Conditions: COVID-19
Keywords: Adintrevimab, ADG20, COVID-19, prevention, prophylaxis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 2582
Healthy volunteers: no

Brief summary:
This placebo-controlled study is intended to evaluate ADG20's safety and ability to prevent COVID-19 infection.

Detailed description:
Phase 2/3, multicenter, double-blind, placebo-controlled, randomized study of the mAb ADG20 in the prevention of symptomatic COVID-19 in adults and adolescents with no known history of SARS-CoV-2 infection but whose circumstances place them at increased risk of acquiring SARS-CoV-2 infection and developing symptomatic COVID-19. This objective was independently evaluated in a cohort of participants with reported recent exposure to an individual diagnosed with a SARS-CoV-2 infection (post-exposure prophylaxis) and in a cohort of participants with no reported exposure to SARS-CoV-2 (pre-exposure prophylaxis). These cohorts included participants whose advanced age (≥55 years old) or health status placed them at risk for severe COVID-19 or COVID-19 complications.

Arms:
arm 1: Participants will be dosed on Day 1 with ADG20 IM arm 2: Participants will be dosed on Day 1 with placebo IM

Interventions: intervention 1: ADG20 intervention 2: Placebo
Intervention descriptions: intervention 1: Single dose of ADG20 intervention 2: Single dose of placebo

Protocol document:
Prot_000.pdf: 
Protocol 
 
Study ID: ADG20-PREV-001 
 
Official Title of Study: A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial to 
Evaluate the Efficacy and Safety of ADG20 in the Prevention of COVID-19 (EVADE) 
 
NCT ID: NCT04859517 
 
IND Identifier: 152327 
 
EudraCT Identifier: 2020‐005598‐28 
 
Date of Document: 05-August-2022 


 
Adagio Therapeutics, Inc. 
 
 
CLINICAL STUDY PROTOCOL 
 
Protocol Title: 
A Phase 2/3 Randomized, Double-blind, Placebo-Controlled 
Trial to Evaluate the Efficacy and Safety of ADG20 in the 
Prevention of COVID-19 (EVADE) 
Protocol Number: 
ADG20-PREV-001 
Clinical Phase: 
Phase 2/3 
Protocol Version and Date: 
6.0, 05 August 2022 
US IND Number: 
152327 
EudraCT Number:  
2020‐005598‐28 
Sponsor: 
Adagio Therapeutics, Inc. 
303 Wyman Street, Suite 300 
Waltham, MA 02451 
 
 
This study will be performed in compliance with Good Clinical Practice, the Declaration of 
Helsinki (with amendments), and local legal and regulatory requirements. 
 
CONFIDENTIAL 
This document and its contents are the property of and confidential to Adagio Therapeutics, Inc 
Any unauthorized copying or use of this document is prohibited. 


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DOCUMENT REVISION HISTORY 
Document 
Date of Issue 
Overall Rationale 
Version 1.0 
01 December 2020 
Original Protocol. 
Version 2.0 
05 March 2021 
Based on US FDA feedback, update the timing of the primary 
endpoint for Cohort A to Day 28; add Cohort B to evaluate ADG20 
for pre-exposure prophylaxis; incorporate a sentinel cohort (across 
Cohorts A and B) into the safety lead-in, as well as other measures 
to reduce risk; and make changes to the analysis plan. Protocol 
Version 2.0 was implemented prior to enrollment of the first 
participant in the study. 
Version 3.0 
11 June 2021 
Based on US FDA feedback, update primary and key secondary 
objectives for Cohort A to reflect “real world” situations and make 
substantial changes to the analysis plan for the study. 
Version 4.0 
11 November 2021 
Allow enrollment of pregnant and breastfeeding participants in 
Cohorts A and B and remove birth control requirements. Refine 
Cohort A to household contacts. Extend the screening window from 
14 to 21 days for pre-exposure prophylaxis participants. Add 
Cohort C to evaluate ADG20 for pre-exposure prophylaxis in 
immune compromised participants at select sites. Version 4.0 of the 
protocol was submitted to the US FDA only and was not 
implemented at study sites. 
Version 5.0 
02 March 2022 
Update the study objectives and endpoints to reflect changes due to 
the emergence of the SARS-CoV-2 Omicron variant, including 
suspending enrollment of Cohorts A and B. Update the statistical 
analysis section to reflect changes to the analysis plan due to the 
emergence of Omicron, including analysis of data collected prior to 
and after the emergence of Omicron. Remove in-home saliva 
collection during the CLI Period. Simplify procedures for participant 
reporting of COVID-19-like illness symptoms. 
Version 4.0 of the protocol was not implemented at study sites. 
Enrollment in Cohorts A and B of the protocol has since been 
suspended and no further participants are expected to be enrolled 
under these cohorts; therefore, updates to the inclusion/exclusion 
criteria to expand the population for these cohorts included in 
Version 4.0 of the protocol were removed in Version 5.0. 
Furthermore, the addition of Cohort C was removed. 
Version 5.0 of the protocol was submitted to the US FDA only and 
was not implemented at study sites. 
Version 6.0 
05 August 2022 
Discontinue study procedures for collection of efficacy endpoint 
data, as analyses of efficacy endpoints of the study are complete; this 
includes monitoring and assessment of CLI symptoms, collection of 
health care resource utilization data, and pre- and post-COVID-19 
vaccination visits. Update the study to remove virtual visits at 
Months 7, 8, 10, and 11, as these were primarily for the purpose of 
CLI monitoring. Update the study to remove virtual visit at 
Month 13, as long-term safety follow-up via in-person visits at 
Months 6 and 12 and virtual visits at Months 9 and 14 is considered 
sufficient based on the experience with ADG20 to date. Update the 
statistical analysis section to reflect the completed and planned 
analyses of efficacy and safety. 


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SIGNATURE PAGE 
Protocol Title: A Phase 2/3 Randomized, Double-blind, Placebo-Controlled Trial to Evaluate the 
Efficacy and Safety of ADG20 in the Prevention of COVID-19 (EVADE). 
The undersigned have reviewed the format and content of this protocol and have approved the 
clinical study protocol. The undersigned agree that the trial will be carried out in compliance 
with the clinical study protocol, Good Clinical Practice, with the Declaration of Helsinki (with 
amendments), and with the laws and regulations of the countries in which the study takes place. 
Any modifications of the clinical study protocol must be agreed upon by the Sponsor and the 
Investigator and must be documented in writing. 
Sponsor Approval: 
Signature: 
 
 
Date: 
 
Name (print): 
 
 
 
 
Title: 
 
 
 
 
 
Investigator Agreement: 
I have read the clinical study protocol and agree the trial will be carried out in accordance with 
the clinical study protocol, Good Clinical Practice, Declaration of Helsinki (with amendments) 
and laws and regulations of the countries in which the study takes place. 
Signature: 
 
 
Date: 
 
Name (print): 
 
 
 
 
 
 
 
 
 
 
 


Adintrevimab (ADG20) 
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SYNOPSIS 
Sponsor: 
Adagio Therapeutics, Inc. 
Protocol No. 
ADG20-PREV-001 
Title of Study: 
A Phase 2/3 Randomized, Double-blind, Placebo-Controlled Trial to 
Evaluate the Efficacy and Safety of ADG20 in the Prevention of 
COVID-19 (EVADE) 
Study Drug: 
ADG20 
Study Phase: 
2/3 
US IND No. 
152327 
EudraCT No. 
2020‐005598‐28 
No. of Sites/Location: 
Approximately 75 to 120 Sites 
Multinational 
Study Objectives and Endpoints 
The objectives and their corresponding endpoints for each cohort are provided below: 
Cohort A (PEP) Objectives and Endpoints 
For Cohort A (post-exposure prophylaxis, PEP), in participants with no known history of 
SARS-CoV-2 infection and reported recent exposure to SARS-CoV-2, the following objectives 
and endpoints apply: 
Objectives 
Endpoints 
Primary (Cohort A [PEP]) 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
Day 28 in all randomized participants without 
current SARS-CoV-2 infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28. 
 
Supplementary:  
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
Probability of RT-PCR-confirmed symptomatic COVID-19 
through Day 28. 
To evaluate the safety and tolerability of 
ADG20 compared with placebo following 
intramuscular administration in all treated 
participants. 
Assessment of safety based on: 
• 
Incidence of treatment-emergent adverse events. 
• 
Incidence of solicited injection site reactions through 
Day 4. 
• 
Changes from baseline in clinical laboratory tests (ie, 
complete blood count with differential and serum 
chemistry). 
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic 
blood pressure). 


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Secondary (Cohort A [PEP]) 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of RT-PCR-confirmed 
symptomatic COVID-19 through Day 28 in 
each of the following populations:  
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28.  
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19 diagnosis. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through Day 28. 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of SARS-CoV-2 infection (based 
on RT-PCR or serology) regardless of 
symptoms through Day 28 in each of the 
following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19) as determined by 
positive RT-PCR or serology through Day 28.  
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19). 
• 
Probability of SARS-CoV-2 infection (asymptomatic or 
symptomatic COVID-19) through Day 28. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 3 
months in each of the following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months.  
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of SARS-CoV-2 
infection (based on RT-PCR or serology) 
regardless of symptoms through 3 months, in 
each of the following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19) as determined by 
positive RT-PCR or serology through 3 months. 
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19). 
• 
Probability of SARS-CoV-2 infection (asymptomatic or 
symptomatic COVID-19) through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
Day 28 in all randomized participants with prior 
but not current SARS-CoV-2 infection at 
baseline.  
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through Day 28. 


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To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of asymptomatic 
SARS-CoV-2 infection, in all randomized 
participants without prior or current 
SARS-CoV-2 infection at baseline. 
• 
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by RT-qPCR 
(nasal sample) on Days 8 and 15. 
• 
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by serology 
through Day 28. 
To evaluate the impact of ADG20 compared 
with placebo on viral load in all randomized 
participants with asymptomatic SARS-CoV-2 
infection detected by RT-qPCR (nasal sample) 
at baseline via surveillance.  
• 
Peak post-baseline SARS-CoV-2 viral load as measured 
by RT-qPCR 
• 
SARS-CoV-2 viral load as assessed by RT-qPCR change 
from baseline to Day 8 and Day 15. 
To evaluate the effect of ADG20 on the 
following clinical and virologic parameters in 
all randomized participants with laboratory 
confirmed symptomatic COVID-19 through CLI 
Day 28: 
 
Severity of COVID-19. 
Proportion of participants with RT-PCR-confirmed mild, 
moderate, or severe/critical COVID-19 through CLI Day 28. 
Duration of COVID-19. 
Time to sustained resolution of COVID-19 symptoms through 
CLI Day 28. 
COVID-19-related medically attended 
outpatient visits. 
Proportion of participants with at least 1 COVID-19-related 
medically attended outpatient visit (physician’s office, 
telemedicine, emergency rooms, or urgent care centers) 
through CLI Day 28. 
COVID-19-related hospitalization. 
Proportion of participants with a COVID-19-related 
hospitalization through CLI Day 28. 
COVID-19-related mortality. 
COVID-19-related mortality through CLI Day 28. 
All-cause mortality. 
All-cause mortality through CLI Day 28. 
SARS-CoV-2 viral load. 
Viral load from CLI Day 1 sample assessed by RT-qPCR. 
To evaluate the pharmacokinetics of ADG20 in 
serum. 
PK parameters of ADG20 including but not limited to: 
AUC0-inf, AUC0-last, Cmax, Tmax, CL, t1/2, and Vss. 
To evaluate the immunogenicity of ADG20. 
Incidence of ADAs against ADG20.  
ADA=antidrug antibody; AUC =area under the plasma concentration–time curve; AUC0-inf: AUC extrapolated to infinite time; 
AUC0-last=AUC from zero up to the last concentration ≥lower limit of quantification; CL=clearance; CLI=COVID-19-like illness; 
Cmax=maximum plasma concentration; PEP=post-exposure prophylaxis; RT-(q)PCR=(quantitative) reverse transcription-
polymerase chain reaction; t½=plasma concentration half-life; Tmax=time to reach Cmax; Vss=apparent volume of distribution at 
steady state. 


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Cohort B (PrEP) Objectives and Endpoints 
For Cohort B (pre-exposure prophylaxis, PrEP), in participants with no known history of 
SARS-CoV-2 infection and no known recent exposure to SARS-CoV-2, but whose 
circumstances put them at increased risk of exposure to SARS-CoV-2 and symptomatic 
COVID-19, the following objectives and endpoints apply: 
Objectives 
Endpoints 
Primary (Cohort B [PrEP]) 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
3 months in all randomized participants 
without prior or current SARS-CoV-2 
infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic COVID-19 
through 3 months. 
To evaluate the safety and tolerability of 
ADG20 compared with placebo following 
intramuscular administration. 
Assessment of safety based on: 
• 
Incidence of treatment-emergent adverse events. 
• 
Incidence of solicited injection site reactions through Day 4. 
• 
Changes from baseline in clinical laboratory tests (ie, 
complete blood count with differential and serum 
chemistry). 
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure). 
Secondary (Cohort B [PrEP]) 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of RT-PCR-confirmed 
symptomatic COVID-19 through 3 months in 
all randomized participants without current 
SARS-CoV-2 infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic COVID-19 
through 3 months. 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of SARS-CoV-2 infection 
(based on RT-PCR or serology) regardless of 
symptoms through 3 months, in each of the 
following populations:  
• 
All randomized participants without prior 
or current SARS-CoV-2 infection at 
baseline. 
• 
All randomized participants without 
current SARS-CoV-2 infection at 
baseline.  
Proportion of participants with SARS-CoV-2 infection 
regardless of symptoms through 3 months. 
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection.  
• 
Probability of SARS-CoV-2 infection through 3 months. 


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Objectives 
Endpoints 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
3 months in all randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of 
SARS-CoV-2 infection (based on RT-PCR or 
serology) regardless of symptoms through 
3 months in all randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
regardless of symptoms through 3 months. 
 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of 
asymptomatic SARS-CoV-2 infection (based 
on serology) in all randomized participants 
without prior or current SARS-CoV-2 
infection at baseline. 
Proportion of participants with asymptomatic SARS-CoV-2 
infection as determined by serology at Month 6. 
To evaluate the effect of ADG20 on the 
following clinical and virologic parameters in 
all randomized participants with laboratory 
confirmed symptomatic COVID-19 through 
CLI Day 28: 
 
Severity of COVID-19. 
Proportion of participants with RT-PCR-confirmed mild, 
moderate, or severe/critical COVID-19 through CLI Day 28. 
Duration of COVID-19. 
Time to sustained resolution of COVID-19 symptoms through 
CLI Day 28. 
COVID-19-related medically attended 
outpatient visits. 
Proportion of participants with at least 1 COVID-19-related 
medically attended outpatient visit (physician’s office, 
telemedicine, emergency rooms, or urgent care centers) through 
CLI Day 28. 
COVID-19-related hospitalization. 
Proportion of participants with a COVID-19-related 
hospitalization through CLI Day 28. 
COVID-19-related mortality. 
COVID-19-related mortality through CLI Day 28. 
All-cause mortality. 
All-cause mortality through CLI Day 28. 
SARS-CoV-2 viral load. 
Viral load from CLI Day 1 sample assessed by RT-qPCR. 
To evaluate the pharmacokinetics of ADG20 
in serum. 
PK parameters of ADG20 including but not limited to: AUC0-inf, 
AUC0-last, Cmax, Tmax, CL, t1/2, and Vss. 
To evaluate the immunogenicity of ADG20. 
Incidence of ADAs against ADG20.  
ADA=antidrug antibody; AUC =area under the plasma concentration–time curve; AUC0-inf: AUC extrapolated to infinite time; 
AUC0-last=AUC from zero up to the last concentration ≥lower limit of quantification; CL=clearance; CLI=COVID-19-like illness; 
Cmax=maximum plasma concentration; PrEP=pre-exposure prophylaxis; RT-(q)PCR=(quantitative) reverse transcription-
polymerase chain reaction; t½=plasma concentration half-life; Tmax=time to reach Cmax; Vss=apparent volume of distribution at 
steady state. 
Study Design 
This is a Phase 2/3, multicenter, double-blind, placebo-controlled, randomized study of the mAb 
ADG20 in the prevention of symptomatic COVID-19 in adults and adolescents with no known 
history of SARS-CoV-2 infection but whose circumstances place them at increased risk of 
acquiring SARS-CoV-2 infection and developing symptomatic COVID-19. This objective will 


