Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in the United States
Conditions: COVID-19
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
 
 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
 
IND#154,388 
DAIDS study ID # 38746 
 
 
This file contains the current IMPAACT 2032 protocol, 
which is comprised of the following documents, 
presented in reverse chronological order: 
 
• Corrected Clarification Memorandum #2, dated 21July 2021 
• Clarification Memorandum #1, dated 12 April 2021  
• Protocol Version 2.0, dated 18 December 2020 
 
 
 
 

 
Corrected Clarification Memorandum #2 
Page 1 of 1 
21 July 2021  
IMPAACT 2032, Protocol Version 2.0 
Corrected Clarification Memorandum #2 for:  
 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
Version 2.0, dated 18 December 2020 
 
DAIDS Study ID #38746 
IND # 154388 
 
Corrected Clarification Memorandum Date: 21 July 2021  
 
 
Summary of Clarifications and Rationale 
 
This is a corrected version of Clarification Memorandum (CM) #2, which clarifies pharmacokinetic (PK) 
specimen collection procedures for participants who discontinue remdesivir (RDV) after initial PK 
sampling. This CM also updates the Protocol Team Roster. The corrected version of CM#2 replaces the 
original clarification memorandum, which should be disregarded.    
 
 
Implementation 
 
This CM will be submitted to the Johns Hopkins Medicine Institutional Review Board, which serves as 
the single Institutional Review Board (sIRB) for IMPAACT 2032, for their information; however, 
approval of this CM is not required by the study sponsor prior to implementation. Sites may submit this 
CM to their local IRBs/ECs for their information or, if required by the local IRBs/ECs, for their approval 
prior to implementation. This CM and any applicable IRB/EC correspondence should also be filed in 
essential document files for IMPAACT 2032. 
 
The information included in this memorandum will be incorporated into the next protocol amendment.  
 
1. Section 6.7 Early Discontinuation of Remdesivir of the IMPAACT 2032 protocol specifies that 
participants who initiate RDV and undergo PK sampling and then discontinue RDV prior to the 5th 
infusion will have no further PK sampling. This memorandum clarifies that PK sampling includes 
intensive PK, intracellular PK, protein binding plasma, or single PK plasma (48-hour post-last 
infusion data collection timepoint) sampling.   
 
2. To reflect current membership, Polina German is removed from the Protocol Team Roster and 
DaMante’ Curry is added as a protocol laboratory data manager, as shown below.    
 
DaMante’ Curry, BS 
Frontier Science Foundation  
4033 Maple Road  
Amherst, NY 14226  
Phone: 716-834-0900 ext. 7416 
Email: dcurry@frontierscience.org  
 
 
 
 
 

Clarification Memorandum #1 
Page 1 of 3 
12 April 2021  
IMPAACT 2032, Protocol Version 2.0 
Clarification Memorandum #1 for:  
 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
Version 2.0, dated 18 December 2020 
 
DAIDS Study ID #38746 
IND # 154388 
 
Clarification Memorandum Date: 12 April 2021  
 
 
Summary of Clarifications and Rationale 
 
This Clarification Memorandum (CM) updates protocol specifications to reflect current policies of the 
Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), and National 
Institutes of Health (NIH). It also updates the wording related to the IMPAACT Network Certificate of 
Confidentiality and adds the protocol IND number. These updates do not impact the study design or 
study-specific procedures.  
 
 
Implementation 
 
This CM will be submitted to the Johns Hopkins Medicine Institutional Review Board, which serves as 
the single Institutional Review Board (sIRB) for IMPAACT 2032, for their information; however, 
approval of this CM is not required by the study sponsor prior to implementation. Sites may submit this 
CM to their local IRBs/ECs for their information or, if required by the local IRBs/ECs, for their approval 
prior to implementation.  
 
IRBs/ECs may have acknowledged and/or approved remote site monitoring strategies prior to the 
issuance of this CM. If so, sites should file documentation of this acknowledgement and/or approval in 
their essential document files for IMPAACT 2032. This CM and any applicable IRB/EC correspondence 
should also be filed in  essential document files for IMPAACT 2032. 
 
The information included in this memorandum will be incorporated into the next protocol amendment. 
 
A. DAIDS Policy Updates  
 
1. Protocol Section 12 is updated to reflect current DAIDS policies for clinical site monitoring, which 
allow for on-site and remote monitoring. The prior contents of this section are replaced with the 
following: 
 
Under contract to DAIDS or NICHD, site monitors will inspect study site facilities and review 
participant study records — including informed consent forms, paper-based CRFs (if used), 
eCRFs, medical records, laboratory records, and pharmacy records — to ensure protection of 
study participants, compliance with the sIRB approved protocol, and accuracy and 

Clarification Memorandum #1 
Page 2 of 3 
12 April 2021  
IMPAACT 2032, Protocol Version 2.0 
completeness of records. Monitors also will review essential document files to ensure 
compliance with all applicable regulatory requirements. Site investigators will make study 
facilities and documents available for inspection by monitors. 
 
Monitoring visits may be conducted on-site or remotely. Remote visits may include remote 
source document verification using methods specified for this purpose by DAIDS or NICHD. 
Remote monitoring visits may be performed in place of, or in addition to, onsite visits to ensure 
the safety of study participants and data integrity (1). Site investigators will make study 
documents available for site monitors to review utilizing a secure platform that is 21 CFR Part 
11 and HIPAA compliant. Potential platform options include: Veeva SiteVault, Medidata Rave 
Imaging Solution, Medidata Remote Source Review, site-controlled SharePoint or cloud-based 
portal, and direct access to electronic medical records. Other secure platforms that are 21 CFR 
Part 11 and HIPAA compliant may be utilized, as allowed by DAIDS or NICHD. 
 
Reference:  
1. FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 
Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review 
Boards, March 2020, Updated on January 27, 2021. Accessed at: 
https://www.fda.gov/media/136238/download 
 
2. Protocol Section 14.5 refers to the DAIDS policy on identification and classification of critical 
events. This policy has been retired. Section 14.5 is removed from the protocol and Section 13.1 has 
been updated to refer to the reporting requirements that still apply for sites conducting this study. In 
Section 13.1 no changes are made to the first paragraph and the prior contents of the second  
paragraph are replaced with the following:  
 
Prior to study initiation, site investigators must obtain sIRB review and approval of this 
protocol and site-specific informed consent forms in accordance with 45 CFR 46; subsequent to 
initial review and approval, the sIRB must review the study at least annually. Site investigators 
must promptly report to the sIRB any changes in the study and must comply with the 
requirements of 45 CFR 46.108(a)(4) and 21 CFR 56.108(b) for promptly reporting the 
following: unanticipated problems involving risks to participants or others; serious or 
continuing noncompliance with applicable regulations or the requirements or determinations of 
the sIRB; and any suspension or termination of sIRB approval. 
 
3. Protocol Section 14.6 (now re-numbered as Section 14.5) refers to requirements for entry of study 
results into ClinicalTrials.gov. To reflect current NIH and regulatory requirements, the prior contents 
of this section are replaced with the following:  
 
The NIH Policy on Dissemination of NIH-funded Clinical Trial Information establishes the 
expectation that clinical trials funded in whole or in part by the NIH will be registered and have 
summary results information submitted to ClinicalTrials.gov for public posting. The protocol 
team will comply with this policy as well as the requirements of 42 CFR 11. 
 
4. Protocol Sections 11.1, 11.2, 11.3, 13.7, 14.3, and 14.4 refer to the following DAIDS policies: 
 
• 
Requirements for Essential Documents at Clinical Research Sites Conducting DAIDS Funded 
and/or Sponsored Clinical Trials  
• 
Requirements for Source Documentation in DAIDS Funded and/or Sponsored Clinical Trials  
• 
Requirements for Clinical Quality Management Plans 

Clarification Memorandum #1 
Page 3 of 3 
12 April 2021  
IMPAACT 2032, Protocol Version 2.0 
• 
Requirements for Manual of Operational Procedures 
 
These policies have been retired and replaced with instructions for sites that are now contained in the 
DAIDS Site Clinical Operations and Research Essentials (SCORE) Manual. Throughout the protocol, 
references to the above-listed policies are replaced with requirements specified in the DAIDS SCORE 
Manual (edits not shown here). The SCORE Manual is available at: 
https://www.niaid.nih.gov/research/daids-clinical-site-implementation-operations 
 
B. Certificate of Confidentiality 
 
The Certificate of Confidentiality described in protocol Section 13.7 has been deemed issued to the 
IMPAACT Network effective with the start date of the current Network funding cycle (1 December 
2020). The first sentence in the last paragraph of this section is replaced with the following:  
 
In addition to the above, a Certificate of Confidentiality has been deemed issued for the 
IMPAACT Network by the US Department of Health and Human Services.  
 
C. Protocol Cover Page  
 
The IND Number # 154388 is added to the cover page 
 
 
 

IMPAACT 2032 
 
 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 
in Pregnant and Non-Pregnant Women in the United States 
 
 
A Study of the International Maternal Pediatric Adolescent 
AIDS Clinical Trials Network 
 
 
 
Sponsored by: 
National Institute of Allergy and Infectious Diseases 
Eunice Kennedy Shriver 
National Institute of Child Health and Human Development 
National Institute of Mental Health 
 
 
Support Provided by: 
Gilead Sciences, Inc. 
 
 
DAIDS Study ID #38746 
IND # XXXXX Held by DAIDS  
 
 
 
Protocol Chair: 
Mark Mirochnick, MD 
 
Protocol Vice-Chairs:  
Diana Clarke, PharmD 
     Brookie Best, PharmD, MAS 
 
NIAID Medical Officers: 
Patrick Jean-Philippe, MD 
 
Dwight Yin, MD, MPH 
 
NICHD Medical Officer: 
Nahida Chakhtoura, MD, MsGH 
 
Clinical Trials Specialists: 
Elizabeth Greene, MPH 
Kathleen George, MPH 
 
 
 
 
 
 
FINAL Version 2.0  
18 December 2020

IMPAACT 2032, FINAL Version 2.0 
  
Page 2 of 79 
 18 December 2020 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
TABLE OF CONTENTS 
 
1.1 
Background ..................................................................................................................................... 18 
1.2 
Clinical Pharmacology During Pregnancy ....................................................................................... 19 
1.3 
Rationale ......................................................................................................................................... 21 
2.1 
Primary Objectives .......................................................................................................................... 22 
2.2 
Secondary Objectives ...................................................................................................................... 22 
2.3 
Other Objectives .............................................................................................................................. 22 
4.1 
Inclusion Criteria – Arm 1 (Pregnant Women) ................................................................................. 24 
4.2 
Inclusion Criteria – Arm 2 (Non-Pregnant Women) ......................................................................... 24 
4.3 
Exclusion Criteria – Arms 1 and 2 ................................................................................................... 25 
4.4 
Co-Enrollment Considerations ......................................................................................................... 25 
4.5 
Recruitment, Screening, and Enrollment Process ........................................................................... 26 
4.6 
Participant Retention ....................................................................................................................... 27 
4.7 
Participant Withdrawal or Discontinuation from the Study ............................................................... 27 
5.1 
Remdesivir Formulations ................................................................................................................. 27 
5.2 
Dose, Preparation and Administration ............................................................................................. 28 
5.3 
Concomitant Medications ................................................................................................................ 28 
5.4 
Disallowed Medications at Entry ...................................................................................................... 28 
6.1 
Data Collection Requirements ......................................................................................................... 29 
6.2 
Screening/Entry ............................................................................................................................... 29 
6.3 
Pre-infusion ..................................................................................................................................... 30 
6.4 
Infusion Period ................................................................................................................................ 31 
6.5 
Safety Follow-up Period (48-Hour, 7-Day and 4-Week Post-Last Infusion) ..................................... 35 
6.6 
Delivery Period (Arm 1) ................................................................................................................... 37 
6.7 
Early Discontinuation of Remdesivir ................................................................................................ 39 
6.8 
Additional Considerations for Laboratory Procedures ..................................................................... 39 
7.1 
Safety-Related Roles and Responsibilities ...................................................................................... 40 
7.2 
Safety-Related Data Collection ....................................................................................................... 41 
7.3 
Expedited Adverse Event (EAE) Reporting ..................................................................................... 43 
9.1 
General Design Issues .................................................................................................................... 45 
9.2 
Outcome Measures ......................................................................................................................... 46 

IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
9.3 
Randomization and Stratification ..................................................................................................... 48 
9.4 
Sample Size and Accrual ................................................................................................................ 48 
9.5 
Monitoring ........................................................................................................................................ 52 
9.6 
Analyses .......................................................................................................................................... 53 
10.1 
Pharmacology Overview and Objectives ......................................................................................... 54 
10.2 
Definition of PK Evaluable ............................................................................................................... 55 
10.3 
Pharmacology Outcome Measures ................................................................................................. 55 
10.4 
Pharmacology Data Analysis and Modeling .................................................................................... 55 
10.5 
Anticipated Outcomes ..................................................................................................................... 56 
11.1 
Data Management Responsibilities ................................................................................................. 57 
11.2 
Essential and Source Documents and Access to Source Data ....................................................... 57 
11.3 
Quality Control and Quality Assurance ............................................................................................ 58 
13.1 
Institutional Review Board/Ethics Committee Review and Approval ............................................... 58 
13.2 
Pregnant Women, Children, and Vulnerable Participants ............................................................... 59 
13.3 
Informed Consent ............................................................................................................................ 59 
13.4 
Potential Benefits............................................................................................................................. 60 
13.5 
Potential Risks ................................................................................................................................. 60 
13.6 
Reimbursement/Compensation Plan ............................................................................................... 60 
13.7 
Privacy and Confidentiality .............................................................................................................. 60 
13.8 
Management of Incidental Findings ................................................................................................. 61 
13.9 
Management of New Information Pertinent to Study Participation .................................................. 61 
14.1 
Regulatory Oversight ....................................................................................................................... 62 
14.2 
Protocol Registration ....................................................................................................................... 62 
14.3 
Study Implementation ...................................................................................................................... 63 
14.4 
Protocol Deviation Reporting ........................................................................................................... 63 
14.5 
Critical Event Reporting ................................................................................................................... 63 
14.6 
ClinicalTrials.gov ............................................................................................................................. 63 
Appendix II, Part 1: MASTER Sample Informed Consent Form .................................................................... 69 
Appendix II, Part 2: SITE-SPECIFIC Consent Information ............................................................................ 76 
 
LIST OF FIGURES 
Figure 1: Overview of Study Design ............................................................................................................................. 17 
Figure 2: Remdesivir and sofosbuvir structure. ............................................................................................................ 19 
Figure 3: Expected PK of Remdesivir and GS-441524 and the potential effect of pregnancy ..................................... 19 
 
LIST OF TABLES 
Table 1. Plasma PK Parameters of RDV and GS-441524 Following 30-minute IV Infusion(s) of RDV 200 mg on Day 
1 and 100 mg Daily on Days 2-5 in Healthy Adults (Preliminary Analysis)(15) ............................................................ 20 
Table 2: Data Collection Requirements for Pre-infusion Period ................................................................................... 30 
Table 3: Data Collection Requirements for Infusion Period ......................................................................................... 32 
Table 4: Intensive PK Schedule and Volumes ............................................................................................................. 34 

IMPAACT 2032, FINAL Version 2.0 
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Table 5: Data Collection Requirements for Safety Follow-up Period ........................................................................... 36 
Table 6: Data Collection Requirements for Delivery Period ......................................................................................... 38 
Table 7. Outcome Measures ........................................................................................................................................ 46 
Table 8. Percentile range and width of 90% Confidence Intervals for the mean PK parameter ................................... 49 
Table 9. Power to conclude that pharmacokinetic parameters are not more than 30% different (90% CI within 0.7 – 
1.43) ............................................................................................................................................................................. 49 
Table 10. Precision (exact binomial 95% confidence interval) for estimating the percentage of participants 
experiencing a ≥ Grade 3 adverse event or adverse pregnancy outcome................................................................... 50 
Table 11. Probability of observing no event and of observing 1-10 event(s)................................................................ 50 
 

IMPAACT 2032, FINAL Version 2.0 
  
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 18 December 2020 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
DAIDS Study ID #38746 
 
 
Version 2.0 
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 2032, FINAL Version 2.0 
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18 December 2020 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
ABBREVIATIONS AND ACRONYMS 
 
AAG 
α1-acid glycoprotein 
AE 
adverse event  
ALT 
alanine transaminase 
AST 
aspartate aminotransferase 
ATP 
adenosine triphosphate 
AUC 
area under the curve 
CBC 
complete blood count 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CMC 
Clinical Management Committee 
COVID-19 
coronavirus disease of 2019 
CRP 
C-reactive protein 
CV 
coefficient of variation 
DAIDS 
Division of AIDS  
DBS 
dried blood spots 
DMC 
Data Management Center 
EAE 
expedited adverse event 
ECMO 
extracorporeal membrane oxygenation 
EUA 
Emergency Use Authorization 
EC 
ethics committee 
ECG 
electrocardiogram 
ESR 
 
erythrocyte sedimentation rate 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate  
EMA 
European Medical Association 
FDA 
Food and Drug Administration 
FDAAA 
United States Food and Drug Administration Amendments Act of 2007 
GCP 
good clinical practices 
GFR 
glomerular filtration rate  
GMR 
geometric mean ratio 
GS-5734TM 
remdesivir 
GS-441524 
remdesivir dephosphorylated nucleoside analog 
GS-443902 
remdesivir active triphosphate form 
HIV 
human immunodeficiency virus 
hs 
 
high sensitivity 
ICU 
intensive care unit 
IMPAACT 
International Maternal Pediatric Adolescent AIDS Clinical Trials Network 
IRB  
institutional review board 
IND 
investigational new drug 
INR 
 
international normalized ratio  
IoR 
Investigator of Record  
IV 
intravenous 
LAR 
legally authorized representative 

IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
LDH 
 
lactate dehydrogenase  
LDMS 
laboratory data management system 
LPC 
laboratory processing chart 
MERS-CoV 
Middle East respiratory syndrome 
MMWR 
Morbidity and Mortality Weekly Report CDC 
MOG 
Management Oversight Group 
MOP 
manual of procedures 
NCA 
non-compartmental pharmacokinetic analysis 
NIAID 
National Institute of Allergy and Infectious Diseases 
NICHD 
National Institute of Child Health and Human Development 
NIH 
National Institutes of Health 
OHRP 
Office for Human Research Protection 
PBMCs 
peripheral blood mononuclear cells 
PCD 
primary completion date 
PID 
participant identification number 
PK 
pharmacokinetic 
PRO 
Protocol Registration Office 
PT 
 
prothrombin time 
PTT 
 
partial thromboplastin time 
RDV 
remdesivir 
RSC 
Regulatory Support Center 
SAE 
serious adverse event 
SARS-CoV-1 serious acute respiratory syndrome coronavirus 1 
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2  
SMC 
Study Monitoring Committee 
SOF 
sofosbuvir 
TAF 
tenofovir alafenamide 
 
 
 

IMPAACT 2032, FINAL Version 2.0 
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IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
PROTOCOL TEAM ROSTER 
 
 
Protocol Chair 
Mark Mirochnick, MD 
Department of Pediatrics, Boston University 
School of Medicine 
801 Albany Street, Room 2020 
Boston, MA 02118  
Phone: 617-414-3754 
Email: markm@bu.edu 
 
Protocol Vice Chairs 
Diana Clarke, PharmD 
Section of Pediatric Infectious Diseases 
670 Albany Street, 6th Floor 
Boston Medical Center  
Boston, MA 02118 
Phone: 617-414-7508 
Email: diana.clarke@bmc.org 
 
Brookie Best, PharmD, MAS 
Univ. of California San Diego 
9500 Gilman Drive, MC 0657 
La Jolla, CA 92093-0657 
Phone: 858-822-5550 
Email: brookie@ucsd.edu 
 
Clinical Trials Specialists 
Elizabeth Greene, MPH 
IMPAACT Operations Center 
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701, USA 
Phone: 919-544-7040 x11124 
Email: egreene@fhi360.org  
 
Kathleen George, MPH 
IMPAACT Operations Center 
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701, USA 
Phone: 919-544-7040 x11150 
Email: kgeorge@fhi360.org 
 
NIAID Medical Officers 
Patrick Jean-Philippe, MD DAIDS/NIAID/NIH 
Maternal, Adolescent and Pediatric Research 
Branch  
Prevention Sciences Program  
5601 Fishers Lane, Room 8B21  
Rockville, MD 20852  
Phone: 240-292-4790  
Email: jeanphilippep@niaid.nih.gov 
 
Dwight Yin, MD, MPH 
Maternal Adolescent and Pediatric Research 
Branch 
Prevention Sciences Program 
DAIDS/NIAID/NIH 
5601 Fishers Lane, Room 8B25 
Rockville, MD 20852  
Office: 301-761-5006 
Email: dwight.yin@nih.gov 
 
NICHD Medical Officer 
Nahida Chakhtoura, MD, MsGH 
Maternal and Pediatric Infectious Disease 
Branch 
Eunice Kennedy Shriver National Institute of 
Child Health and Human Development 
(NICHD) 
National Institutes of Health 
6710B Rockledge Drive, Rm 2140 
Bethesda, MD 20817-7002 
Phone: 301-435-6872 
Email: nahida.chakhtoura@nih.gov 
 
Protocol Pharmacologists 
Edmund Capparelli, PharmD  
Univ. of California San Diego 
9500 Gilman Drive, MC 0760 
La Jolla, CA 92093-0760  
Phone: 858-246-0009 
Email: ecapparelli@ucsd.edu 
 

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Jeremiah Momper, PharmD, PhD 
Univ. of California San Diego 
9500 Gilman Drive, MC 0657 USA 
La Jolla, CA 92093-0657 
Phone: 858-822-0913 
Email: jmomper@ucsd.edu 
 
Kristina M. Brooks, PharmD 
Department of Pharmaceutical Sciences, 
University of Colorado Skaggs School of 
Pharmacy and Pharmaceutical Sciences 
12850 E Montview Blvd, Room V20-4107  
Aurora, CO 80045  
Phone: (303)724-0395 
E-mail: kristina.brooks@cuanschutz.edu 
 
Protocol Statisticians 
David E. Shapiro, PhD 
Harvard T. H. Chan School of Public Health 
Center for Biostatistics in AIDS Research 
(CBAR) FXB Building 
651 Huntington Avenue 
Boston, MA 02115  
Phone: 617-432-2426 
Email: shapiro@sdac.harvard.edu 
 
Kristin Baltrusaitis, PhD 
Harvard T. H. Chan School of Public Health 
Center for Biostatistics in AIDS Research 
(CBAR) FXB Building 
651 Huntington Avenue 
Boston, MA 02115  
Phone: 617-432-7496 
Email: kbaltrus@sdac.harvard.edu 
 
Protocol Investigators 
Kathleen Powis, MD, MPH 
Massachusetts General Hospital 
125 Nashua Street, Office 8426 
Boston, MA 02145  
Phone: 617-643-2054 
Email: kpowis@mgh.harvard.edu 
 
Protocol Obstetricians 
Ahizechukwu Eke, MD MPH  
Johns Hopkins University School of Medicine 
Department of Gynecology & Obstetrics, 
600 N. Wolfe Street, Phipps 228, 
Baltimore, MD 21287  
Phone: 410-504-7454 
Email: aeke2@jhu.edu 
Alice Stek, MD 
Univ. of Southern California School of 
Medicine  
Los Angeles County Medical Center Maternal, 
Child and Adolescent HIV Program 
Obstetrics and Gynecology  
2020 Zonal Ave, IRD Building, room 218 
Los Angeles, CA 90033  
Phone: 323-409-3536 or 323-409-3416 
Email: stek@usc.edu  
 
Protocol Data Managers 
Christina Reding, MPH 
Frontier Science Foundation 
4033 Maple Road 
Amherst, NY 14226-1056  
Phone: 716-834-0900 x7339 
E-mail: reding@frontierscience.org      
 
