
 
 
 
 
 
 
 
 
 
 
1mL 
VRC01LS 
Plasma levels14 
 
2mL 
1mL 
1-2mL14 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
PBMC 15 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VRC01LS 
serum16 
 
0-1mL 
 
0-1mL16 
0-1mL 
0-1mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
Anti-VRC01LS 
Ab17 
 
X 
 
 
 
X 
X 
 
 
X 
X 
X 
X 
Oral secretions18 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Total Blood 
Volume Infant 
(mL)19 
3-4mL 
2-3mL 
1mL 
4-6mL 
5-6mL 
2-3mL 
7mL 
6mL 
4mL 
7mL 
7mL 
7mL 
10mL 
 
NOTE: 17 - 23mL from birth to 8 weeks19 
 
 
 
 
 
 
 

 
 
IMPAACT P1112 Version 4.0 
Page 105 of 144 
06 November 2018 
Footnotes 
1. Screening evaluations should be completed as soon as possible after birth.  The laboratory testing needed for inclusion/exclusion (CBC, ALT) 
must be completed and eligibility confirmed in time so that the VRC01LS is administered ideally within 24 hours to less than 72 hours after 
birth and not more than the 5th day of life.   
2. The Entry/Day 0 visit can take place on the same day as the Screening Visit.  Blood for the Entry/Day 0 evaluations may be drawn with the 
screening blood or at the time of entry but must be drawn before the VRC01LS immunization is administered.   
3. Hours (hr) after dose administration.  
4. An Early Discontinuation visit should be scheduled if participant comes off study after receiving any doses of VRC01LS.   
5. A complete history is required at birth and includes date of birth, race, ethnicity, gender, maternal risk factor meeting the inclusion criteria, all 
diagnoses, all signs and symptoms, all antiretroviral medications (ARV) with start and stop dates and doses, all injected medications (i.e. 
vitamin K, Hepatitis B vaccine) including location of injection.  At subsequent visits the history should include ARV doses with start and stop 
dates, other medications and vaccinations (including sites of injections), diagnoses, and signs and symptoms.  Results of HIV-1 testing done 
outside of the study should be abstracted.  Feeding history to determine breast milk exposure will be obtained at each visit until complete 
cessation of breastfeeding.  
6. Complete physical exam including vitals (temperature, heart rate, respiratory rate, and, if possible, blood pressure), weight, length, and head 
circumference at all visits except Day 1 and 14 and Week 14.  Targeted physical exam including vitals (as above) and weight at Days 1 and 14 
and Week 14 visits.  Examination of VRC01LS injection site should occur at all visits for good clinical care, but data will only be recorded on 
CRFs through the Day 28 visit (for all participants) and the Week 16 visit (for Cohort 2 participants who received the second injection), with 
the exception that if there are still signs of a reaction present at those visits or any reaction noted at a later visit, data will be recorded at 
scheduled visits until resolved or until no further resolution is expected.   
7. An initial VRC01LS immunization, 80 mg (if <4.5 kg) or 100 mg (if ≥ 4.5 kg) subcutaneous injection, must be administered no later than the 
5th day of life (see MOP for administration instructions).  A second immunization of VRC01LS, 100 mg subcutaneous injection, will be 
administered at Week 12 only if the infant has not had complete cessation of breastfeeding. Complete cessation of breastfeeding is defined as 
having completely stopped all exposure to breast milk for > 28 days.  There should be no administration of VRC01LS if the infant has had a 
positive HIV PCR test result. 
• 
Infants should be monitored for a minimum of 4 hours after initial study treatment injection, with assessments at 15, 30 and 60 minutes 
post dose.  Clinic personnel must observe participant for any potential adverse reactions to the study immunization.  Equipment, supplies, 
and properly skilled medical personnel must be immediately available for emergency use in the event of an unexpected adverse reaction.  
The subsequent injection should be monitored for a minimum of 60 minutes (+ 30 minutes), with assessments at 15, 30 and 60 minutes 
post dose. 
• 
Infants will also be evaluated for local reactions and pain at 1 hour (+30 minutes) after each injection and results recorded on a study CRF. 
• 
Caregivers of participants will be provided with a diary card on which to note any reactions at the injection site.  Study staff will contact 
caregivers between 3 to 5 days following the injection.   
8. Hematology should include CBC with differential and platelet count.  (Not required at screening if collected clinically at birth and results are 
available).  
9. Chemistries should include AST, ALT, total bilirubin, and creatinine.  (Not required at screening if collected clinically at birth and ALT 
results are available).  Obtain additional ALT and AST measurements upon evidence of hepatic-related clinical adverse events (jaundice, 
enlargement of the liver). 

 
 
IMPAACT P1112 Version 4.0 
Page 106 of 144 
06 November 2018 
10. HIV-1 NAT (nucleic acid testing) by a method that detects DNA is required for diagnostic testing since VRC01LS might suppress HIV-1 
RNA.  For NAT at Screening, see footnote 11.  HIV-1 NAT testing must be run in a VQA-approved laboratory.  If the infant has a positive 
HIV-1 NAT at any time, confirmation and additional HIV testing should be performed as per APPENDIX IC: HIV-1 Infected Infant 
Schedule of Evaluations (all dose groups)1.  Infants confirmed to be HIV-1-infected should be evaluated according to both APPENDIX IF: 
Schedule of Evaluations (Dose Group 4, Cohort 2: breastfeeding) and APPENDIX IC: HIV-1 Infected Infant Schedule of 
Evaluations (all dose groups)1, but without duplication of specific blood tests if the study visit dates are concurrent.  When possible, 
APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 visits should be scheduled to coincide with 
APPENDIX IF: Schedule of Evaluations (Dose Group 4, Cohort 2: breastfeeding).  
11. Blood for HIV-1 NAT drawn at Screening must be obtained prior to 48 hours of life AND prior to VRC01LS administration.  It may be drawn 
with the Entry blood.  Results may be pending at study entry.  If an HIV-1 NAT (DNA or RNA or combined) was collected clinically prior to 
48 hours of life and tested in a laboratory with VQA approval, the test does not need to be duplicated for the study; in this case, results will be 
abstracted for the study. 
12. HIV antibody testing should be performed at the approved site-associated DAIDS-monitored laboratory.  If the infant remains antibody 
positive at or after 72 weeks, notify the protocol team. If HIV antibody is negative at Week 48 or later, subsequent HIV antibody testing is not 
required. 
13. Lymphocyte subsets include CD3/CD4/CD8 counts and percentages.  Results are not needed for study entry.  Draw with CBC.  Testing should 
be performed at the approved site-associated DAIDS-monitored laboratory. 
14. Samples for VRC01LS plasma levels should be obtained prior to VRC01 administration.  For infants with birth weight <2.6kg use lower 
sample volume at Day 14.  Plasma for VRC01LS levels and anti-VRC01LS levels will be processed and batch shipped per the LPC.  Leftover 
plasma will be stored per the LPC for future HIV-related studies overseen per IMPAACT SOP.  See LPC for collection procedure, processing, 
storage, and shipping instructions. 
15. PBMC from the VRC01LS plasma level sample will be isolated if site is capable of PBMC isolation and storage (see LPC for qualifications).  
PBMC will be used for HIV characterization if there are infants with HIV infection.  Leftover PBMC will be stored per the LPC for future 
HIV-related studies (possibly including genetic testing) per IMPAACT SOP.  See LPC for collection procedure, processing, storage, and 
shipping instructions. 
16. Samples for VRC01LS serum should be obtained prior to VRC01LS administration.  For infants with birth weight <2.6kg: do not collect 
VRC01LS serum samples at Entry, Day 14, Day 28, and Week 8.  Serum for VRC01LS antibody levels and neutralization assays will be 
processed and batch shipped to central testing laboratory.  Leftover serum may be stored per the LPC for future HIV-related studies per 
IMPAACT SOP.  See LPC for collection procedure, processing, storage, and shipping instructions.   
17. Anti-VRC01LS Ab will be tested using plasma collected for VRC01LS levels.     
18. Oral fluid is collected with Weck-cel Sponge oral fluid collection device.  Sample at Entry should be collected prior to VRC01LS 
administration as baseline.  Assay will be performed to detect VRC01LS antibody level sample.  Leftover oral fluid will be stored per the LPC 
for future HIV-related studies per IMPAACT SOP.  See LPC for collection procedure, processing, storage, and shipping instructions. 
19. For infants with birth weight <2.6kg lower sample volume will be collected.  See also Footnotes 14 and 16.  Volumes equate to < 3ml/kg 
drawn within 24 hours and < 9.0 ml/kg drawn over 8 weeks.  These are below the NIH Clinical Center guidelines allowing a maximum of 
5ml/kg within 24 hours and 9.5ml/kg drawn over an 8-week period.    
 
 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
Priority for blood samples: 1: HIV-1NAT; 2: CBC, chemistry; 3: VRC01LS plasma levels; 4: VRC01LS serum; 5: HIV-1 antibody; 6: 
Lymphocyte subsets.  At Day 28, Week 12, and 24 VRC01LS plasma levels are first priority. 

 
 
IMPAACT P1112 Version 4.0 
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APPENDIX IG: Schedule of Evaluations (Dose Group 5, Cohort 1: non-breastfeeding) 
 
 
 
 
 
Screen1 
Entry/Day 02 
0 Hour 
Day 1/24 hrs3   
± 6 hrs 
Day 3 
± 1 day 
Day 7 
+/-3 days 
Day 14 
+/-3 days 
Day 28 
+/-3 days 
Wk 8 
+/-1 wks 
Wk 12; 
 +/-1 wk 
Wk 24 
+/- 1 wk 
 
Wk 36 
 +/- 1 wk  
Wks 48, 60, 72, 84 
+/-2 wk 
Wk 96: End of Study 
+/- 2 wk  
  
Early Study D/C4 
History5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PE6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VRC07-523LS7 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
LABORATORY EVALUATIONS 
Hematology8 
0-1mL 
 
 
 
 
 
1mL 
 
1mL 
1mL 
 
 
 
1mL 
Chemistries9 
1mL 
 
 
 
 
 
1mL 
 
1mL 
1mL 
 
 
 
1mL 
HIV-1 NAT10 
1mL11 
 
 
 
 
1mL 
1mL 
 
1mL 
1mL 
1mL 
 
 
1mL 
HIV Ab test12 
 
 
 
 
 
 
 
 
 
 
 
2mL 
2mL 
2mL 
VRC07-523LS plasma levels13 
 
2-3mL13 
1mL 
1mL 
1mL 
2mL 
2mL 
3mL 
3mL 
3mL 
3mL 
3mL 
3mL 
3mL 
PBMC14 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VRC07-523LS serum15 
 
0-1mL15 
 
 
 
0-1mL15 
0-1mL15 
0-
1mL15 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
Anti-VRC07-523LS Ab16 
 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Oral secretions17 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Total blood volume infant 
(mL)18 
2-3mL 
2-4mL 
1mL 
1mL 
1mL 
3-4mL 
5-6mL 
3-4mL 
8mL 
8mL 
6mL 
7mL 
7mL 
10mL 
 
NOTE: 18-24mL from birth to 8 weeks18 
 
 
 
 
 
 

 
 