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be independently evaluated in participants with reported recent exposure to an individual 
diagnosed with a SARS-CoV-2 infection (Cohort A, PEP) and in a cohort of participants with no 
reported exposure to SARS-CoV-2 (Cohort B, PrEP). These cohorts will be enriched for 
participants whose advanced age (≥55 years old) or health status places them at risk for severe 
COVID-19 or COVID-19 complications.  
This Phase 2/3 study will enroll in two parts: a Phase 2 safety lead-in consisting of 200 adult 
participants enrolled across Cohorts A and B and a separate Phase 3 expansion for enrolling the 
remainder of participants in each cohort. The first 30 participants (across both cohorts) in Phase 
2 will constitute a sentinel group and will undergo extended monitoring as detailed below. After 
a combined number of approximately 200 adult participants (aged ≥18 years) across Cohorts A 
and B are enrolled in Phase 2 (inclusive of the 30 sentinel participants) and followed for 4 weeks, 
an interim analysis of safety will be performed and reviewed by the iDMC. Enrollment of adult 
participants will continue during this review and will follow Phase 2 post-injection monitoring 
requirements. Enrollment of adolescents in each cohort will open only upon sponsor 
communication to sites after iDMC review of Phase 2 data and only in regions permitted by 
health authorities and local ethics committees. Pausing guidelines triggering iDMC ad hoc 
reviews and additional details on safety monitoring are provided in Section 5.12. 
The participants in Phase 2 will be combined with the corresponding Phase 3 expansion 
population in each cohort for the final efficacy and safety analyses.  
The participant population, study procedures, and endpoints will be identical in Phase 2 and the 
Phase 3 expansion portions of the study with the following exceptions: 
• The sentinel group will be restricted to adult participants (aged ≥18 years) and the post 
injection monitoring period will be 4 hours. Participants will then be assessed daily by 
telephone through Day 4 for hypersensitivity reactions. 
• In the remainder of Phase 2, enrollment will be restricted to adult participants (aged ≥18 
years) and the post-injection monitoring period may be reduced to no less than 2 hours after 
safety data review. 
• After iDMC review of Phase 2 data, enrollment will include both adult (aged ≥18 years) and 
adolescent (aged 12 to <18 years) participants (only in regions permitted by health authorities 
and local ethics committees). The post-injection monitoring period for adult participants may 
be decreased to a minimum of 1 hour based on iDMC recommendation. The post-injection 
monitoring period will be 2 hours for the first 20 adolescent participants. If no 
hypersensitivity reactions are observed in this group, the post-injection monitoring period for 
subsequent adolescent participants may also be reduced to a minimum of 1 hour.  
If any hypersensitivity reactions are observed in Phase 2, subsequent participants will be 
monitored for 2 hours post-injection. This period may be reduced to a minimum of 1 hour based 
on iDMC recommendation upon review of additional safety data. 
Methodology 
For Cohort A (PEP), the study will consist of a Screening Period of up to 5 days, a 1-month 
Study Period (including dosing on Day 1), a 5-month follow-up Period, and an 8-month 


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long-term follow-up (LTFU) Period. For Cohort B, the study will consist of a Screening Period 
of up to 21 days, a 6-month Study Period (including dosing on Day 1), and an 8-month LTFU 
Period. Each cohort of the study will be considered completed when the last telephone visit 
(Month 14) or Early Termination (ET) visit for the last participant in each cohort is complete. 
All participants will undergo assessments as indicated in the main SoA. 
Participants will receive a single IM dose of study drug on Day 1. Participants will record any 
ISRs using an e-Diary (or paper back-up) daily on Day 1 postdose through Day 4. The first diary 
entry will be completed by the participant with assistance of study staff prior to the end of the 
postdose monitoring period. 
As of protocol clarification letter 6, the use of an e-Diary for recording CLI qualifying 
symptoms and collection of saliva samples beyond CLI Day 1 were discontinued. As of 
protocol version 6.0, monitoring for CLI symptoms and CLI visits are discontinued. 
Spontaneously reported CLI symptoms will be captured as AEs as per Section 4.1.1 and 
Section 4.1.3 of the protocol. Safety monitoring will be performed via site phone calls or in-
person visits through Month 14. Prior to implementation of protocol clarification letter 6 and 
protocol version 6.0 at each clinical site, the following procedures were in place for CLI 
monitoring and are described here for reference only:  
Participants will be instructed to monitor for any CLI symptoms and report them to the site if 
they occur at any time during the study. Surveillance for CLI will be performed via 
participant completion of an e-Diary twice weekly from Day 1 up to the Month 6 Visit, then 
weekly up to the Month 12 Visit. Surveillance for symptomatic COVID-19 will also be 
performed via site phone calls to the participant weekly up to the Month 6 Visit, then monthly 
up to the Month 12 Visit. Participants reporting CLI symptoms will be evaluated via phone 
call to confirm whether their symptoms meet criteria for a CLI visit. If CLI symptoms are 
confirmed by the site, the participant will enter the CLI Period and have an initial CLI visit 
within 48 hours. Participants who enter the CLI Period will be assessed as described in the 
CLI SoA. Study visits described in the main SoA should not be conducted while a participant 
is following the CLI SoA.  
During the initial CLI Visit (CLI Day 1), an NP swab for RT-qPCR testing for SARS-CoV-2 
and a saliva sample for assessing viral load will be collected for processing by a central 
laboratory. For the remainder of the CLI Period, vital signs and severity, duration, and 
outcome of CLI will be collected via daily telemedicine visits (on CLI Days 2 to 21) and at 
the final visit on CLI Day 28. Saliva samples will be collected by participants at home on CLI 
Day 3, 5, 8, 11, 14, and 21 to measure viral shedding over time. Participants will continue in 
the CLI Period unless a negative result on the CLI Day 1 central NP RT-PCR test is 
received. These participants will stop CLI assessments and will continue with the main SoA. 
Participants with positive or pending central NP SARS-CoV-2 results will continue in the 
CLI Period, regardless of symptoms. Continuation in the CLI Period will not be guided by 
local RT-PCR testing. 
As of protocol version 6.0, all participants in Cohort A have completed surveillance for 
asymptomatic SARS-CoV-2 infection and monitoring for CLI symptoms and CLI visits are 


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discontinued. Prior to protocol version 6.0, the following procedures were in place and are 
described here for reference only:  
In Cohort A (PEP) only, surveillance for asymptomatic SARS-CoV-2 infection will be 
performed via SARS-CoV-2 RT-qPCR testing of nasal swabs collected by the Clinical Site on 
Day 1 (predose) and Day 8 and collected by the participant on Day 15. Any participant who 
has a positive result on a nasal swab RT-PCR (Cohort A) or local RT-PCR test (either 
cohort) up to the Month 12 study visit will be instructed to monitor for onset of symptoms and 
to report any symptoms to the clinical site; if the participant reports qualifying symptoms 
within 14 days of collection of the positive RT-PCR, they will enter the CLI Period.  
As of protocol version 6.0, collection of health care resource utilization data is discontinued. 
Prior to protocol version 6.0, the following procedures were in place and are described here 
for reference only: 
The occurrence of RT-PCR confirmed COVID-19 and concomitant therapies associated with 
COVID-19 will be captured for the duration of the study. Every effort will be made to 
capture information from any medical visits (eg, visits to the primary care providers, 
emergency department/urgent care clinic visits, hospitalizations) related to COVID-19 or its 
complications for the purpose of Health Care Resource Utilization analysis.  
Sparse blood samples will be collected for PK and immunogenicity throughout the study, as 
indicated in the main SoA and CLI SoA.  
At the time of study entry, each participant will be asked to indicate to the Clinical Site the 
identity and location of their routine medical care physician and/or facility and the identity and 
location of where they would obtain emergency care and hospitalization, if necessary, should 
they get infected with SARS-CoV-2. If this information is not available, a plan for where such 
care could be obtained should be developed.  
All necessary precautions (as per local regulations) should be taken to protect medical staff and 
other contacts of participants who are suspected of having COVID-19. In the event of a 
confirmed SARS-CoV-2 infection, the participant will be notified, and the participant will be 
asked to adhere to the appropriate measures and restrictions as defined by local regulations.  
Treatment Assignment and Randomization 
Participants will be randomly assigned in a 1:1 ratio in each cohort to receive either IM ADG20 
or IM placebo. The randomization will be assigned in a blinded manner using a centralized 
Interactive Response Technology (IRT) system, in accordance with a pre-generated 
randomization schedule. A participant is considered randomly assigned when a randomization 
transaction is recorded in the IRT. A separate randomization list will be created for each cohort. 
Randomization will be stratified by geography (United States/Western Europe vs Central/Eastern 
Europe vs Rest of the World) and age/risk for severe/critical COVID-19 (12 to <55 years and 
low risk for severe/critical COVID-19 vs 12 to <55 years and high risk for severe/critical 
COVID-19 vs aged ≥55 years).  


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Selection of Study Population 
The study population will comprise adults (aged ≥18 years) and adolescents (aged 12 to <18 
years); enrollment of adolescents will begin during the Phase 3 expansion in regions permitted 
by health authorities and local ethics committees. Participants whose circumstances place them 
at increased risk of acquiring SARS-CoV-2 infection and/or developing symptomatic COVID-19 
will be included. This objective will be independently evaluated in participants with reported 
recent exposure to an individual diagnosed with a SARS-CoV-2 infection (Cohort A, PEP) and 
in participants with no reported recent exposure to SARS-CoV-2 (Cohort B, PrEP).  
Approximately 20% of the study population is anticipated to be comprised of individuals at 
increased risk for severe COVID-19 or COVID-19 complications. Participants aged 12 to 
<55 years who are at an increased risk (as described in Appendix 4) will be included, and 
participants aged ≥55 years will be eligible for enrollment with or without underlying medical 
conditions that might place them at increased risk. These at-risk populations are likely to derive 
the greatest benefit from a preventive mAb therapy. Importantly, participants will be enrolled in 
the study only if they do not intend to receive a COVID-19 vaccine for 6 months after discussion 
of risks/benefits of study enrollment in the setting of current or potential future vaccine 
availability and their underlying risk for development of severe COVID-19.  
Inclusion Criteria 
Participants are eligible to be included in the study only if all the following criteria apply: 
1. Adult aged ≥18 years or adolescent aged 12 to <18 years and weighs at least 40 kg at the 
time of Screening. 
Note: Adolescent enrollment in these cohorts will open only upon sponsor communication to 
sites after review of Phase 2 data, and only if permitted by the local health authority (see 
Appendix 7). 
2. Tests negative for current or previous SARS-CoV-2 infection by RT-PCR and serology at the 
time of Screening.  
Note: Participants may be randomized in Cohort A without RT-PCR results, if these results 
are not available by Day 5 of Screening.  
3. Is at high risk of SARS-CoV-2 infection as assessed by the Investigator, as follows: 
a. Cohort A (PEP): recent exposure to an individual with a diagnosis of SARS-CoV-2 
infection (the index case). 
Note: Randomization must occur within 5 days (120 hours) from both exposure to and 
sample collection from the index case. Participants with recent exposure to a laboratory-
confirmed index case must be asymptomatic at randomization. Exposure is generally 
defined as repeated contact lasting 15 minutes or more within a 24-hour period, where the 
individuals were within 2 meters (approximately 6.5 feet) of each other, and neither party 
was wearing a facemask of respirator. 


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b. Cohort B (PrEP): occupational, housing, recreational and/or social conditions that are 
likely to increase risk of exposure to SARS-CoV-2 as assessed by the criteria in 
Appendix 3.  
4. Agrees to defer receipt of COVID-19 vaccination for a minimum of 180 days (6 months) 
after dosing. 
5. Provides written documentation of informed consent by signing a current IEC/IRB approved 
ICF at the time of screening. A legally authorized representative may be used in cases where 
inclusion criterion 9 is able to be fulfilled. In the case of adolescents, informed consent/assent 
must also be obtained as required by local guidelines. 
6. Participants assigned female sex at birth who are not of reproductive potential are eligible 
without requiring the use of contraception and do not require a pregnancy test. This includes 
female participants who have not undergone menarche or who are documented to be 
surgically sterile (eg, hysterectomy, removal of both ovaries, or tubal ligation) or 
postmenopausal (ie, amenorrhea >1 year and follicle stimulating hormone >40 mIU/mL). 
Follicle stimulating hormone is not required in postmenopausal females with amenorrhea for 
>2 years.  
7. Participants assigned female sex at birth and who are of childbearing potential may be 
enrolled in the study if the participant has practiced adequate contraception or has abstained 
from all sexual activities that could result in pregnancy for at least 28 days before the day of 
dosing (Day 1) and has agreed to continue adequate contraception for sexual activity that 
could lead to pregnancy through 6 months following dosing. 
Adequate contraception for participants assigned female sex at birth is defined as consistent 
and correct use of a contraceptive approved by the local Health Authority and used in 
accordance with the product label. For example: 
a. Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction with 
spermicide. 
b. Intrauterine device. 
c. Hormonal contraceptive taken or administered via oral (pill), transdermal (patch), 
intravaginal, implantable, or injectable method. 
d. Sterilization of a female participant’s male partner before entry into the study. 
e. Sexual abstinence. 
Note: periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. Sexual abstinence 
is considered an effective method only if defined as refraining from heterosexual 
intercourse from providing consent until 6 months after dosing. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred 
and usual lifestyle of the participant. 
8. Participants assigned male sex at birth with partner(s) of childbearing potential who agree to 
use adequate contraception through 6 months after dosing. If their partner is pregnant, males 


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must agree to use a condom. Male participants must also refrain from sperm donation 
through 6 months after dosing. 
9. Able to understand and comply with study requirements/procedures (if applicable, with 
assistance by a caregiver, surrogate, or legally authorized representative) based on the 
assessment of the Investigator. 
Exclusion Criteria 
A potential participant who meets any of the following exclusion criteria must be excluded from 
the study. 
1. Prior receipt of a COVID-19 vaccine, convalescent plasma, or mAb, including in the setting 
of a clinical trial.  
Note: immune compromised participants (eg, due to hematological malignancy, anti-CD20 
medication use, etc.) who have completed a COVID-19 vaccine series and who have a 
documented negative SARS-CoV-2 Spike (“S”) protein serum antibody test drawn a 
minimum of four weeks after completion of the recommended dosing series may be screened 
and subsequently enrolled if other criteria are met, including a confirmatory negative “S” 
protein antibody test at the time of screening. This test must be confirmed negative prior to 
enrollment in either Cohort A or Cohort B. 
2. Receipt of any investigational product within 30 days or 5 half-lives (whichever is longer) 
before the day of enrollment. 
3. Is acutely ill or has any of the following symptoms: 
Fever ≥38 °C (≥100.4 °F) 
Shortness of breath/difficulty breathing 
Chills (shivering) 
Cough 
Fatigue (low energy or tiredness) 
Muscle or body aches 
Headache 
Loss of taste 
Loss of smell 
Sore throat 
Congestion (stuffy or runny nose) 
Nausea 
Vomiting 
Diarrhea 
Note: Participants meeting this criterion may be scheduled for rescreening within the 
relevant window periods. 
4. Has received or plans to receive a non-COVID-19 vaccine within 28 days before or after 
dosing (except for seasonal influenza vaccine, which is not permitted within 14 days before 
or after dosing). 
5. Known allergy/sensitivity or hypersensitivity to the study drug, including excipients. 
6. Is pregnant, as confirmed with a positive pregnancy test at Screening or on the day of dosing 
(Day 1), or breastfeeding.  
7. Known clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or 
platelet disorder), or prior history of significant bleeding or bruising following IM injections 


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or venipuncture. Abnormal coagulation labs or use of anticoagulant medication are not 
exclusionary in the absence of clinical findings. 
8. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal 
disease, liver disease, renal disease, endocrine disorder, autoimmune disease or immune 
compromise, or neurological illness, as judged by the Investigator (mild/moderate well-
controlled comorbidities are allowed; see Appendix 4).  
9. Any serious concomitant systemic disease, condition, or disorder that, in the opinion of the 
Investigator, might confound the results of the study or confer an additional risk to the 
participant by their participation in the study. 
Details of Study Treatments 
ADG20 is a fully human monoclonal immunoglobulin G1 antibody targeted to an epitope in the 
receptor binding domain of the spike glycoprotein of SARS-CoV-2. All participants will receive 
either ADG20 300 mg administered as a single 2 mL or 3 mL IM injection or placebo (normal 
saline) in a volume matched to the active treatment. 
Criteria for Evaluation 
Efficacy: 
Efficacy assessments will include SARS-CoV-2 testing, evaluation of signs and symptoms of 
COVID-19, and determination of health care resource utilization. 
Safety: 
Safety will be assessed in an ongoing manner throughout the study. Safety assessments will 
include the following: complete physical examinations, vital signs, clinical laboratory 
assessments, injection-site reactions, hypersensitivity reactions, and adverse events (AEs, 
including serious AEs, medically attended AEs, AEs of special interest, and solicited AEs for 
injection site reactions). 
Pharmacokinetics/Immunogenicity: 
Blood samples will be collected at specified time points for PK and anti-drug antibody (ADA) 
assessment. Immunogenicity may be assessed by a validated assay designed to detect ADAs in 
the presence of ADG20. Antibodies may be further characterized for their ability to neutralize 
the activity of ADG20. 
Statistical Analysis 
Each cohort will be treated independently under this master protocol. Cohorts A and B will each 
have a separate randomization list. Efficacy and safety analyses will be performed separately for 
each cohort, with each cohort allocated a 2-sided alpha of .05.  
Enrollment in Cohort A (PEP) and in Cohort B (PrEP) was suspended on 11-Jan-2022 after 
emergence and global spread of the Omicron variant in regions enrolling the trial, beginning in 
December 2021, against which 300 mg ADG20 was not expected to have adequate efficacy due 
to decreased neutralization activity. Therefore, the primary analysis is focused on evaluating 