Benjamin Johnston, BS  
Frontier Science Foundation  
4033 Maple Road  
Amherst, NY 14226-1056  
Phone: 716-834-0900 x7407  
Email: johnston@frontierscience.org 
 
Kira Bacon, BA 
Frontier Science Foundation 
4033 Maple Road 
Amherst, NY 14226-1056  
Phone: 716-834-0900 x7269 
Email: kbacon@frontierscience.org 
 
Protocol Laboratory Data Manager 
Frederic Bone  
Frontier Science Foundation  
4033 Maple Road  
Amherst, NY 14226  
Phone: 716-834-0900 ext. 7306  
Email: bone@frontierscience.org 
 
Laboratory Center Representative  
Carolyn Yanavich, PhD 
ACTG Laboratory Center 
IMPAACT Laboratory Center 
University of California Los Angeles 
11075 Santa Monica Boulevard, Suite 200 
Los Angeles, CA 90025  
Phone: 703-980-2471 
Email: cyanavich@milabcentral.org 
 

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Samantha Solomon, BS 
ACTG Laboratory Center 
IMPAACT Laboratory Center 
University of California Los Angeles 
11075 Santa Monica Boulevard, Suite 200 
Los Angeles, CA 90025  
Phone: 314-441-2356 
Email: ssolomon@milabcentral.org 
 
Protocol Laboratory Technologists 
Richard Tustin III BS 
The Children’s Hospital of Philadelphia 
3615 Civic Center Blvd.  
Philadelphia, PA 19104  
ARC 1204B 
Phone: 215-590-2043  
Email: tustinr@email.chop.edu 
 
Paul Harding, MS  
University of  Colorado-Anschutz Medical 
Center  
12700 E. 19th Ave Room # 11460-A 
Aurora, CO 80045  
Phone: 303-724-3404  
Email: paul.harding@cuanschutz.edu 
 
Westat Representative 
Hanna Major-Wilson, MSN, ARNP 
Westat CRA 
1600 Research Boulevard 
Rockville, MD, 20850 
Phone: 240-907-6278 
Email: Hannamajor-Wilson@westat.com 
 
Community Program Manager  
Michele Haber, CMSW 
IMPAACT Operations Center, FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701 
Phone: 919-544-7040 x11152 
Email: MHaber@fhi360.org 
 
Community Advisory Board Members 
Theresa Aldape, LMSW 
Texas Children's Hospital 
Immunology, Allergy and Rheumatology  
1102 Bates Street, Mail Code:  FC 330.01 
Houston, Texas 77030 
Phone: 832-824-1324 
Email: tmaldape@texaschildrens.org   
 
Maurice Williams 
6009 Oxon Hill Rd #309 
Oxon Hill, MD, 20745 
Phone: 240-553-4513 
Email: mauricewilliams527@gmail.com 
 
Pharmaceutical Representatives 
James Rooney, MD  
Vice President, Medical Affairs Research 
Gilead Science, Inc.  
333 Lakeside Drive  
Foster City, CA 94404 
Phone: 650-522-5708  
Email: jim.rooney@gilead.com 
 
Kathryn KersySr. Director, Clinical 
Research - Virology Gilead Sciences, Inc. 
333 Lakeside Drive, Foster City, CA 94404 
Phone: 650-524-3822 
Email: Kathryn.Kersey@gilead.com 
 
Catherine O’Connor, MB BCh BAO, Dip. Clin. 
Ed., MSc. Pharm Med 
Director, Clinical Research Virology 
Gilead Sciences, Inc. 
Dublin, Ireland 
Phone: +3538 7902 5188 
Email: catherine.oconnor3@gilead.com  
 
Heather Maxwell, MPH 
Associate Director, Project and Portfolio 
Management 
Gilead Sciences, Inc. 
 Dublin, Ireland 
Phone: +353-87-408-2992  
Email: Heather.maxwell@gilead.com  
 
Polina German, PharmD 
Executive Director, Clinical Pharmacology 
Gilead Sciences, Inc. 
333 Lakeside Drive  
Foster City, CA 94404 
Phone: 650-522-2990 
Email: Polina.german@gilead.com 
 

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18 December 2020 
Rita Humeniuk 
Sr Clinical Pharmacologist I 
Gilead Sciences, Inc. 
333 Lakeside Drive  
Foster City, CA 94404 
Phone: 650-425-2735 
Email: rita.humeniuk@gilead.com  
 
Ramin Ebrahimi, MS 
Senior Director, Biostatistics 
Gilead Sciences, Inc. 
333 Lakeside Drive  
Foster City, CA 94404  
Phone: 650-522-5988 
Email: Ramin.ebrahimi@gilead.com 
 
Rich Clark, MPH  
Clinical Trials Manager, Clinical Operations – 
Late Phase 
Gilead Sciences, Inc.  
333 Lakeside Drive  
Foster City, CA 94404  
Phone: 650-372-7996 
Email: Rich.clark@gilead.com 
 

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 18 December 2020 
 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
STUDY SITE ROSTER 
 
Site 4001, Lurie Children's Hospital of 
Chicago CRS 
Lurie Children's Hospital of Chicago 
225 East Chicago Ave  
Chicago IL 60611 USA4001 
 
Ellen Chadwick, MD 
Investigator of Record 
Phone: 312-227-4677 
Email: egchadwick@luriechildrens.org 
 
Margaret Ann Sanders, MPH 
Study Coordinator 
Phone: 312-227-8275  
Email: msanders@luriechildrens.org  
 
Site 4601, University of California, UC San 
Diego CRS 
University of California, San Diego 
4076 3rd Avenue, Suite 301 
San Diego, CA 92103 USA 
 
Stephen A. Spector, MD 
Investigator of Record 
Phone: 858-534-7170 
Email: saspector@ucsd.edu 
 
Megan Loughran 
Study Coordinator 
Phone: 714-501-1922 
Email: meloughran@health.ucsd.edu 
 
Site 5013, Jacobi Medical Center Bronx 
NICHD CRS 
Jacobi Medical Center 
1400 Pelham Parkway South  
Bronx, NY 10461 USA 
 
Andrew Wiznia, MD 
Investigator of Record 
Phone: 718-918-4664 
Email: Andrew.Wiznia@nychhc.org 
 
Marlene Burey, MSN, PNP 
Study Coordinator 
Phone: 718-918-4783 
Email: Marlene.Burey@nychhc.org 
 
Site 5030, Emory University School of 
Medicine NICHD CRS 
Emory University School of Medicine 
550 Peachtree St NE, Medical Office Tower 8th 
Floor 
Atlanta, GA 30308 USA 
 
Martina Badell, MD 
Investigator of Record 
Phone:404-778-3401 
Email: mbadell@emory.edu 
 
LaTeshia Thomas-Seaton 
Study Coordinator 
Phone: 404-616-5936 
Email: lseaton@emory.edu 
 
Site 5040, SUNY Stony Brook NICHD CRS 
Stony Brook Children's 
101 Nicolls Road 
Stony Brook, NY 11794-8091 USA 
 
Christy Beneri, DO  
Investigator of Record 
Phone: 631-444-7692 
Email: christy.beneri@stonybrookmedicine.edu 
 
Barsha Chakraborty, BS 
Study Coordinator 
Phone: 631-444-8225 
Email: 
Barsha.Chakraborty@stonybrookmedicine.edu 
 

IMPAACT 2032, FINAL Version 2.0 
  
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 18 December 2020 
 
Site 5048, University of Southern California 
Los Angeles NICHD CRS 
University of Southern California Keck School 
of Medicine 
Keck School of Medicine 
1640 Marengo St. HRA 300 MC 9264 
Los Angeles, CA 90089 USA 
 
Alice Stek, MD 
Investigator of Record 
Phone: 323-865-1585 
Email: stek@usc.edu 
 
Lourdes Topete, RN  
Study Coordinator 
Phone: 323-865-1585 
Email: ltopete@usc.edu 
 
Site 5051, University of Florida Jacksonville 
NICHD CRS 
University of Florida 
UF CARES, 3rd Floor clinical Center 
UF Health, 655 West 8th Street 
Jacksonville, FL 32209 USA 
 
Mobeen Rathore, MD 
Investigator of Record 
Phone: 904798-4179 
Email: Mobeen.Rathore@jax.ufl.edu 
 
Saniyyah Mahmoudi, ARNP 
Study Coordinator 
Phone: 904-244-5331 
Email: saniyyah.Mahmoudi@jax.ufl.edu 
 
Site 5052, University of Colorado Denver 
NICHD CRS 
University of Colorado Children’s Hospital 
Colorado 
Mail Stop 8604 
Aurora, CO 80045 USA 
 
Myron J. Levin. MD 
Investigator of Record 
Phone: 303-724-2451 
Email: Myron.levin@anschutz.edu 
 
Emily Barr, CPNP, CNM, MSN  
Study Coordinator 
Phone: 720-777-6752 
Email: emily.barr@childrenscolorado.org 
Site 5083, Rush University Cook County 
Hospital Chicago NICHD CRS 
Rush/Cook County Hospital 
2020 W Harrison,  
Chicago, IL 60612 USA 
 
Mariam Aziz, MD  
Investigator of Record 
Phone: 312-942-4265 
Email: Mariam_Aziz@rush.edu 
 
Maureen McNichols, MSN, CCRP 
Study Coordinator 
Phone: 312-572-4541 
Email: maureen_mcnichols@rush.edu 
 
Site 5092, Johns Hopkins University 
Baltimore NICHD CRS 
Johns Hopkins University 
200 N. Wolfe St., Rm 3096  
Baltimore, MD 21287 USA 
 
Allison Agwu, MD, ScM 
Investigator of Record 
Phone: 410-614-3917 
Email: ageorg10@jhmi.edu 
 
Aleisha Collinson-Streng, RN, BSN 
Study Coordinator 
Phone: 443-287-8888 
Email: acolli14@jhmi.edu 
 
Site 5112, David Geffen School of Medicine at 
UCLA NICHD CRS 
David Geffen School of Medicine at UCLA 
10833 Le Conte Ave, MDCC 22-442 
Los Angeles, CA 90095-1752 USA 
 
Jaime G. Deville, MD 
Investigator of Record 
Phone: 310-8259660 
Email: jdeville@mednet.ucla.edu 
 
Michele Carter, BS, RN 
Study Coordinator 
Phone: 310-206-6369 
Email: mfcarter@mednet.ucla.edu 
 

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 18 December 2020 
 
Site 5114, Bronx-Lebanon Hospital Center 
NICHD CRS 
Bronx-Lebanon Hospital Center 
1685 Morris Ave Suite 1 G 
Bronx, NY, 10457 USA 
 
Murli Purswani, MD, MBChB 
Investigator of Record 
Phone: 718-960-1018 
Email: mpurswan@bronxcare.org 
 
Martha Cavallo, CPNP  
Study Coordinator 
Phone: 718-960-1016 
Email: mcavallo@bronxcare.org 
 
Site 5127, Pediatric Perinatal HIV Clinical 
Trials Unit 
Pediatric/Perinatal HIV Clinical Trials Unit 
1580 NW 10 Ave Ste# 286  
Miami FL 33136 USA 
 
Gwendolyn B. Scott, MD 
Investigator of Record 
Phone: 305243-6522 
Email: gscott@med.miami.edu 
 
Adriana P. Drada, FMD, CCRP 
Study Coordinator 
Phone: 305-243-4447 
Email: apd86@med.miami.edu 
 
Site 5128, Texas Children's Hospital CRS 
Baylor / Texas Children's Hospital 
1102 Bates, FC330.01,  
Houston, TX 77030 USA 
 
Mary Paul, MD 
Investigator of Record 
Phone: 832-822-1038 
Email: mpaul@bcm.edu 
 
Ruth Eser-Jose, MSN, RN, CPN 
Study Coordinator  
Phone: 832-824-1333 
email: rjeser@texaschildrens.org 
 
Site 5129, University of Puerto Rico Pediatric 
HIV/AIDS Research Program CRS 
University of Puerto Rico  
Pediatric HIV/AIDS Research site 
Biomedical building II  
Medical Sciences Campus 
San Juan, Puerto Rico, 00935 USA 
Pediatric HIV/AIDS Research site 
 
Irma L Febo, MD 
Investigator of Record 
Phone: 787-759-9595 
Email: Irma.febo2@upr.edu 
 
Sylvia Davila, MS 
Study Coordinator 
Phone: 787-67-9192 
Email: sylvia.davila1@upr.edu 
 
Site 6501, St. Jude Children’s Research 
Hospital CRS 
St. Jude Children's Research Hospital 
262 Danny Thomas Place  
Memphis TN 38105 USA 
 
Katherine Knapp, MD  
Investigator of Record 
Phone: 901-595-4645  
Email: katherine.knapp@stjude.org 
 
Nina Sublette, PhD, APRN-BC 
Study Coordinator 
Phone: 901-448-2696 
Email: nsublett@uthsc.edu 
 
 

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 18 December 2020 
 
 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States 
 
SCHEMA 
 
Purpose: 
To describe the pharmacokinetic (PK) properties and safety of 
remdesivir (GS-5734TM) (RDV) administered to pregnant and non-
pregnant women with COVID-19. 
 
Design: 
Phase IV, prospective, open label, non-randomized opportunistic PK 
study 
 
Study Population: 
Pregnant and non-pregnant women of childbearing potential hospitalized 
and receiving RDV for treatment of COVID-19.  
 
Sample Size: 
Arm 1: Target enrollment of 20 pregnant women with evaluable PK data  
Arm 2: Target enrollment of 20 non-pregnant women of childbearing 
potential with evaluable PK data 
 
Drug under study: 
RDV will not be provided as part of the study. Participants will be 
administered RDV intravenously once daily for up to 10 days per clinical 
care. 
 
Study Duration: 
Approximately 15 months total. Accrual is expected to be completed 
within approximately 6 months from first enrollment. Enrolled women in 
Arm 1 will be followed for 4 weeks after the last RDV infusion or 
through delivery, whichever comes later. Enrolled women in Arm 2 will 
be followed for 4 weeks after the last RDV infusion.  
 
Primary Objectives 
 
Arm 1: 
• 
To describe the pharmacokinetics of RDV and its metabolite, GS-441524, after administration to 
pregnant women as part of clinical care.  
• 
To describe the clinical and laboratory safety outcomes through four weeks post-last infusion and 
during delivery in pregnant women receiving RDV as part of clinical care.  
 
Secondary Objectives 
 
Arm 2:  
• 
To describe the pharmacokinetics of RDV and its metabolite, GS-441524, after administration to non-
pregnant women of childbearing potential as part of clinical care. 
• 
To describe the clinical and laboratory safety outcomes through four weeks post-last infusion in non-
pregnant women of childbearing potential receiving RDV as part of clinical care.  
 
 

IMPAACT 2032, FINAL Version 2.0 
  
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 18 December 2020 
 
Other Objectives 
 
Arm 1: 
• 
To describe RDV placenta transfer with collection of plasma and cord blood samples at delivery in 
mothers who have received a dose of RDV within the preceding 5 days. 
 
Arms 1 and 2: 
• 
To compare the pharmacokinetics of RDV and its metabolite, GS-441524, in pregnant women to 
those observed in non-pregnant women of childbearing potential. 
• 
To describe and compare intracellular concentrations of RDV’s active intracellular nucleotide 
triphosphate (GS-443902) in pregnant and non-pregnant women of childbearing potential receiving 
RDV as part of clinical care.  
• 
To  develop a population PK (PopPK) model of RDV and its metabolites in pregnant and non-
pregnant women receiving RDV and evaluate associations between clinical characteristics and RDV 
and GS-441524 pharmacokinetics. 
• 
To assess plasma protein binding of RDV in pregnant women and non-pregnant women of 
childbearing potential. 
• 
To describe the frequency of detection in breast milk and the relative concentrations in breast milk 
and plasma of RDV and GS-441524 in lactating women undergoing RDV PK sampling. 
 

IMPAACT 2032, FINAL Version 2.0  
  
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18 December 2020 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in Pregnant and Non-Pregnant Women in 
the United States 
 
Figure 1: Overview of Study Design 
 
   
 

IMPAACT 2032, FINAL Version 2.0 
  
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 18 December 2020 
 
 
INTRODUCTION 
 
1.1 
Background 
 
As of November 23, 2020, Centers for Disease Control and Prevention (CDC) received 12,175,921 
COVID-19 case reports for the United States (U)S since January 22, 2020. There were slightly more 
women (52%) than men (48%) included in these reports (1). The most recent tracking data from CDC 
includes 39,857 case reports of US pregnant women with COVID-19 received between January 22 and 
November 23, 2020, with 53 deaths and 8,284 hospitalizations, although these data did not distinguish 
between hospitalization for COVID-19 conditions from admissions for pregnancy-related indications, 
such as delivery. The race/ethnicity breakdown of the pregnancy COVID-19 cases was 37% Hispanic, 
35% White Non-Hispanic, 19% Black Non-Hispanic, 3%, Asian and 6% Multiple/Other (2). In an earlier 
MMWR publication describing the period between January 22 and June 7, 2020, CDC reported receiving 
notifications of 326,335 women of reproductive age (15–44 years) with positive SARS-CoV-2 test 
results. Of the 91,412 of these women with pregnancy data, 9% (8,207) were pregnant. Hospitalization 
was reported in 31.5% of pregnant women compared to 5.8% of nonpregnant women but the data did not 
distinguish between hospitalization for COVID-19 conditions from admissions for pregnancy-related 
indications, such as delivery. After adjusting for age, presence of underlying medical conditions, and 
race/ethnicity, pregnant women were significantly more likely to be hospitalized (aRR = 5.4, 95% 
confidence interval [CI] = 5.1-5.6), to be admitted to the intensive care unit (ICU) (aRR = 1.5, 95% CI =  
1.2–1.8) and to receive mechanical ventilation (aRR = 1.7, 95% CI = 1.2–2.4) than nonpregnant women 
(3). Increased need for intensive care during pregnancy has also been reported in Swedish women with 
COVID-19 (4). A review of published data on severe coronavirus infections in pregnancy reported 
adverse pregnancy outcomes, including maternal death, preterm delivery, stillbirth and neonatal death, as 
well as respiratory compromise requiring ICU care and mechanical ventilation, in pregnant women with 
COVID-19, although at lower frequency than with MERS-CoV and SARS-CoV-1 (5).   
 
Despite this reported incidence of severe COVID-19 in pregnant women associated with adverse 
pregnancy and maternal health outcomes, pregnant women are routinely excluded from participation in 
research protocols within COVID-19 drug development programs(6). The physiological changes 
associated with pregnancy can have a dramatic impact on drug disposition and use of therapeutic agents 
during pregnancy poses unique safety concerns(6). As a result, drugs cannot be used safely and 
effectively during pregnancy without their pharmacokinetics (PK) and safety being evaluated in pregnant 
women. Only a few of the many COVID-19 clinical treatment trials currently listed on clinicaltrials.gov 
include pregnant women(7). Those that do involved use of hydroxychloroquine, which has been used 
extensively in pregnant women for malaria treatment but is no longer recommended for routine use in 
treatment of COVID-19 due to a lack of proven efficacy in the presence of significant risk of major 
toxicity(8). 
 
Remdesivir (GS-5734TM) (RDV), a nucleotide prodrug originally developed for the treatment of Ebola 
virus disease and Marburg virus infections, is the first drug licensed for use against COVID-19, the 
disease caused by infection with SARS-CoV-2 virus(9). RDV has been shown to shorten time to recovery 
from severe COVID-19 (10-12). In an activation process analogous to that of tenofovir alafenamide 
(TAF) and sofosbuvir (SOF), RDV is metabolized to an intracellular nucleotide triphosphate which 
inhibits viral RNA polymerases. Now that RDV is licensed, hospitalized pregnant women with COVID-
19 can receive RDV part of clinical care; however, since all RDV research protocols excluded pregnant 
women there are no RDV pregnancy PK data and only limited RDV in pregnancy safety data from 
observational cohorts(13). 
 
The routine exclusion of pregnant women from drug development programs results in therapeutic agents 
typically being licensed for use in non-pregnant adults in the absence of pregnancy specific PK and safety 

IMPAACT 2032, FINAL Version 2.0 
  
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 18 December 2020 
 
data. As a result, these licensed drugs cannot be employed with evidence-based certainty as to their safety  
and efficacy in pregnant women until data are available from the requisite pregnancy PK and safety 
studies, which often require years to complete. Requisite PK and safety studies require years to complete. 
As an example, it took 3-5 years after licensure of cobicistat before its failure as an effective booster of 
elvitegravir and darunavir in pregnant women was recognized and warnings against its use in pregnancy 
were issued, during which time cobicistat was used routinely as part of clinical care for pregnant women 
living with HIV(6). A similar delay in the availability of pregnancy PK and safety data for drugs shown to 
be effective against COVID-19 would be tragic, given the incidence, acuity and observed severity of 
COVID-19 in pregnant women and the current paucity of proven effective therapies. 
 
1.2 
Clinical Pharmacology During Pregnancy 
 
RDV is the first drug with preliminary evidence of efficacy in COVID-19(14). RDV is a prodrug that 
requires several steps of metabolism to generate its active intracellular nucleotide triphosphate (NTP, GS-
443902), following a similar activation sequence as SOF (Figure 2). RDV is a monophosphoramidate 
prodrug of an adenosine analog that is made 
more lipophilic by the addition of alkyl-alanine 
and phenyl phosphate esters. RDV is rapidly 
converted by plasma and liver hydrolases to a 
nucleoside analog monophosphate. Inside cells 
the nucleoside analog monophosphate is rapidly 
converted to the active triphosphate form (GS-
443902), which competes with natural 
adenosine triphosphate (ATP) to selectively 
inhibit RNA-dependent RNA polymerase. 
Dephosphorylation of the nucleoside analog 
results in GS-441524, which is not as efficiently 
rephosphorylated as RDV. 
 
The in vitro EC50 against SARS-CoV-2 has 
been reported at 0.137 µM (83 ng/mL) and 0.77 µM (460 ng/mL) in Vero cells (11, 15). In a human lung 
epithelial cell line (Calu3), in vitro EC50s for RDV and GS-441524 were 0.28 uM (169 ng/mL),and 0.62 
uM (181 ng/mL) by plaque assay. RDV demonstrated greater potency in human airway epithelial cells 
with an EC50 of 0.01 uM (6 ng/mL), likely due 
to higher GS-443902 concentrations in HAE 
cells in comparison to the Calu-3 and Vero E6 
cell types. Due to poor hepatic stability, RDV 
should not be given orally as bioavailability is 
expected to be low. RDV PK data at the 
currently recommended doses for COVID-19 
treatment are primarily limited to healthy non-
pregnant adults studied in preparation for studies 
of RDV use against Ebola(16). See Table 1 
below for summary plasma PK parameters. In 
this study, Day 1 peak plasma concentrations 
after a 200 mg intravenous (IV) dose 
administered over 30 minutes were 9.0 µM 
(5440 ng/mL) for RDV and 0.5 µM (152 
ng/mL) for GS-441524. AUC0-24h were 4.8 µM-h (2920 ng*h/mL) for RDV and 7.7 µM-h (2240 
ng*h/mL) for GS-441524 (15). Sparse PK results in a 66 year old female and a 67 year old male with 
COVID-19 have also been detailed(17). Median peak RDV concentrations of 4.54 uM (2737 ng/mL) and 
Figure 3: Expected PK of Remdesivir and GS-441524 and 
the potential effect of pregnancy 
Figure 2: Remdesivir and sofosbuvir structure. 
0
24
48
72
96
120
144
Time (H)
1
10
100
1000
10000
Conc - ng/mL
Expected PK of Remdesivir and GS441542
Potential Effect of Pregnancy
Remdesivir
GS441542
NOT PREG
GS441542
PREG

IMPAACT 2032, FINAL Version 2.0 
  
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 18 December 2020 
 
5.50 uM (3317 ng/mL) were measured in each of these patients, respectively, on infusion Days 3-9. GS-
441524 AUC0-24h was 10.7 uM-h (3117 ng*h/mL) in the male patient, and 21.1 uM-h (6131 ng*h/mL) in 
the female patient, who had 1.96-fold higher levels due to underlying renal dysfunction.   
 