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Footnotes 
1. Screening evaluations should be completed as soon as possible after birth. The laboratory testing needed for inclusion/exclusion (CBC, ALT) 
must be completed and eligibility confirmed in time so that the VRC07-523LS is administered ideally within 24 hours to less than 72 hours 
after birth.   
2. The Entry/Day 0 visit can take place on the same day as the Screening Visit. Blood for the Entry/Day 0 evaluations may be drawn with the 
screening blood or at the time of entry but must be drawn before the VRC07-523LS immunization is administered.   
3. Hours (hr) after dose administration.  
4. An Early Discontinuation visit should be scheduled if participant comes off study early after receiving VRC07-523LS.   
5. A complete history is required at birth and includes date of birth, race, ethnicity, gender, maternal risk factor meeting the inclusion criteria, all 
diagnoses, all signs and symptoms, all antiretroviral medications (ARV) with start and stop dates and doses, all injected medications (i.e. 
vitamin K, Hepatitis B vaccine) including location of injection. At subsequent visits the history should include ARV doses with start and stop 
dates, other medications and vaccinations (including sites of injections), diagnoses, and signs and symptoms. Results of HIV-1 testing done 
outside of the study should be abstracted.   
6. Complete physical exam including vitals (temperature, heart rate, respiratory rate, and, if possible, blood pressure), weight, length, and head 
circumference at all visits except Day 1, 3, 7 and 14. Targeted physical exam including vitals (as above) and weight at Days 1, 3, 7 and 14 
visits. Examination of VRC07-523LS injection site should occur at all visits. Data will only be recorded on CRFs through the Day 28 visit (for 
all participants), with the exception that if there are still signs of a reaction present at those visits or any reaction noted at a later visit, data will 
be recorded at scheduled visits until resolved or until no further resolution is expected.  
7. The VRC07-523LS immunization, 80 mg (if <4.5 kg) or 100 mg (if ≥ 4.5 kg) subcutaneous injection, must be administered less than 72 hours 
of life (see MOP for administration instructions).   
• 
Infants should be monitored for a minimum of 4 hours after the study treatment injection, with assessments at 15, 30 and 60 minutes post 
dose.  Clinic personnel must observe participant for any potential adverse reactions to the study immunization. Equipment, supplies, and 
properly skilled medical personnel must be immediately available for emergency use in the event of an unexpected adverse reaction.   
• 
Infants will also be evaluated for local reactions and pain at 1 hour (+30 minutes) after the injection and results recorded on a study CRF. 
• 
Caregivers of participants will be provided with a diary card on which to note any reactions at the injection site.  Study staff will review 
the diary card with the caregiver at the Day 3 and Day 7 visits.   
8. Hematology should include CBC with differential and platelet count. (Not required at screening if collected clinically at birth and results are 
available).  
9. Chemistries should include AST, ALT, total bilirubin, and creatinine. (Not required at screening if collected clinically at birth and ALT results 
are available). Obtain additional ALT and AST measurements upon evidence of hepatic-related clinical adverse events (jaundice, enlargement 
of the liver). 
10. HIV-1 NAT (nucleic acid testing) by a method that detects DNA is required for diagnostic testing since VRC07-523LS might suppress HIV-1 
RNA.  For the NAT at Screening, see footnote 11. HIV-1 NAT testing must be run in a CLIA- or VQA-approved laboratory. If the infant has a 
positive HIV-1 NAT at screening at any time, confirmation and additional HIV testing should be performed as per APPENDIX IC: HIV-1 
Infected Infant Schedule of Evaluations (all dose groups)1. Infants confirmed to be HIV-1-infected should be evaluated according to both 
APPENDIX IG: Schedule of Evaluations (Dose Group 5, Cohort 1: non-breastfeeding) and APPENDIX IC: HIV-1 Infected Infant 
Schedule of Evaluations (all dose groups)1, but without duplication of specific blood tests if the study visit dates are concurrent. When 
possible, APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 visits should be scheduled to coincide with 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
APPENDIX IG: Schedule of Evaluations (Dose Group 5, Cohort 1: non-breastfeeding).  
11. Blood for HIV-1 NAT drawn at Screening must be obtained prior to VRC07-523LS administration. It may be drawn with the Entry blood.  
Results may be pending at study entry. If an HIV-1 NAT (DNA or RNA or combined) was collected clinically prior to study entry and tested 
in a laboratory with CLIA or VQA approval, the test does not need to be duplicated for the study; in this case, results will be abstracted for the 
study. 
12. HIV antibody testing should be performed at the approved site-associated DAIDS-monitored laboratory. If the infant remains antibody 
positive at or after 72 weeks, notify the protocol team. If HIV antibody is negative at Week 48 or later, subsequent HIV antibody testing is not 
required. 
13. Samples for VRC07-523LS plasma levels should be obtained prior to VRC07-523LS administration. For infants with birth weight <2.6kg use 
lower sample volume at Entry. Plasma for VRC07-523LS levels and anti-VRC07-523LS levels will be processed and batch shipped per the 
LPC. Leftover plasma will be stored per the LPC for future HIV-related studies overseen per IMPAACT SOP. See LPC for collection 
procedure, processing, storage, and shipping instructions. 
14. PBMC from the VRC07-523LS plasma level sample will be isolated if site is capable of PBMC isolation and storage (see LPC for 
qualifications).  PBMC will be used for HIV characterization if there are infants with HIV infection. Leftover PBMC will be stored per the 
LPC for future HIV-related studies (possibly including genetic testing) per IMPAACT SOP. See LPC for collection procedure, processing, 
storage, and shipping instructions. 
15. Samples for VRC07-523LS serum should be obtained prior to VRC07-523LS administration. For infants with birth weight <2.6kg: do not 
collect VRC07-523LS serum samples at Entry, Day 14, Day 28, and Week 8. Serum for VRC07-523LS antibody levels and neutralization 
assays will be processed and batch shipped to central testing laboratory. Leftover serum may be stored per the LPC for future HIV-related 
studies per IMPAACT SOP. See LPC for collection procedure, processing, storage, and shipping instructions.   
16. Anti- VRC07-523LS Ab will be tested using plasma collected for VRC07-523LS levels.     
17. Oral fluid is collected with Weck-cel Sponge oral fluid collection device. Sample at Entry should be collected prior to VRC07-523LS 
administration as baseline. Assay will be performed to detect VRC07-523LS antibody level sample. Leftover oral fluid will be stored per the 
LPC for future HIV-related studies per IMPAACT SOP. See LPC for collection procedure, processing, storage, and shipping instructions. 
18. For infants with birth weight <2.6kg lower sample volume will be collected. See also Footnotes 13 and 15. Volumes equate to < 3ml/kg drawn 
within 24 hours and < 9.5 ml/kg drawn over 8 weeks. These are below the NIH Clinical Center guidelines allowing a maximum of 5ml/kg 
within 24 hours and 9.5ml/kg drawn over an 8-week period.    
 
 
Priority for blood samples: 1: HIV-1 NAT; 2: CBC, chemistry; 3: VRC07-523LS plasma levels; 4: VRC07-523LS serum; 5: HIV-1 antibody; At 
Day 28, Week 12, and 24, VRC07-523LS plasma levels are first priority. 
 
 
 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
APPENDIX IH: Schedule of Evaluations (Dose Group 5, Cohort 2: breastfeeding) 
 
 
 
VRC07-523LS DOSING PERIOD 
AFTER INITIAL DOSE: SCREENING TO WK 12 
 
 
VRC07-523LS 
DOSING PERIOD 
AFTER 2ND DOSE:  
WK 14 AND 16 
 
OBSERVATION FOLLOWING 
DOSING PERIOD(S) 
 
Screen1 
Entry/Day 02 
0 Hour 
Day 1/24 hrs3   
± 6 hrs 
Day 3 
± 1 day 
Day 7 
+/-3 days 
 
Day 14 
+/-3 days 
 
Day 28 
+/-3 days 
Wk 8 
+/-1 wks 
Wk 12;  
+/-1 wk 
Wk 14 
+/-3 days 
Wk 16 
+/-3 days 
Wk 24 and 36 
+/-1 wk 
Wks 48, 60, 72, 84 
+/-2 wk  
 
Wk 96: End of Study 
+/- 2 wks 
Early St.udy D/C4 
History5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PE6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VRC07-523LS7 
 
X 
 
 
 
 
 
 
(X) 
 
 
 
 
 
 
Hematology8 
0-1mL 
 
 
 
 
 
1mL 
 
1mL 
1mL 
 
1mL 
 
 
1mL 
Chemistries9 
1mL 
 
 
 
 
 
1mL 
 
1mL 
1mL 
 
1mL 
 
 
1mL 
HIV-1 NAT10 
1mL11 
 
 
 
 
1mL 
1mL 
 
1mL 
 
 
1mL 
1mL 
1mL 
1mL 
HIV Ab test12 
 
 
 
 
 
 
 
 
 
 
 
 
2mL 
2mL 
2mL 
VRC07-523LS 
plasma levels13 
 
2-
3mL13 
1mL 
1mL 
1mL 
2mL 
2mL 
3mL 
3mL 
2mL 
2mL 
3mL 
3mL 
3mL 
3mL 
PBMC 14 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
VRC07-523LS 
serum15 
 
0-
1mL16 
 
 
 
0-1mL16 
0-1mL16 
0-
1mL16 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
2mL 
Anti- VRC07-
523LS Ab16 
 
X 
 
 
 
 
 
X 
X 
 
 
X 
X 
X 
X 
Oral secretions17 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Total blood 
volume infant 
(mL)18 
2-3mL 
2-4mL 
1mL 
1mL 
1mL 
3-4mL 
5-6mL 
3-4mL 
8mL 
6mL 
4mL 
8mL 
8mL 
8mL 
10mL 
 
NOTE: 18-24 mL from birth to 8 weeks18 
 
 
 
 
 
 
 

 
 