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ADG20 300 mg IM treatment in the population randomized prior to the emergence of the 
Omicron variant.  
A preliminary efficacy and safety analysis was conducted with a data cutoff of 02-Mar-2022. 
The primary efficacy objective was to assess efficacy of ADG20 in the setting of susceptible 
variants (pre-emergence of Omicron); thus, the primary efficacy population included participants 
randomized on or prior to 30-Nov-2021 and followed for at least 2 weeks (up to 15-Dec-2021) 
when Omicron became the predominant variant in the US. The efficacy of ADG20 after the 
emergence of the Omicron variant was evaluated independently as an exploratory analysis in 
participants randomized after 30-Nov-2021. A full analysis of efficacy following a database soft 
lock (data cutoff: 11-Apr-2022) was carried out when all enrolled participants had a minimum of 
3 months follow-up or had discontinued. A 6-month safety analysis will be carried out following 
a database soft lock when all enrolled participants have a minimum of 6 months follow-up or 
have discontinued. A final safety analysis will occur after all enrolled participants have been 
followed through 14 months/EOS or have discontinued. 
The population for the primary efficacy analyses in each cohort are:  
• Cohort A: RT-PCR-negative participants pre-emergence of Omicron (mFAS-1 pre-Omicron) 
• Cohort B: RT-PCR-negative and seronegative participants pre-emergence of Omicron 
(mFAS pre-Omicron) 
These analysis sets are defined as follows:  
Pre-Emergence of 
Omicron Analysis Set 
Includes all participants randomized on or prior to 30-Nov-2021, allowing participants 
to be followed a minimum of 2 weeks through 15-Dec-2021 when Omicron became 
the predominant variant.  
Modified Full Analysis 
Set – RT-PCR-negative 
and seronegative 
(mFAS) 
Includes all randomized participants without prior or current SARS-CoV-2 infection at 
baseline based on central tests (RT-PCR-negative and seronegative). If either central 
RT-PCR or central serology is missing at baseline, a negative baseline status can be 
imputed for a participant if there is a post-baseline negative central serology sample 
collected at least 14 days from Day 1 and prior to any positive local/central RT-PCR. 
Modified Full Analysis 
Set – RT-PCR-negative 
(mFAS-1) 
Includes all randomized participants without current SARS-CoV-2 infection at 
baseline based on central tests (RT-PCR-negative regardless of serology status). If 
central RT-PCR is missing at baseline, a negative baseline status can be imputed for a 
participant if there is a post-baseline negative central serology sample collected at least 
14 days from Day 1 and prior to any positive local/central RT-PCR. 
In the efficacy analysis, participants will be analyzed based on the treatment they are randomized 
to, irrespective of what they actually might have received.  
Safety analyses will be performed in the Safety Set, defined as all participants who receive study 
drug. In the safety analysis, participants will be analyzed based on the study drug received. 
Cohort A (PEP): The primary endpoint is the proportion of RT-PCR-confirmed symptomatic 
COVID-19 through 28 days after randomization. The original sample size of 1078 participants 
was planned with 90% power, 2-sided α=.05, and a 1:1 randomization ratio to detect a 
statistically significant RR when the true RR is 0.30 (70% efficacy) with an attack rate of 5% per 
28 days in the placebo group and 1.5% in the ADG20 group. A sample size of 1270 participants 


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was planned to account for 15% participants enrolled with a prior or current SARS-CoV-2 
infection at baseline.  
Enrollment was suspended in Cohort A on 11-Jan-2022 following the emergence of Omicron 
variant, against which 300 mg ADG20 was not expected to have adequate efficacy due to 
decreased neutralization activity. As such, the analysis of the primary efficacy endpoint for 
Cohort A only included events through 28 days after randomization or the emergence of 
Omicron, whichever was earlier. Prior to suspension of enrollment, 487 participants were 
randomized in Cohort A, of which approximately 377 were enrolled prior to the emergence of 
Omicron with a minimum of 2 weeks follow-up through 15-Dec-2021, and 351 were estimated 
to be eligible for inclusion in the primary efficacy analysis population (RT-PCR-negative pre-
Omicron). The primary efficacy population yielded approximately 14 events through 28 days or 
emergence of Omicron, whichever was earlier, for the analysis. With 14 events, any observed 
efficacy >68% would be statistically significant at 2-sided α=.05. 
Cohort B (PrEP): The primary endpoint is the proportion of RT-PCR-confirmed symptomatic 
COVID-19 through 3 months. The original sample size of 4628 participants was planned with 
84% power, 2-sided α=.05, and a 1:1 randomization ratio to detect a statistically significant RR 
when the true RR is 0.30 (70% efficacy) with an attack rate of 1% per 3 months in the placebo 
group and 0.3% in the ADG20 group. A sample size of 5142 participants was planned to account 
for 10% participants enrolled with a prior or current SARS-CoV-2 infection at baseline. 
Enrollment was suspended in Cohort B on 11-Jan-2022 following the emergence of Omicron 
variant, against which 300 mg ADG20 was not expected to have adequate efficacy due to 
decreased neutralization activity. As such, the analysis of the primary efficacy endpoint for 
Cohort B only included events through 3 months after randomization or the emergence of 
Omicron, whichever was earlier. Prior to suspension of enrollment, 2094 participants were 
randomized in Cohort B, of which approximately 1639 were enrolled prior to the emergence of 
Omicron with a minimum of 2 weeks follow-up through 15-Dec-2021, and 1477 were estimated 
to be eligible for inclusion in the primary efficacy analysis population (RT-PCR-negative and 
seronegative pre-Omicron). A higher than expected aggregate attack rate resulted in a sufficient 
number of cases to enable this cohort to be a fully powered study to detect clinically meaningful 
and statistically significant treatment differences. Based on a 3.6% aggregate attack rate, 974 
participants in a 1:1 randomization ratio provides 90% power to detect a statistically significant 
treatment effect when the true RR is 0.3 with 2-sided α=.05. Therefore, the current sample size 
of 1477 provided sufficient statistical power to carry out the primary efficacy analysis, as well as 
preliminary evaluation of safety. 


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TABLE OF CONTENTS 
DOCUMENT REVISION HISTORY .............................................................................................2 
SIGNATURE PAGE .......................................................................................................................3 
SYNOPSIS ......................................................................................................................................4 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................23 
1. 
INTRODUCTION ......................................................................................................26 
1.1. 
ADG20 Background ...................................................................................................26 
1.1.1. 
Nonclinical Studies of ADG20 ...................................................................................26 
1.1.2. 
Clinical Studies of ADG20 .........................................................................................26 
1.2. 
Background on the Disease/Condition .......................................................................28 
1.3. 
Study Rationale ...........................................................................................................30 
1.3.1. 
Rationale for Use of a Monoclonal Antibody .............................................................30 
1.3.2. 
Rationale for Use of Placebo-Control .........................................................................31 
1.3.3. 
Pregnant and Breastfeeding Individuals .....................................................................32 
1.3.4. 
Rationale for Dose Selection ......................................................................................32 
1.4. 
Risks and Benefits ......................................................................................................33 
1.4.1. 
Benefits to the Target Study Population .....................................................................33 
1.4.2. 
Risks from Study Participation ...................................................................................34 
1.4.3. 
Overall Benefit-Risk Conclusion ................................................................................35 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................36 
3. 
INVESTIGATIONAL PLAN .....................................................................................41 
3.1. 
Overall Study Design and Plan ...................................................................................41 
3.1.1. 
Study Definitions ........................................................................................................44 
3.1.2. 
Methodology ...............................................................................................................46 
3.2. 
Study Duration ............................................................................................................47 
3.3. 
Selection of Study Population ....................................................................................48 
3.3.1. 
Inclusion Criteria ........................................................................................................48 
3.3.2. 
Exclusion Criteria .......................................................................................................50 
3.3.3. 
Withdrawal from Study ..............................................................................................51 
3.3.4. 
Replacement of Participants .......................................................................................51 
3.4. 
Treatments ..................................................................................................................51 
3.4.1. 
Details of Study Treatments .......................................................................................51 


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3.4.2. 
Treatment Assignment and Randomization ................................................................52 
3.4.3. 
Study Drug Packaging and Labeling ..........................................................................53 
3.4.4. 
Study Drug Storage and Handling ..............................................................................53 
3.4.5. 
Breaking the Blind ......................................................................................................53 
3.4.6. 
Counseling and Unblinding for Participants Wishing to Receive a COVID-
19 Vaccination During the Study ...............................................................................54 
3.4.7. 
Drug Inventory and Accountability ............................................................................54 
3.4.8. 
Study Drug Handling and Disposal ............................................................................55 
3.4.9. 
Prior and Concomitant Treatments .............................................................................55 
3.5. 
Assessments ................................................................................................................56 
3.5.1. 
Schedule of Assessments ............................................................................................56 
3.5.2. 
Study Visits .................................................................................................................61 
3.5.3. 
CLI Period: Study Visits in the Event of COVID-19-Like Illness .............................64 
3.5.4. 
Efficacy Assessments .................................................................................................66 
3.5.5. 
Safety Assessments .....................................................................................................71 
3.5.6. 
Pharmacokinetic and Immunogenicity Assessments ..................................................73 
3.5.7. 
Appropriateness of Measurements .............................................................................74 
4. 
ADVERSE EVENT REPORTING ............................................................................74 
4.1. 
Definitions and Criteria ..............................................................................................74 
4.1.1. 
Adverse Events ...........................................................................................................74 
4.1.2. 
Serious Adverse Events ..............................................................................................74 
4.1.3. 
Adverse Events Based on Signs and Symptoms .........................................................75 
4.1.4. 
Adverse Events Based on Examinations and Tests ....................................................75 
4.1.5. 
Abnormal Laboratory Values .....................................................................................76 
4.1.6. 
Solicited Adverse Events ............................................................................................76 
4.1.7. 
Adverse Events of Special Interest .............................................................................77 
4.1.8. 
Medically Attended Adverse Events ..........................................................................77 
4.1.9. 
Assessing Intensity and Relationship .........................................................................77 
4.2. 
Reporting Procedures and Requirements ....................................................................79 
4.2.1. 
Adverse Events ...........................................................................................................79 
4.2.2. 
Serious Adverse Events ..............................................................................................79 
4.2.3. 
Procedures for Documenting Pregnancy During Study ..............................................80 


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4.2.4. 
Unanticipated Problems Involving Risks and Adverse Events ..................................81 
5. 
STATISTICAL ANALYSIS ......................................................................................82 
5.1. 
Overall Analysis Plan .................................................................................................82 
5.2. 
Blinding ......................................................................................................................82 
5.3. 
Analysis Sets ...............................................................................................................83 
5.4. 
Sample Size Determination ........................................................................................84 
5.5. 
Protocol Deviations ....................................................................................................85 
5.6. 
Participant Disposition ................................................................................................86 
5.7. 
Demographic and Baseline Characteristics ................................................................86 
5.8. 
Concomitant Medication and Medical History ...........................................................86 
5.9. 
Efficacy Analyses .......................................................................................................86 
5.9.1. 
Primary Efficacy Endpoint .........................................................................................91 
5.9.2. 
Secondary Efficacy Endpoints and Analyses .............................................................91 
5.9.3. 
Multiplicity .................................................................................................................92 
5.9.4. 
Exploratory Endpoints ................................................................................................92 
5.10. 
Safety Analyses ..........................................................................................................92 
5.10.1. 
Adverse Events ...........................................................................................................92 
5.10.2. 
Laboratory Data ..........................................................................................................93 
5.10.3. 
Vital Signs ..................................................................................................................93 
5.10.4. 
Immunogenicity ..........................................................................................................93 
5.11. 
Pharmacokinetics ........................................................................................................93 
5.12. 
Independent Data Monitoring Committee Safety Monitoring ....................................94 
6. 
STUDY MANAGEMENT .........................................................................................95 
6.1. 
Ethics and Consent .....................................................................................................95 
6.1.1. 
Regulations and Guidelines ........................................................................................95 
6.1.2. 
Institutional Review Board/Independent Ethics Committees and Competent 
Authorities ..................................................................................................................95 
6.1.3. 
Informed Consent .......................................................................................................95 
6.2. 
Data Protection ...........................................................................................................95 
6.3. 
Discontinuation of the Study by the Sponsor .............................................................96 
6.4. 
Study Documentation .................................................................................................96 
6.5. 
Data Management and Quality Control ......................................................................96 


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6.5.1. 
Electronic Case Report Forms ....................................................................................96 
6.5.2. 
Data Management Considerations ..............................................................................97 
6.5.3. 
Study Monitoring and Quality Assurance ..................................................................97 
6.6. 
Collection and Update of Contacts .............................................................................97 
6.7. 
Retention of Records ..................................................................................................98 
6.8. 
Use of Study Findings ................................................................................................98 
6.9. 
Publications .................................................................................................................98 
7. 
REFERENCES ...........................................................................................................99 
8. 
APPENDICES ..........................................................................................................105 
 
TABLES 
Table 2.1 
Objectives and Endpoints: Cohort A (PEP) ................................................................36 
Table 2.2 
Objectives and Endpoints: Cohort B (PrEP) ..............................................................39 
Table 2.3 
Exploratory Objectives and Endpoints: Cohorts A and B ..........................................41 
Table 3.1 
Guidelines for COVID-19-Like Illness Qualifying Symptoms ..................................44 
Table 3.2 
Details of Study Drug .................................................................................................52 
Table 3.3 
Schedule of Assessments ............................................................................................57 
Table 3.4 
Schedule of Assessments for COVID-19-Like Illness Visits .....................................59 
Table 3.5 
Assessments to be Performed at Unscheduled Visits for Participants 
Intending to Receive COVID-19 Vaccine ...................................................................63 
Table 5.1 
Defined Analysis Sets and Descriptions .....................................................................83 
Table 5.2 
Efficacy Endpoints and Statistical Analyses Methods: Cohort A (PEP) ....................87 
Table 5.3 
Efficacy Endpoints and Statistical Analyses Methods: Cohort B (PrEP) ...................89 
Table 5.4 
Independent Data Monitoring Committee Safety Monitoring ....................................94 
 
FIGURES 
Figure 3.1 Study Design Schematic .............................................................................................43 
 
APPENDICES 
Appendix 1. Injection Site Reaction e-Diary ............................................................................105 
Appendix 2. Collection of Coronavirus Disease 2019 Symptoms ............................................106 
Appendix 3. Worksheet for Assessment of Risk Factors for Exposure to SARS-CoV-2 .........107 


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Appendix 4. Risk Factors for Severe Coronavirus Disease 2019 .............................................108 
Appendix 5. Modified FDA Scale for COVID-19-Like Illness Severity .................................109 
Appendix 6. Clinical Laboratory Tests .....................................................................................111 
Appendix 7. Country-Specific Requirements ...........................................................................112 
 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ACIP 
Advisory Committee on Immunization 
ADA 
anti-drug antibody 
ADE 
antibody-dependent enhancement 
AE 
adverse event 
AESI 
adverse event of special interest 
BMI 
body mass index 
CDC 
Centers for Disease Control and Prevention 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence interval 
CLI 
COVID-19-like illness 
CoV 
coronavirus 
DAIDS 
Division of AIDS 
eCRF 
electronic case report form 
EDC 
electronic data capture 
e-Diary 
electronic diary 
EOS 
end of study 
ET 
early termination 
EUA 
emergency use authorization 
FAS 
full analysis set 
Fc 
fraction crystallizable 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
IB 
Investigator’s Brochure 
IC50 
Half-maximal inhibitory concentration 
ICE 
intercurrent event 
ICF 
informed consent form 
ICU 
intensive care unit 
iDMC 
independent data monitoring committee 
IEC 
independent ethics committee 
IgA 
immunoglobulin A 
IgG 
immunoglobulin G 
IM 
intramuscular(ly) 
IRB 
institutional review board 
IRT 
interactive response technology 
ISR 
injection site reaction 
LTFU 
long-term follow-up 
MAAE 
medically attended adverse event 