No accumulation of RDV occurred with multiple dosing, consistent with its measured half-life in plasma 
of just under 1 hour. Following single doses ranging from 3 – 225 mg IV, PK of GS-441524 were linear.  
GS-441524 reaches steady-state in 4 days and accumulated 1.9-fold based on AUC, consistent with its 
~24-hour half-life. The intracellular phosphorylated metabolite GS-443902 has a median half-life of 
32.23 to 48.38 hours. Renal and biliary excretion were the major routes of elimination in rats and 
monkeys.(15) In the mass balance study, mean total recovery of the dose was greater than 92%, 
consisting of approximately 74% recovered in urine and 18% recovered in feces. The majority of the IV 
RDV dose recovered in urine was the GS-441524 metabolite (49%) followed by RDV (10%) and other 
metabolites(18). The impact of pregnancy on hydrolase activity and RDV PK is unknown. A simulation 
from modelling based on pregnancy PK data for other renally eliminated drugs is presented in Figure 3 
(19-22). The modelling and simulation suggest that increased glomerular filtration rate (GFR) and renal 
tubular secretion associated with pregnancy will increase GS-441524 elimination. Because RDV is 88-
94% protein bound, while its metabolites are only 1-2% protein bound (9), pregnancy related changes in 
plasma protein concentrations due to volume expansion and drug displacement from protein binding sites 
may also affect unbound RDV concentrations. 
 
Table 1. Plasma PK Parameters of RDV and GS-441524 Following 30-minute IV Infusion(s) of RDV 200 mg on 
Day 1 and 100 mg Daily on Days 2-5 in Healthy Adults (Preliminary Analysis)(15) 
 
Cmax and AUC summarized as geometric mean (CV%); t1/2 summarized as median (Q1, Q3) 
 
RDV is currently licensed for use in adults and pediatric patients (12 years of age and older and weighing 
at least 40 kg) for the treatment of coronavirus disease 2019 (COVID-19) requiring hospitalization(9). 
The only RDV PK data currently available are from healthy non-pregnant adult volunteers, for which 
results by sex were not detailed, and sparse PK results from two patients with COVID-19(9, 16, 17). No 
data describing RDV PK in pregnant women or non-pregnant women with COVID-19 are available. 
Clinical data with RDV use in pregnancy are limited to the experience of 6 pregnant women in the 
Democratic Republic of Congo who received RDV as Ebola treatment and 67 pregnant and 19 
postpartum women who received remdesivir for COVID-19 under the Gilead compassionate use 
protocol(13, 23). Remdesivir was well tolerated by the pregnant women treated for Ebola (23).  The 
pregnant and postpartum women who received RDV for COVID-19 under the Gilead compassionate use 
protocol all had room air oxygen saturation 94% or lower. There was one spontaneous miscarriage and 
one postpartum women who died but no pregnant woman or live born infant died. None of the pregnant 
women developed gestational hypertension or pre-eclampsia. Ninety three percent of pregnant women 
and 89% of postpartum women recovered from COVID-19.  Serious adverse events (SAEs) were 
observed in 29% of women, including deep vein thrombosis, hypertension, hypoxia and pleural effusion. 
Elevations of laboratory parameters were common, occurring in 67% (13). 
PK Parameter 
Remdesivir 
GS-441524 
Day 1 (n=8) 
Day 5 (n=7) 
Day 1 (n=8) 
Day 5 (n=7) 
Cmax (ng/mL) 
5440 (20.3) 
2610 (12.7) 
152 (25.9) 
142 (30.3) 
AUC (hr*ng/mL) 
2920 (20.6) 
1560 (13.9) 
2240 (29.1) 
2230 (30.0) 
T1/2 (h) 
0.98 (0.82, 1.03) 
0.89 (0.82, 1.09) 
NA 
25.3 (24.10, 30.32) 

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The use of RDV in pregnant women in the absence of PK and safety data places pregnant women 
receiving RDV at risk for both inadequate therapeutic response and unrecognized maternal toxicity 
including adverse pregnancy outcomes.  
 
1.3 
Rationale 
 
Although pregnant women are routinely excluded from COVID-19 experimental treatment protocols, the 
care providers of pregnant women who develop severe COVID-19 are treating them with potential 
therapies in the absence of pregnancy specific PK and safety data and outside of research protocols. 
Under these circumstances, the fastest way to get the urgently needed RDV pregnancy PK and safety data 
is through an opportunistic RDV PK and safety protocol in pregnant women receiving RDV as part of 
clinical care. IMPAACT 2032 will follow the opportunistic design of the highly successful IMPAACT 
P1026s study which between 2004 and 2019 performed intensive PK sampling and safety evaluations for 
HIV and TB therapeutics in over 1000 pregnant and postpartum women,  successfully evaluating the PK 
and safety of over 25 different HIV and TB medications in pregnant and postpartum women. Because of 
the duration of treatment of HIV and TB, participants in IMPAACT P1026s were studied both during 
pregnancy and postpartum, serving as their own controls. This approach is not possible with RDV, which 
has a treatment duration of 5-10 days. As a result, women treated during pregnancy will generally not be 
receiving the drug postpartum. Under these circumstances the best comparison group for PK and safety 
data from pregnant women would be data from non-pregnant adult women of childbearing potential. 
Since such data are lacking for RDV, IMPAACT 2032 will also simultaneously enroll and study RDV PK 
and safety in a cohort of COVID-19 positive, non-pregnant women of childbearing potential. These non-
pregnant participants will provide the first data describing RDV PK and safety in women receiving RDV 
for COVID-19 and will serve as a comparison group for the IMPAACT 2032 pregnant women.  
 
The recent recognition of the acuity and severity of COVID-19 in pregnant women mandates rapid 
development of a streamlined protocol that can be implemented with minimal delay to provide the critical 
RDV pregnancy specific PK and safety data needed to allow RDV to be used safely and effectively in 
pregnant women. This protocol was designed with recognition of the challenges posed by performing a 
research protocol on hospitalized participants acutely ill with COVID-19 during an ongoing and rapidly 
changing pandemic. Priority has been given to obtaining the urgently needed pregnancy RDV PK and 
safety data as quickly as possible through protocol activities that pose the least risk of violating RDV 
infection control measures, to avoid putting clinical staff, research staff and other hospital patients at 
increased risk of  SARS-CoV-2 infection. The protocol team has endeavored to develop a protocol that 
will acquire RDV PK and safety data in pregnant women as quickly, efficiently and safely as possible 
under these challenging conditions. The team has elected to design the study to facilitate ease and 
practicality of implementation and to focus on acquiring only those data necessary to provide an initial 
evidence base for the use of RDV in pregnant women. This approach is reflected in many aspects of the 
protocol, including the eligibility criteria, participant data collection procedures, PK sampling and 
analysis approach, and duration of follow up. 
 
IMPAACT 2032 will provide critical RDV PK and safety data in women, allowing evaluations of 
exposure of RDV and its metabolites in both pregnant and non-pregnant adult women and of RDV safety 
when used in these populations. This protocol will provide urgently needed RDV PK and safety data in 
women with COVID-19, providing evidence necessary to ensure that RDV can be used safely and 
effectively in both pregnant and non-pregnant women of childbearing potential. 
 
 

IMPAACT 2032, FINAL Version 2.0 
  
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OBJECTIVES 
 
2.1 
Primary Objectives 
 
The primary objectives of this study are to:  
 
 
Arm 1: Describe the pharmacokinetics of RDV and its metabolite, GS-441524, after 
administration to pregnant women as part of clinical care.  
 
 
Arm 1: Describe the clinical and laboratory safety outcomes through four weeks post-last 
infusion and during delivery in pregnant women receiving RDV as part of clinical care.  
 
2.2 
Secondary Objectives 
 
The secondary objectives of this study are to:  
 
 
Arm 2: Describe the pharmacokinetics of RDV and its metabolite, GS-441524, after 
administration to non-pregnant women of childbearing potential as part of clinical care. 
 
 
Arm 2: Describe clinical and laboratory safety outcomes through four weeks post-last 
infusion in non-pregnant women of childbearing potential receiving RDV as part of 
clinical care.  
 
2.3 
Other Objectives 
 
The other objectives of this study are to:  
 
 
Arm 1: Describe RDV placenta transfer with collection of plasma and cord blood 
samples at delivery in mothers who have received a dose of RDV within the preceding 5 
days. 
 
 
Arms 1 and 2: Compare the pharmacokinetics of RDV and its metabolite, GS-441524, in 
pregnant women to those observed in non-pregnant women of childbearing potential. 
 
 
Arms 1 and 2: Describe and compare intracellular concentrations of RDV’s active 
intracellular nucleotide triphosphate (GS-443902) in pregnant and non-pregnant women 
of childbearing potential receiving RDV as part of clinical care.  
 
 
Arms 1 and 2: Develop a population PK (PopPK) model of RDV and its metabolites in 
pregnant and non-pregnant women receiving RDV and evaluate associations between 
clinical characteristics and RDV and GS-441524 pharmacokinetics. 
 
 
Arms 1 and 2: Assess plasma protein binding of RDV in pregnant women and non-
pregnant women of child-bearing potential. 
. 
 
Arms 1 and 2: Describe the frequency of detection in breast milk and the relative 
concentrations in breast milk and plasma of RDV and GS-441524 in lactating women 
undergoing RDV PK sampling. 
 

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STUDY DESIGN 
 
This is a Phase IV prospective, open label, non-randomized opportunistic study to evaluate the 
PK and safety of RDV when administered to pregnant and non-pregnant women of childbearing 
potential for treatment of COVID-19. RDV is not provided as part of this study; a requirement for 
entry is that participants receive RDV as part of their clinical care (i.e., outside of the study). 
Participation in this study will have no effect on the cost of care for treatment of COVID-19 or 
the cost of any RDV received for clinical care. Information on patient support for access to RDV 
can be found at https://www.vekluryhcp.com/patient-support/. As no investigational drug is being 
provided to study participants, the study is opportunistic in nature and clinical care decisions are 
made outside the context of this study, and as the Division of AIDS (DAIDS) at the US National 
Institutes of Health (NIH), as the study sponsor, is not charging for use of RDV in the context of 
this study, 21 CFR 312.8 is not applicable to this study.     
 
A target of 20 PK evaluable pregnant women will be enrolled into Arm 1; a target of 20 PK 
evaluable non-pregnant women of childbearing potential will be enrolled into Arm 2. See Section 
10.2 for a definition of PK evaluable. Refer to Sections 4.1 through 4.3 for the eligibility criteria 
and to Section 4.5 for a description of the recruitment, screening and enrollment process. Study 
sites will be located in the United States.  
 
Participants will be pregnant and non-pregnant women hospitalized for COVID-19 and will 
receive daily RDV infusions, typically for 5 days but in some cases for up to 10 days, as part of 
their clinical care. RDV will be provided and managed by the participants’ treating physician and 
will not be provided as a part of this study. Women may be enrolled prior to starting RDV or after 
starting RDV but must be enrolled prior to the start of the 4th infusion. Participants will undergo 
intensive PK sampling on the day of the 3rd, 4th, or 5th infusion (at site discretion), as described in 
Section 6.4.1. Protein binding capacity of RDV will also be assessed ex vivo from the pre-dose 
intensive PK sample. Participants will also undergo collection of single PK samples with standard 
of care (SOC) labs drawn on the days of the 2nd, 3rd, 4th, and 5th infusions (with the exception of 
the day of intensive PK sampling), and also at 48 hours after the last infusion, as described in 
Section 6.4.2. For Arm 1 participants, maternal and cord blood PK sampling will be performed at 
delivery for a comparison of maternal and fetal plasma RDV concentrations if the participant 
received RDV infusion within the preceding 5 days. Additionally, for women in both Arms who 
are lactating, and who consent  to this sample collection, an optional breast milk sample may be 
collected on the intensive PK sampling day and at 48-hours after the last RDV infusion, to assess 
breast milk concentrations of RDV and its metabolites.  
 
For all women, clinical and laboratory evaluations will be abstracted from the medical record. 
Pregnancy, birth, and infant outcomes will be obtained from pregnant women enrolled in Arm 1. 
See Appendix I and Section 6 for additional details. Arm 1 and Arm 2 participants will be 
followed through 4 weeks after the last infusion of RDV; Arm 1 women who are still pregnant at 
that time will have additional follow-up at the time of delivery. 
 
 

 
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STUDY POPULATION 
 
This study will be conducted among hospitalized pregnant and non-pregnant women receiving 
RDV infusion for treatment of COVID-19 as part of their clinical care (i.e., not as part of this 
study). Women will be assessed for eligibility per the criteria specified in Sections 4.1 through 
4.3, and the requirements in Section 4.4. The study-specific approach to recruitment, screening, 
and enrollment is described in Section 4.5. Considerations related to participant retention and 
withdrawal/discontinuation from the study are provided in Sections 4.6 and 4.7, respectively. 
 
4.1 
Inclusion Criteria – Arm 1 (Pregnant Women) 
 
Women must meet all of the following inclusion criteria to be enrolled in Arm 1.  
 
 
Of legal age or otherwise able to provide independent informed consent as determined by 
site SOPs and consistent with all applicable IRB policies and procedures, and is willing 
and able to provide informed consent for her own participation in this study. 
 
 
Or  
 
 
Of legal age to provide independent informed consent but is unable to provide informed 
consent (e.g. impaired capacity, as determined by site SOPs and consistent with all 
applicable IRB policies and procedures) and a Legally Authorized Representative (LAR) 
is willing and able to provide written informed consent on behalf of the participant in 
accordance with 21 CFR 50.27. 
 
Note: All sites must follow the policies and procedures of all applicable IRBs; this 
includes single IRB (sIRB) policies and procedures. Refer to Section 13.1 for more 
information on sIRB oversight.  
 
 
At study entry, viable intra-uterine pregnancy of any gestational age, based on medical  
records. 
 
 
At study entry, hospitalized AND has confirmed or suspected COVID-19, based on 
medical records.  
 
 
At study entry, receiving or expected to receive RDV for COVID-19 clinical care, as 
prescribed by the clinical care provider and documented in medical records. 
 
Note: The study investigator or designee will confirm that a potential study participant is 
receiving or expected to receive RDV based on information in the medical record. 
 
4.2 
Inclusion Criteria – Arm 2 (Non-Pregnant Women) 
 
Women must meet all of the following inclusion criteria to be enrolled in Arm 2.  
 
 
Of legal age or otherwise able to provide independent informed consent as determined by 
site SOPs and consistent with all applicable IRB policies and procedures, and is willing 
and able to provide informed consent for her own participation in this study. 
 
 
Or  

 
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Of legal age to provide independent informed consent but is unable to provide informed 
consent (e.g. impaired capacity, as determined by site SOPs and consistent with all 
applicable IRB policies and procedures) and a LAR is willing and able to provide written 
informed consent on behalf of the participant in accordance with 21 CFR 50.27. 
 
Note: All sites must follow the policies and procedures of all applicable IRBs; this 
includes sIRB policies and procedures. Refer to Section 13.1 for more information on 
sIRB oversight.  
 
 
At study entry, between 18 and 45 years of age, based on medical records and participant 
report.  
 
 
Assigned female at birth and at study entry not taking cross-sex hormone therapy.  
 
 
At study entry, not suspected to be pregnant, based on participant report and/or 
investigator or designee determination. 
 
 
At study entry, hospitalized AND has confirmed or suspected COVID-19, based on 
medical records.  
 
 
At study entry, receiving or expected to receive RDV for COVID-19 clinical care, as 
prescribed by the clinical care provider and documented in medical records. 
 
Note: The study investigator or designee will confirm that a potential study participant is 
receiving or expected to receive RDV based on information in the medical record. 
 
4.3 
Exclusion Criteria – Arms 1 and 2 
 
Women who meet any of the following criteria will be excluded from enrolling in this study: 
 
4.3.1 
At study entry, has started or received the 4th RDV infusion.  
 
4.3.2 
At study entry, evidence of post-menopausal status (medical or surgical), based on 
medical records and/or participant report. 
 
4.3.3 
At study entry, any contraindications to RDV treatment for COVID-19, based on 
investigator or designee determination.  
 
4.3.4 
Received or administered any disallowed medications listed in Section 5.4 within 48 
hours prior to study entry.  
  
4.3.5 
At study entry, has any other condition, that, in the opinion of the site investigator or 
designee, would make participation in the study unsafe, complicate interpretation of 
study outcome data, or otherwise interfere with achieving study objectives. 
 
4.4 
Co-Enrollment Considerations 
 
Co-enrollment in this study and other studies is permitted without prior approval of the Protocol 
Team, as long as requirements of both studies can safely be met and blood draw maximums will 

 
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not be exceeded (see Section 6.8.1). All investigational agents must be documented as 
concomitant medications (see Section 5.3). 
 
4.5 
Recruitment, Screening, and Enrollment Process 
 
RDV is an approved drug for treatment of COVID-19 in adults and pediatric patients requiring 
hospitalization, who are 12 years of age or older and who weigh at least 40 kg. Recruitment 
methods for this study may vary across sites but are expected to rely on identification of pregnant 
and non-pregnant women hospitalized for COVID-19 in a facility that is affiliated with an 
IMPAACT clinical research site and who recently initiated treatment with RDV or who may 
require treatment with RDV. Clinical research site staff will work with local care providers to 
identify hospitalized pregnant and non-pregnant women with COVID-19.  
 
Due to COVID-19 infection control measures, hospitalized pregnant and non-pregnant women 
are expected to be in isolation. Additionally, participants may be incapacitated and determined, 
per site-specific SOPs and sIRB or other institutional, state, or local guidelines, to be unable to 
provide independent consent for themselves. Site staff must ensure that information about the 
study is provided to the potential participant or her LAR (as applicable) including detailed review 
of the study informed consent form, time to address any questions or concerns the potential 
participant or LAR may have, and an assessment of understanding, before proceeding to informed 
consent decision. Refer to Section 13.3 for further information on informed consent procedures 
for this study, including allowable consenting options in the context of COVID-19. The informed 
consent process will be conducted in accordance with sIRB and other institutional and local 
policies and procedures, and fully documented consistent with the NIAID DAIDS policies 
referenced in Section 11.2 and with 45 CFR 46.117.  
 
Eligibility screening will be initiated after informed consent is provided. Screening evaluations 
must be completed prior to enrollment. Screening evaluations may be performed up to and on the 
day of enrollment; however, all required screening outcomes must be available prior to 
enrollment.  
 
Each site must establish SOPs for eligibility determination that describe where and when 
screening procedures will be performed; roles and responsibilities for performing the required 
procedures; roles and responsibilities for assessing and confirming eligibility; and procedures for 
documenting the process, taking into consideration the required timing of entry.  
 
Prior to enrollment, and after informed consent is obtained, sites will assign a participant 
identification number (PID) to the participant. The IMPAACT Data Management Center (DMC) 
Subject Enrollment System (SES) will be used to enroll participants in this study. For women 
found to be eligible, enrollment will occur upon successful entry of required eligibility data into 
the SES. Successful entry into the SES will generate a study identification number (SID), for each 
enrolled participant. Refer to Section 9.5 for more information on monitoring participant accrual 
in this study.  
 
For Arm 1, only maternal participants will be enrolled in the study; fetuses/infants will not be 
enrolled. However, as some limited data will be collected on infant outcomes at birth as well as 
newborn physical exam findings, participants will be asked to provide consent for data collection 
on their infants, as described in the sample consent forms in Appendix II. PIDs will not be 
assigned to infants and these data will be collected on maternal eCRFs. 
 

 
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4.6 
Participant Retention 
 
Once a participant is enrolled in this study, study staff will make every effort to retain her for the 
protocol-specified duration of follow-up, thereby maximizing evaluability and statistical power 
and minimizing potential biases associated with loss to follow-up. Study sites are responsible for 
developing and implementing local procedures to reach this goal. Refer to Section 9.5 for more 
information on monitoring participant retention in this study. 
 
4.7 
Participant Withdrawal or Discontinuation from the Study 
 
Regardless of the participant retention procedures referenced above, participants or their LAR 
may voluntarily withdraw from the study. Participants may also be discontinued from study 
participation by the site investigator or designee under the following circumstances: 
 
• 
Investigator or designee determines that continued participation in the study would be unsafe 
or otherwise not in the best interest of the participant, after consultation with the Clinical 
Management Committee (CMC). 
• 
The study is stopped or canceled by the sponsors, government or regulatory authorities, or the 
sIRB.  
• 
Site participation in the study is cancelled by the sponsors, government or regulatory 
authorities, or the sIRB.  
• 
The participant does not initiate RDV within 7 days from study entry.   
 
For any participant who withdraws or is discontinued from the study prior to scheduled 
completion of follow-up, study staff will document the reason for the withdrawal or 
discontinuation in detail and enter the reason into the appropriate eCRF. No final evaluations are 
required in the case of early study discontinuation or withdrawal.  
 
 
 
DRUG UNDER STUDY  
 
No study drug is provided as a part of this study. The drug being evaluated in this study is 
remdesivir (RDV) (GS-5734TM) and is referred to as the “drug under study.” RDV will not be 
supplied as part of this study. RDV is approved by the FDA and is expected to be accessed by 
hospitals via existing drug distribution pathways external to the study and will be administered by 
the treating physician consistent with the prescribing information.   
 
The RDV Prescribing Information is  available at:  
https://www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_pi.pdf 
 
5.1 
Remdesivir Formulations 
 
RDV is available in two different formulations: lyophilized powder for reconstitution (100 mg) 
and premixed injection solution 5mg/mL (100 mg). RDV should be stored consistent with details 
as provided by the non-study sources who supply the drug to the participants. The formulation 
administered to each participant at each infusion will be captured on eCRFs as described in 
Section 6.4. 
 

 
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5.2 
Dose, Preparation and Administration 
 
RDV should be prepared and administered consistent with details as provided in the prescribing 
information. The standard dosage of RDV is a single loading dose of 200 mg infused 
intravenously over 30 to 120 minutes on Day 1 followed by once-daily maintenance doses of 100 
mg infused intravenously over 30 to 120 minutes for up to 10 infusions (30 minute infusion 
administration is recommended where possible). Based on the prescribing information, it is 
expected that participants who do not require invasive mechanical ventilation or extracorporeal 
membrane oxygenation (ECMO) will receive a 5-day course of treatment, and participants 
requiring invasive mechanical ventilation or ECMO will receive a 10-day course of treatment; 
however, treatment may be discontinued early in either case as determined by the treating 
physician. After an infusion is complete, at least 30 mL of 0.9% saline will be used to flush the 
line. The prepared diluted solution will not be administered with any other medications. The 
compatibility of RDV injection with IV solutions and medications other than saline is not known. 
The dose and volume administered to each participant at each infusion will be captured on eCRFs 
as described in Section 6.4. 
 
5.3 
Concomitant Medications  
 
The term concomitant medications refers to medications (prescription and non-prescription as 
well as other investigational agents) other than RDV received by enrolled participants. All 
concomitant medications must be source documented; a subset of concomitant medications will 
be entered into eCRFs as part of the medical and medication histories obtained at data collection 
timepoints as described in Section 6. 
 
RDV is rapidly metabolized by hydrolases to a nucleotide monophosphate, which can be further 
phosphorylated to the active triphosphate form, or dephosphorylated to GS-441524. GS-441524 
is predominantly eliminated renally and does not affect common drug metabolism pathways. It is 
not anticipated that RDV will impact the PK of other medications. However, RDV is a substrate 
for P-glycoprotein and OATP1B1 and its transport may be affected by inducers or inhibitors of 
these transporters. PK results will be carefully evaluated in relation to concomitant medications 
during data analysis.  
 