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Footnotes 
1. Screening evaluations should be completed as soon as possible after birth. The laboratory testing needed for inclusion/exclusion (CBC, ALT) 
must be completed and eligibility confirmed in time so that the VRC07-523LS is administered ideally within 24 hours to less than 72 
hours after birth and not more than the 5th day of life.   
2. The Entry/Day 0 visit can take place on the same day as the Screening Visit. Blood for the Entry/Day 0 evaluations may be drawn with the 
screening blood or at the time of entry but must be drawn before the VRC07-523LS immunization is administered.   
3. Hours (hr) after dose administration.  
4. An Early Discontinuation visit should be scheduled if participant comes off study early after receiving any doses of VRC07-523LS.   
5. A complete history is required at birth and includes date of birth, race, ethnicity, gender, maternal risk factor meeting the inclusion criteria, all 
diagnoses, all signs and symptoms, all antiretroviral medications (ARV) with start and stop dates and doses, all injected medications (i.e. 
vitamin K, Hepatitis B vaccine) including location of injection. At subsequent visits the history should include ARV doses with start and stop 
dates, other medications and vaccinations (including sites of injections), diagnoses, and signs and symptoms. Results of HIV-1 testing done 
outside of the study should be abstracted. Feeding history to determine breast milk exposure will be obtained at each visit until complete 
cessation of breastfeeding.  
6. Complete physical exam including vitals (temperature, heart rate, respiratory rate, and, if possible, blood pressure), weight, length, and head 
circumference at all visits except Day 1, 3, 7 and 14 and Week 14. Targeted physical exam including vitals (as above) and weight at Days 1, 3, 
7 and 14 and Week 14 visits. Examination of VRC07-523LS injection site should occur at all visits. Data will only be recorded on CRFs 
through the Day 28 visit (for all participants) and the Week 16 visit (for participants who received the second injection), with the exception 
that if there are still signs of a reaction present at those visits or any reaction noted at a later visit, data will be recorded at scheduled visits until 
resolved or until no further resolution is expected.   
7. An initial VRC07-523LS immunization, 80 mg (if <4.5 kg) or 100 mg (if ≥ 4.5 kg) subcutaneous injection, must be administered no later than 
the 5th day of life (see MOP for administration instructions). A second immunization of VRC07-523LS, 100 mg subcutaneous injection, will 
be administered at Week 12 only if the infant has not had complete cessation of breastfeeding. Complete cessation of breastfeeding is defined 
as having completely stopped all exposure to breast milk for ≥ 28 days. There should be no administration of VRC07-523LS if the infant has 
had a positive HIV PCR test result. 
• 
Infants should be monitored for a minimum of 4 hours after initial study treatment injection, with assessments at 15, 30 and 60 minutes 
post dose.  Clinic personnel must observe participant for any potential adverse reactions to the study immunization. Equipment, supplies, 
and properly skilled medical personnel must be immediately available for emergency use in the event of an unexpected adverse reaction. 
The subsequent injection should be monitored for a minimum of 60 minutes (+ 30 minutes), with assessments at 15, 30 and 60 minutes 
post dose. 
• 
Infants will also be evaluated for local reactions and pain at 1 hour (+30 minutes) after each injection and results recorded on a study CRF. 
• 
Caregivers of participants will be provided with a diary card on which to note any reactions at the injection site. After the initial injection, 
study staff will review the diary card with caregivers at the Day 3 and Day 7 visits. After the Week 12 injection (if administered), study 
staff will contact caregivers between 3 to 5 days following the injection to review the diary card.   
8. Hematology should include CBC with differential and platelet count. (Not required at screening if collected clinically at birth and results are 
available).  
9. Chemistries should include AST, ALT, total bilirubin, and creatinine. (Not required at screening if collected clinically at birth and ALT results 
are available). Obtain additional ALT and AST measurements upon evidence of hepatic-related clinical adverse events (jaundice, enlargement 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018 
of the liver). 
10. HIV-1 NAT (nucleic acid testing) by a method that detects DNA is required for diagnostic testing since VRC07-523LS might suppress HIV-1 
RNA.  For NAT at Screening, see footnote 11. HIV-1 NAT testing must be run in a VQA-approved laboratory. If the infant has a positive 
HIV-1 NAT at any time, confirmation and additional HIV testing should be performed as per APPENDIX IC: HIV-1 Infected Infant 
Schedule of Evaluations (all dose groups)1. Infants confirmed to be HIV-1-infected should be evaluated according to both APPENDIX IH: 
Schedule of Evaluations (Dose Group 5, Cohort 2: breastfeeding) and APPENDIX IC: HIV-1 Infected Infant Schedule of 
Evaluations (all dose groups)1, but without duplication of specific blood tests if the study visit dates are concurrent. When possible, 
APPENDIX IC: HIV-1 Infected Infant Schedule of Evaluations (all dose groups)1 visits should be scheduled to coincide with 
APPENDIX IH: Schedule of Evaluations (Dose Group 5, Cohort 2: breastfeeding).  
11. Blood for HIV-1 NAT drawn at Screening must be obtained prior to VRC07-523LS administration. It may be drawn with the Entry blood. 
Results may be pending at study entry. If an HIV-1 NAT (DNA or RNA or combined) was collected clinically prior to study entry and tested 
in a laboratory with VQA approval, the test does not need to be duplicated for the study; in this case, results will be abstracted for the study. 
12. HIV antibody testing should be performed at the approved site-associated DAIDS-monitored laboratory. If the infant remains antibody 
positive at or after 72 weeks, notify the protocol team. If HIV antibody is negative at Week 48 or later, subsequent HIV antibody testing is not 
required. 
13. Samples for VRC07-523LS plasma levels should be obtained prior to VRC07-523LS administration. For infants with birth weight <2.6kg use 
lower sample volume at Entry. Plasma for VRC07-523LS levels and anti-VRC07-523LS levels will be processed and batch shipped per the 
LPC. Leftover plasma will be stored per the LPC for future HIV-related studies overseen per IMPAACT SOP. See LPC for collection 
procedure, processing, storage, and shipping instructions. 
14. PBMC from the VRC07-523LS plasma level sample will be isolated if site is capable of PBMC isolation and storage (see LPC for 
qualifications).  PBMC will be used for HIV characterization if there are infants with HIV infection. Leftover PBMC will be stored per the 
LPC for future HIV-related studies (possibly including genetic testing) per IMPAACT SOP. See LPC for collection procedure, processing, 
storage, and shipping instructions. 
15. Samples for VRC07-523LS serum should be obtained prior to VRC07-523LS administration. For infants with birth weight <2.6kg: do not 
collect VRC07-523LS serum samples at Entry, Day 14, Day 28, and Week 8. Serum for VRC07-523LS antibody levels and neutralization 
assays will be processed and batch shipped per the LPC. Leftover serum may be stored per the LPC for future HIV-related studies per 
IMPAACT SOP. See LPC for collection procedure, processing, storage, and shipping instructions.   
16. Anti- VRC07-523LS Ab will be tested using plasma collected for VRC07-523LS levels.     
17. Oral fluid is collected with Weck-cel Sponge oral fluid collection device. Sample at Entry should be collected prior to VRC07-523LS 
administration as baseline. Assay will be performed to detect VRC07-523LS antibody level sample. Leftover oral fluid will be stored per the 
LPC for future HIV-related studies per IMPAACT SOP. See LPC for collection procedure, processing, storage, and shipping instructions. 
18. For infants with birth weight <2.6kg lower sample volume will be collected. See also Footnotes 13 and 15. Volumes equate to ≤3ml/kg drawn 
within 24 hours and < 9.5 ml/kg drawn over 8 weeks. These are below the NIH Clinical Center guidelines allowing a maximum of 5ml/kg 
within 24 hours and 9.5ml/kg drawn over an 8-week period.    
 
 
Priority for blood samples: 1: HIV-1 NAT; 2: CBC, chemistry; 3: VRC07-523LS plasma levels; 4: VRC07-523LS serum; 5: HIV-1 antibody;  
At Day 28, Week 12, and 24 VRC07-523LS plasma levels are first priority.

 
 
IMPAACT P1112 Version 4.0 
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APPENDIX IIA: IMPAACT P1112 Sample Informed Consent Template: Dose Group 5, 
Cohort 1 (Non-breastfeeding) 
 
DIVISION OF AIDS  
INTERNATIONAL MATERNAL PEDIATRIC ADOLESCENT AIDS CLINICAL 
TRIALS GROUP (IMPAACT) 
SAMPLE INFORMED CONSENT: DOSE GROUP 5, COHORT 1 (NON-
BREASTFEEDING) 
Protocol IMPAACT P1112 
 
Open-Label, Dose-Escalating, Phase I Study to Determine Safety and Pharmacokinetic 
Parameters of Subcutaneous (SC) VRC01, VRC01LS, and VRC07-523LS, Potent Anti-
HIV Neutralizing Monoclonal Antibodies, in HIV-1 Exposed Infants 
Version 4.0, dated 06 November 2018 
 
Short title for IMPAACT P1112: Immunization Study of VRC01/VRC01LS/VRC07-
523LS in Infants  
  
INTRODUCTION 
 
You and your baby are being asked to take part in this research study because you are 
infected with the Human Immunodeficiency Virus (HIV) and there is an increased risk 
that the infection may be passed onto your baby despite the fact that you may be taking 
antiretroviral medications (medications against HIV).  You are being asked to allow your 
baby to receive an experimental immunization within the first 72 hours after he/she is 
born that may protect against HIV transmission.  This study is sponsored by the National 
Institutes of Health (NIH) which has been developing the immunization for this study.  
The doctor in charge of this study is [insert name].  Before you decide whether you want 
your baby to be a part of this study, we want you to know about the study.  
 
This is a consent form.  It gives you information about this study.  The study staff will 
talk with you about this information.  You are free to ask questions about this study at 
any time.  If you agree to allow you and your baby to take part in this study, you will be 
asked to sign this consent form.  You will get a copy to keep. 
 
WHY IS THIS STUDY BEING DONE? 
 
The transfer of HIV to newborn babies from HIV-infected mothers can occur at the time 
of birth.  You have been identified as a mother who may be at increased risk of passing 
the infection onto your baby.  Your baby may be at increased risk of infection because 
you may not have been taking anti-HIV medications earlier in the pregnancy, or HIV can 
be measured in your blood, or you have had a prolonged rupture of membranes (greater 
than 12 hours) or the HIV virus that is in you is resistant to many of the anti-HIV 
medications available.  This research is being done to help find a safe and effective 

 
 
IMPAACT P1112 Version 4.0 
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06 November 2018  
immunization that will give babies protection against HIV infection.  Immunization is the 
process used to help strengthen the immune system against certain diseases. 
 
The experimental study immunizations are monoclonal antibodies (mAb).  Antibodies are 
one of the ways the human body fights infection.  “Monoclonal” means that all the 
antibodies in the immunization are the same.  This type of immunization is temporary 
because the antibodies will go away over time. There are three very similar 
immunizations being used in this study.  The first two immunizations are called 
“VRC01” and “VRC01LS.”  The immunization your baby is being offered is called 
“VRC07-523LS.” The formal name is “VRC-HIVMAB075-00-AB.”  In this consent 
document, and in scientific publications, this antibody is called “VRC07-523LS”  
 
The VRC01, VRC01LS, and VRC07-523LS immunizations are human antibody that may 
be able to block HIV from infecting the baby.  VRC01 was originally discovered in an 
HIV-infected person, but the immunization is not obtained by collecting it from a person.  
All of these immunizations are made using the same controlled, clean conditions used for 
making medications.  They were developed by the National Institutes of Health (NIH).  
 
The VRC01, VRC01LS, and VRC07-523LS have been shown to attach to and inactivate 
many HIV viruses in laboratory experiments.  VRC01 has been tested in adults and 
babies to look at safety and to see what dose (how much) produces the desired blood 
levels of antibodies.  VRC01LS and VRC07-523LS have been tested in the laboratory 
and in adults. VRC01LS has also been given to babies. We are using information from all 
of these studies to help us choose the correct dose of VRC07-523LS for babies.   
 
In this study, babies will receive a single dose of the VRC07-523LS immunization and 
will be followed for safety and have blood collected to measure the levels of VRC07-
523LS in the baby’s blood.  Another group of babies, who are breastfeeding, will receive 
either one or two doses of the VRC07-523LS. 
 
WHAT DO I HAVE TO DO TO BE IN THE STUDY? 
 
If you decide that you want to be in the study, we will check to make sure you are able to 
enroll in this study.   
 
Screening to see if you can be in the study 
• We will ask for your permission to review your medical records to see if you have 
been diagnosed with HIV according to the study criteria.  If we do not find 
information about your HIV infection in your medical record, we will collect a 5 mL 
(1 teaspoon) sample of your blood to determine if you have HIV. We will also review 
the records for other illnesses that you may have had and that might have an impact 
on your baby’s health.  
• We will ask you questions about other studies you might have been in, and health 
conditions and treatments you might have received.  If your baby is expected to 
receive any immunoglobulin products after birth, then you and your baby cannot 
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• The review of your medical history and the interview with you may be done while 
you are still pregnant or shortly after you deliver your baby.  If it is done while you 
are still pregnant you will also be asked some questions after your baby’s birth. 
• If you are able to be in the study, then we will check to make sure that your baby can 
be in the study. 
 
Entry Visit or Day 0 
• If we have not already done so, we will ask for your permission to review your 
medical records to see if you have been diagnosed with HIV according to the study 
criteria.  We will also review the records for other illnesses you may have had and 
that might have an impact on your baby’s health.  
• We will ask you questions about other studies you might have been in, and health 
conditions and treatments you might have received. 
• We will collect a 20 - 25 mL (1 and ½ tablespoon) sample of your blood.  Some of 
this blood will be used to determine if you have HIV (if it is not clear in your medical 
record)..  The rest of the blood will be stored for future use.  The results of these tests 
will be used for research purposes only and will not be reported to you or your doctor. 
• Please note that the screening and entry visit maybe combined on the same day. 
 
WHAT DOES MY BABY HAVE TO DO IF HE/SHE IS IN THIS STUDY? 
 