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Abbreviation 
Definition 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
modified full analysis set 
NP 
nasopharyngeal 
ODM 
operational data mode 
PBPK 
physiologically based pharmacokinetic 
PCS 
potentially clinically significant 
PEP 
post-exposure prophylaxis 
PK 
pharmacokinetics 
POC 
point of care 
PP 
per-protocol 
PrEP 
pre-exposure prophylaxis 
PT 
preferred term 
QSP 
quantitative systems pharmacology 
RBD 
receptor binding domain 
RR 
risk ratio 
RSV 
respiratory syncytial virus 
RT-PCR 
reverse transcription polymerase chain reaction 
RT-qPCR 
quantitative reverse transcription polymerase chain reaction 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SARS 
severe acute respiratory syndrome 
SoA 
schedule of assessments 
SOC 
system organ class 
SOP 
standard operating procedures 
SOT 
solid organ transplant 
SpO2 
oxygen saturation 
sVNA 
serum virus neutralizing antibody 
TEAE 
treatment-emergent adverse event 
UP 
unanticipated problem 
US 
United States 
USP 
United States Pharmacopeia 
β-hCG 
beta human chorionic gonadotropin 


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PHARMACOKINETIC ABBREVIATIONS 
AUC 
Area under the plasma concentration-time curve 
AUC0-inf 
Area under the plasma concentration-time curve extrapolated to infinite time 
AUC0-last 
Area under the plasma concentration-time curve from zero up to the last concentration above 
the lower limit of quantification 
CL 
Clearance 
Cmax 
Maximum plasma concentration 
t½ 
Plasma concentration half-life 
Tmax 
Time to reach Cmax  
Vss 
Apparent volume of distribution at steady state  
 
 


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1. 
INTRODUCTION 
1.1. 
ADG20 Background 
ADG20 (also known as adintrevimab) is a fully human monoclonal immunoglobulin G1 
antibody targeted to the spike glycoprotein of SARS-CoV-2. ADG20 binds with high affinity to 
a conserved epitope in the RBD of the spike protein of SARS-CoV-2 and related Clade 1 
sarbecoviruses and displays broad and potent in vitro neutralizing activity against SARS-CoV-2, 
SARS-CoV, SARS-CoV-2 D614G, and the bat SARS-like viruses WIV1-CoV and 
SHC014-CoV. In addition to potent neutralization, ADG20 displays Fc-mediated innate immune 
effector activity, including antibody-dependent cellular cytotoxicity, antibody-dependent cellular 
phagocytosis, and antibody-dependent complement deposition. The Fc region of ADG20 has 
also been engineered to contain the Fc heavy chain modification LA (M435L, N441A), resulting 
in an estimated half-life of approximately 97 days in humans based on preliminary data from a 
Phase 1 study (ADG20-1-001) in heathy adult volunteers. No ADG20-specific off target binding 
to human tissues was observed in adult and fetal human tissue cross-reactivity and 
immunohistochemistry studies, and ADG20 was not associated with any toxicologically relevant 
or clinically meaningful findings during or at the end of the in-life portion in a repeat-dose rat 
toxicology study. 
1.1.1. 
Nonclinical Studies of ADG20 
Given the rising prevalence of SARS-CoV-2 variants, nonclinical studies evaluating the ability 
of ADG20 to bind to and neutralize known and emerging variants of concern are performed on 
an ongoing basis. ADG20 has displayed potent binding and neutralizing activity against multiple 
SARS-CoV-2 variants of concern, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and 
B.1.617.2 (Delta) (Dejnirattisai 2021). In vitro activity has been demonstrated against variants 
that have shown relative or absolute resistance to a subset of other clinical stage SARS-CoV-2 
mAb products (Dejnirattisai 2021; Liu 2021a; Liu 2021b; Planas 2021; Starr 2021; Wang 2021; 
Dejnirattisai 2022) and that have been associated with lower rates of vaccine efficacy (Madhi 
2021; Mahase 2021; Voysey 2021). In addition, ADG20 displayed in vitro binding and/or 
neutralizing activity against the SARS-CoV-2 variant B.1.1.529 BA.1 (Omicron), albeit with 
reduced potency compared to activity against prior variants (Liu 2021b; Planas 2021; Starr 2021; 
Wang 2021). The nonclinical program includes in vitro studies evaluating the avid and 
monovalent binding by ADG20 to SARS-CoV-2 RBDs incorporating mutations present in 
known and emerging variants and in vitro neutralization assays using authentic virus variants and 
pseudovirus. A detailed review of nonclinical experience with ADG20 is provided in the IB.  
1.1.2. 
Clinical Studies of ADG20 
Dosing in the EVADE study was initiated in April 2021; follow-up is ongoing. As of 
11-Jan-2022, 487 participants were randomized in Cohort A and 2101 participants were 
randomized in Cohort B; enrollment was suspended on this date due to the global spread of the 
Omicron variant. Pre-specified analyses in the pre-Omicron population demonstrated that 
adintrevimab provided a statistically significant and clinically meaningful reduction in the risk of 
developing symptomatic COVID-19 compared with placebo through Day 28 in adults with no 


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current SARS-CoV-2 infection who were recently exposed to SARS-CoV-2 and through 
3 months in adults with no current or prior SARS-CoV-2 infection who were at high risk for 
acquiring SARS-CoV-2. Further details are provided in the IB. 
In addition to this study, Adagio Therapeutics, Inc. (hereafter referred to as Adagio) is evaluating 
the safety, tolerability, and PK of ADG20 in 2 ongoing trials. 
1.1.2.1. 
Study ADG20-1-001 
Study ADG20-1-001 is a first-in human, Phase 1, randomized, double-blind, placebo-controlled, 
single ascending dose study conducted in the United States in healthy adult volunteers to 
evaluate the safety and PK of ADG20 (100 mg/mL formulation). To date, 48 participants across 
6 dose levels (300 mg IM, 500 mg IV, 600 mg IM, 1200 mg IM, 1200 mg IV, and 4500 mg IV) 
received ADG20 (8 per dose cohort) and 12 received placebo (2 per dose cohort). All 
participants in Cohorts 1-3 have completed the study; safety follow-up is ongoing in Cohorts 4-6. 
Findings from the unblinded analysis of Cohorts 1-3 and preliminary findings from blinded data 
review with a minimum of 4 months of follow-up in Cohorts 3-6 are as follows: 
• No SAEs, AESIs (hypersensitivity reactions or infusion-related reactions), drug-related AEs, 
or ISRs have been reported as of 01-Aug-2022.  
• The observed ADG20 PK appears to be dose proportional, with a median observed half-life 
of approximately 91 days for the 300 mg IM dose.  
• In an exploratory research analysis, 50% sVNA titers following a single 300 mg IM dose of 
ADG20 were compared to peak titers induced 7 to 30 days following 2 doses of the 
AZD1222 (Vaxzevria) or mRNA-1273 (Spikevax) vaccines given according to current on-
label or EUA dosing:  
− By Day 2, 50% sVNA titers against an authentic SARS-CoV-2 D614G variant in 
ADG20-treated participants were similar to peak titers generated following the 
mRNA-1273 vaccine series and significantly exceeded peak titers generated after the 
AZD1222 vaccine series.  
− By Day 7, 50% sVNA titers were significantly higher than peak titers generated by the 
mRNA-123 vaccine series and remained above mRNA-1273-elicited titers for at least 3 
months.  
− By 6 months, 50% sVNA titers in ADG20-treated participants declined to levels similar 
to or exceeding peak responses following the mRNA-1273 or AZD1222 vaccine series, 
respectively. 
1.1.2.2. 
Study ADG20-TRMT-001 (STAMP) 
Study ADG20-TRMT-001 (STAMP) is a randomized, double-blind, placebo-controlled, 
multicenter Phase 2/3 study to evaluate the safety, efficacy, and PK of ADG20 (300 mg IM) 
versus placebo in the treatment of mild to moderate COVID-19 in adult and adolescent 
participants at high risk of disease progression. Dosing in the study was initiated on 
18-Aug-2021; follow-up is ongoing. As of 11-Jan-2022, 399 participants were randomized in the 
study and enrollment was suspended on this date due to the global spread of the Omicron variant. 


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Pre-specified analyses in the population of participants with non-Omicron COVID-19 
demonstrated that treatment with adintrevimab provided a statistically significant and clinically 
meaningful reduction in the risk of COVID-19–related hospitalization or all-cause death through 
Day 29 compared with placebo. Further details on the study are provided in the IB.  
1.2. 
Background on the Disease/Condition 
Coronaviruses are ubiquitous pathogens with high pandemic potential. In recent years, 
3 pathogenic CoVs have crossed into the human population from zoonotic sources: SARS-CoV, 
Middle East respiratory syndrome CoV, and SARS-CoV-2. SARS-CoV-2, the most recent of 
these CoVs, emerged in late 2019 and is the causative agent of COVID-19. As of 27-Jan-2022, 
over 363 million cases have been reported globally, including over 5.6 million deaths. 
Approximately 20% (~73 million) of reported cases have occurred in the US alone with 
>876 000 deaths to date (Johns Hopkins University & Medicine 2022a). In addition to this health 
crisis, the COVID-19 pandemic has led to steep economic recessions in many countries. The 
World Bank reported a 3.5% contraction in global gross domestic product in 2020, the deepest 
global recession since the Second World War (World Bank 2021). The ongoing pandemic has 
had a devastating effect on income growth and inequality that is expected to linger for a 
protracted period, with recovery largely dependent on controlling the ongoing pandemic. 
Symptoms of COVID-19 may appear from 2 to 14 days following exposure to SARS-CoV-2, 
with clinical manifestations ranging from mild symptoms to severe illness and death. The 
majority of infections result in mild to moderate symptoms and asymptomatic infections have 
been estimated to account for as many as 40% to 45% of all SARS-CoV-2 infections (Oran 
2020). In a report from the Chinese CDC that described 44 415 confirmed cases, an estimation of 
disease severity of mild, severe, and critical disease was reported in 81%, 14% and 5% of cases, 
respectively, with a 2.3% case fatality rate (Wu 2020). Common symptoms include fever or 
chills, cough, shortness of breath/difficulty breathing, fatigue, muscle/body aches, headache, new 
loss of sense of taste or smell, sore throat, nasal congestion, nausea/vomiting, and diarrhea (CDC 
2022d). A subset of individuals with initially mild or moderate symptoms may experience 
disease progression. Dyspnea developed after a median of 5 days of symptom onset with hospital 
admission occurring after a median of 7 days of symptom onset in a study of 138 patients 
hospitalized with COVID-19 pneumonia (Wang 2020).  
Complications of COVID-19 include respiratory failure (acute respiratory distress syndrome), 
cardiac and cardiovascular complications (arrythmias, acute cardiac injury, shock, and 
cardiomyopathy), thromboembolic events (pulmonary embolism and acute stroke), and 
inflammatory complications (Guillain-Barré syndrome and multisystem inflammatory syndrome 
similar to Kawasaki disease/toxic shock syndrome in children). Time to recovery is variable and 
appears to be approximately 2 to 3 weeks for mild infection and 2 to 6 weeks for severe disease 
(WHO 2020). In a survey of 350 hospitalized patients in the US, only 39% of patients reported a 
return to baseline health by 14 to 21 days after diagnosis (Tenforde 2020a) and only 13% of 
143 hospitalized patients in Italy reported being symptom-free 60 days after onset of disease 
(Carfì 2020). Recent data suggests that even patients with mild disease may experience 
prolonged symptoms, with only 65% of patients reporting return to baseline health by 14 to 
21 days after diagnosis (Tenforde 2020b).  


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Age is the predominant risk factor for development of severe COVID-19, with older patients, 
particularly those with comorbid disease, displaying the highest risk of morbidity and mortality 
(Garg 2020). In addition to age, the following comorbidities have been identified as risk factors 
for the development of severe COVID-19: cancer, chronic kidney disease, chronic lung disease, 
Down syndrome, heart conditions (heart failure, coronary artery disease, cardiomyopathies, and 
hypertension), immunocompromised state (eg, SOT), obesity (BMI of ≥30 kg/m2), pregnancy, 
sickle cell disease, smoking, and diabetes (CDC 2021b). The symptoms of COVID-19 are 
similar in adolescents and adults although the frequency of specific symptoms may vary (Stokes 
2020). Similar to adults, severe outcomes are more common in adolescents with underlying 
comorbidities, including chronic lung disease, obesity, cardiovascular disease, 
neurologic/developmental disorders, and immunosuppressive conditions (Bixler 2020; Stokes 
2020). Current data suggest that adolescents have similar susceptibility to infection and risk of 
secondary transmission as adults (Boehmer 2020; Leeb 2020; Goldstein 2021; Viner 2021) and 
may play an increasingly important role in ongoing community transmission of SARS-CoV-2. 
The incidence of confirmed infections increased 3-fold among those aged 10 to 19 years in the 
US from May 2020 to August 2020 (Boehmer 2020), and large outbreaks have been reported in 
high schools and university campuses (Salvatore 2020; Stein-Zamir 2020; Wilson 2020). 
There are currently over 20 COVID-19 vaccines spanning several platforms (eg, mRNA, 
adenovirus, inactivated) that are approved or available under emergency use across various 
regions globally, with over 50 in Phase 3 development. However, vaccine roll-out has been 
persistently slow worldwide, with only ~53% of the population fully vaccinated as of 
27-Jan-2022 (Johns Hopkins University & Medicine 2022b), at least in part due to unequal 
vaccine distribution and high rates of vaccine hesitancy in some countries (Solís Arce 2021). 
Furthermore, available data suggest that vaccine efficacy wanes over time, leading to the 
recommendation for booster doses in some regions at 6 months for all adults and some 
adolescents (CDC 2022b). Recent studies have also demonstrated that certain immune 
compromised individuals (eg, those with hematologic malignancies, hematopoietic stem cell, or 
SOT recipients, and people actively receiving chemotherapy for cancer or using 
immunosuppressive medications) mount poor neutralizing antibody responses to currently 
available vaccines (Agha 2021; Boyarsky 2021). In some cases, even a third dose of vaccine fails 
to induce significant antibody responses in SOT recipients (Kamar 2021).  
As the COVID-19 pandemic has persisted over time and the number of vaccinated individuals or 
those with natural infection continues to rise, SARS-CoV-2 breakthrough infections in fully 
vaccinated individuals and re-infections in those who have recovered from prior infection have 
become more common due to emerging variants that are relatively resistant to vaccine-induced 
immunity or natural immunity from prior infection, as well as waning natural/vaccine-induced 
immunity over time (CDC 2021c; Levin 2021; Lipsitch 2022; UKHSA 2022). In particular, 
vaccine efficacy has been shown to be decreased against the Delta variant and even more so 
against the Omicron variant, especially for the endpoint of symptomatic infection (Collie 2021; 
Li 2021; Lopez Bernal 2021). Though breakthrough infections may be less severe, severe 
COVID-19 (CDC 2021a; Wang 2022) and post-acute sequalae of COVID-19 (Bergwerk 2021) 
following breakthrough infections have been reported.  