5.4 
Disallowed Medications at Entry 
 
Due to potential interactions with RDV or the formation of its active triphosphate metabolite, GS-
443902, the following medications are exclusionary if taken or administered within 48 hours prior 
to entry: carbamazepine, hydroxychloroquine, chloroquine, oxcarbazepine, phenobarbital, 
phenytoin, rifampin, rifapentine, rifabutin, ritonavir, St. John’s wort.  
 
 
 
STUDY PROCEDURES AND DATA COLLECTION REQUIREMENTS 
 
An overview of study procedures including PK sampling, blood volumes and data collection 
requirements are presented in the Schedule of Evaluations (SOE) in Appendix I. Presented in this 
section is additional information on study procedures and data collection requirements for each 
study period as follows: baseline, infusion, safety-follow-up, and delivery (for women enrolled in 
Arm 1).  
 

 
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Because study participants will be hospitalized with COVID-19 at study entry and while 
receiving RDV infusions, and given COVID-19 infection control measures, IMPAACT 2032 
study staff are expected to have limited contact with study participants. The treating physician 
(not affiliated with the study) is responsible for RDV management and clinical care. Study 
procedures for this study are limited to data collection and blood specimens for PK. The study 
procedures described in this section are the responsibility of the IMPAACT 2032 study staff. 
With the exception of PK sampling, study procedures will largely be done via medical chart 
abstraction and/or remote contact or telemedicine visit. Refer to Section 10 for more details on 
PK design and analysis. Refer to the IMPAACT 2032 Laboratory Processing Chart (LPC) for 
collection, processing, and shipping instructions for PK samples. 
 
All procedures must be performed at the approved clinical research site or approved associated 
facilities. All procedures must be documented in accordance with the DAIDS policies for source 
documentation; refer to Section 11 for more information on documentation requirements and 
entry of eCRFs. Refer to Section 7 for information on expedited adverse event (EAE) reporting, 
which may be required at any time during follow-up. 
 
In addition to the protocol-specified procedures described in this section and the SOE Appendix, 
study staff may complete other tasks consistent with site SOPs, including but not limited to 
collecting, reviewing, and updating demographic and locator information; reviewing elements of 
informed consent; and providing instructions for contacting study staff. All such tasks should be 
documented consistent with site SOPs. 
 
6.1 
Data Collection Requirements 
 
Collection of clinical and laboratory data is required throughout the study beginning at 48 hours 
before the first infusion and continuing through 4 weeks after the last infusion. Additionally, data 
will be collected at the time of delivery for participants in Arm 1, and limited data will also be 
collected from the birth and newborn exam records of their infants. The specific data collection 
requirements are described in each sub-section below specific to each time period. All 
information should be obtained based on available medical records or remote or telemedicine 
visit, in order to minimize physical contact with the participant. Data abstraction and reporting 
should be targeted to occur as close as possible to the data collection timepoint indicated in the 
SOE; for the infusion time period in particular, sites are encouraged to key data each day that 
infusions are administered, if possible.  
 
Documented medical conditions will be assessed for severity as described in Section 7.2.1, and 
new conditions occurring after infusions begin will also be assessed for relationship to RDV as 
described in Section 8. Relevant dates will be recorded for all conditions and medications.  
 
Abnormal findings identified prior to initiation of RDV infusions will be entered into medical 
history eCRFs, and abnormal findings identified after initiation of RDV infusions will be entered 
into adverse events eCRFs. Administration of RDV will be recorded on an Infusion Treatment 
Log eCRF and use of concomitant medications in the time periods specified below will be 
recorded on the Concomitant Medication Log eCRF. Laboratory test results will be recorded on 
laboratory eCRFs as specified in Section 6.  
 
6.2 
Screening/Entry  
 
Refer to Section 4.5 for a description of the study recruitment, screening, and enrollment process.  
 

 
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Screening procedures may be performed at any point after hospitalization and COVID-19 
diagnosis (or presumed diagnosis), up to and including the day of enrollment. Participants or their 
LAR (as applicable) must provide consent before any activities are performed to determine 
eligibility. See Section 13.3 for more information on the informed consent process. For potential 
participants who do not meet the eligibility criteria, screening should be discontinued once 
ineligibility is determined.  
 
Entry may occur at any time after hospitalization and prior to the start of the 4th RDV infusion. 
Entry should be targeted for prior to or as close to the start of RDV infusions as possible. 
Women who are enrolled but do not initiate RDV within 7 days of entry will be discontinued 
from the study per Section 4.7.  
 
Procedures that may provide information relevant to eligibility for the study should be performed 
first, prior to final eligibility determination. Final eligibility determination must precede 
enrollment. In the event that a woman is found to be ineligible on the day of enrollment, 
enrollment should not occur.  
 
Screening and entry procedures include the following:   
 
• Obtain informed consent  
• Assign PID to woman 
• Obtain participant medical records  
• Document eligibility requirements and demographics in SES 
• Complete final eligibility determination and confirmation (Entry visit only, prior to 
enrollment) 
• Complete paper-based eligibility checklist, enter checklist data into SES to enroll the woman, 
print and file a copy of the confirmation file (Entry visit only) 
• Complete Visit Tracking eCRF 
 
6.3 
Pre-infusion  
 
The Pre-infusion period is defined as 48-hours priors to initiation of RDV infusions for COVID-
19. Clinical and laboratory data will be collected per Table 2 for this time period (unless alternate 
time period is specified for specific data elements). If Screening/Entry occurs within or after 48-
hours prior to the first RDV infusion, the clinical and laboratory data for the Pre-infusion period 
will be collected retrospectively after study entry.  
 
Table 2: Data Collection Requirements for Pre-infusion Period 
Evaluation 
 
Enter into eCRFs or SES 
Medical History  
Record the following as available in the medical records: 
• 
All medical conditions of any grade occurring or ongoing within 48 
hours prior to the first infusion of RDV. These will be considered pre-
existing conditions and unrelated to RDV. 
• 
Arm 1: Major obstetrical diagnoses during the current pregnancy prior 
to start of RDV infusions  
• 
Arm 1: Gestational age at 48 hours prior to first infusion. 
• 
Arm 1: Prior pregnancy information (number and dates of prior 
pregnancies, outcome of prior pregnancies) 
• 
Last menstrual period  

 
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Evaluation 
 
Enter into eCRFs or SES 
• 
Hospitalization for COVID-19 (COVID-19 status at hospitalization, 
COVID-19 symptoms onset date, hospitalization onset date, discharge 
date) 
Concomitant 
Medications 
 
Record the following medications available in the medical records 
EXCEPT RDV:  
• 
All prescription medications 
• 
Blood products and transfusions 
• 
All investigational drugs 
Vital Signs 
Record the following measurements that are available in the medical 
records: 
• 
Record only once: 
o Height  
o Weight  
• 
Record the most abnormal measurement in a 24-hour period: 
o Highest systolic blood pressure  
o Temperature  
o Pulse rate 
o Pulse oximetry  
Respiratory Status 
• 
Record the respiratory and/or ventilation status  
Laboratory Test 
Results 
For each of the following laboratory test results from tests conducted for 
clinical care and documented in the medical record: 
• 
Record the most recent results of any grade for each of the 
following 
o AST, ALT, alk phos, and bilirubin (direct and total)  
o Creatinine and estimated creatinine clearance and method of 
determination, and estimated GFR (eGFR) 
o CBC with differential and platelets 
o Coagulation factors (prothrombin time (PT), international 
normalized ratio (INR), partial thromboplastin time (PTT)) 
o COVID-19 test results (first positive result only) 
o All other laboratory results  
• 
Record the following results only once - at the time closest to the 
start of the first infusion either in the Pre-infusion or Infusion 
period:   
o Inflammatory markers (lactate dehydrogenase (LDH), 
procalcitonin, erythrocyte sedimentation rate (ESR), C-
reactive protein (CRP), high sensitivity (hs) CRP, D-dimer, 
ferritin, troponin I, hs troponin I) 
 
6.4 
Infusion Period 
 
The infusion period begins at the start of the first infusion and continues through the day of last 
infusion, regardless of the duration of RDV treatment. The procedures to be completed for this 
period include clinical and laboratory data collection per Table 3, and PK sampling as described 
below.  
 

 
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Note:  If a participant is enrolled after initiation of RDV infusions, the clinical and laboratory data 
should be abstracted retrospectively after study entry, starting with the Pre-infusion period and 
continuing through any portion of the Infusion period that has already passed.   
 
Table 3: Data Collection Requirements for Infusion Period 
Evaluation 
 
Enter into eCRFs  
Medical History 
and Medical 
Events 
Updates to any medical conditions that were previously ongoing, and 
occurrence of any new conditions available in the medical records, as 
follows: 
• 
Infusion reactions of any grade 
• 
All Grade 3 and higher events 
• 
All serious adverse events (SAEs) 
• 
Updates to hospitalization for COVID-19 
Concomitant 
Medications 
 
Record the following medications available in the medical records 
EXCEPT RDV:  
• 
All prescription medications 
• 
Blood products and transfusions 
• 
All investigational drugs 
Also record any modifications to medications previously recorded during 
this period.  
Vital Signs 
Record the following measurements available in the medical record, as 
follows: 
• 
Record only once, if not recorded in Pre-infusion period: 
o Height  
o Weight  
• 
Record the most abnormal measurement in a 24-hour period: 
o Highest systolic blood pressure  
o Temperature  
o Pulse rate 
o Pulse oximetry  
Respiratory Status 
• 
Record the respiratory and/or ventilation status 

 
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Evaluation 
 
Enter into eCRFs  
Laboratory Test 
Results 
Record highest grade daily result for each of the following available 
laboratory test results from labs drawn for clinical care and available in the 
medical records: 
• 
AST, ALT, alk phos, and bilirubin (direct and total) of any 
grade  
• 
Creatinine and estimated creatinine clearance of any grade and 
eGFR 
• 
Albumin 
• 
CBC with differential and platelets of any grade 
• 
Coagulation factors (PT, INR, PTT) 
• 
COVID-19 test results (first positive result only, if not 
reported in a previous data collection period) 
• 
All grade 3 or 4 other laboratory test results 
 
Record the following results only once - at the time closest to the start of 
the first infusion either in the Pre-infusion or Infusion period:   
• 
Inflammatory markers (LDH, procalcitonin, ESR, CRP,  hs 
CRP, D-dimer, ferritin, troponin I, hs troponin I) 
Remdesivir 
Treatment 
For EACH RDV infusion, from the first through the last infusion, record: 
• 
Infusion number 
• 
Date of infusion 
• 
Start time of infusion 
• 
Stop time of infusion 
• 
Formulation of RDV 
• 
Dose 
• 
Interruption or modifications of dose (stopped or slowed) 
• 
Anatomical location and side of infusion 
• 
Initial rate of infusion 
• 
Volume of infusion prepared and administered 
 
 
Intensive PK Sampling and Optional Breast Milk Sampling 
 
Intensive PK samples will be collected around either the 3rd, 4th, or 5th infusion. Sites may choose 
which infusion is most convenient for collection of the intensive PK samples. Intensive PK 
sample collection must be completed within a single dosing interval (i.e., specific timepoints may 
not be spread over different infusions). Intensive PK timepoints are shown in Table 4 below.  
 
RDV administration will begin after the pre-dose sample is drawn. PK samples should be 
collected from the opposite arm than the one used for infusion to prevent sample contamination. 
If not already in place, an intravenous catheter will be placed in an arm vein for serial blood 
collection. Plasma will be stored at each timepoint; additionally, PBMC and DBS will be isolated 
and stored from these samples at the pre-dose and 23-hour post-end of infusion (EOI) timepoints 
to assess intracellular concentrations of GS-443902. Additional blood volume  will be collected at 
the pre-dose sample to assess the protein binding capacity of RDV, and will be processed 
separately from the intensive PK plasma samples (see LPC). Plasma will also be isolated from the 
pre-dose sample for quantification of α1-acid glycoprotein (AAG). 
 

 
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For lactating women who have consented to provide a breast milk sample, an optional breast milk 
sample will be collected once on the intensive PK day, at either the EOI, 0.75-hour, 1.5-hour, 3-
hour, or 5-hour EOI PK timepoint (at site discretion). Breast milk must be collected within 90 
minutes after one of these timepoints. If the participant has consented to provide this sample but 
circumstances do not permit collection of the breast milk sample (e.g., breast pump not permitted 
in participant room due to infection control measures, participant too sick to express milk), 
collection of this sample may be omitted. The date and time of breast milk sample collection will 
be source documented and entered into eCRFs. See the LPC for processing instructions.  
 
A study staff member must be physically present for each PK sample collection timepoint; 
samples within each block may be collected either by a non-study clinical care provider under the 
supervision of the study staff, or by a study staff member (see Section 6.4.3). Due to the unique 
processing requirements of the specimens (see the LPC), PK sample collection has been 
organized into 4 suggested sample collection “blocks” which do not exceed 4 hours each. The 
IMPAACT 2032 study staff member is responsible for batch transporting specimens to the 
processing lab at the end of each block. Samples may be transported to the processing lab more 
frequently than at the end of each block if time, resources and infection control measures permit, 
as long as a study staff member is able to supervise PK sample collection at each timepoint.  
 
Table 4: Intensive PK Schedule and Volumes 
Suggested 
Sample 
Collection Block 
1 
2 
3 
4 
Timepoint 
Pre-
dose 
End of 
Infusion 
(EOI) 
0.75 hrs 
after EOI 
1.5 hrs 
after 
EOI 
3 hrs 
after 
EOI 
5 hrs 
after EOI 
7 hrs 
after 
EOI 
23 hrs 
after EOI 
Plasma 
Volume 
8 mL* 
2 mL 
2 mL 
2 mL 
2 mL 
2 mL 
2 mL 
2 mL 
PBMC 
Volume 
8 mL 
n/a 
n/a 
n/a 
n/a 
n/a 
n/a 
8 mL 
DBS Volume 
1 mL 
n/a 
n/a 
n/a 
n/a 
n/a 
n/a 
1 mL 
AAG 
X# 
 
 
 
 
 
 
 
Breast milk 
(optional) 
n/a 
[5 
mL]^ 
[5 
mL]^ 
[5 
mL]^ 
[5 
mL]^ 
[5 
mL]^ 
n/a 
n/a 
Window 
-1 hr 
+/- 15 
mins 
+/- 15 
mins 
+/- 15 
mins 
+/- 15 
mins 
+/- 30 
mins 
+/- 30 
mins 
+/- 1 hr 
*6 mL to be processed for protein binding studies (see LPC) 
#Plasma for AAG to be isolated from the DBS blood sample 
^ Breast milk to be collected once, at one timepoint only (at site discretion), and only from women who are 
lactating and have consented to providing this sample. 5 mL is the optimal sample size, but any volume 
>0.5 mL will be accepted.  
 
Refer to the study-specific Manual of Operations (MOP) for additional PK sample collection 
procedures. Specific processing instructions for samples at each timepoint are detailed in the 
LPC.  
 
The timing, dose, formulation and duration of each infusion will be source documented and 
entered into eCRFs as described in Table 4. The date and time of PK sample collection, and the 
anatomical location of blood draw, will also be source documented and entered into eCRFs.  
 

 
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Single Plasma PK Sampling with Standard of Care Labs 
 
A convenience single plasma PK sample will be collected on infusion days 2 through 5, as 
feasible, ideally whenever blood samples are drawn as part of clinical care for standard of care 
(SOC) labs. If possible, a Pre-infusion blood draw should be targeted for this sample collection. 
This sample should be omitted on the day of intensive PK sampling. If no blood samples are 
drawn for clinical care on a particular day, then the single PK sample may be collected by itself if 
circumstances permit; if circumstances do not permit, this sample collection may be omitted for 
that day. Single PK specimens are also subject to the unique PK specimen processing 
requirements (see the LPC). See the LPC for additional instruction. The date and time of PK 
sample collection will also be source documented and entered into eCRFs.  
 
 
PK Sampling Supervision by IMPAACT 2032 Study Staff 
 
As described above in Section 6, while the IMPAACT 2032 study staff  may not actually collect 
the PK samples, they are ultimately responsible for the samples and for ensuring samples are 
collected and processed in accordance with the IMPAACT 2032 protocol and procedures. Study 
staff must be present for the entire duration of PK sample collection, are responsible for all data 
collection around PK sampling, and must provide direct supervision to any clinical care providers 
who collect the PK samples. If PK sampling cannot be performed by the IMPAACT 2032 study 
staff given COVID-19 infection control measures, PK sampling must be done by a non-study 
clinical care provider under direct supervision of the IMPAACT 2032 study staff. Blood draws 
will be done by the non-study clinical care provider in accordance with hospital standard policies 
and procedures for phlebotomy. Individuals collecting specimens from COVID-19 infected 
participants and all research personnel involved in the study will strictly follow local hospital 
institutional standard operating procedures for infection control.  
 
Direct supervision of clinical staff by research staff for PK sampling should be conducted through 
real-time video or in-person visual observation of the procedures, while allowing the study staff 
member to maintain physical distance from the participant and avoiding the need for personal 
protective equipment that may be in short supply. The IMPAACT 2032 study staff are 
responsible for ensuring samples are collected in the appropriate tubes at the appropriate 
timepoints, tubes are labeled correctly, and specimens are processed per protocol. Sites must 
determine the best process for interacting with and supervising the non-study clinical care 
providers for successful completion of PK sampling.  
 
6.5 
Safety Follow-up Period (48-Hour, 7-Day and 4-Week Post-Last Infusion) 
 
The Safety Follow-up period begins from the first day after the last RDV infusion and continues 
for 4-weeks after the last RDV infusion. The last infusion may be the 5th infusion, or may be an 
infusion earlier (if RDV was discontinued by the treating physician), or an infusion between 5 
and 10 days depending on the treatment course for the participant. The procedures for this period 
include clinical and laboratory data collection per Table 5, as well as collection of one single PK 
sample, and optional collection of breast milk in lactating women at 48-hours after the last 
infusion.   
 
This period is divided into three data collection timepoints: 48-Hour, 7-Day, and 4-Week Post 
Last Infusion. In addition to chart abstraction, telemedicine visits may be used to obtain and/or 
supplement or clarify medical history information after the participant has been discharged from 
the hospital. At each data collection timepoint, a data lookback will take place beginning from the 

 
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first day after the end of the prior data collection timepoint until the current data collection 
timepoint; only the data elements specified in Table 5 for that data collection timepoint period 
will be recorded on eCRFs.  
 
For Arm 1 participants who deliver within the Safety Follow-up period, and for all Arm 2 
participants, study participation will conclude and participants will be taken off study once the 4-
week post-last infusion data collection is complete. For Arm 1 participants, who deliver after the 
Safety Follow-up period, study participation will end after delivery data collection period is 
complete.  
 
NOTE: For Arm 1 participant if delivery falls within the Safety Follow-up period, data for both 
periods should still be collected and reported. If there is a gap in time between the Safety Follow-
up and Delivery periods, no data are to be collected during that time unless specified in Table 6.  
 
Table 5: Data Collection Requirements for Safety Follow-up Period 
Evaluation 
 
Enter into eCRFs or SES 
Medical History 
and Medical 
Events 
Updates to any medical conditions that were previously ongoing at the 
time of the prior data collection timepoint, and occurrence of any new 
conditions since the prior data collection timepoint as follows: 
• 
All Grade 3 and higher events 
• 
All SAEs 
• 
Updates to hospitalization for COVID-19 
Concomitant 
Medications 
 
Record the following medications: 
• 
All prescription medications 
• 
All investigational drugs 
Also record any modifications to medications previously recorded. 
Vital Signs 
Record the following measurements that are available in the participant 
chart: 
• 
Record only once, if not recorded at Pre-infusion or Infusion periods: 
o Height  
o Weight  
• 
Record the most abnormal measurement since the last data collection 
timepoint: 
o Highest systolic blood pressure  
o Temperature  
o Pulse rate 
o Pulse oximetry  
Respiratory Status 
Record the most recent respiratory and ventilation status at each data 
collection timepoint 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
Evaluation 
 
Enter into eCRFs or SES 
Laboratory Test 
Results 
Record: a) the highest grade; and b) the resolution value (if abnormal and 
since resolved), or the most recent value (if normal or not resolved), for 
each of the following available laboratory test results from labs drawn for 
clinical care since the last data collection timepoint : 
• 
AST, ALT, alk phos, and bilirubin (direct and total) of any 
grade  
• 
Creatinine and estimated creatinine clearance of any grade and 
eGFR 
• 
CBC with differential and platelets of any grade 
• 
Coagulation factors (PT, INR, PTT) 
• 
COVID-19 test results (only if a positive result was not 
reported at any previous timepoint) 
• 
Any new  (since the last data collection timepoint) grade 3 or 4 
other laboratory test results 
 
 
Single Plasma PK at 48-hours Post Last Infusion 
 
For women who are still hospitalized 48 hours after receiving their last infusion only, a single 
plasma PK sample will be collected at the 48-hour post-last infusion data collection timepoint 
(within a window of +/- 12 hours). Ideally this sample will be drawn at a time when other blood 
samples are drawn as part of clinical care for SOC labs. If no blood samples are drawn for clinical 
care within the window for the 48-hour post-last infusion PK sample, then the single PK sample 
should be collected by itself if circumstances permit. If circumstances do not permit, this sample 
collection may be omitted. This single PK specimen is also subject to the unique PK specimen 
processing requirements (see the LPC for additional instruction). The date and time of PK sample 
collection will also be source documented and entered into eCRFs.  
 
 
Breast Milk Sample Collection at 48-Hours Post Last Infusion 
 
At the 48-Hour Post Last Infusion data collection timepoint only, an optional breast milk sample 
will be collected from postpartum lactating women who are still hospitalized and who consented 
to provide a breast milk sample.  
 
Breast milk samples may be collected within a window of +/- 12 hours of the 48-Hour Post Last 
Infusion timepoint. If possible, collection of breast milk should be targeted to within 90-minutes 
on either side of the 48-Hour Post Last Infusion single plasma PK sample collection. If 
circumstances do not permit collection of the breast milk sample within +/-12-hour window (e.g., 
breast pump not permitted in participant room due to infection control measures, participant too 
sick to express milk), collection of this sample may be omitted. The date and time of breast milk 
sample collection will be source documented and entered into eCRFs. See the LPC for processing 
instructions.  
 
6.6 
Delivery Period (Arm 1) 
 
The Delivery period is for Arm 1 women only. The Delivery period is defined as from onset of 
labor or start of Cesarean section through 24 hours after delivery. In the Delivery period, 
procedures include collection of clinical and laboratory data per Table 6 for the mother and 
infant; as well as PK sampling for the subset of participants who have received a RDV infusion 
within 5 days prior to delivery per Section 6.6.1. 

 
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If delivery occurs after the end of the Safety Follow-up period, study participation will conclude 
and participants will be taken off study after the Delivery period data collection is complete. If 
delivery falls within the Safety Follow-up period, data collection should be collected for both 
periods, and study participation will conclude and participants will be taken off study after the 
Safety Follow-up period data collection is complete. 
 
