Phase I/II Multisite, Randomized, Controlled Study of Monoclonal Antibody VRC01 With Combination Antiretroviral Therapy to Promote Clearance of HIV-1-Infected Cells in Infants
Phase: PHASE1
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Clarification Memorandum #2 
Page 1 of 3 
01 April 2020 
IMPAACT 2008 Protocol Version 2.0 
Clarification Memorandum #2 for: 
 
IMPAACT 2008 
Phase I/II Multisite, Randomized, Controlled Study of Monoclonal Antibody VRC01 
with Combination Antiretroviral Therapy  
to Promote Clearance of HIV-1-Infected Cells in Infants 
 
Version 2.0, dated 29 May 2017 
 
 DAIDS ES # 20735 
IND # 133,017 Held By DAIDS 
 
Clarification Memorandum Date: 01 April 2020   
 
 
Summary of Clarifications 
 
This Clarification Memorandum (CM) is being issued to safeguard the health and well-being of 
IMPAACT 2008 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 ongoing contact with participants and to prioritize the conduct of clinically and 
scientifically important evaluations when possible. 
 
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 2008 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Team will determine when, in the future, the guidance provided in this CM is no longer applicable.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 2008. 
 
 
 
 

Clarification Memorandum #2 
Page 2 of 3 
01 April 2020 
IMPAACT 2008 Protocol Version 2.0 
Implementation 
 
This CM provides operational guidance to study sites from the IMPAACT 2008 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/or Clinical Management Committee and should contact the Clinical Management 
Committee (impaact.2008cmc@fstrf.org) with any questions or concerns regarding this CM or 
management of study participants.  
 
Visit Scheduling 
• 
Sites that anticipate operational disruptions or closures in the near future are advised to conduct study 
visits early in the allowable visit window. Visits conducted prior to opening of the allowable window 
would also be preferred to completely missing a visit at a later date. 
• 
Sites that are currently experiencing operational disruptions or closures are advised to conduct study 
visits late in the allowable visit window. Visits conducted after closing of the allowable window 
would also be preferred to completely missed visits.  
• 
Effective with the issuance of this CM, the allowable window for the Week 24 and Week 36 visits is 
broadened to ±6 weeks; the allowable visit window for the Week 48 visit is broadened to -6 to +12 
weeks. 
• 
In the event that any scheduled visits or procedures are missed, all participants should remain on-
study for the full duration of follow-up (i.e., through the Week 48 visit) if possible.    
 
Prioritization of Study Visit Procedures 
• 
Sites with full capacity to conduct study visits in-person at the study clinic should continue to do so in 
full compliance with the protocol.  
• 
Sites may also conduct study visits — in full or in part — off-site if permitted by applicable 
government, health authority, and institutional policies. Where this option is permitted, site staff 
should communicate with participants’ caregivers 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, as determined by the site Investigator of Record (IoR), with attention paid to occupational 
health, biohazard containment, and specimen and data chain of custody. These staff should also be 
adequately qualified and trained to immediately assess and/or manage any adverse events or social 
impacts that may occur during the visits. If adverse events requiring further evaluation or 
management are identified during an off-site visit, staff conducting the visit should arrange for 
appropriate clinical management, in consultation with the IoR or designee as needed.  
• 
Sites with limited capacity to conduct study visits should prioritize the visits outlined below for 
participants in both study arms. When applicable, specimen collection should be prioritized per 
protocol Section 6.17.1.  
- First priority visits:   
• 
Weeks 2, 6, and 10: These visits include VRC01 administration (for Arm 1 participants) and 
specimen collection (for all participants). VRC01 administration must be performed on-
site with personnel and supplies available in case of an immediate hypersensitivity reaction. 
If these visits cannot be conducted on-site, procedures other than VRC01 administration may 
be performed off-site if the requirements listed above, particularly the requirements 
pertaining to specimen collection and transport, can be met. If specimen collection cannot be 

Clarification Memorandum #2 
Page 3 of 3 
01 April 2020 
IMPAACT 2008 Protocol Version 2.0 
performed off-site, other visit procedures (e.g., history taking, cART adherence assessment) 
may be performed remotely rather than in-person.  
• 
Week 14: These visits include specimen collection for assessment of primary study outcome 
measures. These visits may be conducted off-site if the requirements listed above, particularly 
the requirements pertaining to specimen collection and transport, can be met. If specimen 
collection cannot be performed off-site, other visit procedures (e.g., history taking, cART 
adherence assessment) may be performed remotely rather than in-person.  
• 
Weeks 3, 7, and 11: These visits should be conducted in-person (on-site or off-site) whenever 
possible. If in-person visits are not possible, reactogenicity assessments and history taking 
may be performed remotely.   
- Second priority visits: 
• 
+3-Day Contacts after Weeks 2, 6, and 10: Per protocol Section 6.16, these contacts may be 
conducted remotely. 
• 
Weeks 24, 36, and 48: These visits involve specimen collection and may be conducted off-
site if the requirements listed above can be met. If specimen collection cannot be performed 
off-site, other visit procedures (e.g., history taking, cART adherence assessment) may be 
performed remotely rather than in-person.  
- Third priority visits:  
• 
Weeks 16 and 20: These visits are of lowest priority. They involve specimen collection and 
may be conducted off-site if the requirements listed above can be met. If specimen collection 
cannot be performed off-site, other visit procedures (e.g., history taking, cART adherence 
assessment) may be performed remotely rather than in-person. 
 
Study Drug Supply 
• 
No changes in procedures for preparing, dispensing, or administering study product (VRC01) are 
permitted. 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 2008.  
• 
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  
• 
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. Once this Network-
level guidance is available, it will be provided in a separate communication to all sites.