If you allow your baby to be in this study, your baby will receive a one-time dose of the 
VRC07-523LS immunization within the first 72 hours of his/her life.  The dose of the 
immunization is based on your baby’s weight.  Depending on the dose of the 
immunization, the immunization will be given in either one or two injections into the skin 
of the upper leg(s).  He/she will then be followed on the study for two years. 
 
All babies who are enrolled and immunized on the study will be seen and evaluated 
several times throughout a two-year study period.  If at any time during this period, the 
safety assessments show that the immunization maybe unsafe, no new babies will be 
immunized and the babies already on the study will continue to have follow-up 
evaluations until the end of the two-year period. 
 
Study visits for your baby 
Including the screening visit to check whether your baby is eligible for the study, there 
are 16 study visits. If your baby is found to be HIV-infected during the study, he/she will 
return for visits through Week 96; the number of visits will depend on the age of your 
baby at the time the HIV infection was discovered.  If your baby was less than 2.6 kg at 
birth, we will collect less blood than if your baby was larger at birth.  If this applies to 
your child, the study doctor or nurse will inform you. 
 
[Sites that intend to conduct home visits should include detail throughout this section on 
the time study time points when home visits may be done in lieu of a clinic visit.] 
 

 
 
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Screening visit to see if your baby can be in the study  
If you agree to allow your baby to be in this study, we will do some tests to make sure 
your baby is able to enter this study.  This visit will last about 1-2 hours.  At this visit, we 
will: 
• Ask if you are willing for your baby to complete all scheduled study visits. 
• Ask about your baby’s medical history, which will include how your baby has 
been doing, if he/she has been sick, conditions he/she may have and any 
medicines he/she has been taking.  This will also include your permission to 
review your baby’s medical records to check for medical conditions and any 
treatment your baby may have received.  
• Collect some demographic data such as race, ethnicity and gender. 
• Do a physical examination that may include length, weight, head measurement 
and vital signs such as temperature, blood pressure, heart rate, and respiratory 
rate (how fast the baby breathes). 
• Draw blood from either a vein (called a venipuncture) and/or from your baby’s 
heel (called a heel stick).  We will test your baby for HIV if this has not already 
been done as part of your baby’s standard of care (the care your baby receives 
regardless of the study).  In addition, routine blood tests will be done to tell us 
well your baby’s liver and kidneys are working: again, these tests will only be 
performed for the study if they were not already collected for your baby’s 
medical care.   The total amount of blood drawn at this visit will be 2-3 mL 
(about half a teaspoon).   
• In addition, study staff may contact your baby’s doctor (if you have one) to 
inform the doctor about this study.  
 
Entry Visit or Day 0 
If your baby is able to be in the study, Day 0 is the day that he/she receives the VRC07-
523LS immunization.  Because the immunization must be given to the baby within 72 
hours of his/her birth, the entry day or Day 0 may also be the same day as the screening 
day.  This visit will last for a minimum of 4 hours. 
• If the entry day is on a different day than the screening day, we will ask about 
any medical history since the screening visit and will also do a physical exam.   
• In addition to the blood tests for screening, we will draw 2-3 mL (about a half 
teaspoon) of blood to measure a baseline of VRC07-523LS levels and anti-
VRC07-523LS antibody levels to compare results at your baby’s next visit.  This 
will be drawn before your baby receives the VRC07-523LS injection.  If the 
screening visit and entry (or Day 0) visit are done on the same day, then we may 
draw all the blood, a total of 6-7 mL (about 1½ teaspoon) all at the same time.  
Some of this blood may be stored for future use.   
• We will also collect about 1 mL (¼ teaspoon) of saliva from your baby’s mouth 
by placing a small pad (about the size of a thumbnail attached to stick) between 
the gum and cheek of your baby.  After a minute or two we will remove the pad 
and put it in a container.  The pad will be tested to measure the amount of 
VRC07-523LS in your baby’s saliva. 
• Depending on your baby’s weight, your baby will be given one or two injections 
of VRC07-523LS in the skin of the upper leg.  After your baby has received the 

 
 
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immunization, your baby will be observed for at least four hours so that we can 
check the immunization injection site and to make sure that he/she is well. 
• You will be given a diary card to take with you. For a few days after this visit, 
you will be asked to note any reactions at the injection site(s) and other 
information about your baby’s health on the diary card.  
 
Day 1 visit 
There will be a visit of about 1½ hours duration one day after your baby has received the 
immunization.  At this visit, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s).  
• Draw 1 mL (¼ teaspoon) of blood to measure the amount of VRC07-523LS in your 
baby’s blood. Some of this blood may be stored for future use.   
• Collect a small amount of saliva from your baby’s mouth.  
 
Day 3 visit 
There will be a visit of about 1½ hours duration three days after your baby has received 
the immunization.  At this visit, we will: 
• Ask about your baby’s medical history and review the diary card. 
• Do a physical examination and check the immunization site(s).  
• Draw 1 mL (¼ teaspoon) of blood to measure the amount of VRC07-523LS in your 
baby’s blood. Some of this blood may be stored for future use.   
 
Day 7 visit 
There will be a visit of about 1½ hours duration 7 days after your baby has received the 
immunization.  At this visit, we will: 
• Ask about your baby’s medical history and review the diary card. 
• Do a physical examination and check the immunization site(s). 
• Draw 1 mL (¼ teaspoon) of blood to measure the amount of VRC07-523LS in your 
baby’s blood. Some of this blood may be stored for future use.   
• Collect a small amount of saliva from your baby’s mouth. 
 
Day 14 and 28 and Week 8 
There will be visits of about 1½ hours duration each at Day 14 and 28 and Week 8 after 
your baby has received the immunization. At these visits, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s).  
• Draw 3 to 6 mL (about ½ teaspoon to slightly more than a teaspoon) of blood.  
Depending on the visit, we will measure the amount of VRC07-523LS in your baby’s 
blood, measure your baby’s response to the VRC07-523LS, test your baby for HIV, 
to tell us about your baby’s blood cells and check how well your baby’s liver and 
kidneys are working.  Some of this blood may be stored for future use. 
• Collect a small amount of saliva from your baby’s mouth.  
 

 
 
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Week 12, 24 and 36 visits 
There will be visits of about 1½ hours duration at 12, 24 and 36 weeks after your baby 
has received the immunization.  At these visits, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s). 
• Draw up to 8 mL (about 1½ teaspoon) of blood to test your baby for HIV, and to 
measure the baby’s response to the VRC07-523LS as well as the amount of VRC07-
523LS in your baby’s blood, and also (at Week 12 and Week 24) to tell us about your 
baby’s blood cells and how well your baby’s liver and kidneys are working.  Some of 
this blood may be stored for future use. 
• Collect a small amount of saliva from your baby’s mouth. 
 
Week 48, 60, 72 and 84 visits 
There will be visits of about 1½ hours duration 48, 60, 72 and 84 weeks after your baby 
has received the immunization.  At these visits, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s). 
• Draw 7 mL (slightly more than a teaspoon) of blood to test your baby for HIV, and to 
measure the baby’s response to the VRC07-523LS as well as the amount of VRC07-
523LS in your baby’s blood.  Some of this blood may be stored for future use. 
• Collect a small amount of saliva from your baby’s mouth. 
 
Week 96 visit  
There will be a visit of about 1½ hours duration 96 weeks after your baby has received 
the immunization.  At this visit, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s). 
• Draw 7 mL (slightly more than a teaspoon) of blood for HIV testing and to measure 
the baby’s response to the VRC07-523LS as well as the amount of VRC07-523LS in 
your baby’s blood.  Some of this blood may be stored for future use.    
• Collect a small amount of saliva from your baby’s mouth. 
 
Early Discontinuation visit 
If your baby is not able to continue with the study after he/she has received the VRC07-
523LS immunization, we will ask you to return for a final Early Discontinuation visit.  
This visit will take about 1 ½ hours.  At this visit, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s). 
• Draw 10 mL (2 teaspoons) of blood to test your baby for HIV, and to measure the 
baby’s response to the VRC07-523LS as well as the amount of VRC07-523LS in 
your baby’s blood, to tell us about your baby’s blood cells, and how well your baby’s 
liver and kidneys are working.  Some of this blood may be stored for future use. 
• Collect a small amount of saliva from your baby’s mouth 
 

 
 
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Testing for HIV  
Your baby will be tested for HIV at different time intervals as part of his/her standard of 
care.  [Sites: please insert details about HIV testing as part of local standard of care and 
reporting requirements of a positive test.]   
 
If your baby has a positive HIV test:  
• It means that your baby may have HIV virus in his/her blood.  It will be important 
that your baby return to the clinic as soon as possible for a test to confirm whether the 
baby is infected with HIV.  About 5 mL (almost 1 teaspoon) of blood will be drawn 
to look for how much HIV is in your baby’s blood and to measure your baby’s T 
cells.  We will ask about medical history since the last visit, do a physical 
examination and will draw an additional 1 mL (less than ¼ teaspoon) to look at the 
amount of VRC07-523LS in your baby’s blood. If you consent, an additional 1 mL of 
blood will be drawn for storage. 
• You and your baby will return about 2 weeks later when the results of the 
confirmatory test are available.  These results will be shared with you and with your 
baby’s healthcare provider. If your baby is confirmed to be HIV-infected, you will be 
asked to return at 2 weeks, 4 weeks, and monthly until your child’s doctor begins 
ART for your child.  Whenever possible, these will be scheduled to coincide with 
scheduled study visits.  At each visit the following will be done: 
• History 
• Physical examination 
• Blood collection for HIV virus level 
• Blood collection for VRC07-523LS level  
• If you consent, an additional 1 mL of blood will be drawn for storage 
• Once your baby is started on anti-HIV medications, your baby’s study visits can be 
according to the standard of care.  [Sites to insert follow up for HIV-infected infants.]  
Your baby will continue to return for study visits as regularly scheduled.  At each of 
these visits, if your baby is having blood drawn as part of standard of care, and if you 
consent, an additional 1 mL (less than ¼ teaspoon) of blood will be drawn for storage.   
 
Results of Tests 
Throughout the study, you will be informed of the results of the HIV testing and routine 
blood tests when they become available.  The results of the other blood tests and the 
results of the saliva testing will be used for research purposes only.  These results will not 
be reported to you or your doctor.   
 
Storage of Blood Samples  
Some of your and your baby’s blood and saliva will be stored (with protectors of identity) 
and used for future IMPAACT-approved, HIV-related research.  Your baby can still 
participate in this study even if you decide that you do not want to have his/her blood 
stored for later testing. 
 
Your/your baby’s samples will be shipped to and stored at a special laboratory facility in 
the United States.  Only approved researchers will have access to them.  People who 
work at the facility will also have access to your/your child’s samples to keep track of 

 
 
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them.  These people won’t have information that directly identifies you/your child.  
Your/your baby’s samples will not be sold or directly used to produce commercial 
products.  All proposed research studies using your/your baby’s samples will be reviewed 
by the United States National Institutes of Health (NIH).  There is no time limit on how 
long your/your baby’s samples will be stored.  
 
The researchers do not plan to contact you or your baby’s regular doctor with the results 
of studies done using your/your baby’s stored samples.  This is because research studies 
are often done with experimental procedures.  The results of such studies should not be 
used to make decisions about your/your child’s medical care.  If the researchers decide 
that the result of a certain study provides important information for your/your baby’s 
medical care, your/your baby’s study doctor will be notified.  If you would like to be 
contacted with this sort of information, you must notify the study staff of any changes in 
your address or phone number.  
 
You may decide that you do not want your/your baby’s samples stored for future research 
studies.  You/your baby can still participate in this study even if you make this decision.   
 