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In conclusion, novel approaches are urgently needed to ensure the availability of safe and 
effective options for the broader population to curtail the current COVID-19 pandemic and 
potentially address future emergent CoVs with pandemic potential. 
1.3. 
Study Rationale 
1.3.1. 
Rationale for Use of a Monoclonal Antibody 
Given the global magnitude of the COVID-19 pandemic, efforts to develop safe and effective 
prophylaxis have taken on unprecedented urgency, with a primary focus on vaccines. However, 
there are still several unanswered questions regarding the available vaccines. Chief among these 
are the duration of protection, long-term safety profile, effectiveness against emerging viral 
variants, the ability to prevent transmission, and effectiveness in pediatric and 
immunocompromised populations.  
The therapeutic use of passive polyclonal antibodies to prevent viral infections, including 
hepatitis B, varicella, cytomegalovirus, rabies, and RSV, is well established. More recently, 
mAbs have been approved for the prevention or treatment of viral infections, including 
palivizumab for the prevention of RSV infection, ibalizumab for the treatment of HIV-1 
infection in heavily treatment-experienced adults, atoltivimab/maftivimab/odesivimab 
combination and ansuvimab for treatment of Zaire ebolavirus infection, and SII RMab for 
post-exposure prophylaxis of rabies in India. Notably, mAb prophylaxis is the only currently 
licensed therapy for RSV. 
The unique properties of mAbs address several limitations of vaccines in disease prevention. 
While vaccines require several weeks, and in some cases, multiple doses, to induce a protective 
immune response, the protection provided by mAbs is nearly immediate, making them 
well-suited for post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP).  
In support of the use of mAbs in PEP, results from two SARS-CoV-2 mAb programs 
demonstrate the ability to protect non-immune (seronegative) and non-infected (RT-PCR 
negative), recently exposed individuals from symptomatic COVID-19 across a variety of 
exposure settings, including households and nursing homes (Eli Lilly and Company 2022; 
Regeneron 2022). These data led to emergency use authorizations for casirivimab/imdevimab 
and bamlanivimab/etesevimab in individuals with suboptimal immunity and known recent 
exposure to an active case. However, the authorizations for these mAbs were revised in 
January 2022 based on the finding that neither product retains in vitro activity against the 
Omicron variant, which is currently the predominant variant circulating in the United States. As 
such, both products are currently not authorized for use in any region of the US at this time 
(FDA 2022). 
The use of mAbs in PrEP is supported by data from the tixagevimab/cilgavimab program, which 
demonstrated the ability of this combination mAb product to provide durable protection due to 
the extended half-life through a median of 3 months of follow-up in the primary analysis and 6.5 
months of follow-up in a post-hoc analysis (AstraZeneca 2022). These data led to emergency use 
authorization for tixagevimab co-packaged with cilgavimab for PrEP in individuals who are not 
currently infected with and have not had a known recent exposure to an individual infected with 
SARS-CoV-2 who have moderate to severe immune compromise and either may not mount an 


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adequate immune response to COVID-19 vaccination or for whom vaccination is not 
recommended due to a history of severe adverse reaction to a COVID-19 vaccine or its 
components. 
Monoclonal antibodies do not rely on an intact immune system for efficacy, and thus may confer 
protection in those with impaired immune function, such as the immune compromised and 
patients on immunosuppressive therapy. Another potential limitation of vaccines is variable 
initial antibody responses coupled with waning of immunity over time. Extended half-life mAbs 
address this limitation by providing more predictable antibody levels and duration of protection. 
As they do not alter the immunologic repertoire, mAbs may also act additively with vaccines, 
providing a bridge of protection until the vaccine reaches maximal efficacy or augmenting the 
immunological response triggered by the vaccine. 
Given these potential advantages of mAbs in the prevention of respiratory virus infection and 
disease, several mAbs are currently in clinical development for prevention of respiratory virus 
infection and/or disease, including agents for influenza virus, RSV, and SARS-CoV-2 (Corti 
2017; Walker 2018).  
The potential for ADG20 to provide broad immediate and longer-term protection to a wide range 
of individuals is supported by nonclinical data (see Section 1.1.1), in which ADG20 displayed 
binding and/or neutralizing activity against multiple SARS-CoV-2 variants, and preliminary 
clinical data (see Section 1.1.2.1) that demonstrate the extended half-life of ADG20 (97 days) 
and robust sVNA titers against the D614G variant through 6 months following a single 300 mg 
IM injection of ADG20. Considering this potential, Adagio is developing ADG20 for PEP for 
individuals with documented, recent exposure to SARS-CoV-2 and for PrEP for individuals with 
high ongoing risk of exposure to SARS-CoV-2 due to their occupation, housing situation, or 
other activities.  
The study will be conducted in compliance with the protocol, GCP, and applicable regulatory 
requirements. 
1.3.2. 
Rationale for Use of Placebo-Control  
Despite the availability of COVID-19 vaccines for pre-exposure prophylaxis for adults and, in 
some regions, adolescents and children 5 years of age and older, a placebo-controlled study is 
acceptable as these vaccines may not be widely available for use globally and a sizeable portion 
of the global population remains resistant to vaccination. Only those participants who intend to 
delay vaccination for 6 months after discussion of the risks/benefits of trial enrollment in the 
setting of current or potential future vaccine availability and their underlying risk for 
development of severe COVID-19 are eligible for enrollment in the trial. Participants who 
receive vaccine within the first 6 months of enrollment into the study may undergo additional 
assessments to evaluate the potential impact of ADG20 on vaccine-induced immunity. 
Prior to protocol version 6.0, if a participant wished to receive a vaccine during the study, they 
could request unblinding to support informed decision making; as of protocol version 6.0, 
unblinding is no longer necessary.  
Similarly, despite availability of SARS-CoV-2 mAbs for PEP or PrEP for certain individuals 
under emergency use authorization in some regions, a placebo-controlled study is acceptable as 


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these mAbs are not widely available for use globally. Potential participants under consideration 
for enrollment in the study and who are eligible for mAbs offered under EUA or similar 
authorization outside the US will be advised of their availability and provided information 
regarding how to obtain them as part of the informed consent process.  
1.3.3. 
Pregnant and Breastfeeding Individuals 
Pregnant individuals are at increased risk for severe illness from COVID-19 when compared to 
nonpregnant individuals and may also be at increased risk for other poor outcomes, such as 
preterm birth (CDC 2022a). The risks of ADG20 treatment for pregnancy and the developing 
fetus are unknown. As with other COVID-19 mAb products (FDA 2021b; FDA 2021a), no 
specific risks to pregnant individuals and their fetuses or to breastfeeding individuals and their 
infants have been identified based on ADG20 nonclinical safety data. Because ADG20 is 
directed against an exogenous antigen, administration is not anticipated to impact endogenous 
pathways. 
Human IgG1 antibodies are known to cross the placental barrier; therefore, ADG20 has the 
potential to be transferred from the mother to the developing fetus. Similarly, maternal IgG is 
known to be present in breastmilk. Robust secretion of SARS-CoV-2-specific IgA and IgG 
antibodies was observed in breastmilk for 6 weeks after vaccination (Low 2021; Perl 2021). 
However, because of the large size of ADG20, it is unlikely to be absorbed from the infant gut in 
large quantities. Additionally, no effect on infant health from possible absorption of ADG20 is 
anticipated given the antibody targets an exogenous protein not present in the human body.  
Addition of pregnant women is also supported by the results of nonclinical studies. Specifically, 
in a tissue cross-reactivity study using human fetal tissues, no specific binding of ADG20 was 
observed. For additional details regarding the fetal tissue cross-reactivity study, please refer to 
the IB. Further, based on unblinded review of Phase 2 safety data in the first 200 participants 
enrolled across Cohorts A and B of this study (EVADE), the iDMC endorsed opening of 
enrollment in these cohorts to pregnant and breastfeeding women. Based on the increased risk 
for poor COVID-19 outcomes for pregnant individuals, the low assessed risk associated with 
ADG20 administration, and the iDMC recommendation, enrollment of pregnant or breastfeeding 
individuals may be opened in the Phase 3 portion of this trial in regions permitted by health 
authorities and local ethics committees. 
All women of childbearing potential will undergo pregnancy testing prior to dosing and at the 
end of study. Participants who become pregnant during the study will be followed for the 
outcome of their pregnancy for the duration of the study.  
Information regarding pregnancies occurring in female partners of male study participants will 
not be solicited as the risk of exposure is negligible in this scenario. 
1.3.4. 
Rationale for Dose Selection  
ADG20 will be administered IM at a dose of 300 mg. This dose was selected based on the 
ADG20 target and mechanism of action, in vitro/in vivo toxicology data, the no observed 
adverse-effect level observed in the pivotal toxicology study, and estimations of human PK 


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projected using a QSP whole-body PBPK model. Human PK projections were used to determine 
safety margins based on exposures anticipated from the proposed dose. 
The QSP/PBPK model projects that the 300 mg IM dose is expected to maintain serum ADG20 
concentrations ~500-fold greater than the in vitro IC50 (0.001 μg/mL) against authentic 
SARS-CoV-2 (USA-WA1/2020) in Vero E6 cells for a minimum of 6 months in ≥90% of 
simulated patients. This threshold is similar to the 50% SARS-CoV-2 geometric mean titer 
observed on Day 35 (7 days after a second vaccine dose) with the COVID-19 vaccine BNT62b1 
(Mulligan 2020), which has been shown to confer 95% protection against COVID-19 through 
2 months after the second dose (Polack 2020). 
Further, in the context of a prevention study, it is also likely that a small subset of participants, 
particularly in the subgroup with known recent exposure, will have very early asymptomatic 
SARS-CoV-2 infection and low or undetectable viral load at baseline. At the 300 mg IM dose, 
the QSP/PBPK model forecasted ADG20 lung interstitial concentrations range from 
approximately 100 to 275-times the ADG20 IC90 against authentic virus (USA-WA1/2020) at 
28 days postdose. These ADG20 lung interstitial exposures indexed to IC90 exceed those 
projected for bamlanivimab, a SARS-CoV-2-specific mAb that has shown clinical benefit and 
reductions in viral load in ambulatory patients with symptomatic, mild to moderate COVID-19 
and high viral load (Chen 2021). Thus, ADG20 has the potential to provide adequate exposure to 
prevent progression of early SARS-CoV-2 infection in participants infected with SARS-CoV-2 
variants for which a dose of 300 mg IM is anticipated to provide adequate tissue exposure, such 
as Alpha, Beta, Delta, and Gamma. These findings suggest that the 300 mg IM dose is 
appropriate for both prevention of infection in individuals without prior exposure to 
SARS-CoV-2, as well as for prevention of disease progression in individuals with very early 
asymptomatic or pre-symptomatic infection associated with relatively low or undetectable viral 
load. 
The dose level is fixed, with no dose adjustment required for body weight, renal impairment, or 
moderate hepatic impairment. Similarly, no dose adjustment is required for adolescents weighing 
at least 40 kg.  
Preliminary safety, PK, and sVNA titer data from the 300 mg IM cohort of the Phase 1 Study 
ADG20-1-001 further support the appropriateness of the 300 mg IM dose chosen for study (see 
Section 1.1.2.1). 
Further details on dose selection are provided in the IB. 
1.4. 
Risks and Benefits 
1.4.1. 
Benefits to the Target Study Population  
Two target populations are included in this trial and will be enrolled in separate cohorts. 
Cohort A (PEP) will enroll adults and adolescents with no known history of SARS-CoV-2 
infection and who are at risk of SARS-CoV-2 infection and COVID-19 due to reported recent 
exposure (within 5 days) to an individual with a laboratory-confirmed diagnosis of SARS-CoV-2 
infection (index case).  


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Cohort B (PrEP) will enroll adults and adolescents with no known history of SARS-CoV-2 
infection who are at risk of SARS-CoV-2 infection and COVID-19 due to risk of ongoing 
SARS-CoV-2 exposure based on occupation, housing situation, social activities, and/or religious 
activities. Examples of high-risk occupations may include health care workers and staff of 
nursing homes or correctional facilities. High-risk housing situations may include long-term care 
facilities or student housing. Participants (including adolescents) may also be considered at risk 
due to participation in sports or recreation requiring close contact. A worksheet designed to 
facilitate assessment of risk factors for SARS-CoV-2 exposure is presented in Appendix 3.  
Additionally, the study will allow enrollment of participants with risk factors associated with 
severe complications from COVID-19 in the event they acquire a SARS-CoV-2 infection, 
including older adults (≥55 years of age), and those with underlying conditions such as chronic 
cardiopulmonary disease, diabetes, obesity, or an immune compromised state, and may include 
pregnant/breastfeeding women (allowed following the iDMC review of the Phase 2 safety data in 
regions permitted by health authorities and local ethics committees). A detailed list of risk 
factors associated with severe complications from COVID-19 is presented in Appendix 4. 
These populations that are at high risk of SARS-CoV-2 acquisition, including the subset with 
elevated risk of severe COVID-19 disease, are likely to derive the greatest benefit from a 
preventive mAb. 
1.4.2. 
Risks from Study Participation 
Because ADG20 targets an exogenous epitope (spike protein) that is not present in humans, 
significant safety issues are not expected. No safety concerns for ADG20 have been identified in 
data generated across the ADG20 pre-clinical and clinical development program to date 
(Section 1.1.2). The anticipated safety risks are those common to the mAb therapeutic class and 
include ISRs and, rarely, hypersensitivity reactions such as anaphylaxis, angioedema, 
bronchospasm, hypotension, and hypoxia. Most administration-related reactions occur within the 
first 24 hours after administration. Severe reactions are rare (see Section 1.1.2 and the IB) and 
are more often associated with mAbs targeting human proteins rather than exogenous targets. 
Experience with mAbs directed against cell surface targets, particularly on lymphocytes, has 
been associated with cytokine release syndrome (Bugelski 2009). Cytokine release syndrome 
reactions have been attributed to lysis of the target cells and generally present within the first few 
hours following the first infusion as the target cell burden is greatest under these conditions.  
As a further precaution for acute injection reactions, study drug administration will occur in a 
setting where health care providers have immediate access to medications to treat a severe 
injection reaction, such as anaphylaxis, and the ability to activate the emergency medical system, 
as necessary. Participants will be monitored at the administration site for up to 4 hours postdose, 
depending on enrollment group. 
There is a risk that receipt of ADG20 may lead to false positive serology testing results using 
commercially available assays that detect antibodies to the SARS-CoV-2 spike protein. For this 
reason, participants will be encouraged not to seek testing outside the study. If a participant 
requires testing outside of the protocol-mandated testing schedule, the Sponsor will provide 


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guidance to the Clinical Site regarding an appropriate assay that identifies antibodies to the viral 
nucleocapsid protein (and not the spike protein). 
There is a risk that receipt of a SARS-CoV-2 monoclonal antibody such as ADG20 may result in 
a decreased immune response (ie, effectiveness) to COVID-19 vaccines during the period when 
ADG20 remains at significant concentrations in the body. The Advisory Committee on 
Immunization Practices (ACIP; CDC 2022c) originally recommended delaying COVID-19 
vaccination for 90 days (approximately 2.5 half-lives based on authorized mAbs) after receipt of 
a SARS-CoV-2 mAb and enrolled participants were advised of the potential risk of receiving a 
vaccine while participating in this trial. Participants were also made aware of the risk involved in 
delaying vaccination during an active pandemic as part of the informed consent process. On 
11-Feb-2022, ACIP updated its guidance based on recent data (Benschop 2021) and no longer 
recommends a delay in vaccination after the receipt of a SARS-CoV-2 mAb (CDC 2022c). 
Participants dosed with study drug (ADG20 or placebo) were notified of this change in ACIP 
recommendation. Participants who receive a vaccine during study conduct may undergo 
additional assessments as detailed in Section 3.5.2.7.  
There is a theoretical risk that receipt of a mAb against SARS-CoV-2 may cause a paradoxical 
increase in the risk of disease acquisition or/disease severity. This phenomenon, known as ADE 
of disease, is based on the rare occurrence of vaccine-associated disease enhancement, which 
was first seen in the 1960s with two formalin-inactivated whole virus vaccines designed to 
protect children against infection with RSV (Chin 1969) or measles (Fulginiti 1967). Disease 
enhancement has also been proposed as a possible explanation for cases of more serious disease 
associated with dengue vaccination (Thomas 2019; WHO 2019). ADE is thought to be the 
consequence of low affinity or cross-reactive antibodies that bind to viral entry proteins but have 
limited or no neutralizing activity or sub-optimal titers of otherwise potentially neutralizing 
antibodies.  
Available data suggests a low risk of ADE with the use of ADG20 in the treatment of acute 
COVID-19. Nonclinical studies of ADG20 demonstrated no increased viral uptake by FcγR-
expressing cells across a range of antibody concentrations, including sub-neutralizing 
concentrations. Clinical experience with other highly potent mAbs against the SARS-CoV-2 
spike protein suggests a favorable benefit/risk profile in ambulatory patients with mild to 
moderate COVID-19 (Eli Lilly and Company 2022; GlaxoSmithKline 2022; Regeneron 2022). 
These data suggest that ADE-mediated immune complex deposition or release of pathogenic 
cytokines upon antibody administration in the presence of high viral load is low with ADG20. To 
monitor the risk of enhanced disease in this study, the incidence and severity of COVID-19 cases 
will be monitored and reviewed by the iDMC. 
1.4.3. 
Overall Benefit-Risk Conclusion 
All participants included in this study will have no known history of prior or current 
SARS-CoV-2 infection and will be at risk of SARS-CoV-2 acquisition either due to reported 
recent exposure to an individual with a diagnosis of SARS-CoV-2 infection (index case) or a 
high risk of ongoing SARS-CoV-2 exposure based on occupation, housing situation, or other 
activities. The study will be enriched for participants at increased risk of complications from 
COVID-19 based on age or underlying comorbidities, as these at-risk populations are likely to 


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derive the greatest benefit from a preventive mAb therapy. Importantly, only individuals who 
agree to delay vaccination for at least 6 months after discussion of potential risks/benefits and 
alternative available options for prophylaxis of COVID-19, will be enrolled in the study. 
Considering the persistent lack of universal adoption of COVID-19 vaccines, the ongoing 
emergence of SARS-CoV-2 variants, the need for vaccine alternatives for immune compromised 
individuals and the low assessed risk of safety concerns with a mAb targeting an exogenous non-
host epitope, the overall benefit-risk assessment for this study is considered favorable for 
prevention of disease due to variants for which a dose of 300 mg IM is anticipated to provide 
adequate tissue exposure. Notably, ADG20 has been shown to bind to and neutralize multiple 
SARS-CoV-2 variants, as detailed in the Investigator’s Brochure. 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
For Cohort A (PEP), in participants with no known history of SARS-CoV-2 infection and 
reported recent exposure to SARS-CoV-2 (as defined by the criteria in Section 3.3.1), the 
following objectives and endpoints apply (Table 2.1): 
Table 2.1 
Objectives and Endpoints: Cohort A (PEP) 
Objectives 
Endpoints 
Primary (Cohort A [PEP]) 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
Day 28 in all randomized participants without 
current SARS-CoV-2 infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28. 
 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through Day 28. 
To evaluate the safety and tolerability of 
ADG20 compared with placebo following 
intramuscular administration in all treated 
participants. 
Assessment of safety based on: 
• 
Incidence of treatment-emergent adverse events. 
• 
Incidence of solicited injection site reactions through 
Day 4. 
• 
Changes from baseline in clinical laboratory tests (ie, 
complete blood count with differential and serum 
chemistry). 
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic 
blood pressure). 