Table 6: Data Collection Requirements for Delivery Period 
Evaluation 
 
Enter into eCRFs or SES 
Medical History 
and Medical 
Events 
Updates to any medical conditions that were ongoing at last data collection 
period, and occurrence of any new conditions from onset of labor or 
Cesarean section through 24 hours after delivery that meet the following 
requirements: 
• 
All congenital anomalies of the infant 
• 
All Grade 3 and higher events 
• 
All SAEs  
• 
Updates to hospitalization for COVID-19 
Concomitant 
Medications 
 
Only collect: 
• 
Prescription medications for new onset conditions at time of delivery 
• 
All investigational drugs  
Routine labor and delivery medications should NOT be reported.  
Also record any modifications to medications previously recorded, if 
available. 
Vital Signs 
Record the following measurements that are available in the medical 
record as follows: 
• 
Record the most abnormal measurement in a 24-hour period: 
o Highest systolic blood pressure  
o Temperature  
o Pulse rate 
o Pulse oximetry  
Respiratory Status 
Record the most recent respiratory and ventilation status.  
Laboratory Test 
Results 
Record the following results available in the medical record: 
• 
Any new grade 3 or 4 laboratory test results 
Pregnancy/ Birth 
Outcomes 
• 
Pregnancy outcome (outcome of pregnancy, congenital anomalies, 
date of outcome, narrative)  
• 
Birth outcome (outcome location, type of delivery, infant date of 
birth, infant time of birth, infant gestational age, intrauterine growth 
classification, infant birth weight, infant biological sex at birth, Apgar 
scores, infant head circumference).   
 
 
Delivery PK 
 
For Arm 1 women who have received at least one RDV infusion within the 5 days preceding 
delivery, transplacental passage of RDV will be assessed by measurement of drug concentrations 
in cord blood and maternal plasma at the time of delivery. For these women only, a sample will 
be drawn at delivery at the time the cord is clamped (within 1 hour). A sample will also be 
obtained from the umbilical cord, immediately after the cord is clamped (or within 1 hour). 
Delivery PK specimens are also subject to the unique PK specimen processing requirements (see 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
the LPC). The date and time of PK sample collection will also be source documented and entered 
into eCRFs. 
 
6.7 
Early Discontinuation of Remdesivir 
 
Women who discontinue RDV after initial PK sampling but prior to the 5th infusion will have no 
further PK sampling done. These women will be followed for safety and clinical outcomes 
throughout the duration of the study follow-up period, and clinical and laboratory data will 
continue to be collected as indicated in the SOE.  
 
6.8 
Additional Considerations for Laboratory Procedures 
 
Each study site and laboratory involved in this study will comply with the DAIDS policy on 
Requirements for DAIDS Funded and/or Sponsored Laboratories in Clinical Trials Policy, which 
is available at: 
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-procedures 
 
 
Specimen Collection 
 
Specimens will be collected for this study as indicated in the SOE and per detailed guidance 
provided in the LPC, which will be available on the study-specific webpage at: 
http://impaactnetwork.org/studies/IMPAACT_2032.asp. 
 
In accordance with NIH recommendations, for participants 18 years of age or older, adult blood 
collection will not exceed 10.5 mL/kg or 550 mL, whichever is smaller, over any eight-week 
period. For participants less than 18 years of age, pediatric blood collection will not exceed 5 
mL/kg in a single day or 9.5 mL/kg in any eight-week period.  
 
Site investigators should review the participant chart to ensure that blood volume limits have not 
been exceeded prior to PK sampling. If limits will be reached, PK sampling should not be done or 
should be limited. In the event that blood collection must be limited, available specimens should 
be prioritized for use in the following order: (1) plasma for PK, (2) DBS for PK, (3) PBMC for 
PK. In this event, the CMC should also be notified and may provide guidance.  
 
 
Specimen Preparation, Testing, Storage, and Shipping 
 
PK specimens are subject to unique plasma processing requirements: blood samples must be kept 
on ice before processing, a precisely measured proportion of stabilizing agent must be added to 
the specimens during plasma separation, and processed plasma samples must be frozen at -70 
degrees Celsius or colder within 4 hours of specimen collection. All specimens collected for this 
study will be labeled, transported, processed, tested, stored, and/or shipped in accordance with the 
DAIDS policy referenced in Section 6.8, site and local laboratory SOPs, and the LPC. The 
frequency of specimen collection will be directed by the SOE. Plasma, DBS, and PBMC 
specimens will be stored on-site and shipped for batch testing, according to the schedule listed in 
the LPC. Refer to the LPC for additional instruction related to PK specimens shipping. The 
Laboratory Data Management System (LDMS) will be used to document specimen collection, 
testing, storage, and shipping as specified in LPC.  
 

 
IMPAACT 2032, FINAL Version 2.0 
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Biohazard Containment 
 
Transmission of SARS-CoV-2 and other respiratory pathogens are transmitted primarily by 
inhalation of droplet nuclei. Transmission of blood borne pathogens can occur through contact 
with contaminated needles, blood, and blood products. Appropriate respiratory, blood, and 
secretion precautions will be employed by all personnel in the collection of clinical samples and 
the shipping and handling of all clinical samples for this study, as currently recommended by the 
CDC in the United States, the World Health Organization (WHO) internationally and the NIH. 
The current CDC guidelines for SARS-CoV-2 specimen collection and handling are available: 
https://www.cdc.gov/coronavirus/2019-ncov/lab/resources.html.  
 
All specimens will be shipped using packaging that meets requirements specified by the 
International Air Transport Association Dangerous Goods Regulations for United Nations (UN) 
3373, Biological Substance, Category B, and Packing Instruction 650. If samples are processed 
through an intermediate location, central lab or other, should again decontaminate the outside of 
the Styrofoam shipment container prior to shipment to lab. Samples from this study must be 
shipped separately from any other studies. No sharing of a single container for multiple studies. 
 
 
 
SAFETY ASSESSMENT, MONITORING, AND REPORTING 
 
Participant safety will be carefully assessed, monitored, and reported at multiple levels 
throughout this study. Section 7 describes safety-related roles, responsibilities, and procedures for 
site investigators. The safety monitoring roles of the Protocol Team and the IMPAACT Study 
Monitoring Committee (SMC) are briefly referenced in Section 7.1 and described in greater detail 
in Section 9.5. Unless otherwise noted, the specifications of this section apply to all study arms. 
 
7.1 
Safety-Related Roles and Responsibilities 
 
IMPAACT 2032 is an opportunistic study and RDV is not provided as part of this study; it is 
expected that site investigators will not be the treating physicians of COVID-19 infected patients 
receiving RDV. The treating physician has primary responsibility for RDV clinical management 
and toxicity monitoring. It is expected that RDV will be provided, administered, and managed by 
the participants’ non-study treating physician consistent with the prescribing information for 
RDV.  
 
 
IMPAACT 2032 Site Investigators 
 
IMPAACT 2032 site investigators are responsible for additional close monitoring of safety data 
as described in Section 7.2 and for alerting the Protocol Team if unexpected concerns arise. Site 
investigators will enter safety-related data into eCRFs as indicated in Section 7.2 and complete 
EAE reporting as indicated in Section 7.3. Site investigators are also responsible for prompt 
reporting of any unanticipated problems involving risks to participants or others to the sIRB and 
any other applicable review bodies, per the procedures of each applicable review body. All 
investigators must follow sIRB requirements for prompt reporting, which are available at: 
https://www.hopkinsmedicine.org/institutional_review_board/guidelines_policies/organization_p
olicies/prompt_reporting_policy.html 
 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
 
Clinical Management Committee  
  
The following Protocol Team Members comprise the Clinical Management Committee (CMC): 
Chair and Vice-Chairs, Medical Officers, Protocol Investigators, Pharmacologists, Statisticians, 
Data Managers, and Clinical Trial Specialists. The CMC will provide guidance as needed 
including but not limited to participant eligibility and PK sampling procedures.  
 
On behalf of the full Protocol Team, the CMC will monitor participant safety through routine 
review of study data reports as described in Section 9.5.1, and will review adverse event (AE) 
reports to assess and/or confirm initial investigator assessment of relatedness to RDV. Refer to 
Section 8 for more information on participant management including relatedness assessments. 
 
7.2 
Safety-Related Data Collection 
 
The definition of the term adverse event provided in Version 2.0 of the Manual for Expedited 
Reporting of Adverse Events to DAIDS (DAIDS EAE Manual) will be used in this study. This 
definition will be applied to all participants, beginning at the time of the first infusion until 4 
weeks after the last infusion (and for Arm 1 participants, during the Delivery period, if that occurs 
after Safety Follow-up period). Any untoward medical conditions occurring prior to the first 
infusion will be considered pre-existing conditions.  
 
Pre-existing conditions, adverse events, and laboratory test results will be graded initially by the 
site investigator according to Section 8 and entered into eCRFs as specified below and in Section 
6.  
 
 
Pre-Existing Conditions 
 
All pre-existing conditions that meet the criteria specified below will be entered into Medical 
History eCRFs.  
 
• 
All medical conditions of any grade occurring or ongoing within 48 hours prior to the first 
infusion of RDV.  
• 
Arm 1: Major obstetrical diagnoses during the current pregnancy prior to start of RDV 
infusions.  
• 
Arm 1: Gestational age at 48 hours prior to first infusion. 
• 
Hospitalization for COVID-19  
 
 
Adverse Events 
 
The following adverse events that meet the criteria and specific to the time periods listed below 
will be entered into Adverse Event log eCRFs. 
 
Infusion and Safety Follow-up Periods: 
• 
Infusion reactions of any grade 
• 
All Grade 3 and higher events 
• 
All SAEs as defined in Version 2.0 of the DAIDS EAE Manual  
 
Arm 1: Delivery Period (onset of labor through 24 hours after delivery): 
• 
All congenital anomalies of the infant 
• 
All Grade 3 and higher events 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
• 
All SAEs as defined in Version 2.0 of the DAIDS EAE Manual  
 
 
Laboratory Test Results 
 
All laboratory test results that are available in medical records from lab tests done for clinical 
care, and that meet the criteria and specific to the time periods below, will be entered into 
laboratory eCRFs as specified. 
 
Pre-infusion Period: 
Record the most recent result for each of the following laboratory test results of any grade from 
labs drawn within 48 hours prior to infusion and up until the start of the first infusion: 
• 
AST, ALT, bilirubin (direct and total) 
• 
Creatinine and estimated creatinine clearance and method of determination and eGFR 
• 
CBC with differential and platelets 
• 
Coagulation factors (PT, INR, PTT) 
• 
All other laboratory results  
• 
Inflammatory markers (LDH, procalcitonin, ESR, CRP, hs CRP, D-dimer, ferritin, troponin I, 
hs troponin I) (record any available markers only once, refer to Table 2 and 3) 
 
Infusion Period: 
Record any available inflammatory markers (LDH, procalcitonin, ESR, CRP, hs CRP, D-dimer, 
ferritin, troponin I, hs troponin I) only once, refer to Table 2 and 3. 
 
Record highest grade daily result for each of the following from labs drawn after the start of the 
first infusion through the day of the last infusion: 
• 
AST, ALT, and bilirubin (direct and total) of any grade  
• 
Creatinine and estimated creatinine clearance and eGFR of any grade 
• 
Albumin 
• 
CBC with differential and platelets of any grade 
• 
Coagulation factors (PT, INR, PTT) 
• 
COVID-19 test results(first positive result only, if not reported previously) 
• 
All grade 3 or 4 other laboratory test results 
 
Safety Follow-up Period: 
At each data collection timepoint (48-Hour, 7-Day, and 4-Week Post Last Infusion), record the 
highest grade as well as either the resolution value (if abnormal and since resolved) or the most 
recent value (if normal or not resolved), since the last data collection timepoint, for each of the 
following:  
• 
AST, ALT, alk phos, and bilirubin (direct and total) of any grade  
• 
Creatinine and estimated creatinine clearance of any grade and eGFR 
• 
CBC with differential and platelets of any grade 
• 
Coagulation factors (PT, INR, PTT) 
• 
COVID-19 test results (only if a positive result was not reported in any previous timepoint) 
• 
Any new (since the last data collection timepoint) grade 3 or 4 other laboratory test results 
 
Delivery Period: 
Record the following results from onset of labor through 24 hours after delivery: 
• 
Any new grade 3 or 4 laboratory test results 
 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
 
7.3 
Expedited Adverse Event (EAE) Reporting 
 
 
EAE Reporting to DAIDS 
 
Requirements, definitions and methods for expedited reporting of adverse events are outlined in 
Version 2.0 of the DAIDS EAE Manual, which is available 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 EAE reporting to DAIDS. In the event of system outages or technical 
difficulties, EAEs may be submitted using the DAIDS EAE Form. This form is available 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 
 
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 
 
 
EAE Reporting Requirements for this Study 
 
The SAE Reporting Category, as defined in Version 2.0 of the DAIDS EAE Manual, will be used 
for this study. 
 
Expedited reporting will be required for remdesivir (RDV), the drug under study.  
 
In addition to the SAE Reporting Category identified above, any fetal loss under 20 weeks of 
gestational age, or fetal death 20 weeks of gestational age or over, must be reported in an 
expedited manner (i.e., as an EAE). 
 
 
Grading the Severity of Events (applies to EAEs and all other adverse events) 
 
Adverse events will be graded, initially by the IMPAACT 2032 site investigator as described in 
Section 8, according to the Division of AIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017, 
which is available on the RSC website at: 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables 
 
For participants who are entering the study during pregnancy (Arm 1), creatinine and creatinine 
clearance will be graded based on absolute values only and not change from baseline.  
 
Note: The DAIDS AE Grading Table Parameter for unintentional weight loss excludes 
postpartum weight loss. Therefore, maternal weight loss after delivery in Arm 1 women will not 
be graded in this study. 
 

 
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EAE Reporting Period 
 
The EAE reporting period for this study begins at the first RDV infusion administration and ends 
when the participant completes all study follow-up. This includes any gap in time between the 
end of the Safety Follow-up Period and Delivery for women in Arm 1 -- EAEs should be reported 
for this time period if the site becomes aware of them.  
 
After the protocol-defined EAE reporting period, unless otherwise noted, only suspected 
unexpected serious adverse reactions (SUSARs) as defined in Version 2.0 of the DAIDS EAE 
Manual will be reported to DAIDS if the study staff become aware of the events on a passive 
basis (from publicly available information).  
 
 
PARTICIPANT MANAGEMENT 
 
No study drug is provided as a part of this study. As such, all clinical management and toxicity 
monitoring of participants receiving RDV will be the responsibility of the non-study treating 
physician.  
 
All adverse events identified in this study will be source documented in participant research 
records, consistent with the policies and procedures referenced in Section 11. Among other 
details, source documentation will include the severity of each event (graded as described in 
Section 7.3.3). Relationship assessments will be made initially by the IMPAACT 2032 site 
investigator with guidance, as is feasible, from the treating physician. If relationship assessment is 
not able to be made by the site investigator, the attribution should be marked as “unknown.” The 
CMC will review and confirm all classifications; in cases where relationship was marked as 
“unknown,” the CMC will be responsible for classifying the event if possible. Where there is 
discordant assessment between the IMPAACT 2032 site investigator and the CMC, the site will 
be queried for more information. Ultimately, the CMC classification will be used for data 
analysis. Relationship assessments will be according to the following categories and definitions: 
 
Related 
There is a reasonable possibility that the adverse event may be related to RDV 
Not related 
There is not a reasonable possibility that the adverse event may be related to 
RDV 
 
Further standardized guidance on determining whether there is a reasonable possibility of a 
relationship is available in the DAIDS EAE Manual, referenced in Section 7.2 above. 
 
All grade 3 or higher adverse events considered related to RDV must be followed to resolution 
(return to baseline) or stabilization, while the participant is on study.  
 
With respect to IMPAACT 2032 data collection, adverse events should be entered into eCRFs per 
Section 6. 
 
 

 
IMPAACT 2032, FINAL Version 2.0 
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STATISTICAL CONSIDERATIONS 
 
9.1 
General Design Issues 
 
This is a Phase IV prospective, open label, non-randomized opportunistic study to describe the 
PK properties and safety of RDV administered intravenously as part of clinical care among 
hospitalized pregnant and non-pregnant women with COVID-19. This study is comprised of two 
arms specific to the study population. The first arm will include pregnant women, while the 
second arm will include non-pregnant women of childbearing potential. PK sampling will be 
performed during the RDV infusions and women will be followed for safety for four weeks after 
the last infusion; Arm 1 women who are still pregnant at that time will continue to be followed 
for safety at delivery.  
 
The target sample size is 20 PK-evaluable women for each arm. A participant’s PK data will be 
deemed unevaluable by a protocol pharmacologist for a specific analysis if they do not have 
adequate PK evaluations to determine the PK parameter of interest for that analysis (see Sections 
9.6 and 10.2 for details). If a participant is deemed unevaluable for PK, the CMC will determine 
how to proceed with replacement. All women who receive any amount of RDV after enrollment 
will be evaluable for the safety analyses. 
   
The primary objectives are to describe the pharmacokinetics of RDV and its metabolite, GS-
441524, after administration to pregnant women as part of clinical care and to describe clinical 
and laboratory safety outcomes in pregnant women receiving RDV as part of clinical care. The 
secondary objectives are to describe the pharmacokinetics of RDV and its metabolite, GS-
441524, after administration to non-pregnant women of childbearing potential as part of clinical 
care, and to describe clinical and laboratory safety outcomes in non-pregnant women receiving 
RDV as part of clinical care. Other objectives are to describe placental transfer with collection of 
plasma and cord blood samples at delivery in mothers who have received RDV within the 
preceding 5 days, to compare the pharmacokinetics of RDV and its metabolite, GS-441524, in 
pregnant women to those observed in non-pregnant women of childbearing potential, to describe 
and compare intracellular concentrations of RDV’s active intracellular nucleotide triphosphate 
(GS-443902) in pregnant and non-pregnant women, to develop a PopPK model of RDV and its 
metabolites in pregnant and non-pregnant women and evaluate associations between clinical 
characteristics and RDV and GS-441524 pharmacokinetics, to assess plasma protein binding of 
RDV in pregnant women and non-pregnant women of childbearing potential, and to describe the 
frequency of detection and the relative concentrations in breast milk and plasma of RDV and GS-
441524 in lactating women undergoing RDV PK sampling. 
 
A challenge in designing this study is the current paucity of data on the PK parameters of RDV, 
particularly when given to adults with COVID-19, and their variability, as well as how they might 
differ during pregnancy. As discussed in more detail in Section 10.5, while pregnancy is expected 
to alter RDV and GS-411524 drug disposition, the differences in  RDV PK in pregnant versus 
non-pregnant women are not expected to be of sufficient magnitude to require dosing 
modifications from the standard adult doses of RDV. A preliminary analysis approach for this 
study is to assess if drug exposure during pregnancy is within 30% of the PK outcome measure(s) 
for a comparison population of non-pregnant adults, including healthy non-COVID-19 infected 
adults (see Table 1 in Section 1.2) as well as adults with COVID-19 and non-pregnant women 
enrolled in Arm 2 of this study. Additional analyses to assess adequacy of dosing during 
pregnancy will be performed as more information on the PK and pharmacodynamics of RDV in 
adults with COVID-19 becomes available, including data from Arm 2 (non-pregnant women) of 
this study. The statistical analysis plan (SAP) will be updated as more data become available. 

 
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This study design is opportunistic in that it enrolls women who may have already received at least 
one infusion of RDV. Consequently, the results may be overly optimistic. Because participants 
can be enrolled any time prior to the 4th infusion, the study population will potentially not include 
women who started RDV and discontinued it prior to the 4th infusion due to toxicity, intolerance, 
virologic failure, or any other reason. Thus, this study may not be able to identify 
pharmacokinetic, safety, or tolerance issues that occur very soon after drug initiation and 
estimates of the frequency of adverse outcomes may be overly optimistic. The fact that the results 
of this study may not generalize to the full population of women who start RDV will be discussed 
as a limitation of the study in presentations and publications of results. 
 
The Primary Completion Date (PCD) for this study will be the date on which data collection is 
complete for all the primary outcome measures, i.e., the last study visit. The primary data 
analyses will be performed after study completion. 
 
9.2 
Outcome Measures 
 
Note: The numbering of the outcome measures in this section corresponds to the numbering of 
the objectives in Section 2. 
 
Primary and secondary outcome measures listed below in Table 7 will be addressed in the study’s 
primary SAP, which will define the content of the Primary Analysis Report. This report will form 
the basis for the primary manuscript and results reporting to ClinicalTrials.gov. Outcomes of 
interest for other objectives intended for subsequent publications are listed under “Other Outcome 
Measures”. 
 
Table 7. Outcome Measures 
Primary Outcome Measures 
Arm 1 
9.2.1.1 
Non-compartmental PK parameters: 
• 
RDV area under the plasma concentration-time curve (AUC) 
• 
RDV half-life (T1/2) 
 
• 
GS-441524 trough concentration  (Ctrough) 

 
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9.2.1.2 
• 
Maternal renal adverse events of any grade through 7 days post-
last infusion 
• 
Maternal hepatic adverse events of any grade through 7 days 
post-last infusion 
• 
Maternal hematologic events of any grade through 7 days post-
last infusion 
• 
Adverse events through four weeks post-last infusion and 
during delivery: 
o 
Maternal Grade 3 or higher adverse events  
o 
Serious adverse events 
o 
Maternal Grade 3 or higher adverse events assessed as 
related to RDV by the CMC (see Section 8) 
• 
Labor/delivery outcomes: 
o Pregnancy loss 
o congenital anomalies 
o preterm birth (< 37 weeks, < 34 weeks) 
o small for gestational age (SGA) (< 10th percentile for 
gestational age) 
• 
Newborn physical exam: 
o birth weight 
o length 
o head circumference 
Secondary Outcome Measures 
Arm 2 
9.2.2.1 
Non-compartmental PK parameters: 
• 
RDV AUC 
• 
RDV T1/2 
 
• 
GS-441524 Ctrough 
9.2.2.2 
• 
Renal adverse events of any grade through 7 days post-last 
infusion 
• 
Hepatic adverse events of any grade through 7 days post-last 
infusion 
• 
Hematologic events of any grade through 7 days post-last 
infusion 
• 
Adverse events through four weeks post-last infusion and 
during delivery: 
o 
Grade 3 or higher adverse events  
o 
Serious adverse events 
o 
Grade 3 or higher adverse events assessed as related to 
RDV by the CMC (see Section 8) 
Other Outcome 
Measures 
 
Arm 1 
9.2.3.1 
• 
Ratio of cord blood/maternal plasma RDV and GS-441524 
concentrations 
 
Arms 1 and 2 
9.2.3.2 
PopPK parameters: 
• 
RDV AUC  
• 
GS-441524 AUC  
9.2.3.3 
• 
Intracellular GS-443902 concentrations (DBS and PBMC) 

 
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9.2.3.4 
PopPK parameters: 
• 
RDV clearance (CL) 
• 
RDV volume of distribution (V) 
• 
RDV AUC  
 
• 
GS-441524 CL 
• 
GS-441524 V 
• 
GS-441524 AUC 
9.2.3.5 
• 
RDV free fraction 
9.2.3.6 
• 
Detection of RDV in breast milk 
• 
Detection of GS-441524 in breast milk 
• 
RDV maternal breast milk/maternal plasma concentration ratio 
• 
GS-441524 maternal breast milk/maternal plasma concentration 
ratio 
 
9.3 
Randomization and Stratification 
 
There is no randomization or stratification in this study. 
 
9.4 
Sample Size and Accrual 
 
 
Sample Size 
 
As noted in Section 9.1, the target number of participants in each arm is 20 PK-evaluable women. 
This target was selected based on sample size calculations (below) regarding the ability of the 
study to indicate whether or not the PK outcome measures in pregnant women are within 30% of 
the PK outcome measures for non-pregnant comparison populations. We also calculated the 
precision provided for estimating the risk of adverse events and the probability of observing zero 
events and of observing 1-10 event(s). As described in more detail in Section 9.5.2, the data 
analyses that address the primary objectives will include descriptive statistics for the PK 
parameter of interest at specified timepoints as well as descriptive statistics of safety outcomes.  
 