You may withdraw your consent for the storage and use of your/your baby’s samples at 
any time.  If you withdraw your consent, these stored samples will be destroyed. 
 
There are two types of testing that can be done with the specimens that are in storage.  
Please read the following statements carefully and then mark your initials and date in the 
appropriate space provided. 
 
1. Testing for General HIV-related studies  
 
Researchers would like to store your/your baby’s specimens to understand how HIV 
causes disease and complications, and how best to treat or prevent HIV infection and its 
complications.  They need specimens from people who have HIV and from those who do 
not.  Sometimes, too, the specimens can be used to learn something about new problems 
that people with HIV have like liver disease, diabetes, and heart disease.  These general 
studies would not include any genetic testing (looking at what makes up you/your child’s 
cells). 
 
Benefits:  There are no direct benefits to you/your baby.  You/Your baby will be 
helping researchers learn more about how to help people with HIV or at risk of 
HIV infection. 
 
Risks: The specimens would be collected as part of you/your baby’s study visits.  
Blood collection can cause bruising, pain and infrequently fainting or 
lightheadedness.  Once in storage, there are few risks.  You/your baby’s name will 
not be available to the staff at the laboratory or to the scientists who may be doing 
any future test. 
 

 
 
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I agree to allow my blood samples to be stored for use in future IMPAACT-
approved, general HIV-related research studies. 
__________ Yes 
 
__________ No 
 
__________ Date 
 
I agree to allow my baby’s blood and saliva samples to be stored for use in future 
IMPAACT-approved, general HIV-related research studies. 
__________ Yes 
 
__________ No 
 
__________ Date 
 
2. Testing for Special HIV-related studies 
 
Researchers in this study would also like to store your/your baby’s specimens to 
understand how HIV causes disease and complications, and how best to treat or prevent 
HIV infection and its complications through looking at how each person’s genetic 
makeup (you/your baby’s DNA or unique cell makeup) either protects them or puts them 
at greater risk.  It may be that researchers use some of your/your baby’s blood to make a 
“cell line.”  That means the blood cells can keep dividing and give an endless supply of 
you/your baby’s DNA for tests to be done in the future.  This kind of information will be 
particularly important as scientists work toward a vaccine that could protect people from 
AIDS.  They need specimens from people who have HIV and from those who do not.  
 
Benefits:  There are no direct benefits to you/your baby.  You/your baby will be 
helping researchers learn more about how to help people with HIV or at risk of HIV 
infection. 
 
Risks: The specimens would be collected as part of you/your baby’s study visits.  
Blood collection can cause bruising, pain and infrequently fainting or 
lightheadedness.  Once in storage, there are few risks.  Your/your baby’s name will 
not be available to the laboratory staff or to the scientists who may be doing any 
future test.  Since there are no plans to give participants the results of the tests 
performed on their stored specimens, you will not receive any information on 
you/your baby’s genetic makeup.  
 
I agree to allow my blood samples to be stored for use in future IMPAACT-approved, 
special HIV-related research studies. 
__________ Yes 
 
__________ No 
 
__________ Date 
 
I agree to allow my baby’s blood and saliva samples to be stored for use in future 
IMPAACT-approved, special HIV-related research studies. 
__________ Yes 
 
__________ No 
 
__________ Date 
 
 
 

 
 
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HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
 
About 39 mothers and their babies will be part of the VRC01 portion of this study.  
About 20 mothers and their babies will be part of the VRC01LS portion of this study. 
About 20 mothers and their babies will be part of the VRC07-523LS portion of this 
study. 
 
HOW LONG WILL I/MY CHILD/BABY BE IN THIS STUDY? 
 
You will only be in the study for as long as it takes to screen you and determine that you 
are eligible for the study (about one day) and have your blood collected.  Your baby will 
be in this study for 96 weeks (about two years).   
 
WHY WOULD THE DOCTOR TAKE MY BABY OFF THIS STUDY EARLY? 
 
The study doctor may need to take you/your baby off the study early without your 
permission if: 
• Your infant does not receive the VRC07-523LS immunization. 
• You are unable to return for infant follow-up evaluations. 
• The investigator determines that further participation would be detrimental to you or 
your baby’s health or well-being. 
• You are unable to comply with the study requirements so as to seriously interfere 
with the validity of the study results. 
• The study may be discontinued by the NIH, Office of Human Research Protection 
(OHRP), U.S. Food and Drug Administration (FDA), the IMPAACT Network, an 
Institutional Research Board (IRB)/Ethics Committee (EC) or local government 
regulatory agency.  An IRB or EC is a committee who watches over the safety and 
rights of research participants. 
 
WHAT ARE THE RISKS OF THE STUDY? 
 
This section describes the risks we know about.  There may also be unknown risks, even 
serious ones which we do not know about.  We will tell you if we learn anything new that 
may affect you/your baby’s health and/or willingness to stay in the study. 
 
Risks of routine medical procedures:  
In this study, we will do some routine medical procedures including taking blood and 
collecting saliva.  Blood collection can cause bruising, pain and infrequently fainting or 
lightheadedness.  The saliva pad may be slightly uncomfortable for a few minutes while 
in the baby’s mouth.  
 
Risks from subcutaneous (SC) injections 
It is possible that your baby may have some side effects from the VRC07-523LS 
injection.  General risks of an injection method include stinging, discomfort, pain, 
soreness, redness, bruising, swelling or a tiny cut at the needle insertion site and, rarely, 
local infection.   

 
 
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Risks of the VRC07-523LS 
This study is the first time that VRC07-523LS is being given to babies, but to date, 26 
adults have received VRC07-523LS and more than 40 infants have received the very 
similar VRC01 and VRC01LS immunizations.   
 
There have been several studies of VRC01 in adults.  So far, there have been no serious 
side effects seen in the adults who have received VRC01, VRC01LS or VRC07-523LS.  
There have been mild and brief local reactions such as redness, itching and swelling and 
mild pain in about 14% of the adults receiving an injection of VRC01.  In those studies, 
about one half of the adults had one or more mild side effects such as a general feeling of 
discomfort, muscle aches, headache, nausea, rash and joint pain but most of these were 
mild.   
 
In this study, nearly 40 babies have received VRC01 and 21 have received the VRC01LS.  
So far, there have been no serious side effects seen in the babies who have received 
VRC01 or VRC01LS.  There has been some bruising, swelling and redness at the 
injection site, but these get better quickly.  Most side effects tend to occur within the first 
24 hours.  Your baby will be observed for at least four hours after he/she has received the 
VRC07-523LS. 
 
Side effects are expected to be rare but may include fever, chills, shaking, nausea, 
vomiting, pain, headache, dizziness, trouble breathing, high or low blood pressure, 
itchiness, rash, hives, lip or face swelling, diarrhea, racing heart or chest pain.  These 
reactions may be related to how fast the antibody product is given.  The immunization 
will be given to your baby slowly. 
 
Monoclonal antibody products have a small risk of serious allergic reactions, including 
anaphylaxis.  Anaphylaxis may include difficulty breathing, low blood pressure, hives or 
rash, swelling in the mouth and face. These reactions are life-threatening.  Such reactions 
usually occur quickly after the injection. Therefore, your baby will be observed in clinic 
for at least four hours after receiving the VRC07-523LS.  The clinics are prepared to treat 
allergic reactions.     
 
Serum sickness is a delayed type of allergic reaction that may occur a week or two after a 
product is given.  This reaction may include hives or rash, fever, big lymph nodes (glands 
in the neck and along the body), and pains in the joints.  You will be contacted after the 
visit to make sure your baby is not having this type of reaction. 
 
In adults who have received VRC01 and VRC01LS, allergic reactions have been seen but 
they have been rare and responded to treatment.  
 
Some women will be offered enrollment while a confirmatory HIV test is pending.  If this 
happens, there is a very small chance that your HIV infection will not be confirmed and 
that you are not HIV-infected.  If so, your baby may have received VRC07-523LS even 
though he/she is not at risk of getting HIV.   

 
 
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In addition to the possible risks that are listed above, VRC07-523LS may have other side 
effects that are not yet known.  It is also possible that the VRC07-523LS will have 
unknown effects on the course of your baby’s HIV infection (if he/she becomes infected).   
 
Risks of disclosure of your personal information 
We will take several steps to protect you and your baby’s personal information.  
Although the risk is very low, it is possible that you or your baby’s 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.  
 
ARE THERE BENEFITS TO TAKING PART IN THIS STUDY? 
 
If you or your baby takes part in this study, it is possible that the immunization may 
prevent the transmission of HIV to the baby from the mother.  However, the studies of 
VRC07-523LS have not looked at whether VRC07-523LS is good at preventing 
transmission of HIV.  It is also possible that your baby may receive no benefit from being 
in this study.  Information learned from this study may help others who are exposed to or 
infected with HIV. 
  
WHAT OTHER CHOICES DOES MY BABY HAVE BESIDES THIS STUDY? 
 
You and your baby do not have to participate in this study.  You may choose to have 
standard of care.  You and your baby will still receive care without being in the study.  
All babies will receive standard antiretroviral medications after their birth in order to 
decrease the likelihood that they may become HIV-infected whether on study or not. 
 
WHAT ABOUT CONFIDENTIALITY? 
 
To help us protect your privacy, we have obtained a Certificate of Confidentiality from 
the National Institutes of Health; this is enforceable only for United States sites.  With 
this Certificate, the researchers cannot be forced to disclose information that may identify 
you, even by a court subpoena, in any federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings.  The researchers will use the Certificate 
to resist any demands for information that would identify you, except as explained below.  
The Certificate cannot be used to resist a demand for information from personnel of the 
United States Government that is used for auditing or evaluation of federally funded 
projects or for information that must be disclosed in order to meet the requirements of the 
federal Food and Drug Administration (FDA).   
 
People who may review your records include the U.S. Food and Drug Administration or 
other Drug Regulatory Authority [international sites: insert as appropriate], Office of 
Human Research Protection (OHRP), the site IRB or EC [insert name of site IRB or EC], 
the National Institutes of Health, the IMPAACT network, study staff, study monitors, and 
their designees, and other local, US, and international regulatory entities. 

 
 
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You should understand that a Certificate of Confidentiality does not prevent you or a 
member of your family from voluntarily releasing information about you or your baby’s 
participation in this research.  If an insurer, employer, or other person obtains your 
written consent to receive research information, then the researchers may not use the 
Certificate of Confidentiality to withhold that information. 
 
The Certificate of Confidentiality does not prevent the researchers from disclosing 
voluntarily, without your consent, information that would identify you as a participant in 
the research project under certain circumstances such as child abuse.  
 
As part of this study, you and your baby will be tested for HIV.  We are required to report 
all positive HIV test results to [add local Health Department/State Board of Health].  
The results will be kept confidential to the extent permissible under the law. 
 
WHAT ARE THE COSTS TO ME? 
 
There is no cost to you for the study visits, examinations, blood tests or the immunization 
you will be given.  You or your insurance will be responsible for costs that are considered 
standard of care that is the care you or your baby would receive whether or not you or 
your baby are on the study.  [Note to sites: This statement can be modified as needed for 
your site.] 
 
Taking part in this study may lead to added costs to you and your insurance company.  In 
some cases, it is possible that your insurance company will not pay for these costs 
because you are taking part in a research study.  [Note to sites: Language related to 
insurance can be deleted if it is not relevant to your site.] 
 
WILL I RECEIVE ANY PAYMENT? 
 
You will not be paid for your baby to be in this study.  You may be paid back for the cost 
of transportation, meals and other personal expenses for this study.  [Sites – modify per 
local guidelines.]  
 
WHAT HAPPENS IF I AM/MY CHILD/BABY IS INJURED? 
 