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Objectives 
Endpoints 
Secondary (Cohort A [PEP]) 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of RT-PCR-confirmed 
symptomatic COVID-19 through Day 28 in 
each of the following populations:  
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28.  
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19 diagnosis. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through Day 28. 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of SARS-CoV-2 infection (based 
on RT-PCR or serology) regardless of 
symptoms through Day 28 in each of the 
following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19) as determined by 
positive RT-PCR or serology through Day 28.  
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19). 
• 
Probability of SARS-CoV-2 infection (asymptomatic or 
symptomatic COVID-19) through Day 28. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 3 
months in each of the following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months.  
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of SARS-CoV-2 
infection (based on RT-PCR or serology) 
regardless of symptoms through 3 months, in 
each of the following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19) as determined by 
positive RT-PCR or serology through 3 months. 
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19). 
• 
Probability of SARS-CoV-2 infection (asymptomatic or 
symptomatic COVID-19) through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
Day 28 in all randomized participants with prior 
but not current SARS-CoV-2 infection at 
baseline.  
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through Day 28. 


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Objectives 
Endpoints 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of asymptomatic 
SARS-CoV-2 infection, in all randomized 
participants without prior or current 
SARS-CoV-2 infection at baseline. 
• 
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by RT-qPCR 
(nasal sample) on Days 8 and 15. 
• 
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by serology 
through Day 28. 
To evaluate the impact of ADG20 compared 
with placebo on viral load in all randomized 
participants with asymptomatic SARS-CoV-2 
infection detected by RT-qPCR (nasal sample) 
at baseline via surveillance.  
• 
Peak post-baseline SARS-CoV-2 viral load as measured 
by RT-qPCR 
• 
SARS-CoV-2 viral load as assessed by RT-qPCR change 
from baseline to Day 8 and Day 15. 
To evaluate the effect of ADG20 on the 
following clinical and virologic parameters in 
all randomized participants with laboratory 
confirmed symptomatic COVID-19 through CLI 
Day 28: 
 
Severity of COVID-19. 
Proportion of participants with RT-PCR-confirmed mild, 
moderate, or severe/critical COVID-19 through CLI Day 28. 
Duration of COVID-19. 
Time to sustained resolution of COVID-19 symptoms through 
CLI Day 28. 
COVID-19-related medically attended 
outpatient visits. 
Proportion of participants with at least 1 COVID-19-related 
medically attended outpatient visit (physician’s office, 
telemedicine, emergency rooms, or urgent care centers) 
through CLI Day 28. 
COVID-19-related hospitalization. 
Proportion of participants with a COVID-19-related 
hospitalization through CLI Day 28. 
COVID-19-related mortality. 
COVID-19-related mortality through CLI Day 28. 
All-cause mortality. 
All-cause mortality through CLI Day 28. 
SARS-CoV-2 viral load. 
Viral load from CLI Day 1 sample assessed by RT-qPCR. 
To evaluate the pharmacokinetics of ADG20 in 
serum. 
PK parameters of ADG20 including but not limited to: 
AUC0-inf, AUC0-last, Cmax, Tmax, CL, t1/2, and Vss. 
To evaluate the immunogenicity of ADG20. 
Incidence of ADAs against ADG20.  
ADA=antidrug antibody; AUC =area under the plasma concentration–time curve; AUC0-inf: AUC extrapolated to infinite time; 
AUC0-last=AUC from zero up to the last concentration ≥lower limit of quantification; CL=clearance; CLI=COVID-19-like illness; 
Cmax=maximum plasma concentration; PEP=post-exposure prophylaxis; RT-(q)PCR=(quantitative) reverse transcription-
polymerase chain reaction; t½=plasma concentration half-life; Tmax=time to reach Cmax; Vss=apparent volume of distribution at 
steady state. 
 


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For Cohort B (PrEP), in participants with no known history of SARS-CoV-2 infection and no 
known recent exposure to SARS-CoV-2, but whose circumstances put them at increased risk of 
exposure to SARS-CoV-2 and symptomatic COVID-19, the following objectives and endpoints 
apply (Table 2.2). 
Table 2.2 
Objectives and Endpoints: Cohort B (PrEP) 
Objectives 
Endpoints 
Primary (Cohort B [PrEP]) 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
3 months in all randomized participants 
without prior or current SARS-CoV-2 
infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic COVID-19 
through 3 months. 
To evaluate the safety and tolerability of 
ADG20 compared with placebo following 
intramuscular administration. 
Assessment of safety based on: 
• 
Incidence of treatment-emergent adverse events. 
• 
Incidence of solicited injection site reactions through Day 4. 
• 
Changes from baseline in clinical laboratory tests (ie, 
complete blood count with differential and serum 
chemistry). 
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure). 
Secondary (Cohort B [PrEP]) 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of RT-PCR-confirmed 
symptomatic COVID-19 through 3 months in 
all randomized participants without current 
SARS-CoV-2 infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic COVID-19 
through 3 months. 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of SARS-CoV-2 infection 
(based on RT-PCR or serology) regardless of 
symptoms through 3 months, in each of the 
following populations:  
• 
All randomized participants without prior 
or current SARS-CoV-2 infection at 
baseline. 
• 
All randomized participants without 
current SARS-CoV-2 infection at 
baseline.  
Proportion of participants with SARS-CoV-2 infection 
regardless of symptoms through 3 months. 
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection.  
• 
Probability of SARS-CoV-2 infection through 3 months. 


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Objectives 
Endpoints 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
3 months in all randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of 
SARS-CoV-2 infection (based on RT-PCR or 
serology) regardless of symptoms through 
3 months in all randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
regardless of symptoms through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of 
asymptomatic SARS-CoV-2 infection (based 
on serology) in all randomized participants 
without prior or current SARS-CoV-2 
infection at baseline. 
Proportion of participants with asymptomatic SARS-CoV-2 
infection as determined by serology at Month 6. 
To evaluate the effect of ADG20 on the 
following clinical and virologic parameters in 
all randomized participants with laboratory 
confirmed symptomatic COVID-19 through 
CLI Day 28: 
 
Severity of COVID-19. 
Proportion of participants with RT-PCR-confirmed mild, 
moderate, or severe/critical COVID-19 through CLI Day 28. 
Duration of COVID-19. 
Time to sustained resolution of COVID-19 symptoms through 
CLI Day 28. 
COVID-19-related medically attended 
outpatient visits. 
Proportion of participants with at least 1 COVID-19-related 
medically attended outpatient visit (physician’s office, 
telemedicine, emergency rooms, or urgent care centers) through 
CLI Day 28. 
COVID-19-related hospitalization. 
Proportion of participants with a COVID-19-related 
hospitalization through CLI Day 28. 
COVID-19-related mortality. 
COVID-19-related mortality through CLI Day 28. 
All-cause mortality. 
All-cause mortality through CLI Day 28. 
SARS-CoV-2 viral load. 
Viral load from CLI Day 1 sample assessed by RT-qPCR. 
To evaluate the pharmacokinetics of ADG20 
in serum. 
PK parameters of ADG20 including but not limited to: AUC0-inf, 
AUC0-last, Cmax, Tmax, CL, t1/2, and Vss. 
To evaluate the immunogenicity of ADG20. 
Incidence of ADAs against ADG20.  
ADA=antidrug antibody; AUC =area under the plasma concentration–time curve; AUC0-inf: AUC extrapolated to infinite time; 
AUC0-last=AUC from zero up to the last concentration ≥lower limit of quantification; CL=clearance; CLI=COVID-19-like illness; 
Cmax=maximum plasma concentration; PrEP=pre-exposure prophylaxis; RT-(q)PCR=(quantitative) reverse transcription-
polymerase chain reaction; t½=plasma concentration half-life; Tmax=time to reach Cmax; Vss=apparent volume of distribution at 
steady state. 
 


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Exploratory endpoints for Cohort A (PEP) and Cohort B (PrEP) are provided in Table 2.3. 
Table 2.3 
Exploratory Objectives and Endpoints: Cohorts A and B 
Objectives  
Endpoints 
To evaluate the impact of ADG20 compared 
with placebo on medically attended visits or 
death in participants with asymptomatic 
SARS-CoV-2 infection at baseline. 
Proportion of participants with asymptomatic SARS-CoV-2 
infection at baseline (defined by positive SARS-CoV-2 RT-PCR 
test and lack of symptoms of COVID-19) with medically 
attended visits (outpatient, telemedicine, or hospitalization) or 
death through Day 28.  
To evaluate the impact of ADG20 compared 
with placebo on Health Resource Utilization 
in participants with RT-PCR-confirmed 
symptomatic COVID-19. 
Health Care Resource Utilization of participants who develop 
COVID-19 (incidence and duration of ICU stay and incidence of 
emergency room visits). 
To evaluate the emergence of resistance to 
ADG20. 
Genotypic characterization of viral isolates for reduced 
susceptibility to ADG20, with phenotypic evaluation as 
appropriate. 
To evaluate the impact of ADG20 compared 
with placebo on COVID-19 vaccination-
induced immune response in a subset of 
participants. 
Pre- and post-vaccination SARS-CoV-2 neutralizing antibody 
titers in participants who choose to receive COVID-19 vaccine 
during the study. 
ICU=intensive care unit; RT-PCR=reverse transcription-polymerase chain reaction. 
3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
This is a Phase 2/3, multicenter, double-blind, placebo-controlled, randomized study of the mAb 
ADG20 in the prevention of symptomatic COVID-19 in adults and adolescents with no known 
history of SARS-CoV-2 infection but whose circumstances place them at increased risk of 
acquiring SARS-CoV-2 infection and developing symptomatic COVID-19. This objective will 
be independently evaluated in participants with reported recent exposure to an individual 
diagnosed with a SARS-CoV-2 infection (Cohort A, PEP) and in a cohort of participants with no 
reported exposure to SARS-CoV-2 (Cohort B, PrEP). These cohorts will be enriched for 
participants whose advanced age (≥55 years old) or health status places them at risk for severe 
COVID-19 or COVID-19 complications.  
This Phase 2/3 study will enroll in two parts: a Phase 2 safety lead-in consisting of 200 adult 
participants enrolled across Cohorts A and B and a separate Phase 3 expansion for enrolling the 
remainder of participants in each cohort. The first 30 participants (across both cohorts) in Phase 
2 will constitute a sentinel group and will undergo extended monitoring as detailed below. After 
a combined number of approximately 200 adult participants (aged ≥18 years) across Cohorts A 
and B are enrolled in Phase 2 (inclusive of the 30 sentinel participants) and followed for 4 weeks, 
an interim analysis of safety will be performed and reviewed by the iDMC. Enrollment of adult 
participants will continue during this review and will follow Phase 2 post-injection monitoring 
requirements. Enrollment of adolescents in each cohort will open only upon sponsor 
communication to sites after iDMC review of Phase 2 data and only in regions permitted by 


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health authorities and local ethics committees. Pausing guidelines triggering iDMC ad hoc 
reviews and additional details on safety monitoring are provided in Section 5.12. 
The participants in Phase 2 will be combined with the corresponding Phase 3 expansion 
population in each cohort for the final efficacy and safety analyses.  
The participant population, study procedures, and endpoints will be identical in Phase 2 and the 
Phase 3 expansion portions of the study with the following exceptions: 
• The sentinel group will be restricted to adult participants (aged ≥18 years) and the 
post-injection monitoring period will be 4 hours. Participants will then be assessed daily by 
telephone through Day 4 for hypersensitivity reactions. 
• In the remainder of Phase 2, enrollment will be restricted to adult participants (aged 
≥18 years) and the post-injection monitoring period may be reduced to no less than 2 hours 
after safety data review. 
• After iDMC review of Phase 2 data, enrollment will include both adult (aged ≥18 years) and 
adolescent (aged 12 to <18 years) participants (only in regions permitted by health authorities 
and local ethics committees). The post-injection monitoring period for adult participants may 
be decreased to a minimum of 1 hour based on iDMC recommendation. The post-injection 
monitoring period will be 2 hours for the first 20 adolescent participants. If no 
hypersensitivity reactions are observed in this group, the post-injection monitoring period for 
subsequent adolescent participants may also be reduced to a minimum of 1 hour.  
If any hypersensitivity reactions are observed in Phase 2, subsequent participants will be 
monitored for 2 hours post-injection. This period may be reduced to a minimum of 1 hour based 
on iDMC recommendation upon review of additional safety data. 
The study design is shown in Figure 3.1.


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Figure 3.1 
Study Design Schematic 
 
Note: Enrollment of adults will continue during iDMC review. 
 
IM=intramuscular; iDMC=independent data monitoring committee; LTFU=long-term follow-up; PEP=post-exposure prophylaxis; PrEP=pre-exposure prophylaxis 


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3.1.1. 
Study Definitions 
3.1.1.1. 
COVID-19-Like Illness  
As of protocol version 6, monitoring for CLI symptoms (Table 3.1) is discontinued. 
Spontaneously reported CLI symptoms will be captured as AEs as per Section 4.1.1 and 
Section 4.1.3 of the protocol.  
Table 3.1 
Guidelines for COVID-19-Like Illness Qualifying Symptoms 
Duration 
Symptom 
Any duration 
Fever 
Shortness of breath/difficulty breathing 
Loss of taste or smell 
Present for ≥2 days 
Chills (shivering) 
Cough 
Fatigue (low energy or tiredness) 
Muscle or body aches 
Headache 
Sore throat 
Congestion (stuffy or runny nose) 
Nausea 
Vomiting 
Diarrhea 
 
3.1.1.2. 
Symptomatic COVID-19 
Symptomatic COVID-19 will be defined as having laboratory confirmed (RT-PCR) 
SARS-CoV-2 infection and an onset of symptoms as defined below occurring no more than 
14 days from the date of positive RT-PCR test sample collection: 
At least ONE of the following respiratory signs/symptoms: 
• Clinical evidence of pneumonia (eg, SpO2 ≤94% on room air, requiring new initiation of 
supplemental oxygen or radiographic evidence of pneumonia). 
• New or worsening dyspnea/shortness of breath, OR 
At least TWO of the following systemic symptoms: 
• Fever ≥38 °C (≥100.4 °F) 
• Cough 
• Myalgia/muscle pain. 
• Fatigue that interferes with activities of daily living 
• Vomiting and/or diarrhea (only one finding to be counted toward endpoint definition) 


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• Anosmia and/or ageusia (only one finding to be counted toward endpoint definition) 
• Headache 
• Sore throat 
Severe/critical COVID-19 is defined as having laboratory confirmed (RT-PCR) SARS-CoV-2 
infection plus any of the following: 
• Clinical signs indicative of severe systemic illness (respiratory rate ≥30 breaths per minute, 
heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea level or partial pressure of 
oxygen to fraction of inspired oxygen ratio <300) 
• Evidence of shock (systolic blood pressure <90 mmHg, diastolic blood pressure <60 mmHg, 
or requiring vasopressors) 
• Respiratory distress (defined as needing oxygen therapy, noninvasive ventilation, mechanical 
ventilation, or extracorporeal membrane oxygenation) 
• Significant acute renal, hepatic, cardiovascular, or neurologic dysfunction 
• Admission to an ICU 
• Death 
See Appendix 5 for severity categorization as adapted from the FDA Guidance for Industry 
“COVID-19: Developing Drugs and Biological Products for Treatment or Prevention” (FDA 
2021a). 
3.1.1.3. 
COVID-19 Time to Sustained Resolution 
In participants with laboratory confirmed symptomatic COVID-19, time from the reported 
symptom onset to sustained resolution of symptoms from CLI Day 1 through CLI Day 28 will be 
defined in the SAP. 
3.1.1.4. 
COVID-19-Related Hospitalization 
COVID-19-related hospitalizations include visits for attention to worsening signs or symptoms 
attributed to COVID-19, in the opinion of the investigator. 
Hospitalization is defined as ≥24 hours of acute care in a hospital or acute care facility (includes 
emergency rooms, ICUs, acute care facilities created for COVID-19 pandemic hospitalization 
needs, or other acute care facilities).  
3.1.1.5. 
COVID-19-Related Medically Attended Outpatient Visits 
COVID-19-related medically attended visits include in-person or telemedicine visits not 
specified by the protocol and lasting <24 hours. These include unscheduled in-person or 
telemedicine visits conducted by the investigator for the purposes of evaluating worsening signs 
or symptoms attributed to COVID-19 or emergency room, urgent care center, or physician office 
visits, for attention to worsening signs or symptoms attributed to COVID-19, in the opinion of 
the investigator. 