To determine an appropriate sample size for the PK primary objective, we considered the 
precision for estimating the PK parameter with different target sample sizes, as measured by the 
width of the resulting confidence intervals (CI) expressed as a percentage of the mean value. CI 
were calculated using the modified Cox approach(24). Currently, there is limited PK data 
available for RDV in humans(15, 16). As was shown in Table 1, coefficient of variation (CV) 
estimates for RDV and GS-441524 AUCs and Cmax range from 12.7% to 30.3% (i.e., 0.127 to 
0.303), based on data from 8 healthy adult non-pregnant volunteers(15). Because the protocol 
team expects study participants will have a wider range in age, disease severity, and stage of 
pregnancy (for Arm 1), resulting in a higher variability than the available data, we describe the 
precision with an assumed CV of 0.2, 0.3, or 0.4.  
 
Table 8 below illustrates the upper and lower confidence limits and width of the 90% CI for the 
mean PK parameter (e.g., AUC, T1/2, or Ctrough), expressed as a percentage of the mean, for 
different N and CV. With a sample size of 20 evaluable women and a CV equal to 0.3, the 90% 
CI will range from 89 – 112.3% of the mean, and the corresponding CI width will be 23.3% of 
the mean. This relatively narrow CI would provide a very good indication of whether or not our 
data suggest a greater than 30% difference from the PK parameter in non-pregnant comparison 
populations. 
 

 
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Table 8. Percentile range and width of 90% Confidence Intervals for the mean PK parameter 
 
Because an important objective, if feasible, is to compare PK parameters between Arm 1 and 
Arm 2, we also calculated the power to achieve this objective, namely correctly detecting whether 
or not the PK parameter during pregnancy is more than 30% different from the PK parameter in 
non-pregnant women. We used an equivalence framework; i.e., we used PASS 15 to calculate the 
power to conclude that the 90% CI for the geometric mean ratio (GMR) of the PK parameter is 
within 0.7 to 1.43 (25).  
 
Table 9 below presents the power to conclude that the PK parameter in study pregnant women is 
not more than 30% different than the PK parameter in non-pregnant women (i.e.: the 90% CI of 
the GMR is within 0.7 to 1.43) under the assumption that the geometric means of the PK 
parameter are the same (GMR = 1.0) or the geometric mean of pregnant women is 10% less than 
the geometric mean of non-pregnant women (GMR = 0.9). For a GMR = 0.9, the power to 
conclude that there is evidence that the PK parameters are not more than 30% different for N = 20 
in both arms is 0.99, 0.84, or 0.63 with CVs=0.2, 0.3, or 0.4, respectively. Thus, a sample size of 
at least 20 evaluable women in each arm is necessary to provide a power above 63% if the CV is 
0.4 or less. With a sample size of 20 evaluable pregnant women and only 10 evaluable non-
pregnant women, the probability would still be above 68% if the CV is 0.3 or less but only 42% if 
the CV is 0.4.  
 
Table 9. Power to conclude that pharmacokinetic parameters are not more than 30% different (90% 
CI within 0.7 – 1.43) 
 
 
 
For the safety primary objective, we calculated the precision for potential proportions of 
participants experiencing Grade 3 or higher adverse events or adverse pregnancy outcome that 
may be observed and the probability of observing events with sample sizes ranging from 15 to 25. 
Table 10 below presents the exact binomial (Clopper-Pearson) 95% upper and lower confidence 
limits. With a sample size of 20 evaluable women and an observed adverse event rate of 20%, the 
95% CI will range from 6% – 44%. 
 
N  
CV = 0.2 
CV = 0.3 
CV = 0.4 
Range  
Width 
Range  
Width 
Range  
Width 
15 
91.3- 109.5% 
18.2% 
87.2- 114.6% 
27.4% 
83.4- 120.0% 
36.6% 
20 
92.6- 108.0% 
15.5% 
89.0- 112.3% 
23.3% 
85.7- 116.7% 
31.1% 
25 
93.4- 107.1% 
13.7% 
90.2- 110.8% 
20.6% 
87.2- 114.7% 
27.5% 
N Arm 1 
(Pregnant 
Women) 
N Arm 2 
(Non-
pregnant 
Women) 
GMR = 1.0 
GMR = 0.9 
CV = 0.2 
CV = 0.3 
CV = 0.4 CV = 0.2 CV = 0.3 CV = 0.4 
15 
10 
  99.2 
  78.6 
  42.3 
91.5 
63.4 
34.9 
20 
  100.0 
  93.4 
  68.7 
97.7 
78.9 
55.3 
 
 
 
 
20 
10 
  99.6 
  84.3 
  50.8 
94.0 
68.5 
41.5 
20 
 100.0 
  96.7 
  78.1 
98.9 
84.4 
63.0 
 
 
 
 
25 
10 
  99.8 
  87.5 
  56.4 
95.3 
71.8 
45.7 
20 
 100.0 
  98.1 
  83.6 
99.4 
87.7 
67.9 

 
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Table 10. Precision (exact binomial 95% confidence interval) for estimating the percentage of 
participants experiencing a ≥ Grade 3 adverse event or adverse pregnancy outcome 
N 
n (%) with ≥Grade 3 
Adverse Events or Adverse 
Pregnancy Outcome 
Exact 95% CI 
15 
0 (0%) 
0% - 22% 
20 
0 (0%) 
0% - 17% 
25 
0 (0%) 
0% - 14% 
 
15 
2 (13%) 
2% - 40% 
20 
2 (10%) 
1% - 32% 
25 
3 (12%) 
3% - 31% 
 
15 
3 (20%) 
4% - 48% 
20 
4 (20%) 
6% - 44% 
25 
5 (20%) 
7% - 41% 
 
 
 
15 
5 (33%) 
12% - 62% 
20 
6 (30%) 
12% - 54% 
25 
8 (32%) 
15% - 54% 
 
15 
6 (40%) 
16% - 68% 
20 
8 (40%) 
19% - 64% 
25 
10 (40%) 
21% - 61% 
 
15 
8 (53%) 
27% - 79% 
20 
10 (50%) 
27% - 73% 
25 
13 (52%) 
31% - 72% 
 
Table 11 below presents the probability of observing no event (e.g., ≥ Grade 3 or higher adverse 
event or adverse pregnancy outcome) and of observing at least 1-10 event(s) for sample sizes 
ranging from 15-25. With a sample size of 20 evaluable women and a true event probability of 
20%, the probability of observing at least two events is 93%. Note that the non-negligible 
probability of observing zero events when the true event rate is less than 10% indicates that this 
study may not detect such events; the protocol team acknowledges this as a limitation. 
 
Table 11. Probability of observing no event and of observing 1-10 event(s) 
N 
True 
probability of 
an event 
Probability of observing 
0 events 
≥1 event 
≥2 events 
≥5 events 
≥10 
events 
15 
1% 
86% 
14% 
1% 
0% 
0% 
20 
1% 
82% 
18% 
2% 
0% 
0% 
25 
1% 
78% 
22% 
3% 
0% 
0% 
 
15 
5% 
46% 
54% 
17% 
0% 
0% 

 
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20 
5% 
36% 
64% 
26% 
0% 
0% 
25 
5% 
28% 
72% 
36% 
1% 
0% 
 
15 
10% 
21% 
79% 
45% 
1% 
0% 
20 
10% 
12% 
88% 
61% 
4% 
0% 
25 
10% 
7% 
93% 
73% 
10% 
0% 
 
15 
20% 
4% 
96% 
83% 
16% 
0% 
20 
20% 
1% 
99% 
93% 
37% 
0% 
25 
20% 
0% 
100% 
97% 
58% 
2% 
 
15 
30% 
0% 
100% 
96% 
48% 
0% 
20 
30% 
0% 
100% 
99% 
76% 
5% 
25 
30% 
0% 
100% 
100% 
91% 
19% 
 
15 
40% 
0% 
100% 
99% 
78% 
3% 
20 
40% 
0% 
100% 
100% 
95% 
24% 
25 
40% 
0% 
100% 
100% 
99% 
58% 
 
15 
50% 
0% 
100% 
100% 
94% 
15% 
20 
50% 
0% 
100% 
100% 
99% 
59% 
25 
50% 
0% 
100% 
100% 
100% 
89% 
 
 
 Accrual 
 
Each arm will open to accrual independently and will accrue independently over approximately 6 
months from the first enrollment in each arm. If it takes longer to reach the accrual target for Arm 
2 (non-pregnant women) than for Arm 1 (pregnant women), the protocol team may decide to 
close accrual to Arm 2 if it has not yet fully accrued when 20 PK-evaluable Arm 1 women have 
completed their study follow-up, since the study primary objectives only involve Arm 1 women 
and do not involve Arm 2 women.   
 
The initial enrollment limit will be 25 in each arm, based on an anticipated 20% unevaluable. The 
determination of evaluable participants is done by the protocol pharmacologists (see Section 
10.2). The CMC may increase the enrollment limit in either arm to achieve the target number of 
20 PK-evaluable women. Changes to the enrollment limit will be implemented in the Statistical 
and Data Management Center’s (SDMC) enrollment system and sites will be notified and 
instructed via email. The IMPAACT Management Oversight Group (MOG) will also be notified.  
 
Refer to Section 9.5.2 for the definitions of unevaluable for PK and Section 9.6 for the definition 
of unevaluable for safety.  
 

 
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9.5 
Monitoring 
 
Implementation of this study will be monitored at multiple levels, consistent with standard 
IMPAACT procedures. Detailed plans for study monitoring will be outlined in a Study Progress, 
Data, and Safety Monitoring Plan (SPDSMP) developed by the SDMC prior to enrollment of the 
first participant. Sections 11 and 12 provide more information on on-site monitoring and quality 
management at the site level. Further information on monitoring of study progress, quality of 
study conduct, and participant safety across sites is provided below. 
 
 
Monitoring by the Protocol Team 
 
Study Progress and Quality of Study Conduct 
 
The Protocol Team is responsible for continuous monitoring of study progress, including timely 
achievement of key milestones, and quality of study conduct.  
 
The Protocol Team will monitor the timing of site-specific study activation, which will determine 
when each site will begin accruing participants, and actual accrual following activation. For any 
site that is delayed in completing the study activation process, or that falls short of its accrual 
projections, the team will communicate with the site to identify the barriers the site has 
encountered and the operational strategies and action plans to address these. If relatively few of 
the eligible sites have been activated after the study has been opened to accrual, the team will 
periodically re-assess the feasibility of the study and the reasons why sites have not been 
activated and may make adjustments as needed. 
 
The team will closely monitor total study accrual based on reports that will be generated at least 
monthly by the SDMC. Accrual performance will be reported by the DMC, by site and across 
sites, and the team will review and discuss study progress at least monthly. If Arm 1 has not yet 
enrolled at least 10 pregnant women within 6 months after the first Arm 1 enrollment, or has not 
fully enrolled within 12 months after the first Arm 1 enrollment, the protocol team will assess 
whether the study remains feasible or needs modification and will make a recommendation to the 
IMPAACT MOG regarding study continuation or modification.  
 
The Protocol Team will similarly review participant retention and other key indicators of the 
quality of study conduct (e.g., data and specimen completeness) based on reports generated by the 
SDMC and take action with study sites as needed to ensure high quality study conduct throughout 
the period of study implementation.  
 
Determination of PK evaluability will be made by a protocol pharmacologist and tracked in the 
study database (see Section 10.2 for the definition of PK unevaluable). If a participant is deemed 
unevaluable, the CMC will determine how to proceed with replacement, and the SDMC will 
implement the decision in the data management system and SES.  
 

 
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Participant Safety 
 
On behalf of the Protocol Team, the CMC will closely review participant safety through routine 
review of safety data reports generated by the SDMC. These reports will provide listings of 
adverse events specified for entry into eCRFs, as described in Section 7.2. The CMC will review 
these reports via conference call or other meeting at least monthly (see Section 8 for details of the 
review of the assessed relationship of adverse events to RDV). At the time of each call, the 
DAIDS Medical Officer may, when possible, also review any EAEs (defined in Section 7.3) 
reported to the DAIDS Safety Office that are not yet reflected in the data reports. As drugs are not 
being provided in this study, there are no planned safety-related study action triggers or stopping 
rules; however, the CMC (and specifically, the clinician members) will continually evaluate the 
pattern and frequency of reported events and assess for any individual occurrences or trends of 
concern. If recurrent instances of a serious toxicity are observed, appropriate authorities, such as 
the FDA and/or the pharmaceutical company, may be notified. 
   
 
Monitoring by the IMPAACT MOG and Study Monitoring Committee (SMC)  
 
An independent IMPAACT SMC will review the SPDSMP in an introductory initial review, 
following policies described in the IMPAACT MOP.  
 
After the initial review, SMC reviews will only occur on an ad hoc basis if any issues or concerns 
arise, as determined by the IMPAACT MOG. The MOG will regularly review, at a minimum, 
accrual and retention reports. Also, as described above in Section 9.5.1, the CMC will closely 
monitor the study and will raise any issues or concerns to the IMPAACT MOG, particularly with 
regard to accrual, feasibility, and participant safety.  The MOG will then determine if an ad hoc 
SMC review should be convened. For ad hoc SMC reviews, limited data will be reviewed, 
focusing on the events that triggered the reviews.   
 
Based on any of its reviews, the SMC may recommend that the study proceed as currently 
designed, proceed with design modifications, or be discontinued. The SMC may also provide 
operational recommendations to help address any study implementation challenges that may be 
identified during their reviews.  
 
9.6 
Analyses 
 
This section provides a brief summary of the planned statistical analyses. Details will be specified 
in a separate, comprehensive SAP. Section 10.4 describes the pharmacology data analyses and 
modelling, including the non-compartmental and population PK analyses.  
 
The data analyses to address the primary and secondary PK and safety objectives will include 
descriptive statistics. PK outcome measures will be summarized using geometric means, 
arithmetic means, % CVs, and 90% CIs. The 90% CI for the arithmetic mean will be calculated 
on the log scale using the modified Cox approach(24). Continuous safety outcome measures, such 
as newborn birth weight, will be summarized using mean and median as measures of location and 
the standard deviation and quantiles of minimum, 25th percentile, 75th percentile, and maximum 
as measures of dispersion. Categorical safety outcome measures will be summarized using 
proportions and exact binomial (Clopper-Pearson) 95% CIs. Descriptive statistics will also be 
presented by trimester for Arm 1 
 

 
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For the objectives that compare PK parameters between arms, 90% CIs for the geometric mean 
ratio (GMR) of the PK parameters in study pregnant women versus non-pregnant women will be 
calculated to assess whether or not there is a greater than 30% difference in exposure in pregnant 
women versus non-pregnant women. The confidence coefficient will be 90% rather than 95% to 
match the usual practice in the PK literature. We will use Schuirmann’s two one-sided tests 
(TOST) approach to show that the means of the two groups do not differ by more than the 30% 
margin of equivalence, i.e.: the 90% CI of the GMR is between 0.7 and 1.43(26). As discussed in 
Section 9.1, the 30% margin is a preliminary analysis approach (due to paucity of available data), 
and the SAP will be updated to include additional analyses to assess adequacy of dosing during 
pregnancy as more information on the PK and pharmacodynamics of RDV in adults with 
COVID-19 becomes available. 
 
For women who deliver within 5 days after receiving RDV, placental transfer will be assessed by 
comparing the drug concentrations of RDV and GS-441524 in plasma from cord blood with 
concentrations in maternal plasma at delivery using the GMR with a 90% CI.  
 
The intracellular concentrations of GS-443902 at each timepoint and in each arm will be 
summarized using descriptive statistics and compared between pregnant and non-pregnant 
women using the GMR with a 90% CI. Individual-level concentrations over time will also be 
visualized using spaghetti plots and compared within individual .  
 
The RDV free fraction from ex vivo experiments will be summarized using descriptive statistics 
for pregnant and non-pregnant women, as will the unbound RDV concentrations (calculated as 
follows: total concentration x free fraction) and the Albumin and AAG concentrations.  
 
For lactating women meeting breast milk collection criteria, the number and percentage of 
women with detectable maternal breast milk concentrations for RDV and GS-441524, and the 
breast milk/plasma ratios, will be calculated and summarized using descriptive statistics. Timing 
of breast milk and plasma sample collection since EOI will also be summarized.  
 
All analyses will include all participants with evaluable data for that analysis (see Section 10.2 for 
the definition of PK-unevaluable. For the safety analyses, a participant will only be deemed 
unevaluable if she does not receive any amount of RDV.  
 
 
CLINICAL PHARMACOLOGY PLAN 
 
The design and analysis plans for the primary, secondary and other pharmacology objectives are 
described in this section. Detailed PK sample collection, processing, storage and shipping 
instructions are provided in the LPC. 
 
10.1 
Pharmacology Overview and Objectives 
 
This is an opportunistic study designed to assess the PK and safety of RDV in pregnant and non-
pregnant women with COVID-19. Arm 1 of this study will include women at any stage of 
pregnancy who have COVID-19 and will receive RDV as part of their clinical care, at the 
standard adult dose of 200 mg IV on day 1, followed by 100 mg IV on days 2 through 5 to 10. 
Arm 2 of this study will include non-pregnant women of childbearing potential who have 
COVID-19 and will receive RDV as part of their clinical care, at the standard adult dose of 200 
mg IV on day 1, followed by 100 mg IV on days 2 through 5 to 10. Intensive PK samples will be 
collected on the day of the 3rd, 4th, or 5th infusion (at site discretion), as described in Section 6.4.1. 
PMBC and DBS for intracellular assessments of GS-443902 will be isolated with the pre-dose 

 
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and 23-hour post-dose samples on the intensive PK day. Additional blood will be collected with 
the pre-dose intensive PK sample to assess RDV protein binding ex vivo. A sparse PK sample 
will also be collected with standard of care (SOC) labs on the days of the 2nd, 3rd, 4th, and 5th 
infusions, as described in Section 6.4.2, and 48 hours after the last RDV infusion in women who 
are still hospitalized, as described in Section 6.5.1. Sparse samples will not be collected on the 
day that intensive PK samples are collected. For women who receive a RDV dose within 5 days 
prior to delivery, a single maternal sample at delivery and a cord blood sample at the time when 
the cord is clamped will also be collected. For lactating women meeting breast milk collection 
criteria, breast milk samples will also be collected at one of the scheduled time points between 
EOI and 5 hours EOI during the intensive PK assessments, and at the 48 hour post-last infusion 
time point. 
 
The pharmacology objectives for this protocol include all of the objectives listed in Section 2, 
except 2.1.2 and 2.2.2.  
 
10.2 
Definition of PK Evaluable  
 
Women will be considered PK evaluable for the intensive PK assessment if at least 3 out of 4 of 
the 1st block (pre-dose through 3 hours post-EOI) intensive PK samples are collected, and at least 
1 sample in the 2nd block (5 or 7 hours post-EOI), and either the pre-dose or 23 hour post-EOI 
sample is collected. In addition to these minimum requirements for sample collections, drug 
concentrations will also be reviewed once available to further assess whether the participant is PK 
evaluable. Profiles with missing samples will be assessed for evaluability by the pharmacologists 
and CMC on a case-by-case basis. Participants deemed unevaluable will be replaced to achieve a 
target of 20 PK evaluable participants in each Arm. Every effort should be made to collect all 
timepoints of interest. PK results from women who had incomplete PK sampling due to early 
discontinuation of RDV may be included in population PK modeling and simulations. 
 
10.3 
Pharmacology Outcome Measures 
 
Pharmacology outcome measures are described in Section 9.2.  
 
10.4 
Pharmacology Data Analysis and Modeling 
 
 Non-Compartmental PK Analyses 
 
Descriptive presentation of the concentrations and the various collection times will be 
summarized. A non-compartmental PK analysis (NCA) will be performed on the plasma 
concentration-time data generated for each participant. Calculated PK parameters will include, as 
permitted by data: 
  
• 
RDV AUC  
• 
RDV Cmax  
• 
GS-441524 Ctrough  
• 
RDV terminal elimination rate constant (λz) and  
• 
RDV the terminal elimination half-life (T1/2). 
 
RDV Cmax will be taken directly from the observed concentration-time data and is expected to 
occur at the end of the infusion. Data permitting, the RDV terminal slope, λz, will be determined 
from log-linear portion of the curve and the terminal half-life (T1/2) calculated as 0.693/ λz. RDV 

 
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AUC will be determined using the linear trapezoidal method. In absence of adequate PK data to 
perform an NCA, other appropriate compartmental analyses may be undertaken to describe the 
plasma PK of RDV and GS-441524. The random sparse (single) PK sample concentrations on 
days 2-5 and 48 hours post-last-infusion, intracellular concentrations in DBS and PBMC, RDV 
protein binding results, and among lactating women, frequency of RDV and/or GS-441524 
detection in breast milk and maternal breast milk/plasma ratio will be summarized descriptively. 
 
 Population PK Analyses 
 
Population PK analyses will be performed for RDV and GS-441524 using the IMPAACT 2032 
PK data alone using appropriate methodology. These data may be combined with other non-
pregnant adult PK data, as they become available. PK analyses of collected data, including 
population PK evaluations, may be performed to assist the study team with assessment of safety 
or adequacy of dosing during pregnancy. With data from 20 pregnant and 20 non-pregnant 
women, the population PK modeling and approximately 12 PK samples per participant, the power 
to build complex PK models will be limited. Thus, the population PK analysis will focus on 
determination of mean clearance (CL) and volume of distribution (V) for GS-4451524 and RDV 
and their variabilities. A limited number of key clinical variables will be assessed as potential 
covariates including pregnancy stage, gestational age, weight, renal function and age. 
 
10.5 
Anticipated Outcomes  
 
Based on simulations presented in Section 1.2, RDV and GS-441524 exposures in pregnant 
women are expected to achieve concentrations within the range of those observed in healthy 
adults. While pregnancy is expected to alter RDV and GS-441524 drug disposition, the pathways 
responsible for RDV metabolism and elimination have not been previously studied in pregnancy. 
It is expected that the PK of RDV and its metabolites will differ between pregnant and non-
pregnant women but that these will not be of sufficient magnitude to require dosing modifications 
from the standard adult doses of RDV. A preliminary analysis approach for this study is to assess 
if drug exposure during pregnancy is within 30% of the PK outcome measures for a comparison 
population of non-pregnant adults, including healthy non-COVID infected adults (see Table 1 in 
Section 1.2) as well as adults with COVID-19 and nonpregnant women enrolled in Arm 2 of this 
study. If toxicities are noted, relationships with RDV and GS-441524 exposures may be explored. 
Additional analyses to assess adequacy of dosing during pregnancy will be performed as more 
information on the PK and pharmacodynamics of RDV in adults with COVID-19 becomes 
available, including data from Arm 2 (non-pregnant women) of this study. Since this is an 
observational and opportunistic study, which does not dictate therapy, actual dose modifications 
in study participants will not occur and are not applicable. 
 
 

 
IMPAACT 2032, FINAL Version 2.0 
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DATA HANDLING AND RECORD KEEPING 
 
11.1 
Data Management Responsibilities 
 
As described in Section 4.5, data on enrollment in this study will be collected using the DMC 
SES. Study sites must maintain adequate and accurate research records containing all information 
pertinent to the study for all screened and enrolled women, including paper-based CRFs (if used), 
eCRFs, and supporting source data. In maintaining these records, sites must comply with the 
standards of source documentation specified in the DAIDS policy on Requirements for Source 
Documentation in DAIDS Funded and/or Sponsored Clinical Trials (available on the website 
referenced in Section 11.2). 
 
eCRFs and an eCRF completion guide will be made available to study sites by the DMC. Study 
site staff will enter required data into eCRFs, with system checks applied and data queries 
generated immediately upon saving the entered data. Data must be entered within timeframes 
specified by the DMC; queries must also be resolved in a timely manner. Selected laboratory data 
will be transferred electronically to the DMC through the LDMS.  
 
Further information on eCRFs and IMPAACT data management procedures will be provided by 
the DMC. A User Manual for the Subject Enrollment System is available on the DMC portal at: 
https://www.frontierscience.org. 
 