If your baby is injured as a result of being in this study, your baby will be given 
immediate treatment for his/her injuries.  The cost for this treatment will be charged to 
you or your insurance company.  There is no program for compensation either through 
this institution or the National Institutes of Health (NIH).  You will not be giving up any 
of your legal rights by signing this consent form. 
 

 
 
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WHAT ARE MY/MY BABY’S RIGHTS AS A RESEARCH PARTICIPANT? 
 
Taking part in this study is completely voluntary.  You may choose not to take part in this 
study or not to allow your baby to take part in this study.  You may leave this study or 
take your baby out of the study at any time.  You and your baby will be treated the same 
no matter what you decide. 
 
We will tell you about new information from this or other studies that may affect 
you/your baby’s health, welfare or willingness to stay in this study.  If you want to know 
the final results of the study, let the study staff know. 
 
[Site: if appropriate, include language here regarding the legal requirement to report 
positive HIV tests.] 
 
WHAT DO I DO IF I HAVE QUESTIONS OR PROBLEMS? 
 
For questions about this study or a research-related injury, contact: 
• name of the investigator or other study staff 
• telephone number of above  
 
For questions about your/your child’s/baby’s rights as a research participant, contact: 
• name or title of person on the Institutional Review Board (IRB) or other 
organization appropriate for the site 
• telephone number of above   

 
 
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SIGNATURE PAGE   
 
If you have read this consent form (or had it explained to you), all your questions have 
been answered and you agree take part in this study and you agree to allow your baby to 
be in this study, please sign your name below. 
 
 
____________________________                ____________________________________ 
Mother’s Name (print) 
 
 
Mother’s Signature, Date and Time   
 
 
____________________________                ____________________________________ 
Study Staff Conducting 
 
            Study Staff Signature, Date and Time 
 
Consent Discussion (print)  
 
 
____________________________                ____________________________________ 
Witness’ Name (print) 
 
            Witness’s Signature, Date and Time  
 
(As appropriate) 
 
 
____________________________                ____________________________________ 
Father’s Name 
 
 
 
Father’s Signature, Date and Time 
(If father’s consent is required) 
 
(If father’s consent is required)  
 
 
 
 
 

 
 
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APPENDIX IIB: IMPAACT P1112 Sample Informed Consent Template: Dose Group 5, 
Cohort 2 (breastfeeding) 
 
DIVISION OF AIDS  
INTERNATIONAL MATERNAL PEDIATRIC ADOLESCENT AIDS CLINICAL 
TRIALS GROUP (IMPAACT) 
SAMPLE INFORMED CONSENT 
Protocol IMPAACT P1112: Dose Group 5, Cohort 2 (breastfeeding) 
 
Open-Label, Dose-Escalating, Phase I Study to Determine Safety and Pharmacokinetic 
Parameters of Subcutaneous (SC) VRC01, VRC01LS, and VRC07-523LS, Potent Anti-
HIV Neutralizing Monoclonal Antibodies, in HIV-1 Exposed Infants 
Version 4.0, dated 06 November 2018 
 
 
Short title for IMPAACT P1112: Immunization Study of VRC01/VRC01LS/VRC07-
523LS in Infants  
  
INTRODUCTION 
 
You and your baby are being asked to take part in this research study because you are 
infected with the Human Immunodeficiency Virus (HIV) and you are breastfeeding.  
Even though you or your baby may be taking antiretroviral medications (medications 
against HIV), there is a chance your child could get HIV.  You are being asked to allow 
your baby to receive a dose of an experimental immunization within the first 5 days after 
he/she is born and another dose at 12 weeks if you are still breastfeeding. This may 
protect against HIV transmission during the period that you are breastfeeding. This study 
is sponsored by the National Institutes of Health (NIH) which has been developing the 
immunization for this study.  The doctor in charge of this study is [insert name].  Before 
you decide whether you want your baby to be a part of this study, we want you to know 
about the study.  
 
This is a consent form.  It gives you information about this study.  The study staff will 
talk with you about this information.  You are free to ask questions about this study at 
any time.  If you agree to allow you and your baby to take part in this study, you will be 
asked to sign this consent form.  You will get a copy to keep. 
 
WHY IS THIS STUDY BEING DONE? 
 
The transfer of HIV to newborn babies from HIV-infected mothers can occur at the time 
of birth and during breastfeeding.  Your baby is at ongoing risk of HIV because you will 
be breastfeeding your baby.  This research is being done to help find a safe and effective 
immunization that will give babies protection against HIV infection.  Immunization is the 
process used to help strengthen the immune system against certain diseases. 
 

 
 
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The experimental study immunizations are monoclonal antibodies (mAb).  Antibodies are 
one of the ways the human body fights infection.  “Monoclonal” means that all the 
antibodies in the immunization are the same.  This type of immunization is temporary 
because the antibodies will go away over time. There are three very similar 
immunizations being used in this study.  The first two immunizations are called 
“VRC01” and “VRC01LS.”  The immunization your baby is being offered is called 
“VRC07-523LS.” The formal name is “VRC-HIVMAB075-00-AB.”  In this consent 
document, and in scientific publications, this antibody is called “VRC07-523LS”.   
 
The VRC01, VRC01LS, and VRC07-523LS immunizations are human antibody that may 
be able to block HIV from infecting the baby.  VRC01 was originally discovered in an 
HIV-infected person, but the immunization is not obtained by collecting it from a person.  
All of these immunizations are made using the same controlled, clean conditions used for 
making medications.  They were developed by the National Institutes of Health (NIH).  
 
The VRC01, VRC01LS, and VRC07-523LS have been shown to attach to and inactivate 
many HIV viruses in laboratory experiments.  VRC01 has been tested in adults and 
babies to look at safety and to see what dose (how much) produces the desired blood 
levels of antibodies.  VRC01LS and VRC07-523LS have been tested in the laboratory 
and in adults.  VRC01LS has also been given to babies.  We are using information from 
all of these studies to help us choose the correct dose of VRC07-523LS for babies.   
 
In this study, babies will receive either one or two doses of the VRC07-523LS 
immunization and will be followed for safety and have blood collected to measure the 
levels of VRC07-523LS in the baby’s blood.  Another group of babies, who are not 
breastfeeding, will receive a single dose of the VRC07-523LS.   
 
WHAT DO I HAVE TO DO TO BE IN THE STUDY? 
 
If you decide that you want to be in the study, we will check to make sure you are able to 
enroll in this study.   
 
Screening to see if you can be in the study 
• We will ask for your permission to review your medical records to see if you have 
been diagnosed with HIV according to the study criteria.  If we do not find 
information about your HIV infection in your medical record, we will collect a 5 mL 
(1 teaspoon) sample of your blood to determine if you have HIV. We will also review 
the records for other illnesses that you may have had and that might have an impact 
on your baby’s health.  
• We will ask you questions about other studies you might have been in, and health 
conditions and treatments you might have received.  If your baby is expected to 
receive any immunoglobulin products after birth, then you and your baby cannot 
participate. 
•  The review of your medical history and the interview with you may be done while 
you are still pregnant or shortly after you deliver your baby.  If it is done while you 
are still pregnant you will also be asked some questions after your baby’s birth. 

 
 
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• If you are able to be in the study, then we will check to make sure that your baby can 
be in the study. 
 
Entry Visit or Day 0 
• If we have not already done so, we will ask for your permission to review your 
medical records to see if you have been diagnosed with HIV according to the study 
criteria.  We will also review the records for other illnesses you may have had and 
that might have an impact on your baby’s health.  
• We will ask you questions about other studies you might have been in, and health 
conditions and treatments you might have received. 
• We will collect a 20 mL (1 and ½ tablespoon) sample of your blood.  Some of this 
blood will be used to determine if you have HIV (if it is not clear in your medical 
record), how much HIV is in your blood and how much it may have affected your 
immune system.  The rest of the blood will be stored for future use.  The results of 
these tests will be used for research purposes only and will not be reported to you or 
your doctor. 
• Please note that the screening and entry visit maybe combined on the same day. 
 
WHAT DOES MY BABY HAVE TO DO IF HE/SHE IS IN THIS STUDY? 
 
If you allow your baby to be in this study, your baby will receive a dose of the VRC07-
523LS immunization within the first 5 days of his/her life and then again at 12 weeks of 
life if you are still breastfeeding. The dose of the immunization is based on your baby’s 
weight.  Depending on the dose of the immunization, the immunization will be given in 
either one or two injections into the skin of the upper leg(s).   
 
All babies who are enrolled and immunized on the study of VRC07-523LS will be seen 
and evaluated several times throughout a two-year study period.  If at any time during 
this period, the safety assessments show that the immunization maybe unsafe, no new 
babies will be immunized and the babies already on the study will continue to have 
follow-up evaluations until the end of the two-year period. 
 
Study visits for your baby 
The number of visits will depend on how long you breastfeed your baby and whether 
your baby receives one or two doses of the immunization.  If you breastfeed only a short 
time (less than 2 months), your baby will have 15 visits.  If you breastfeed for longer than 
2 months, your baby will have 17 visits. 
 
If your baby is found to be HIV-infected, he or she will return for visits through the end 
of the study.  If your baby is found to be HIV-infected before he or she is 12 weeks old, 
your baby will not receive a second immunization.   
 
If your baby was less than 2.6 kg at birth, we will collect less blood than if your baby was 
larger at birth.  If this applies to your child, the study doctor or nurse will inform you. 
 

 
 
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[Sites that intend to conduct home visits should include detail throughout this section on 
the time study time points when home visits may be done in lieu of a clinic visit.] 
 
Screening visit to see if your baby can be in the study  
If you agree to allow your baby to be in this study, we will do some tests to make sure 
your baby is able to enter this study.  This visit will last about 1-2 hours.  At this visit, we 
will: 
• Ask if you are willing for your baby to complete all scheduled study visits. 
• Ask about your baby’s medical history, which will include how your baby has been 
doing, if he/she has been sick, conditions he/she may have and any medicines he/she 
has been taking.  This will also include your permission to review your baby’s 
medical records to check for medical conditions and any treatment your baby may 
have received.  
• Collect some demographic data such as race, ethnicity and gender. 
• Do a physical examination that may include length, weight, head measurement and 
vital signs such as temperature, blood pressure, heart rate, and respiratory rate (how 
fast the baby breathes). 
• Draw blood from either a vein (called a venipuncture) and/or from your baby’s heel 
(called a heel stick).  We will test your baby for HIV if this has not already been done 
as part of your baby’s standard of care (the care your baby receives regardless of the 
study).  In addition, routine blood tests will be done to tell us how well your baby’s 
liver and kidneys are working: again, these tests will only be performed for the study 
if they were not already collected for your baby’s medical care.  The total amount of 
blood drawn at this visit will be 2-3 mL (about half a teaspoon).   
• In addition, study staff may contact your baby’s doctor (if you have one) to inform 
the doctor about this study.  
 
Entry Visit or Day 0 
If your baby is able to be in the study, Day 0 is the day that he/she receives the first dose 
of the VRC07-523LS immunization.  Because the immunization must be given to the 
baby within the first 5 days of his/her birth, the entry day or Day 0 may also be the same 
day as the screening day.  This visit will last for a minimum of 4 hours. 
 