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3.1.2. 
Methodology 
For Cohort A (PEP), the study will consist of a Screening Period of up to 5 days, a 1-month 
Study Period (including dosing on Day 1), a 5-month follow-up Period, and an 8-month 
long-term follow-up (LTFU) Period. For Cohort B, the study will consist of a Screening Period 
of up to 21 days, a 6-month Study Period (including dosing on Day 1), and an 8-month LTFU 
Period. Each cohort of the study will be considered completed when the last telephone visit 
(Month 14) or Early Termination (ET) visit for the last participant in each cohort is complete. 
All participants will undergo assessments as indicated in the main SoA (Table 3.3) and described 
in Section 3.5.2. 
Participants will receive a single IM dose of study drug on Day 1. Participants will record any 
ISRs using an e-Diary (or paper back-up) daily on Day 1 postdose through Day 4. The first diary 
entry will be completed by the participant with assistance of study staff prior to the end of the 
postdose monitoring period. 
As of protocol clarification letter 6, the use of an e-Diary for recording CLI qualifying 
symptoms and collection of saliva samples beyond CLI Day 1 were discontinued. As of 
protocol version 6.0, monitoring for CLI symptoms (Table 3.1) and CLI visits are 
discontinued. Spontaneously reported CLI symptoms will be captured as AEs as per 
Section 4.1.1 and Section 4.1.3 of the protocol. Safety monitoring will be performed via site 
phone calls or in-person visits through Month 14. Prior to implementation of protocol 
clarification letter 6 and protocol version 6.0 at each clinical site, the following procedures 
were in place for CLI monitoring and are described here for reference only:  
Participants will be instructed to monitor for any CLI symptoms (according to the 
guidelines in Table 3.1) and report them to the site if they occur at any time during the 
study. Surveillance for CLI will be performed via participant completion of an e-Diary twice 
weekly from Day 1 up to the Month 6 Visit, then weekly up to the Month 12 Visit. 
Surveillance for symptomatic COVID-19 will also be performed via site phone calls to the 
participant weekly up to the Month 6 Visit, then monthly up to the Month 12 Visit. See 
Section 3.5.4.1 for further details. Participants reporting CLI symptoms will be evaluated 
via phone call to confirm whether their symptoms meet criteria for a CLI visit. If CLI 
symptoms are confirmed by the site, the participant will enter the CLI Period and have an 
initial CLI visit within 48 hours. Participants who enter the CLI Period will be assessed as 
described in the CLI SoA (Table 3.4 and Section 3.5.3). Study visits described in the main 
SoA should not be conducted while a participant is following the CLI SoA.  
During the initial CLI Visit (CLI Day 1), an NP swab for RT-qPCR testing for SARS-CoV-2 
and a saliva sample for assessing viral load will be collected for processing by a central 
laboratory. For the remainder of the CLI Period, vital signs and severity, duration, and 
outcome of CLI will be collected via daily telemedicine visits (on CLI Days 2 to 21) and at 
the final visit on CLI Day 28. Saliva samples will be collected by participants at home on 
CLI Day 3, 5, 8, 11, 14, and 21 to measure viral shedding over time. Participants will 
continue in the CLI Period unless a negative result on the CLI Day 1 central NP RT-PCR 
test is received. These participants will stop CLI assessments and will continue with the 
main SoA (Table 3.3). Participants with positive or pending central NP SARS-CoV-2 results 


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will continue in the CLI Period, regardless of symptoms. Continuation in the CLI Period 
will not be guided by local RT-PCR testing. 
As of protocol version 6.0, all participants in Cohort A have completed surveillance for 
asymptomatic SARS-CoV-2 infection and monitoring for CLI symptoms and CLI visits are 
discontinued. Prior to protocol version 6.0, the following procedures were in place and are 
described here for reference only:  
In Cohort A (PEP) only, surveillance for asymptomatic SARS-CoV-2 infection will be 
performed via SARS-CoV-2 RT-qPCR testing of nasal swabs collected by the Clinical Site 
on Day 1 (predose) and Day 8 and collected by the participant on Day 15.  
Any participant who has a positive result on a nasal swab RT-PCR (Cohort A) or local RT-
PCR test (either cohort) up to the Month 12 study visit will be instructed to monitor for 
onset of symptoms and to report any symptoms to the clinical site; if the participant reports 
qualifying symptoms within 14 days of collection of the positive RT-PCR, they will enter the 
CLI Period.  
As of protocol version 6.0, collection of health care resource utilization data is discontinued. 
Prior to protocol version 6.0, the following procedures were in place and are described here 
for reference only: 
The occurrence of RT-PCR confirmed COVID-19 and concomitant therapies associated 
with COVID-19 will be captured for the duration of the study. Every effort will be made to 
capture information from any medical visits (eg, visits to the primary care providers, 
emergency department/urgent care clinic visits, hospitalizations) related to COVID-19 or its 
complications for the purpose of Health Care Resource Utilization analysis.  
Sparse blood samples will be collected for PK and immunogenicity throughout the study, as 
indicated in the main SoA (Table 3.3) and CLI SoA (Table 3.4).  
At the time of study entry, each participant will be asked to indicate to the Clinical Site the 
identity and location of their routine medical care physician and/or facility and the identity and 
location of where they would obtain emergency care and hospitalization, if necessary, should 
they get infected with SARS-CoV-2. If this information is not available, a plan for where such 
care could be obtained should be developed.  
All necessary precautions (as per local regulations) should be taken to protect medical staff and 
other contacts of participants who are suspected of having COVID-19. In the event of a 
confirmed SARS-CoV-2 infection, the participant will be notified, and the participant will be 
asked to adhere to the appropriate measures and restrictions as defined by local regulations.  
3.2. 
Study Duration 
For Cohort A (PEP), the study will consist of a Screening Period of up to 5 days, a 1-month 
Study Period (including dosing on Day 1), a 5-month follow-up Period, and an 8-month LTFU 
Period.  
For Cohort B (PrEP), the study will consist of a Screening Period of up to 21 days, a 6-month 
Study Period (including dosing on Day 1), and an 8-month LTFU Period.  


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3.3. 
Selection of Study Population 
The study population will comprise adults (aged ≥18 years) and adolescents (aged 12 to 
<18 years); enrollment of adolescents will begin during the Phase 3 expansion in regions 
permitted by health authorities and local ethics committees. Participants whose circumstances 
place them at increased risk of acquiring SARS-CoV-2 infection and/or developing symptomatic 
COVID-19 will be included. This objective will be independently evaluated in participants with 
reported recent exposure to an individual diagnosed with a SARS-CoV-2 infection (Cohort A, 
PEP) and in participants with no reported recent exposure to SARS-CoV-2 (Cohort B, PrEP).  
Approximately 20% of the study population is anticipated to be comprised of individuals at 
increased risk for severe COVID-19 or COVID-19 complications. Participants aged 12 to 
<55 years who are at an increased risk (as described in Appendix 4) will be included, and 
participants aged ≥55 years will be eligible for enrollment with or without underlying medical 
conditions that might place them at increased risk. These at-risk populations are likely to derive 
the greatest benefit from a preventive mAb therapy. Importantly, participants will be enrolled in 
the study only if they do not intend to receive a COVID-19 vaccine for 6 months after discussion 
of risks/benefits of study enrollment in the setting of current or potential future vaccine 
availability and their underlying risk for development of severe COVID-19.  
Specific entry criteria are detailed in Section 3.3.1 and Section 3.3.2. 
3.3.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all the following criteria apply: 
1. Adult aged ≥18 years or adolescent aged 12 to <18 years and weighs at least 40 kg at the 
time of Screening. 
Note: Adolescent enrollment will open only upon sponsor communication to sites after 
review of Phase 2 data, and only if permitted by the local health authority (see Appendix 7). 
2. Tests negative for current or previous SARS-CoV-2 infection by RT-PCR and serology at the 
time of Screening.  
Note: Participants may be randomized in Cohort A without RT-PCR results, if these results 
are not available by Day 5 of Screening.  
3. Is at high risk of SARS-CoV-2 infection as assessed by the Investigator, as follows: 
a. Cohort A (PEP): recent exposure to an individual with a diagnosis of SARS-CoV-2 
infection (the index case). 
Note: Randomization must occur within 5 days (120 hours) from both exposure to and 
sample collection from the index case. Participants with recent exposure to a laboratory-
confirmed index case must be asymptomatic at randomization. Exposure is generally 
defined as repeated contact lasting 15 minutes or more within a 24-hour period, where the 
individuals were within 2 meters (approximately 6.5 feet) of each other, and neither party 
was wearing a facemask of respirator. 


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b. Cohort B (PrEP): occupational, housing, recreational, and/or social conditions that are 
likely to increase risk of exposure to SARS-CoV-2 as assessed by the criteria in 
Appendix 3.  
4. Agrees to defer receipt of COVID-19 vaccination for a minimum of 180 days (6 months) 
after dosing.  
5. Provides written documentation of informed consent by signing a current IEC/IRB approved 
ICF at the time of screening. A legally authorized representative may be used in cases where 
inclusion criterion 9 is able to be fulfilled. In the case of adolescents, informed consent/assent 
must also be obtained as required by local guidelines. 
6. Participants assigned female sex at birth who are not of reproductive potential are eligible 
without requiring the use of contraception and do not require a pregnancy test. This includes 
female participants who have not undergone menarche or who are documented to be 
surgically sterile (eg, hysterectomy, removal of both ovaries, or tubal ligation) or 
postmenopausal (ie, amenorrhea >1 year and follicle stimulating hormone >40 mIU/mL). 
Follicle stimulating hormone is not required in postmenopausal females with amenorrhea for 
>2 years. 
7. Participants assigned female sex at birth and who are of childbearing potential may be 
enrolled in the study if the participant has practiced adequate contraception or has abstained 
from all sexual activities that could result in pregnancy for at least 28 days before the day of 
dosing (Day 1) and has agreed to continue adequate contraception for sexual activity that 
could lead to pregnancy through 6 months following dosing. 
Adequate contraception for participants assigned female sex at birth is defined as consistent 
and correct use of a contraceptive approved by the local Health Authority and used in 
accordance with the product label. For example: 
a. Barrier method (such as condoms, diaphragm, or cervical cap) used in conjunction with 
spermicide. 
b. Intrauterine device. 
c. Hormonal contraceptive taken or administered via oral (pill), transdermal (patch), 
intravaginal, implantable, or injectable method. 
d. Sterilization of a female participant’s male partner before entry into the study. 
e. Sexual abstinence. 
Note: periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. Sexual abstinence 
is considered an effective method only if defined as refraining from heterosexual 
intercourse from providing consent until 6 months after dosing. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred 
and usual lifestyle of the participant. 
8. Participants assigned male sex at birth with partner(s) of childbearing potential who agree to 
use adequate contraception through 6 months after dosing. If their partner is pregnant, males 


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must agree to use a condom. Male participants must also refrain from sperm donation 
through 6 months after dosing. 
9. Able to understand and comply with study requirements/procedures (if applicable, with 
assistance by a caregiver, surrogate, or legally authorized representative) based on the 
assessment of the Investigator. 
3.3.2. 
Exclusion Criteria 
A potential participant who meets any of the following exclusion criteria must be excluded from 
the study. 
1. Prior receipt of a COVID-19 vaccine, convalescent plasma, or mAb, including in the setting 
of a clinical trial.  
Note: immune compromised participants (eg, due to hematological malignancy, anti-CD20 
medication use, etc.) who have completed a COVID-19 vaccine series and who have a 
documented negative SARS-CoV-2 Spike (“S”) protein serum antibody test drawn a 
minimum of four weeks after completion of the recommended dosing series may be screened 
and subsequently enrolled if other criteria are met, including a confirmatory negative “S” 
protein antibody test at the time of screening. This test must be confirmed negative prior to 
enrollment in either Cohort A or Cohort B. 
2. Receipt of any investigational product within 30 days or 5 half-lives (whichever is longer) 
before the day of enrollment. 
3. Is acutely ill or has any of the following symptoms: 
Fever ≥38 °C (≥100.4 °F) 
Shortness of breath/difficulty breathing 
Chills (shivering) 
Cough 
Fatigue (low energy or tiredness) 
Muscle or body aches 
Headache 
Loss of taste 
Loss of smell 
Sore throat 
Congestion (stuffy or runny nose) 
Nausea 
Vomiting 
Diarrhea 
Note: Participants meeting this criterion may be scheduled for rescreening within the 
relevant window periods. 
4. Has received or plans to receive a non-COVID-19 vaccine within 28 days before or after 
dosing (except for seasonal influenza vaccine, which is not permitted within 14 days before 
or after dosing). 
5. Known allergy/sensitivity or hypersensitivity to the study drug, including excipients. 
6. Is pregnant, as confirmed with a positive pregnancy test at Screening or on the day of dosing 
(Day 1), or breastfeeding.  
7. Known clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or 
platelet disorder), or prior history of significant bleeding or bruising following IM injections 


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or venipuncture. Abnormal coagulation labs or use of anticoagulant medication are not 
exclusionary in the absence of clinical findings. 
8. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal 
disease, liver disease, renal disease, endocrine disorder, autoimmune disease or immune 
compromise, or neurological illness, as judged by the Investigator (mild/moderate well-
controlled comorbidities are allowed; see Appendix 4).  
9. Any serious concomitant systemic disease, condition, or disorder that, in the opinion of the 
Investigator, might confound the results of the study or confer an additional risk to the 
participant by their participation in the study. 
3.3.3. 
Withdrawal from Study 
A participant will be considered to have completed the study when they complete the Month 14 
telephone visit or an ET visit. If a participant withdraws at any time after randomization into the 
study, the Investigator will make every effort to complete the ET assessments as indicated in 
Table 3.3. 
Participation in the study is strictly voluntary. A participant has the right to withdraw from the 
study at any time and for any reason. If he/she chooses to withdraw, the Investigator must be 
informed immediately.  
A termination eCRF page should be completed for every participant who receives the study drug, 
whether or not the participant completes the study. The reason for any ET should be indicated on 
this form.  
3.3.4. 
Replacement of Participants 
Participants prematurely withdrawn from the study for any reason will not be replaced. 
3.4. 
Treatments 
3.4.1. 
Details of Study Treatments 
ADG20 is a fully human monoclonal immunoglobulin G1 antibody targeted to an epitope in the 
RBD of the spike glycoprotein of SARS-CoV-2. Information about the study drug is provided in 
Table 3.2. 