11.2 
Essential and Source Documents and Access to Source Data 
 
All DAIDS policies referenced in this section are available at: 
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-procedures 
 
Study sites must comply with DAIDS policies on Requirements for Essential Documents at 
Clinical Research Sites Conducting DAIDS Funded and/or Sponsored Clinical Trials and 
Requirements for Source Documentation in DAIDS Funded and/or Sponsored Clinical Trials. In 
its policy on Requirements for Manual of Operational Procedures, DAIDS requires sites to 
establish SOPs for maintaining essential and source documents in compliance with these policies. 
Site SOPs should be updated and/or supplemented as needed to describe roles, responsibilities, 
and procedures for this study, and site SOPs should be followed throughout the study.  
 
Per the DAIDS policy on Storage and Retention of Clinical Research Records, study records must 
be stored in a manner that ensures privacy, confidentiality, security, and accessibility during the 
conduct of the study and after the study is completed. Records must be retained for a minimum of 
three years after the completion of the study. Per 21 CFR 312.62, records must be maintained for 
two years after the date a marketing application is approved for one or more of the study products 
for the indication for which it is evaluated in this study; or, if no application is filed, or if the 
application is not approved for this indication, records must be retained two years after the study 
is discontinued and the FDA is notified. 
 

 
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All study records must be accessible for inspection, monitoring, and/or auditing during and after 
the conduct of the study by authorized representatives of the study sponsors and their contracted 
monitors, IMPAACT, Gilead Sciences, Inc., the US Food and Drug Administration, site drug 
regulatory authorities, the sIRB and any applicable local IRBs, Office for Human Research 
Protections (OHRP), and other US, local, and international regulatory entities. Records must be 
kept on-site throughout the period of study implementation; thereafter, instructions for off-site 
storage may be provided by NIAID or NICHD. No study records may be removed to an off-site 
location or destroyed prior to receiving approval from NIAID or NICHD.  
 
11.3 
Quality Control and Quality Assurance 
 
Study sites must ensure that essential documents and participant research records are subject to 
continuous quality control and quality assurance procedures consistent with the DAIDS policy on 
Requirements for Clinical Quality Management Plans, which is available at: 
https://www.niaid.nih.gov/research/daids-clinical-research-policies-standard-procedures 
 
 
 
CLINICAL SITE MONITORING 
 
Site monitors under contract to NIAID or NICHD will visit study sites to inspect study facilities 
and review participant study records — including informed consent forms, paper-based CRFs (if 
used), eCRFs, medical records, laboratory records, and pharmacy records — to ensure protection 
of study participants, compliance with the sIRB approved protocol, and accuracy and 
completeness of records.  
 
The monitors also will review essential document files to ensure compliance with all applicable 
regulatory requirements. Site investigators will make study facilities and documents available for 
inspection by the monitors.  
 
 
 
HUMAN SUBJECTS PROTECTIONS 
 
13.1 
Institutional Review Board/Ethics Committee Review and Approval  
 
The Johns Hopkins Medicine IRB serves as the single IRB (sIRB) for IMPAACT studies at US 
sites; site IRBs also provide local context reviews for US sites. Site investigators are responsible 
for awareness of and adherence to the policies and procedures of all applicable IRBs. All such 
policies and procedures must be followed and complete documentation of all correspondence to 
and from all applicable IRBs must be maintained in site essential document files. Sites must 
submit documentation of both initial review and approval and continuing review to the DAIDS 
Protocol Registration Office (PRO) in accordance with the DAIDS Protocol Registration Manual 
(see also Section 14.2). 
 
Prior to study initiation, site investigators must obtain sIRB review and approval of this protocol 
and site-specific informed consent and assent forms in accordance with 45 CRF 46; subsequent to 
initial review and approval, the sIRB must review the study at least annually. Site investigators 
must also promptly report to the sIRB any changes in the study and any unanticipated problems 
involving risks to participants or others. 
 

 
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18 December 2020 
13.2 
Pregnant Women, Children, and Vulnerable Participants 
 
The NIH is mandated by law to ensure that pregnant women and children be included in clinical 
research when appropriate(27, 28). Recent national and international guidance also recommends 
the inclusion of pregnant women in clinical trials(29, 30). This study responds to these mandates 
and will provide clinical research data to inform treatment of COVID-19 in pregnant women. Per 
the US Code of Federal Regulations (CFR), the sIRB and local IRB must consider the potential 
risks and benefits to maternal participants, and their fetuses, as described in 45 CFR 46 Subpart B 
(for pregnant women, fetuses, and neonates) and 45 CFR 46 Subpart D (for children). 
Additionally, women who are severely ill with COVID-19 to the point of being incapable of 
giving consent would be considered vulnerable per the definition of ICH E6 (R2) 1.61, and thus 
the sIRB and local IRB must pay special attention to safeguarding the rights, safety, and well-
being of these participants. While fetuses/infants of Arm 1 participants will not be enrolled in this 
study, participants in Arm 1 will be asked to consent to collection of a limited amount of data on 
the outcomes of their infants at birth.   
 
With respect to 45 CFR 46 Subpart B, the specifications of 45 CFR 46.204 (d) are expected to 
apply to this study. There is no prospect of direct benefit for the woman nor the fetus, risk to the 
fetus from participation in this study (which is limited to blood draws on the mother while the 
fetus is in utero) is not greater than minimal, and the purpose of this research is the development 
of important biomedical knowledge that cannot be obtained by any other means (as further 
described in Section 1.3). Therefore, pregnant participants (or their LAR) will be asked to provide 
informed consent for their own study participation (including abstraction of infant outcome data) 
under 45 CFR 46 Subpart A, and as described in Section 13.3.  
 
With respect to 45 CFR 46 Subpart D as it applies to collection of infant data after birth, the 
specifications of 45 CFR 46.404 are expected to apply. The extent of the research activities with 
the infant are limited to collection of clinical data that would otherwise be collected in the 
medical record. No procedures are performed directly on the infant. As such, the research is not 
greater than minimal risk. Per 45 CFR 46.408 (b), it is expected that the sIRB will find that the 
consent of one parent is sufficient for research to be conducted under 46.404. 
 
13.3 
Informed Consent 
 
Refer to Section 4.5 and the study-specific MOP for further information on informed consent 
procedures for this study. A sample informed consent form is provided in Appendix II.  
 
Informed consent for study participation will be obtained from each participant before any study-
specific procedures are performed. If the participant is unable to provide informed consent (e.g. 
impaired capacity, as determined by site SOPs and consistent with sIRB policies and procedures) 
written informed consent will be obtained from the participant’s LAR on behalf of the participant 
in accordance with 21 CFR 50.27.  
 
Per FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public 
Health Emergency dated March 2020, updated May 14, 2020, while FDA regulations generally 
require that the informed consent of a participant be documented by the use of a written consent 
form that has been approved by the IRB and signed and dated by the participant at the time of 
consent (21 CFR 50.27(a)), in light of COVID-19 infection control measures, if the participant is 
in COVID-19 isolation, electronic methods of obtaining informed consent and verbal 
confirmation will be considered as determined by site SOPs and consistent with sIRB and local 
IRB policies and procedures. The method used to assess the decision-making capacity of the 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
participant and how consent was obtained must be documented in the participant’s research 
record. 
 
In obtaining and documenting informed consent, the site investigator must comply with 
applicable regulatory requirements, ICH GCP guidelines, and ethical principles. The informed 
consent form must be approved by the sIRB prior to its use. The informed consent process will 
include information exchange, detailed discussion, and assessment of understanding of all 
required elements of informed consent, including the potential risks, benefits, and alternatives to 
study participation.  
 
In light of the circumstances presented by conducting research during COVID-19, the informed 
consent SOPs for all sites must include the following information: 
 
• 
The method to be used to assess the decision-making capacity of participants. 
• 
The process for obtaining consent when a participant is not capable to consent on her own 
behalf (i.e., lacks decision-making capacity). 
• 
Information about who can serve as a LAR and the process for LAR selection, in accordance 
with applicable local laws. 
 
13.4 
Potential Benefits 
 
There will be no direct benefit to participants who take part in this study. Information learned 
from this study may be of benefit to participants and others in the future. 
 
13.5 
Potential Risks  
 
The potential risks of participation in this study include risks associated with study procedures. 
Most study procedures are routine medical procedures that are associated with minimal to no risk 
in participants. Blood collection may cause pain, bruising, swelling, or fainting. There is a very 
small chance of infection where the needle is inserted.  
 
13.6 
Reimbursement/Compensation Plan 
 
Pending sIRB approval, participants will be compensated for time and inconvenience associated 
with completing data collection and PK sampling visits as part of this study. Specific 
compensation amounts will be determined by the sIRB in collaboration with local IRB and will 
take into consideration local cost of living and intensity of each visit/data collection. Participants 
will be compensated one payment between $10 - $50 for each data collection time period (i.e., 
baseline, infusion period, safety follow-up, and delivery) for a total of up to 4 payments just for 
data collection. On days where there is also PK sampling, participants will receive an additional 
$50-250 for each PK sampling day depending on intensity of sampling as determined in 
consultation with the sIRB and local context review. Participants will not be compensated for the 
cost of their COVID-19 treatment. 
 
13.7 
Privacy and Confidentiality 
 
Every effort will be made to protect participant privacy and confidentiality to the extent possible. 
Participant information will not be released without written permission to do so except as 
necessary for review, monitoring, and/or auditing as described in Section 11.2. Data or 
information from the study may be shared with drug companies who have agreements with 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
IMPAACT and/or the US NIH, or regulatory entities, but individual participants will not be 
identified. 
 
All study-related information will be stored securely. Participant research records will be stored 
in locked areas with access limited to study staff. All laboratory specimens, CRFs, and other 
documents that may be transmitted off-site will be identified by PID only. Likewise, 
communications between study staff and Protocol Team members regarding individual 
participants will identify participants by PID only.  
 
Study sites are encouraged but not required by DAIDS policies to store study records that bear 
participant names or other personal identifiers separately from records identified by PID. All local 
databases must be secured with password protected access systems. Lists, logbooks, appointment 
books, and any other documents that link PID numbers to personal identifying information should 
be stored in a separate, locked location in an area with limited access.  
 
In addition to the above, a Certificate of Confidentiality has been obtained for this study from the 
US Department of Health and Human Services. This certificate protects study staff from being 
compelled to disclose study-related information by any US Federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings. It thus serves to protect the identity and privacy 
of study participants.  
 
13.8 
Management of Incidental Findings 
 
The results of PK evaluations are not planned to be provided to participants as these evaluations 
will be performed after follow-up has been completed and are not expected to be relevant to 
clinical care and management, especially given the short treatment duration of RDV. If, however, 
new information becomes available during the course of the study indicating that the results of 
these evaluations are of clinical relevance, the results will be provided to study participants. 
 
13.9 
Management of New Information Pertinent to Study Participation 
 
Participating women will be provided with any new information learned over the course of the 
study that may affect their willingness to remain in follow-up in the study.  
 
 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
 
ADMINISTRATIVE PROCEDURES 
 
14.1 
Regulatory Oversight 
 
This study is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and 
the Eunice Kennedy Shriver National Institute of Child Health and Human Development 
(NICHD), which are part of the United States National Institutes of Health (NIH). Gilead 
Sciences, Inc. provide funding to support limited aspects of this study but will not provide 
regulatory sponsorship or oversight of the study.  
 
Within the NIAID, DAIDS is responsible for regulatory oversight of this study. DAIDS will 
distribute safety-related information pertaining to remdesivir  prior to and during the conduct of 
the study, in accordance with its sponsor obligations. 
NIAID and NICHD provide funding to the clinical research sites at which this study will be 
conducted. Each institute contracts with independent clinical site monitors who will perform 
monitoring visits as described in Section 12. As part of these visits, monitors will inspect study-
related documentation to ensure compliance with all applicable US and local regulatory 
requirements. 
 
14.2 
Protocol Registration 
 
Prior to implementation of this protocol, and any subsequent full version amendments, each site 
must have the protocol and the protocol ICFs approved by the sIRB and, as applicable, their local 
IRBs/ECs and any other applicable regulatory entity. Upon receiving final approval, sites will 
submit all required protocol registration documents to the DAIDS PRO at the RSC. The DAIDS 
PRO will review the submitted protocol registration packet to ensure that all required documents 
have been received.  
 
Site-specific 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. 
 
For any future protocol amendments, upon receiving final sIRB and any other applicable 
regulatory entity approvals, 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 required documents 
have been received. Site-specific ICFs 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, which is available on the RSC website:  
https://rsc.niaid.nih.gov/clinical-research-sites/daids-protocol-registration-policy-and-procedures-
manual  
 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
14.3 
Study Implementation 
 
This study will be conducted in accordance with the protocol, international good clinical practice 
guidelines, and all applicable US and local regulations. Study implementation will also be guided 
by the IMPAACT MOP, study-specific MOP, LPC, and other study implementation materials, 
which will be available on the study-specific website:  
https://impaactnetwork.org/studies/IMPAACT2032.asp 
 
Study implementation at each site will also be guided by site-specific SOPs. The DAIDS policy 
on Requirements for Manual of Operations specifies the minimum set of SOPs that must be 
established at sites conducting DAIDS funded and/or sponsored clinical trials (available on the 
website referenced in Section 11.2). These SOPs should be updated and/or supplemented as 
needed to describe roles, responsibilities, and procedures for this study. 
 
14.4 
Protocol Deviation Reporting 
 
Per the policy for Requirements for Source Documentation in DAIDS Funded and/or Sponsored 
Clinical Trials (available at the website referenced in Section 11.2), all protocol deviations must 
be documented in participant research records. Reasons for the deviations and corrective and 
preventive actions taken in response to the deviations should also be documented.  
 
Deviations should be reported to the sIRB and any other applicable review bodies in accordance 
with the policies and procedures of these review bodies; this includes the sIRB, per the prompt 
reporting requirements available at the website cited in Section 7.1.1. Serious deviations that are 
associated with increased risk to one or more study participants and/or significant impacts on the 
integrity of study data must also be reported within IMPAACT, following procedures specified in 
the IMPAACT MOP. 
 
14.5 
Critical Event Reporting 
 
Per the DAIDS policy on Identification and Classification of Critical Events, a critical event is 
defined as an unanticipated study-related incident that is likely to cause harm or increase the risk 
of harm to participants or others or has a significant adverse impact on study outcomes or 
integrity. All such events must be reported following procedures specified in the DAIDS Critical 
Events Manual, which is available at: 
https://www.niaid.nih.gov/sites/default/files/criticaleventsmanual.pdf 
 
14.6 
ClinicalTrials.gov 
 
This protocol is subject to the United States Food and Drug Administration Amendments Act of 
2007 (FDAAA), including registration in ClinicalTrials.gov. 
 
 
PUBLICATIONS 
 
All presentations and publications of data collected in this study are governed by IMPAACT 
policies, which are available in the IMPAACT MOP.  
 
 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
 
REFERENCES 
 
1. 
(CDC) CfDCaP. CDC COVID Data Tracker 2020 [Available from: https://covid.cdc.gov/covid-
data-tracker/#cases_casesper100klast7days. 
2. 
(CDC) CfDCaP. Data on COVID-19 during pregnancy: Severity of maternal illness 2020 
[Available from: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special-populations/birth-
data-on-covid-19.html. 
3. 
Ellington S, Strid P, Tong VT, Woodworth K, Galang RR, Zambrano LD, et al. Characteristics of 
Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status—
United States, January 22–June 7, 2020. Morbidity and Mortality Weekly Report. 2020;69(25):769. 
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Collin J, Byström E, Carnahan A, Ahrne M. Public Health Agency of Sweden's Brief Report: 
Pregnant and postpartum women with severe acute respiratory syndrome coronavirus 2 infection in 
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5. 
Galang RR, Chang K, Strid P, Snead MC, Woodworth KR, House LD, et al. Severe Coronavirus 
Infections in Pregnancy: A Systematic Review. Obstetrics and Gynecology. 2020. 
6. 
Colbers A, Mirochnick M, Schalkwijk S, Penazzato M, Townsend C, Burger D. Importance of 
Prospective Studies in Pregnant and Breastfeeding Women Living With Human Immunodeficiency Virus. 
Clin Infect Dis. 2019;69(7):1254-8. 
7. 
La Course SM, John-Stewart G, Adams Waldorf KM. Importance of inclusion of pregnant and 
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FDA. Medication Guide accessed at https://www.fda.gov/drugs/drug-safety-and-availability/fda-
cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or, accessed 
May 7, 2020. 
9. 
Gilead Sciences I. Veklury Prescribing Information. 2020. 
10. 
Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of 
remdesivir for patients with severe Covid-19. New England Journal of Medicine. 2020;382(24):2327-36. 
11. 
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively 
inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71. 
12. 
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al. Remdesivir for 
the Treatment of Covid-19 — Final Report. New England Journal of Medicine. 2020;383(19):1813-26. 
13. 
Burwick RM, Yawetz S, Stephenson KE, Collier A-RY, Sen P, Blackburn BG, et al. 
Compassionate use of remdesivir in pregnant women with severe COVID-19. Clinical Infectious 
Diseases. 2020. 
14. 
FDA. Authorization Letter accessed at https://www.fda.gov/media/137564/download on May 7, 
2020. 
15. 
EMA. Summary on compassionate use - Remdesivir Gilead,  Accessed at 
https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf 
on May 7, 2020. 
16. 
Humeniuk R, Mathias A, Cao H, Osinusi A, Shen G, Chng E, et al. Safety, tolerability, and 
pharmacokinetics of remdesivir, an antiviral for treatment of COVID‐19, in healthy subjects. Clinical and 
translational science. 2020;13(5):896-906. 
17. 
Tempestilli M, Caputi P, Avataneo V, Notari S, Forini O, Scorzolini L, et al. Pharmacokinetics of 
remdesivir and GS-441524 in two critically ill patients who recovered from COVID-19. Journal of 
Antimicrobial Chemotherapy. 2020;75(10):2977-80. 
18. 
Gilead Sciences.  https://www.gilead.com/purpose/advancing-global-health/covid-19/emergency-
access-to-remdesivir-outside-of-clinical-trials, accessed 5/5/20. 
19. 
Momper JD. , Best BM, Wang J, Stek A, Cressey TR, Burchett S, Kreitchmann R, Shapiro DE, 
Smith E, Chakhtoura N, Capparelli EV, Mirochnick M, IMPAACT P1026s Protocol Team.  Tenofovir 
alafenamide pharmacokinetics with and without cobicistat in pregnancy. 22nd International AIDS 
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20. 
Stek AM, Best BM, Luo W, Capparelli E, Burchett S, Hu C, et al. Effect of pregnancy on 
emtricitabine pharmacokinetics. HIV Med. 2012;13(4):226-35. 
21. 
Best BM, Burchett S, Li H, Stek A, Hu C, Wang J, et al. Pharmacokinetics of tenofovir during 
pregnancy and postpartum. HIV Med. 2015;16(8):502-11. 
22. 
Liu XI, Momper JD, Rakhmanina N, van den Anker JN, Green DJ, Burckart GJ, et al. 
Physiologically Based Pharmacokinetic Models to Predict Maternal Pharmacokinetics and Fetal Exposure 
to Emtricitabine and Acyclovir. J Clin Pharmacol. 2020;60(2):240-55. 
23. 
Mulangu S, Dodd LE, Davey RT, Jr., Tshiani Mbaya O, Proschan M, Mukadi D, et al. A 
Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. N Engl J Med. 2019;381(24):2293-
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24. 
Olsson U. Confidence Intervals for the Mean of a Log-Normal Distribution. Journal of Statistics 
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25. 
NCSS L. PASS 15 Power Analysis and Sample Size Software Kaysville. Utah, USA[Google 
Scholar]. 2017. 
26. 
Schuirmann DJ. A comparison of the Two One-Sided Tests Procedure and the Power Approach 
for assessing the equivalence of average bioavailability. Journal of Pharmacokinetics and 
Biopharmaceutics. 1987;15(6):657-80. 
27. 
National Institutes of Health. Guidelines for the Inclusion of Women and Minorities as Subjects 
in Clinical Research. Federal Register.; 1994 March 18. 
28. 
National Institutes of Health. NIH Policy and Guidelines on the Inclusion of Children as 
Participants in Research Involving Human Subjects. 1998 March 6. 
29. 
Byrne JJ, Saucedo AM, Spong CY, editors. Task force on research specific to pregnant and 
lactating women. Seminars in Perinatology; 2020: Elsevier. 
30. 
Organization WH, Sciences CfIOoM. International ethical guidelines for health-related research 
involving humans. Geneva: Council for International Organizations of Medical Sciences; 2016. 
 
 

IMPAACT 2032, FINAL Version 2.0 
 
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APPENDICES 
Appendix I 
Schedule of Evaluations  
Period 
Baseline 
Infusion  
Safety Follow-up4 
Delivery
4,5 
(Arm 1 
ONLY) 
Screening 
/ Entry1 
Pre-
infusion2 
First  
Second  
Third  
Fourth  
Fifth  
Post-
Fifth3 
48-hours 
Post Last 
Infusion 
7-Days 
Post Last 
Infusion 
4-Weeks 
Post Last 
Infusion 
CLINICAL DATA 
COLLECTION 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent/Subject 
Enrollment System 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical and Medications 
History/Chart Abstractions6 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
LABORATORY DATA 
COLLECTION6 
 
 
 
 
 
 
 
 
 
 
 
 
Chemistries - Cr, eGFR, 
ALT, AST, alk phos, 
bilirubin 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Albumin 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
Coagulation factors –  
(PT, INR, PTT)  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Hematology – CBC with 
differential and platelets 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Other laboratory test results 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Inflammatory markers - 
(LDH, procalcitonin, ESR, CRP, 
hs CRP, D-dimer, ferritin, 
troponin I, hs troponin I)  
 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
[X] 
 
 
 
 
PHARMACOLOGY 
 
 
 
 
 
 
 
 
 
 
 
 
Intensive PK plasma 
sampling7 
 
 
 
 
[16 mL] 
[16 
mL]  
[16 
mL] 
 
 
 
 
 
Intracellular PK sampling 
(store DBS, PBMC) 7 
 
 
 
 
[18 mL] 
[18 
mL] 
[18 
mL] 
 
 
 
 
 
Protein binding plasma 
sample7,8 
 
 
 
 
[6 mL] 
[6 mL] 
[6 mL] 
 
 
 
 
 

 
IMPAACT 2032, FINAL Version 2.0 
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18 December 2020 
Period 
Baseline 
Infusion  
Safety Follow-up4 
Delivery
4,5 
(Arm 1 
ONLY) 
Screening 
/ Entry1 
Pre-
infusion2 
First  
Second  
Third  
Fourth  
Fifth  
Post-
Fifth3 
48-hours 
Post Last 
Infusion 
7-Days 
Post Last 
Infusion 
4-Weeks 
Post Last 
Infusion 
CLINICAL DATA 
COLLECTION 
 
 
 
 
 
 
 
 
 
 
 
 
Alpha-1 acid glycoprotein9 
 
 
 
 
[X] 
[X] 
[X] 
 
 
 
 
 
Single PK sampling with 
SOC labs (plasma) 
 
 
 
2 mL10 
[2 mL]10 
[2 
mL]10 
[2 
mL]10 
 
[2 mL]11 
 
 
 
Breast milk sample12 
 
 
 
 
[5 mL]13 
[5 
mL]13 
[5 
mL]13 
 
[5 mL] 11 
 
 
 
Single maternal delivery PK 
sample (plasma)14 
 
 
 
 
 
 
 
 
 
 
 
[2 mL] 
Cord blood PK sample14 
 
 
 
 
 
 
 
 
 
 
 
[2 mL] 
TOTAL MAXIMUM PK 
BLOOD VOLUME 
0 mL 
0 mL 
0 mL 
2 mL 
40 mL 
40 mL 
40 mL 
0 mL 
2 mL 
0 mL 
0 mL 
4 mL 
[  ] indicate procedures that are not required at each time indicated or not for all participants.   
  