• If the entry day is on a different day than the screening day, we will ask about any 
medical history since the screening visit and will also do a physical exam.   
• In addition to the blood tests for screening we will draw 2-4 mL (about a half 
teaspoon) of blood to measure a baseline of VRC07-523LS levels and anti-VRC07-
523LS antibody levels to compare results at your baby’s next visit.  This will be 
drawn before your baby receives the VRC07-523LS injection.  If the screening visit 
and entry (or Day 0) visit are done on the same day, then we may draw all the blood, a 
total of 4-7 mL (up to 1½ teaspoon) all at the same time.  Some of this blood may be 
stored for future use.   
• We will also collect about 1 mL (¼ teaspoon) of saliva from your baby’s mouth by 
placing a small pad (about the size of a thumbnail attached to stick) between the gum 
and cheek of your baby.  After a minute or two we will remove the pad and put it in a 

 
 
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container.  The pad will be tested to measure the amount of VRC07-523LS in your 
baby’s saliva. 
• Depending on your baby’s weight, your baby will be given one or two injections of 
VRC07-523LS in the skin of the upper leg.  After your baby has received the 
immunization, your baby will be observed for at least four hours so that we can check 
the immunization injection site(s) and to make sure that he/she is well. 
• You will be given a diary card to take with you. For a few days after this visit, you 
will be asked to note any reactions at the injection site(s) and other information about 
your baby’s health on the diary card. 
  
Day 1 visit 
There will be a visit of about 1½ hours duration 1 day after your baby has received the 
immunization.  At this visit, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s).  
• Draw 1 mL (¼ teaspoon) of blood to measure the amount of VRC07-523LS in your 
baby’s blood. Some of this blood may be stored for future use.   
• Collect a small amount of saliva from your baby’s mouth.  
 
Day 3 visit 
There will be a visit of about 1½ hours duration 3 days after your baby has received the 
immunization.  At this visit, we will: 
• Ask about your baby’s medical history and review the diary card. 
• Do a physical examination and check the immunization site(s).  
• Draw 1 mL (¼ teaspoon) of blood to measure the amount of VRC07-523LS in your 
baby’s blood. Some of this blood may be stored for future use.   
 
Day 7 visit 
There will be a visit of about 1½ hours duration 7 days after your baby has received the 
immunization.  At this visit, we will: 
• Ask about your baby’s medical history and review the diary card. 
• Do a physical examination and check the immunization site(s). 
• Draw 1 mL (¼ teaspoon) of blood to measure the amount of VRC07-523LS in your 
baby’s blood. Some of this blood may be stored for future use.   
• Collect a small amount of saliva from your baby’s mouth. 
 
Day 14 and 28 and Week 8 
There will be visits of about 1½ hours duration each at Day 14 and 28 and Week 8 after 
your baby has received the immunization. At these visits, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s).  
• Draw 3 to 6 mL (about ½ teaspoon to slightly more than a teaspoon) of blood.  
Depending on the visit, we will measure the amount of VRC07-523LS in your baby’s 
blood, measure your baby’s response to the VRC07-523LS, test your baby for HIV, 

 
 
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to tell us about your baby’s blood cells and check how well your baby’s liver and 
kidneys are working.  Some of this blood may be stored for future use. 
• Collect a small amount of saliva from your baby’s mouth.  
 
Week 12 
There will be a visit 12 weeks after your baby has received the immunization.  If your 
baby has not been at your breast at all during the prior 28 days, this visit will be of about 
1½ hours.  If your baby has been at your breast, even once, in the past 28 days, your baby 
will receive another immunization at this visit.  If your baby receives an immunization, 
this visit will last at least 2 hours. 
 
At this visit, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization sites.  
• Draw 8 mL (about 1½ teaspoon) of blood to measure the amount of VRC07-523LS in 
your baby’s blood, measure your baby’s response to the VRC07-523LS, test your 
baby for HIV, tell us about your baby’s blood cells, and check how well your baby’s 
liver and kidneys are working.  Some of this blood may be stored for future use. 
• Collect a small amount of saliva from your baby’s mouth.  
• If your baby receives an immunization at this visit, he/she will be observed for at least 
one hour so that we can check the immunization injection site(s) and to make sure 
that he/she is well.  We will then phone you between 3 and 5 days after the 
immunization to make sure all is still well. 
 
Week 14 and Week 16 (if your baby receives a second immunization)  
If your baby receives a second immunization at Week 12, there will be visits 2 weeks and 
4 weeks after that second immunization.  These visits will take approximately 1 ½ hours.  
At this visit we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization sites.  
• Draw 4-6 mL (about 1 teaspoon) of blood to measure VRC07-523LS levels.  Two 
weeks after the second immunization, we will draw 2 more mL of blood to tell us 
about your baby’s blood cells and how well your baby’s liver and kidneys are 
working.  Some of this blood may be stored for future use.   
• Collect a small amount of saliva from your baby’s mouth.  
 
Weeks 24, 36, 48, 60, 72, and 84 
Once your baby has been in the study 24 weeks, we will ask you and your baby to return 
to the clinic every 12 weeks (3 months). These visits will last about 1 ½ hours.  At these 
visits we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s).  
• Draw about 8 mL (about 1½ teaspoons) of blood to test your baby for HIV, to 
measure VRC07-523LS levels and your baby’s response to VRC07-523LS and also 
to tell us about your baby’s blood cells and how well your baby’s liver and kidneys 
are working (at Weeks 24 and 36).  Some of this blood may be stored for future use.    

 
 
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• Collect a small amount of saliva from your baby’s mouth.  
 
Week 96 visit  
There will be a visit of about 1½ hours duration 96 weeks after your baby started the 
study.  At this visit, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s). 
• Draw 8 mL (about 1½ teaspoons) of blood for HIV testing and to measure the baby’s 
response to the VRC07-523LS as well as the amount of VRC07-523LS in your 
baby’s blood.  Some of this blood may be stored for future use.    
• Collect a small amount of saliva from your baby’s mouth 
 
Early Discontinuation visit  
If your baby is not able to continue with the study after receiving the VRC07-523LS 
immunization, we will ask you to return for a final Early Discontinuation visit.  This visit 
will take about 1½ hours.  At this visit, we will: 
• Ask about your baby’s medical history. 
• Do a physical examination and check the immunization site(s). 
• Draw 10 mL (2 teaspoons) of blood to of blood to test your baby for HIV, and to 
measure the baby’s response to the VRC07-523LS as well as the amount of VRC07-
523LS in your baby’s blood, to tell us about your baby’s blood cells, and how well 
your baby’s liver and kidneys are working.  Some of this blood may be stored for 
future use. 
• Collect a small amount of saliva from your baby’s mouth 
 
Visits if your baby is found to be HIV-infected  
As noted in the visit details, your baby will be tested for HIV at most study visits.  [Sites: 
please insert details about HIV testing as part of local standard of care and reporting 
requirements of a positive test.]   
 
If your baby has a positive HIV test:  
• It means that your baby may have HIV virus in his/her blood.  If requested, it will be 
It will be important that your baby return to the clinic as soon as possible for a test to 
confirm whether the baby is infected with HIV.  About 5 mL (almost 1 teaspoon) of 
blood will be drawn to look for how much HIV is in your baby’s blood and to 
measure your baby’s T cells.  If this visit is not a regular study visit day, we will ask 
about medical history since the last visit, do a physical examination and will draw an 
additional 1 mL (less than ¼ teaspoon) to look at the amount of VRC07-523LS in 
your baby’s blood. If you consent, an additional 1 mL of blood will be drawn for 
storage. 
• You and your baby will return about 2 weeks later when the results of the 
confirmatory test are available.  These results will be shared with you and with your 
baby’s healthcare provider. If your baby is confirmed to be HIV-infected, you will be 
asked to return at 2 weeks, 4 weeks, and monthly until your child’s doctor begins 

 
 
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ART for your child.  Whenever possible, these will be scheduled to coincide with 
scheduled study visits.  At each visit the following will be done: 
• History 
• Physical examination 
• Blood collection for HIV virus level 
• Blood collection for VRC07-523LS level  
• If you consent, an additional 1 mL of blood will be drawn for storage 
• Once your baby is started on anti-HIV medications, your baby’s study visits can be 
according to the standard of care.  [Sites to insert follow up for HIV-infected infants.]  
Your baby will continue to return for study visits as regularly scheduled.  At each of 
these visits, if your baby is having blood drawn as part of standard of care, and if you 
consent, an additional 1 mL (less than ¼ teaspoon) of blood will be drawn for storage.   
 
Results of Tests 
Throughout the study, you will be informed of the results of the HIV testing and routine 
blood tests when they become available.  The results of the other blood tests and the 
results of the saliva testing will be used for research purposes only.  These results will not 
be reported to you or your doctor.   
 
Storage of Blood Samples  
Some of your and your baby’s blood and saliva will be stored (with protectors of identity) 
and used for future IMPAACT-approved, HIV-related research.  Your baby can still 
participate in this study even if you decide that you do not want to have his/her blood 
stored for later testing. 
 
Your/your baby’s samples will be shipped to and stored at a special laboratory facility in 
the United States.  Only approved researchers will have access to them.  People who 
work at the facility will also have access to your/your child’s samples to keep track of 
them.  These people won’t have information that directly identifies you/your child.  
Your/your baby’s samples will not be sold or directly used to produce commercial 
products.  All proposed research studies using your/your baby’s samples will be reviewed 
by the United States National Institutes of Health (NIH).  There is no time limit on how 
long your/your baby’s samples will be stored.  
 
The researchers do not plan to contact you or your baby’s regular doctor with the results 
of studies done using your/your baby’s stored samples.  This is because research studies 
are often done with experimental procedures.  The results of such studies should not be 
used to make decisions about your/your child’s medical care.  If the researchers decide 
that the result of a certain study provides important information for your/your baby’s 
medical care, your/your baby’s study doctor will be notified.  If you would like to be 
contacted with this sort of information, you must notify the study staff of any changes in 
your address or phone number.  
 
You may decide that you do not want your/your baby’s samples stored for future research 
studies.  You/your baby can still participate in this study even if you make this decision.   
 

 
 
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You may withdraw your consent for the storage and use of your/your baby’s samples at 
any time.  If you withdraw your consent, these stored samples will be destroyed. 
 
There are two types of testing that can be done with the specimens that are in storage.  
Please read the following statements carefully and then mark your initials and date in the 
appropriate space provided. 
 
1. Testing for General HIV-related studies  
 
Researchers would like to store your/your baby’s specimens to understand how HIV 
causes disease and complications, and how best to treat or prevent HIV infection and its 
complications.  They need specimens from people who have HIV and from those who do 
not.  Sometimes, too, the specimens can be used to learn something about new problems 
that people with HIV have like liver disease, diabetes, and heart disease.  These general 
studies would not include any genetic testing (looking at what makes up you/your child’s 
cells). 
 
Benefits:  There are no direct benefits to you/your baby.  You/your baby will be 
helping researchers learn more about how to help people with HIV or at risk of HIV 
infection. 
 
Risks: The specimens would be collected as part of you/your baby’s study visits.  
Blood collection can cause bruising, pain and infrequently fainting or 
lightheadedness.  Once in storage, there are few risks.  You/your baby’s name will 
not be available to the staff at the laboratory or to the scientists who may be doing 
any future test. 
 
I agree to allow my blood samples to be stored for use in future IMPAACT-approved, 
general HIV-related research studies. 
__________ Yes 
 
__________ No 
 
__________ Date 
 
I agree to allow my baby’s blood and saliva samples to be stored for use in future 
IMPAACT-approved, general HIV-related research studies. 
__________ Yes 
 
__________ No 
 
__________ Date 
 
2. Testing for Special HIV-related studies 
 
Researchers in this study would also like to store your/your baby’s specimens to 
understand how HIV causes disease and complications, and how best to treat or prevent 
HIV infection and its complications through looking at how each person’s genetic 
makeup (you/your baby’s DNA or unique cell makeup) either protects them or puts them 
at greater risk.  It may be that researchers use some of your/your baby’s blood to make a 
“cell line.”  That means the blood cells can keep dividing and give an endless supply of 
you/your baby’s DNA for tests to be done in the future.  This kind of information will be 

 
 
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particularly important as scientists work toward a vaccine that could protect people from 
AIDS.  They need specimens from people who have HIV and from those who do not.  
 