APPENDIX I FOOTNOTES 
1. Entry may occur at any point after hospitalization and prior to the start of the 4th infusion.  
2. Pre-infusion period is defined as 48 hours prior to start of first infusion. Collect data retrospectively if enrollment occurs after this 48-hour window has 
started or passed.  
3. 
For any participants whose treatment is continued past the 5th infusion, clinical and laboratory data will be abstracted and recorded for each infusion day 
while infusions are ongoing per Section 6.4.    
4. The Safety Follow-up Period may occur before or after Delivery. For Arm 1 women, if Delivery occurs within the Safety Follow-up Period, data for 
both periods should still be collected and reported. 
5. Delivery procedures are for Arm 1 women only. If an RDV infusion was NOT given within 5 days preceding delivery, PK sampling will not be 
performed. Delivery period is from onset of labor through 24-hours after delivery. 
6. See Section 6 for data collection requirements for each period.  
7. Only perform intensive PK sampling schedule once, with the 3rd, 4th or 5th infusion. See Section 6.4.1 for collection timepoints. 
8. Collect only once on the intensive PK day, with the pre-dose sample only. 
9. To be measured from leftover blood sample used for DBS, see LPC. 
10. Collect when blood samples are drawn as part of clinical care (preferably prior to infusion administration on that day) – if no SOC bloods are drawn on 
a given day, single PK sample may be collected if circumstances permit, but if unable to collect, the sample may be omitted for that day. Do not collect 
on the day that intensive PK sampling is performed.  

 
IMPAACT 2032, FINAL Version 2.0 
                  Page 68 of 79 
18 December 2020 
11. Only collect samples for women still hospitalized. If the participant has already been discharged, omit this sample collection. If still hospitalized and if 
possible, collect single PK sample when blood samples are drawn as part of clinical care. If no bloods are drawn on this day for clinical care, draw blood 
specifically for single PK sample. See Section 6.5. 
12. Only for women who have consented to provide breast milk samples, and only if women are lactating at the time of PK sampling. 
13. Collect only one breast milk sample, on the intensive PK day. See Section 6.4.1 for collection timepoints. 5 mL is the optimal volume, but any 
volume >0.5 mL will be accepted.  
14. Only perform if RDV received within 5 days prior to delivery. See Section 6.6.1 for collection details. 
   
 
 

 
 
Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 69 of 79 
18 December 2020 
Appendix II: Sample Informed Consent Forms  
 
Appendix II, Part 1: MASTER Sample Informed Consent Form  
 
[Sites may NOT modify Part 1 of this consent form] 
 
PART 1: MASTER INFORMED CONSENT FORM 
 
IMPAACT 2032 
Pharmacokinetics and Safety of Remdesivir for Treatment of COVID-19 in 
Pregnant and Non-Pregnant Women in the United States  
 
Version 2.0, 18 December 2020 
 
Introduction 
 
You are being asked to take part in the research study named above.  
 
This consent form gives information about the study. Please read it, or have it read to you, and ask any questions 
you may have. You may have as much time as needed to fully understand the study. We will ask you questions to 
see if we have explained the study clearly.  
 
This study is a multi-site study, meaning it will take place at several different locations. Because this is a multi-
site study, this informed consent form includes two parts. Part 1 of the consent form includes general study 
information that applies to all study sites. Part 2 of the consent form includes information only about the study site 
where you are being asked to enroll. Before making your decision, both parts of this form will be reviewed with 
you. You will have the opportunity to discuss any questions about this form and both of its parts with your site’s 
study team. 
 
Key Information 
 
Here is a summary of important information about the study: 
 
• 
You are being asked to take part in this study because you are hospitalized with COVID-19 and are 
currently getting, or may get in the future, remdesivir medication for treatment of COVID-19. 
• 
 You will not receive remdesivir through this study if you choose to join this study. You will continue 
to get care and treatment for COVID-19 by your clinical care provider.  Participation in this study 
will not impact whether or not you receive remdesivir for treatment of COVID-19.   
• 
The primary purpose of the study is to determine how much of the remdesivir medication is in a 
woman’s blood. Another purpose is to look at how safe remdesivir is for a woman.  
• 
If you choose to join the study, you will have blood samples taken at the same time that you are  
having remdesivir infusions. 

 
 
Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 70 of 79 
18 December 2020 
• 
If you choose to join this study, information from your medical records will be collected for the time 
right before you start remdesivir, while you are receiving remdesivir, and for one month after you 
finish your remdesivir.   
• 
If you choose to join this study, the study staff may contact you up to three times during the month 
after your last remdesivir infusion to ask you questions about your health.  
• 
If you choose to join the study and you are pregnant, information from your medical records will also 
be collected about your pregnancy and your delivery. Information will also be collected from your 
medical records and/or your baby’s newborn medical records about your baby’s examination(s) 
within the first day of life.  
• 
It is possible to join this study and then not receive remdesivir infusions. If you do not start 
remdesivir infusions within 7 days after joining the study, you will not stay in the study.  
• 
There is  no direct benefit to you from being in the study. However, this study may help doctors learn 
information that will help in the treatment of future patients with remdesivir for COVID-19.  
• 
The most likely risk to you is from blood drawing- including pain, which is usually minor, and 
infection, which is rare.  
• 
There could be risks of disclosure of your information. 
• 
Your decision about this study will have no effect on the medical care that you would normally 
receive from your clinical care provider, the cost of your care, or your clinical care provider’s 
decision to treat you with remdesivir. Your access to services, and the benefits and rights you 
normally have, will not be affected. 
 
More information is given in both parts of this form about the study, its risks and benefits. You should feel that 
you understand the study before deciding whether to participate. After you understand the study, and if you decide 
that you will join the study, you will be asked to sign or make your mark on this form. You will be offered a copy 
to keep. You do not give up any rights by signing this form. 
 
About the study 
 
This study is being done by the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 
(IMPAACT).  
 
The study will measure the amount of remdesivir in the blood of pregnant women and non-pregnant women. The 
study will include about 40 women who are in the hospital for treatment of COVID-19 in the United States. You 
will be in this study while you are receiving remdesivir infusions and for one month after. In addition if you are 
pregnant we will collect information on your delivery and  birth outcome. We will also collect information on 
your baby from the physical examination done on your baby by your clinical care provider on the day of your 
baby’s birth. We may also collect breast milk from women who are lactating (making breast milk).  
 
The United States National Institutes of Health and Gilead Sciences, Inc. are paying for this study.  
 
1. 
The study will measure the amounts of remdesivir in the blood of pregnant women and non-pregnant women 
being treated for COVID-19.  
 
The amount of remdesivir needed during pregnancy to treat COVID-19 while being safe for pregnant women and 
their babies has not yet been studied. In this study, we will measure the levels of remdesivir medicine in the blood 

 
 
Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 71 of 79 
18 December 2020 
of pregnant and non-pregnant women and compare them to each other. For women who are pregnant and deliver 
their baby after recently receiving remdesivir, we will also measure the amount of remdesivir found in blood from 
the baby’s umbilical cord and compare that to the amount of remdesivir in mother’s blood at the time of delivery. 
We will also try to measure the amount of remdesivir found in breast milk of women whose bodies are making 
breast milk around the time of receiving remdesivir. 
 
2. 
Only pregnant women and non-pregnant women who are eligible can join the study. 
 
If you decide to join the study, we will first talk to you about the study and collect some information about you to 
find out if you are eligible. More information about this is given in section #4 below. If you are eligible, you can 
join the study. If you are not eligible, you cannot join the study.  
 
3. 
It is your decision whether or not you join the study. 
 
Deciding to join the study is voluntary (your choice). If you are eligible, you can choose if you want to join the 
study or not. You are free to join or not join. Your decision will have no effect on the medical care that you would 
normally receive from the hospital, including your care provider’s decision to treat you with remdesivir, or the 
cost of your care. Your access to services, and the benefits and rights you normally have, will not be affected. If 
you decide to join, we will tell you any new information from this study or other studies that may affect your 
willingness to stay in the study. You are welcome to ask questions or request more information at any time. 
 
Take your time and consider your decision carefully. If you wish, you can talk to other people about the study. 
You can bring other people here to learn about the study with you. 
 
4. 
Finding out if you are eligible for the study and entering the study 
 
To find out if you can join, we will talk to you about what you will have to do if you decide to join the study. We 
will collect some information from your medical records about you and your health. If you are pregnant, we will 
collect information about your pregnancy. We will tell you if you are or are not eligible for the study. If you are 
eligible, you will enter the study. 
 
Being in the study 
 
5. 
You will continue to receive care for COVID-19. 
 
Remdesivir or any other medicines you are receiving are not supplied as part of this study. If you join the study, 
you will continue to be taken care of by your clinical care provider for COVID-19. If you have already started to 
take remdesivir, you will continue to take remdesivir if that is what your clinical care provider decides. If you 
have not yet started to take remdesivir, the decision as to whether or not to start remdesivir will be made by you 
and your clinical care provider. Participation in this study will not change the care that you will receive. If you 
join the study and do not start remdesivir within 7 days, your study participation will end.  
 
6. 
You will have medical information collected from your medical records.  
 
Information about your health, including any medications taken and any clinical laboratory test results that you 
have, will be recorded from your medical records. We will collect information from your medical records 

 
 
Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 72 of 79 
18 December 2020 
beginning a couple days before you started taking remdesivir, while you are taking remdesivir, and about a month 
after your last remdesivir infusion. We may also contact you by phone up to three times during the month after 
your last infusion to see how you are doing.  
 
7. 
If you are pregnant, we will collect information about you and your baby at birth.  
 
If you are pregnant, information from your medical records about your pregnancy and your delivery will be 
collected. For your delivery, we will only collect information from the time you start labor through one day after 
you give birth. We will also collect information from your medical records and/or your baby’s newborn medical 
records about the health of your baby when you deliver, and your baby’s physical examination(s) within the first 
day of life.  
 
8. 
You will have multiple samples drawn to measure remdesivir in your blood. 
 
If you enroll in the study and receive remdesivir, you will have blood collected while you are receiving 
remdesivir.  
 
• 
On one infusion day (either your 3rd, 4th or 5th infusion), 8 samples over 24 hours will be collected. For the 
first sample, we will draw 17 mL (a little over 3 teaspoons).  For the next 6 samples, at each collection 
time we will draw 2 mL (about ½ teaspoon) of blood, for a total of 12 mL (about 2.5 teaspoons). For the 
last sample, we will collect 11 mL (a little more than 2 teaspoons) of blood. If one is not already there, a 
small plastic catheter (soft tube) will be placed in a vein in your arm on this day before we start collecting 
the blood samples, so that blood can be drawn multiple times without having to stick you with a needle 
several times. The tube may stay in place until all of the blood samples are drawn for this day.  
 
• 
On each infusion day from your 2nd infusion through your 5th infusion, one 2 mL blood sample will be 
collected at the time you are having blood drawn for other reasons on that day. If no blood is drawn for 
other reasons on that day, we may try to collect this sample separately, or you may not have this sample 
collected. This sample will not be drawn on the one day you have the 8 blood samples collected over 24 
hours. Additionally, if you are still in the hospital on the second day after completing your remdesivir 
treatment (2 days after your last infusion), we will also collect this 2mL blood sample in the same way.  
 
If you start receiving remdesivir, but then stop receiving it before your 5th infusion, we will not collect any more 
blood samples from you after you stop your remdesivir, but you will stay in the study and we will continue to 
collect information from your medical records.  
 
9. 
If you are pregnant and received remdesivir close to the time you deliver, you will have blood drawn at the 
time of delivery. 
 
If you received remdesivir within 5 days before you give birth, at or near the time of delivery, we will:  
 
• 
Draw one 2 mL sample from you (about a ½ teaspoon).  
• 
Draw a small amount of blood from the umbilical cord that is attached to the placenta after the cord is 
clamped, right after your baby is born. This will be used to measure the amount of remdesivir that may 
get into your baby’s blood, but this blood comes from the placenta, and not from your baby.  
 

 
 
Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 73 of 79 
18 December 2020 
10. 
For women who are pregnant or lactating only. If you are lactating around the time you received remdesivir, 
and if you agree, we may collect a breast milk sample.  
 
If you have recently given birth and your body is making breast milk (lactating) around the time you received 
remdesivir, we would like to collect a sample (5 mL, about a teaspoon) of your breast milk. If you agree, we will 
collect this sample on the day you have the 8 blood samples taken over 24 hours, and also around  2 days after 
your last remdesivir infusion, if you are still in the hospital at the time. 
 
You do not have to agree to provide this breast milk sample. You can still join this study even if you do not agree 
to provide this breast milk sample.  
 
Pregnant or lactating women: Please write your initials or make your mark below to indicate your decision 
about providing a breast milk sample.  
 
 
If I am making breast milk (lactating) around the time of receiving remdesivir: 
 
_______ 
I AGREE to have samples of my breast milk collected. 
 
_______ 
I DO NOT AGREE to have samples of my breast milk collected.  
 
 
 
 
11. 
Tests to determine the amount of remdesivir in your samples will be sent to a laboratory in the US that is not 
in this hospital.  
 
Tests to determine the amount of remdesivir in your samples will be done at other laboratories in the US that have 
special tests for this. You or your doctor will not be told the results of these tests. You will not be told the 
level of remdesivir that is in your blood or your breast milk (if you provide it).  
 
12. 
We may take you off of the study early. 
 
The study doctor or nurse may need to take you off the study early without your permission if: 
 
• 
The study is stopped for any reason.  
• 
We determine that staying in the study might harm you.  
• 
You do not start remdesivir within 7 days of joining the study. 
 
13. 
Please tell us if you want to leave the study. 
 
You are free to leave the study at any time for any reason. The care that you receive at this hospital will not be 
affected, but it is important for us to know about your decision.  
 
Risks of the study 
 

 
 
Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 74 of 79 
18 December 2020 
Taking part in this study may involve some risks and discomfort.  
 
14. 
Risk from blood draws  
 
Blood drawing may cause pain, fainting, lightheadedness or some discomfort. In about 1 in 10 cases a small 
amount of bleeding under the skin will produce a bruise. The risk of a blood clot forming in the vein is about 1 in 
100 while the risk of infection or significant blood loss is about 1 in 1000. 
 
15. 
There could be risks of disclosure of your information. 
 
We will make every effort to keep your information private and confidential. Study records and specimens will be 
kept in secure, locked locations. All specimens and most records will be labeled only with a code number. 
However, your name will be written on some records.  
 
Benefits of the study 
 
16. 
There is no direct benefit to you from being in the study. 
 
If you take part in this study, there is no direct benefit to you. Information learned from this study may help others 
who have COVID-19.  
 
Other information about the study 
 
17. 
There are no costs from being in the study. 
 
There is no cost for the study-related visits, blood draws and test results. Participation in this study will have no 
effect on the cost of your care outside of this study for treatment of COVID-19. Remdesivir is not provided to 
study participants as part of this study. More information about patient support for access to remdesivir can be 
found at: https://www.vekluryhcp.com/patient-support/.   
 
18. 
Study records may be reviewed by study staff and groups that oversee the study. 
 
Groups that oversee the study include:  
 
• 
The United States National Institutes of Health and its study monitors 
• 
The United States Office for Human Research Protections 
• 
The United States Food and Drug Administration (FDA) 
• 
Other US, local, and international regulatory entities 
• 
The IMPAACT Network that is coordinating the study 
• 
Gilead Sciences, Inc. 
• 
The IRB(s) overseeing this study 
 
The study staff and these groups are required to keep study records private and confidential.  
 
The results of the study may be presented publicly or published. However, no presentation or publication will use 
your name or identify you personally.  

 
 
Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 75 of 79 
18 December 2020 
 
A description of this study will be available on ClinicalTrials.gov, as required by US law. This website will not 
include information that can identify you. At most, the website will include a summary of the results. You can 
search this website at any time. If you want the results from this study, please tell the study staff. 
 
Your study information may be given to other authorities if required by law.  
 
19. 
What will happen with your data and specimens after the study.  
 
The samples collected from you will only be used for the testing described in this form. The samples will not be 
used for other research now or in the future. The samples will not be sold or used for commercial profit. For 
example, the samples will not be used to make a new product that could be sold.  
 
Other information collected for this study may be used for other research in the future. For example, researchers 
may use information from this study to try to answer different questions about COVID-19. Any future research 
done with the information from this study must be approved by the IMPAACT Network. If any future research is 
done, information about you may be used. Your information will be labeled with a code number, and the only link 
between the code number and your name will be kept at this site. Your name will not be given to other 
researchers. 
 
Data or information from the study may be shared with drug companies who have agreements with the 
IMPAACT Network and/or the US NIH, or regulatory entities, but you will never be identified personally.  
 
20. 
Certificate of Confidentiality 
 
To help us protect your privacy, we have obtained a Certificate of Confidentiality that protects us from being 
forced to release information that may identify you, such as by the courts or police. The certificate cannot be used 
in all situations, but it can be used to resist demands for information that would identify you. The certificate does 
not protect against requests for information from the US federal government or from the US Food and Drug 
Administration. Regardless of the certificate, you can release information about your participation in the study to 
others, if you wish. 
 

IMPAACT 2032, FINAL Version 2.0 
 
  Page 76 of 79 
 18 December 20200 
Appendix II, Part 2: SITE-SPECIFIC Consent Information 
 
 
PART 2: SITE-SPECIFIC CONSENT INFORMATION 
 
 
Site Name: 
Study Title: Pharmacokinetics and Safety of Remdesivir for Treatment 
of COVID-19 in Pregnant and Non-Pregnant Women in the United 
States  
JHM IRB Application Number: <<insert>> 
Site Investigator of Record: 
Site Principal Investigator Contact Information: 
Emergency Contact: 
Other Study Contact(s):  
 
 
Introduction 
 
This study is being done at multiple sites. This part of the consent form includes information about your 
site and is specific to participation at your site only. Before making your decision, both the site-specific 
information and general study information will be reviewed with you. You will have the opportunity to 
discuss any questions, including questions about this portion of the consent document, with your site’s 
study team.  
 
Costs to Study Participants:  
<<Brief description of costs to participants. Only include if different than costs as described in the main 
consent document. >>  
 
Payment for Study Participation: 
<<Brief description of payments and/or reimbursements. >>>>  
 
Compensation for Research-Related Injury:  
Your health is important to us. We will make every effort to protect your well-being and minimize risks.  
 
<<Add any locally-required language for research-related injury and contact information outlining who 
participants should call in the event of any research-related injuries. Sites may not delete the statement 
about no compensation through the US NIH.>> 
If you are injured as a result of being in this study, you will be given immediate treatment for your injury.  
The cost for this treatment may be charged to you or your insurance company. There is no program for 
compensation through the United States National Institutes of Health (NIH). You will not be giving up 
any of your legal rights by signing this consent form. 
 

Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 77 of 79 
18 December 2020 
Contact Information: 
If you have questions, concerns, or problems at any time, use these contacts. 
 
• 
If you have questions about the study:  
<< insert name and telephone number of investigator or other study staff >> 
 
• 
If you have any health or other problems that may be related to study participation:  
<< insert name and telephone number of investigator or other study staff >> 
 
• 
If you want to leave the study:  
<< insert name and telephone number of investigator or other study staff >> 
 
• 
This study has been reviewed by an Institutional Review Board (IRB), a group of people that reviews 
human research studies. The IRB protects the rights and welfare of the people taking part in those 
studies. The IRB can help you if you have questions about your rights as a research participant or if 
you have other questions, concerns or complaints about this research study. If you have questions 
about your rights as research participants or concerns about how you are being treated in the study:  
o For this multi-site study, Johns Hopkins has agreed to serve as the single IRB (sIRB) 
providing oversight for all sites. You may contact the Johns Hopkins IRB at 410-502-2092 or 
jhmeirb@jhmi.edu with your questions or concerns.  
o You may also contact the [site specific IRB contact information] with your questions or 
concerns. << If your site wishes to include local IRB contact information, please include this 
here. If this is not required, please delete this section. >> 
 
Additional information about your local site: 
<<Please insert any additional required language for your site, as applicable for this study. Examples 
may include 
• 
Local regulatory authorities that may review study records (in addition to those listed in Part 1 #18) 
• 
Local language regarding state law requirements for reporting of communicable diseases or other 
mandated reporting requirements  
• 
Locally required language for any specific research procedures, e.g. commercialization of cell lines  
• 
Local conflict of interest disclosures 
 
How will your privacy be maintained and how will the confidentiality of your data be protected?  
<< Insert locally-required HIPAA authorization language. The following language has already been 
approved by the JHM IRB. Please consider whether this language may be used at your site:  
o If this language is acceptable, it may remain in this section.  
o If this language is not acceptable, and locally-approved HIPAA authorization language is 
required, please delete the language and replace it with your own language. 
o Alternatively, if your site requires use of a separate HIPAA authorization, please delete this 
section and include the following sentence: “[Add site name] requires that you sign a 
separate authorization form related to the use of your protected health information for this 
research study. This is required for participation in this study.” >> 
 

Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 78 of 79 
18 December 2020 
HIPAA Authorization for Disclosure of Protected Health Information  
 
What information is being collected, used, or shared? 
To do this research, we will need to collect, use, and share your private health information and, if you are 
pregnant, your baby’s private health information. By signing this document, you agree that your health 
care providers may release your, and your baby’s (if applicable) private health information to us, and that 
we may use any and all of your information that the study team believes it needs to conduct the study. 
Your private information may include things learned from the procedures described in this consent form, 
as well as information from your medical record (which may include information such as HIV status, 
drug, alcohol or STD treatment, genetic test results, or mental health treatment). 
 
Who will see, use or share the information?  
The people who may request, receive or use your private health information include the researchers and 
their staff. Additionally, we may share your information with other people at << insert site name >>, for 
example if needed for your clinical care or study oversight. By signing this form, you give permission to 
the research team to share your information with others outside of << insert site name >>. This may 
include the sponsor of the study and its agents or contractors, outside providers, study safety monitors, 
government agencies, other sites in the study, data managers and other agents and contractors used by the 
study team. We try to make sure that everyone who sees your information keeps it confidential, but we 
cannot guarantee that your information will not be shared with others. If your information is disclosed by 
your health care providers or the research team to others, federal and state confidentiality laws may no 
longer protect it.  
 
Do you have to sign this Authorization? 
You do not have to sign this Authorization, but if you do not, you may not join the study. 
 
How long will your information be used or shared?  
Your Authorization for the collection, use, and sharing of your information does not expire. Additionally, 
you agree that your information may be used for similar or related future research studies. 
 
What if you change your mind? 
You may change your mind and cancel this Authorization at any time. If you cancel, you must contact the 
Principal Investigator in writing to let them know by using the contact information provided in this consent 
form. Your cancellation will not affect information already collected in the study, or information that has 
already been shared with others before you cancelled your authorization. 
 
 

Do not use this form for consenting research  
participants unless a stamp appears here. 
<<US sites only.>> 
Lead Study Investigator:  
Master Informed Consent Approval Date: 
Site Specific Consent Information Approval Date: 
JHM IRB Application No.:  
 
 
 
IMPAACT 2032, FINAL Version 2.0 
                  Page 79 of 79 
18 December 2020 
Signature Lines: 
 
<< If your site wishes to include site-specific signature lines, please include them here. If your site does 
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If you agree to participate in this study, please sign or make your mark below. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Participant 
 
Signature of Participant  
 
Date 
 (print) 
 
OR 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Legally  
 
Signature of LAR 
 
 
Date 
Authorized Representative (LAR)            
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Study Staff Conducting 
Signature of Study Staff  
 
Date 
Consent Process Name (print) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name of Witness 
 
 
Signature of Witness 
 
 
Date 
(as appropriate; print)