Benefits:  There are no direct benefits to you/your baby.  You/your baby will be 
helping researchers learn more about how to help people with HIV or at risk of HIV 
infection. 
 
Risks: The specimens would be collected as part of you/your baby’s study visits.  
Blood collection can cause bruising, pain and infrequently fainting or 
lightheadedness.  Once in storage, there are few risks.  Your/your baby’s name will 
not be available to the laboratory staff or to the scientists who may be doing any 
future test.  Since there are no plans to give participants the results of the tests 
performed on their stored specimens, you will not receive any information on 
you/your baby’s genetic makeup.  
 
I agree to allow my blood samples to be stored for use in future IMPAACT-approved, 
special HIV-related research studies. 
__________ Yes 
 
__________ No 
 
__________ Date 
 
I agree to allow my baby’s blood and saliva samples to be stored for use in future 
IMPAACT-approved, special HIV-related research studies. 
__________ Yes 
 
__________ No 
 
__________ Date 
 
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? 
 
About 39 mothers and their babies will be part of the VRC01 portion of this study.  
About 20 mothers and their babies will be part of the VRC01LS portion of this study. 
About 20 mothers and their babies will be part of the VRC07-523LS portion of this 
study. 
 
HOW LONG WILL I/MY CHILD/BABY BE IN THIS STUDY? 
 
You will only be in the study for as long as it takes to screen you and determine that you 
are eligible for the study (about one day) and have your blood collected.  Your baby will 
be in this study for at 96 weeks (about two years).   
 
WHY WOULD THE DOCTOR TAKE MY BABY OFF THIS STUDY EARLY? 
 
The study doctor may need to take you/your baby off the study early without your 
permission if: 
• Your infant does not receive the VRC07-523LS immunization. 
• You are unable to return for infant follow-up evaluations. 
• The investigator determines that further participation would be detrimental to you or 
your baby’s health or well-being. 

 
 
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• You are unable to comply with the study requirements so as to seriously interfere 
with the validity of the study results. 
• The study may be discontinued by the NIH, Office of Human Research Protection 
(OHRP), U.S. Food and Drug Administration (FDA), the IMPAACT Network, an 
Institutional Research Board (IRB) /Ethics Committee (EC) or local government 
regulatory agency.  An IRB or EC is a committee who watches over the safety and 
rights of research participants. 
 
WHAT ARE THE RISKS OF THE STUDY? 
 
This section describes the risks we know about.  There may also be unknown risks, even 
serious ones which we do not know about.  We will tell you if we learn anything new that 
may affect you/your baby’s health and/or willingness to stay in the study. 
 
Risks of routine medical procedures:  
In this study, we will do some routine medical procedures including taking blood and 
collecting saliva.  Blood collection can cause bruising, pain and infrequently fainting or 
lightheadedness.  The saliva pad may be slightly uncomfortable for a few minutes while 
in the baby’s mouth.  
 
Risks from subcutaneous (SC) injections 
It is possible that your baby may have some side effects from the VRC07-523LS 
injection.  General risks of an injection method include stinging, discomfort, pain, 
soreness, redness, bruising, swelling or a tiny cut at the needle insertion site and, rarely, 
local infection.   
 
Risks of the VRC07-523LS  
This study is the first time that VRC07-523LS is being given to babies, but to date, 26 
adults have received VRC07-523LS and more than 40 infants have received the very 
similar VRC01 and VRC01LS immunization.   
 
There have been several studies of VRC01 in adults.  So far there have been no serious 
side effects seen in the adults who have received VRC01, VRC01LS, or VRC07-523LS.  
There have been mild and brief local reactions such as redness, itching and swelling and 
mild pain in about 14% of the adults receiving an injection of VRC01.  In those studies, 
about one half of the adults had one or more mild side effects such as a general feeling of 
discomfort, muscle aches, headache, nausea, rash and joint pain but most of these were 
mild.   
 
In this study, nearly40 babies have received VRC01 and 21 have received the VRC01LS.  
So far, there have been no serious side effects seen in the babies who have received 
VRC01 or VRC01LS.  There has been some bruising, swelling and redness at the 
injection site, but these get better quickly.  Most side effects tend to occur within the first 
24 hours.  Your baby will be observed for at least four hours after he/she has received the 
first dose of VRC07-523LS. If your baby receives a second dose of VRC07-523LSat 
Week 12, he/she will be observed for at least one hour after that dose. 

 
 
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Side effects are expected to be rare but may include fever, chills, shaking, nausea, 
vomiting, pain, headache, dizziness, trouble breathing, high or low blood pressure, 
itchiness, rash, hives, lip or face swelling, diarrhea, racing heart or chest pain.  These 
reactions may be related to how fast the antibody product is given.  The immunization 
will be given to your baby slowly. 
 
Monoclonal antibody products have a small risk of serious allergic reactions, including 
anaphylaxis.  Anaphylaxis may include difficulty breathing, low blood pressure, hives or 
rash, swelling in the mouth and face. These reactions are life-threatening.  Such reactions 
usually occur quickly after the injection. Therefore, your baby will be observed in clinic 
for at least four hours after the first dose and at least one hour after the second dose (if 
received). The clinics are prepared to treat allergic reactions.     
 
Serum sickness is a delayed type of allergic reaction that may occur a week or two after a 
product is given.  This reaction may include hives or rash, fever, big lymph nodes (glands 
in the neck and along the body), and pains in the joints.  You will be contacted after the 
visit to make sure your baby is not having this type of reaction. 
 
In adults who have received VRC01 and VRC01LS, allergic reactions have been seen but 
they have been rare and responded to treatment.  
 
Some women will be offered enrollment while a confirmatory HIV test is pending.  If this 
happens, there is a very small chance that your HIV infection will not be confirmed and 
that you are not HIV-infected.  If so, your baby may have received VRC07-523LS even 
though he/she is not at risk of getting HIV.   
 
In addition to the possible risks that are listed above, VRC07-523LS may have other side 
effects that are not yet known.  It is also possible that the VRC07-523LS will have 
unknown effects on the course of your baby’s HIV infection (if he/she becomes infected).   
 
Risks of disclosure of your personal information 
We will take several steps to protect you and your baby’s personal information.  
Although the risk is very low, it is possible that you or your baby’s 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.  
 
ARE THERE BENEFITS TO TAKING PART IN THIS STUDY? 
 
If you or your baby takes part in this study, it is possible that the immunization may 
prevent the transmission of HIV to the baby from the mother.  However, the studies of 
VRC07-523LS have not looked at whether VRC07-523LS is good at preventing 
transmission of HIV.  It is also possible that your baby may receive no benefit from being 
in this study.  Information learned from this study may help others who are exposed to or 
infected with HIV. 

 
 
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WHAT OTHER CHOICES DOES MY BABY HAVE BESIDES THIS STUDY? 
 
You and your baby do not have to participate in this study.  You may choose to have 
standard of care.  You and your baby will still receive care without being in the study.  
All babies will receive standard antiretroviral medications after their birth in order to 
decrease the likelihood that they may become HIV-infected whether on study or not. 
 
WHAT ABOUT CONFIDENTIALITY? 
 
To help us protect your privacy, we have obtained a Certificate of Confidentiality from 
the National Institutes of Health; this is enforceable only for United States sites.  With 
this Certificate, the researchers cannot be forced to disclose information that may identify 
you, even by a court subpoena, in any federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings.  The researchers will use the Certificate 
to resist any demands for information that would identify you, except as explained below.  
The Certificate cannot be used to resist a demand for information from personnel of the 
United States Government that is used for auditing or evaluation of federally funded 
projects or for information that must be disclosed in order to meet the requirements of the 
federal Food and Drug Administration (FDA).   
 
People who may review your records include the U.S. Food and Drug Administration or 
other Drug Regulatory Authority [international sites: insert as appropriate], Office of 
Human Research Protection (OHRP), the site IRB or EC [insert name of site IRB or EC], 
the National Institutes of Health, the IMPAACT network, study staff, study monitors, and 
their designees, and other local, US, and international regulatory entities. 
 
You should understand that a Certificate of Confidentiality does not prevent you or a 
member of your family from voluntarily releasing information about you or your baby’s 
participation in this research.  If an insurer, employer, or other person obtains your 
written consent to receive research information, then the researchers may not use the 
Certificate of Confidentiality to withhold that information. 
 
The Certificate of Confidentiality does not prevent the researchers from disclosing 
voluntarily, without your consent, information that would identify you as a participant in 
the research project under certain circumstances such as child abuse.  
 
As part of this study, you and your baby will be tested for HIV.  We are required to report 
all positive HIV test results to [add local Health Department/State Board of Health].  
The results will be kept confidential to the extent permissible under the law. 
 
 

 
 
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WHAT ARE THE COSTS TO ME? 
 
There is no cost to you for the study visits, examinations, blood tests or the immunization 
you will be given.  You or your insurance will be responsible for costs that are considered 
standard of care that is the care you or your baby would receive whether or not you or 
your baby are on the study.  [Note to sites: This statement can be modified as needed for 
your site.] 
 
Taking part in this study may lead to added costs to you and your insurance company.  In 
some cases, it is possible that your insurance company will not pay for these costs 
because you are taking part in a research study.  [Note to sites: Language related to 
insurance can be deleted if it is not relevant to your site.] 
 
WILL I RECEIVE ANY PAYMENT? 
 
You will not be paid for your baby to be in this study.  You may be paid back for the cost 
of transportation, meals and other personal expenses for this study.  [Sites – modify per 
local guidelines.]  
 
WHAT HAPPENS IF I AM/MY CHILD/BABY IS INJURED? 
 
If your baby is injured as a result of being in this study, your baby will be given 
immediate treatment for his/her injuries.  The cost for this treatment will be charged to 
you or your insurance company.  There is no program for compensation either through 
this institution or the National Institutes of Health (NIH).  You will not be giving up any 
of your legal rights by signing this consent form. 
 
WHAT ARE MY/MY BABY’S RIGHTS AS A RESEARCH PARTICIPANT? 
 
Taking part in this study is completely voluntary.  You may choose not to take part in this 
study or not to allow your baby to take part in this study.  You may leave this study or 
take your baby out of the study at any time.  You and your baby will be treated the same 
no matter what you decide. 
 
We will tell you about new information from this or other studies that may affect 
you/your baby’s health, welfare or willingness to stay in this study.  If you want to know 
the final results of the study, let the study staff know. 
 
[Site: if appropriate, include language here regarding the legal requirement to report 
positive HIV tests.] 
 
WHAT DO I DO IF I HAVE QUESTIONS OR PROBLEMS? 
 
For questions about this study or a research-related injury, contact: 
• name of the investigator or other study staff 

 
 
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• telephone number of above  
 
For questions about your/your child’s/baby’s rights as a research participant, contact: 
• name or title of person on the Institutional Review Board (IRB) or other 
organization appropriate for the site 
• telephone number of above   

 
 
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SIGNATURE PAGE   
 
If you have read this consent form (or had it explained to you), all your questions have 
been answered and you agree take part in this study and you agree to allow your baby to 
be in this study, please sign your name below. 
 
 
____________________________                ____________________________________ 
Mother’s Name (print) 
 
 
Mother’s Signature, Date and Time   
 
 
____________________________                ____________________________________ 
Study Staff Conducting 
 
            Study Staff Signature, Date and Time 
 
Consent Discussion (print)  
 
 
____________________________                ____________________________________ 
Witness’ Name (print) 
 
            Witness’s Signature, Date and Time  
 
(As appropriate) 
 
 
____________________________                ____________________________________ 
Father’s Name 
 
 
 
Father’s Signature, Date and Time 
(If father’s consent is required) 
 
(If father’s consent is required)