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Table 3.2 
Details of Study Drug 
 
3.4.2. 
Treatment Assignment and Randomization 
Participants will be randomly assigned in a 1:1 ratio in each cohort to receive either IM ADG20 
or IM placebo. The randomization will be assigned in a blinded manner using a centralized 
Interactive Response Technology (IRT) system, in accordance with a pre-generated 
randomization schedule. A participant is considered randomly assigned when a randomization 
transaction is recorded in the IRT. A separate randomization list will be created for each cohort.  
Randomization will be stratified by: 
• Geography  
− United States/Western Europe (US/WEU)  
− Central/Eastern Europe (CEU/EEU)  
− Rest of the World (RoW) 
• Age/risk for severe/critical COVID-19 
− Aged 12 to <55 years and low risk for severe/critical COVID-19 
− Aged 12 to <55 years and high risk for severe/critical COVID-19 (see Appendix 4) 
− Aged ≥55 years 
 
Preparations to Be Administered 
Study Drug 
Placebo 
Study Drug Name 
ADG20 
Normal saline 
Manufacturer 
WuXi Biologics 
Commercially available 
Sourcing 
Provided centrally by the Sponsor  
Sourced based on local requirements 
Dose Form 
Solution for injection 100 mg/mL OR 
Solution for injection 150 mg/mL 
Solution for injection, 0.9% 
(weight/volume)  
Route of 
Administration 
Intramuscular 
Intramuscular 
Formulation 
100 mg/mL: ADG20, 20 mM L-histidine, 
150 mM sodium chloride, 0.01% polysorbate 80, 
pH 6.5 (all sites, including those in the US) 
150 mg/mL: ADG20, 10 mM L-histidine, 100 
mM sucrose, 75 mM L-arginine hydrochloride, 
0.03% polysorbate 80, pH 5.5 (US sites only) 
0.9% (weight/volume) sodium 
chloride 
Dose 
300 mg, administered as a single 2 mL or 3 mL 
injection 
Matched volume of normal saline 
Packaging and 
Labeling 
Will be provided in a vial within an individual 
carton. Each carton and vial will be labeled as 
required per country requirement. 
As required per local regulations 


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3.4.3. 
Study Drug Packaging and Labeling 
ADG20 drug product will be supplied in glass vials as a sterile solution. Each ADG20 drug 
product vial is supplied to the study site in a tamper-evident sealed and labeled carton. ADG20 
will be labeled per country requirement. 
The placebo is commercially available 0.9% sodium chloride (normal saline) injection, which 
meets the criteria of the USP.  
Prepared doses of study drug and placebo will be labelled by study site staff according to the 
Pharmacy Manual.  
3.4.4. 
Study Drug Storage and Handling 
ADG20 will be shipped to the study site with temperature monitored throughout the transit 
period, and with temperature tracings available for review upon receipt. The investigator or 
designee must confirm appropriate temperature conditions per the Pharmacy Manual have been 
maintained during transit for all study drug received and any discrepancies are reported and 
resolved before use of the study drug. ADG20 drug product must be stored according to the 
Pharmacy Manual. 
Placebo (normal saline) will be stored in the Clinical Site’s pharmacy or designated area under 
conditions specified by the manufacturer. 
All study drug must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the Pharmacy Manual and with access limited to the 
Investigator and authorized Clinical Site staff. 
Please refer to the Pharmacy Manual for details on preparing and administering ADG20 and 
placebo dosing solutions and special handling instructions. 
3.4.5. 
Breaking the Blind  
The IRT will be programmed with blind-breaking instructions. In case of an emergency, the 
Investigator has the sole responsibility for determining if unblinding of a participant’s study 
intervention assignment is warranted. Participant safety must always be the first consideration in 
making such a determination. If the Investigator decides that unblinding is warranted, the 
Investigator should make every effort to contact the Sponsor or medical monitor before 
unblinding a participant’s treatment assignment unless this could delay further management of 
the participant.  
If a participant’s treatment assignment is unblinded, the Sponsor must be notified within 
24 hours after breaking the blind without revealing the study treatment. The date and reason that 
the blind was broken must be documented.  
The study-specific IRT reference manual will provide further details on the use of the IRT 
system. 


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3.4.6. 
Counseling and Unblinding for Participants Wishing to Receive a COVID-19 
Vaccination During the Study 
Participants were counseled prior to enrollment regarding the risk of ADG20 receipt potentially 
interfering with COVID-19 vaccine induced immunogenicity and/or efficacy. Participants were 
only enrolled in the study if they did not intend to receive COVID-19 vaccination for at least 180 
days (~6 months) following randomization. The ACIP originally recommended delaying 
COVID-19 vaccination after receipt of a SARS-CoV-2 mAb due to the potential for interference 
with vaccine-induced immunity (CDC 2022c) and enrolled participants were advised of this 
potential risk. Participants were also made aware of the risk involved in delaying vaccination 
during an active pandemic as part of the informed consent process. On 11-Feb-2022, ACIP 
updated its guidance based on recent data (Benschop 2021) and no longer recommends a delay in 
vaccination after the receipt of a SARS-CoV-2 mAb (CDC 2022c). The Sponsor instructed sites 
to communicate this updated guidance to study participants that received study drug (ADG20 or 
placebo). Vaccination(s) received during the study should be recorded as concomitant 
medications. 
As of protocol version 6.0, additional counseling and assessments for participants who 
decide to proceed with vaccination are discontinued. Prior to protocol version 6.0, the 
following procedures were in place and are described here for reference only: 
If a participant becomes eligible for and wishes to receive a COVID-19 vaccine, the 
participant should inform the Investigator. Upon notification of the participant’s wish to be 
vaccinated, the Investigator should counsel the participant on the potential risk of ADG20 
interfering with vaccine immunogenicity and/or efficacy, particularly within the first 6 
months after dosing. The Investigator should also communicate updated ACIP 
recommendations that any delay in vaccination after receipt of a SARS-CoV-2 mAb is no 
longer recommended. The Investigator should offer to unblind any participant who wishes 
to be vaccinated to better inform decision-making. If the participant chooses to be 
unblinded, the Sponsor must be notified within 24 hours after breaking the blind without 
revealing the study treatment. If after counseling the participant chooses to proceed with 
vaccination, the Investigator should encourage the participant to remain in the study for 
ongoing assessments.  
Participants who inform the Investigator of their decision to proceed with vaccination may 
undergo additional assessments pre- and post-vaccination, as described in Section 3.5.2.7. 
For these participants, treatment status must be unblinded to allow clinical site personnel to 
perform these assessments. The Sponsor should be notified within 24 hours after breaking 
the blind.  
For all instances of unblinding, the date the blind was broken must be recorded.  
3.4.7. 
Drug Inventory and Accountability 
It is the responsibility of the unblinded Pharmacist or unblinded designee to ensure that current 
written records of study drug inventory and accountability are maintained. Records must be 
readily available for inspection by the Sponsor or Sponsor’s unblinded representative and 
applicable regulatory authorities at any time. 


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Upon receipt of study drugs, the Pharmacist, or designee will acknowledge receipt, visually 
inspect the shipment, verify that the number shipped were received, document the condition of 
the study drugs received, and store the study drugs at the appropriate temperature. Refer to the 
Pharmacy Manual for additional information. 
3.4.8. 
Study Drug Handling and Disposal 
Participants are dosed at the site or during an at-home visit and will receive the study drug 
directly from the investigator or qualified designee. The date and time of each dose administered 
in the clinic will be recorded in the source documents and recorded in the eCRF.  
The investigator will maintain accurate records of receipt of ADG20, including dates of receipt. 
In addition, accurate records will be kept by unblinded site personnel regarding when and how 
much study drug is dispensed for use by each participant in the study. Only participants enrolled 
in the study may receive study drug, and only authorized site personnel may supply or administer 
study drug. Reasons for departure from the expected dispensing regimen must also be recorded. 
At the completion of the study, to satisfy regulatory requirements regarding drug accountability, 
ADG20 will be reconciled and returned or destroyed according to applicable regulations. Further 
guidance and information for the final disposition of unused study drug are provided in the 
Pharmacy Manual. 
3.4.9. 
Prior and Concomitant Treatments 
Information about prior medications (including any prescription or over-the-counter medications, 
vaccines, or blood products), taken by the participant within the 30 days before dosing (Day 1) 
must be recorded at Screening and before dosing on Day 1. Concomitant therapies, defined as 
treatments taken after dosing, associated with AEs (including COVID-19 illness), will be 
collected and recorded in the eCRF from the moment of dosing (Day 1) until the end of study.  
3.4.9.1. 
Permitted Prior/Concomitant Medications 
Participants may take concomitant medications prescribed by their primary care provider for 
management of chronic medical conditions and/or for health maintenance. Primary care 
providers, or where appropriate, Investigators, should prescribe appropriate concomitant 
medications or treatments deemed necessary to provide full supportive care and comfort during 
the study. Local standard-of-care treatment, including investigational agents, agents available 
under emergency use authorization, or other SARS-CoV-2 mAbs, is permitted in participants 
who develop COVID-19 after dosing.  
Non-COVID-19 vaccinations (other than influenza) are permitted if administered ≥28 days 
before or after dosing. Licensed influenza vaccines are permitted if administered ≥14 days before 
or after dosing. Though participants were enrolled only if they intended to defer vaccination for 
at least 6 months, COVID-19 vaccination is permitted after dosing (see Section 3.4.6). Vaccines 
indicated in a postexposure setting (eg, rabies or tetanus), are permitted at any time during study. 


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3.4.9.2. 
Prohibited Prior/Concomitant Medications 
The use of the following medications and/or vaccines are prohibited. Use of these concomitant 
medications by any participant should be recorded in the eCRF, but will not require withdrawal 
of the participant from the study: 
• Any investigational or licensed non-vaccine products indicated or being studied for the 
prevention of SARS-CoV-2 or COVID-19 (eg, other SARS-CoV-2 mAbs, ivermectin).  
Note: Participants who develop confirmed COVID-19 at any time after study drug 
administration should be treated per local standard of care, which can include the use of these 
medications. 
• Any vaccine (licensed or investigational), other than licensed influenza vaccines or vaccines 
indicated in a post-exposure setting, if received within 28 days before or after dosing.  
• Any COVID-19 vaccine received prior to enrollment. This does not apply to immune 
compromised individuals who may have received a COVID-19 vaccine prior to enrollment 
but have no detectable antibody response (see Exclusion Criterion 1). 
• Any seasonal influenza vaccine if received within 14 days before or after dosing. 
• Receipt of any investigational product within 30 days or 5 half-lives (whichever is longer) 
before the day of enrollment. 
• Any investigational agent or device is prohibited through 90 days after study drug 
administration (excluding products listed in Section 3.4.9.1 for the treatment of participants 
who develop COVID-19).  
3.5. 
Assessments 
Unless otherwise indicated, all assessments will be performed by the Investigator or designated 
study personnel. 
3.5.1. 
Schedule of Assessments 
The procedures to be performed throughout the study are outlined in the main SoA (Table 3.3) 
and a detailed description is provided in Section 3.5.2.  
As of protocol version 6.0, CLI visits are discontinued, and the CLI SoA (Table 3.4) is no 
longer applicable. Prior to protocol version 6.0, participants following the CLI SoA did not 
concurrently perform assessments in the main SoA; once the CLI SoA procedures were 
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b All participants will enter the Home Collection Period and perform daily assessments until the result of the CLI Day 1 SARS-CoV-2 central laboratory test is known. Participants who 
test positive will continue in the CLI Period through Day 28. Participants who test negative will exit the CLI Period at the time the test result is received and return to the main schedule 
of study assessments. 
c A CLI Recurrence Visit should be performed for participants who experience a recurrence of site-confirmed CLI qualifying symptoms after resolution of previously confirmed 
symptomatic COVID-19. 
d Visits will be performed at the clinical site, in-person (at the clinical site or at home), or via telemedicine/virtually (telephone, telehealth, videoconference, etc) as indicated. 
e Daily telemedicine visits (CLI Days 2 to 21) may be performed by medically qualified staff appropriately delegated by the Investigator. Telemedicine visits should be done in the evening 
if possible. The participant will be asked to verbally report all required information. If the participant assessed their vital signs more than once that day, only the highest temperature, 
lowest SpO2, and highest heart rate should be recorded in the eCRF. The Investigator will determine if medical attention is required due to worsening of COVID-19 and will assign and 
record an overall COVID-19 severity grade for that day.  
f Concomitant medications reporting should focus on medications taken to treat current illness/symptoms. 
g At in person visits, heart rate, pulse oximetry, blood pressure, respiratory rate, and temperature will be assessed. During the Home Collection Period, participants will self-assess their 
temperature, SpO2, and heart rate at approximately the same time daily and record the results on a memory aid provided by the site. Additional measurements may be taken at other 
times during the day if the participant feels feverish or short of breath at rest. Participants will be provided with the necessary equipment to perform these assessments. 
h Record new onset AEs, including serious AEs, and medically attended AEs. The first instance of COVID-19 or SARS-CoV-2 infection and associated sequelae in a given participant will 
not be recorded as an AE; these data will be captured as efficacy assessment data. Recurrence of CLI symptoms in the same participant will be recorded as AEs. 
i Record information regarding health care utilization including COVID-19-related emergency room visits, urgent care visits, visits to other outpatient medical facilities, hospital 
admissions, and ICU stays. 
j Samples for testing at local laboratory for the purposes of case management may also be collected per local standard of care. Clinical care should be delivered per local standard of 
care and not wait for results of the central laboratory test. Any local positive RT-PCR test result should be recorded in source and eCRF. 
k Collection of these samples was discontinued with protocol clarification letter 6. 


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3.5.2. 
Study Visits  
3.5.2.1. 
Screening/Baseline 
Screening visit requirements are outlined in the main SoA (Table 3.3). The assessments during 
the Screening Period will determine a participant’s eligibility for the study and a participant’s 
ability to comply with protocol requirements by completing all Screening assessments. Screening 
procedures are to be completed within 5 days prior to study drug dosing in Cohort A or within 
21 days prior to study drug dosing in Cohort B.  
Written informed consent must be obtained before performing any protocol-specific procedure; 
this includes discussion of vaccine availability and the potential risks of vaccine deferral and/or 
administration within 180 days of receipt of study drug. 
In addition to review of inclusion and exclusion criteria, for Cohort B, risk of exposure to 
SARS-CoV-2 will be reviewed with the participant using the risk worksheet in Appendix 3.  
Participants may be rescreened once after initially failing to meet the inclusion/exclusion criteria.  
3.5.2.2. 
Treatment Period  
After the completion of the Screening assessments, eligible participants will be randomized to 
treatment on Day 1. Participants in Cohort A may be randomized on the same day as Screening. 
If this occurs, Day 1 predose procedures only need to be performed if they were not completed as 
part of Screening on the same day. Cohort A participants may be randomized before 
SARS-CoV-2 RT-PCR results are available but must have a negative serology result from a local 
or point of care test. Participants in Cohort B must have negative results from both RT-PCR and 
central serology prior to randomization. 
Procedures to be performed predose and postdose on Day 1 are outlined in the SoA (Table 3.3). 
Before dosing on Day 1, the participant will be provided with access to the e-Diary for ISR 
assessments and instructed on its usage (see Section 3.5.5.4).  
After study drug administration, the participant will be monitored for 1 to 2 hours, depending on 
the study phase. Participants in the sentinel group will be monitored for 4 hours and will be 
assessed daily by telephone for hypersensitivity reactions through Day 4 (see Section 3.5.5.5). 
Study staff will assist the participant in reporting any Day 1 ISR findings in the e-Diary. 
Participants may be provided with a paper back-up copy of the ISR diary if study staff assesses 
that this may be needed. In addition to the post-injection monitoring procedures outlined in the 
SoA, participants will be assessed during the same time points (or more frequently, as needed) 
for overall general health. 
Note: as of protocol clarification letter 6, the use of an e-Diary for recording CLI qualifying 
symptoms was discontinued. 


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3.5.2.3. 
Follow-up Visits (Day 8 to Month 9) 
The participant will return to the Clinical Site or will be visited at home for in-person follow-up 
visits on Days 8 and 28 and at Month 6. Procedures to be performed during these visits are 
outlined in the SoA (Table 3.3).  
For Cohort A (PEP) only, a nasal swab for SARS-CoV-2 RT-qPCR central laboratory analysis 
will be collected by site staff on Day 8. The participant will be provided with a kit and 
instructions for self-collection of a nasal swab on Day 15 (see Section 3.5.4.4). 
During the Follow-up Period, participants will be contacted for safety follow-up via phone once 
weekly through Month 6 and again at Month 9. During these phone calls, information on AEs, 
SAEs, MAAEs (including new onset chronic disease), and concomitant medications will be 
collected.  
As of protocol clarification letter 6, the use of an e-Diary for recording CLI qualifying 
symptoms was discontinued. As of protocol version 6.0, monitoring for CLI symptoms 
(Table 3.1), including follow-up calls at Months 7, 8, 10, and 11, is discontinued. CLI 
symptoms reported spontaneously during the Follow-up Period will be captured as AEs as 
per Section 4.1.1 and Section 4.1.3 of the protocol.  
3.5.2.4. 
Month 12 Visit 
The participant will return to the Clinical Site or will be visited at home for the Month 12 Visit. 
Procedures to be performed during this visit are outlined in the SoA (Table 3.3). As indicated in 
the SoA, blood collection for PK analysis and ADA analysis is to be performed until Sponsor 
notification that these samples are no longer required.  
3.5.2.5. 
Month 14 
Participants will be contacted by telephone at Month 14 for safety monitoring (collection of AEs 
and concomitant medications), as indicated in the SoA (Table 3.3).  
As of protocol version 6.0, the follow-up telephone contact at Month 13 for safety 
monitoring is discontinued. 
3.5.2.6. 
Premature Termination Visit 
If a participant withdraws or is withdrawn from the study for any reason, the participant will be 
encouraged to attend an ET Visit. Procedures to be performed during this visit are outlined in the 
SoA (Table 3.3). 
3.5.2.7. 
Unscheduled Pre- and Post-COVID-19 Vaccination Visits  
As of protocol version 6.0, unscheduled pre- and post-COVID-19 vaccination visits are 
discontinued. Prior to protocol version 6.0, the following procedures were in place and are 
described here for reference only: 
If at any time during the study a participant is eligible for and wishes to receive a COVID-19 
vaccine, the participant should inform the Investigator and be counseled as described in 
Section 3.4.6.  


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After counseling, participants who choose to receive a COVID-19 vaccine may have their 
treatment status unblinded to undergo the pre- and post-vaccination procedures described in this 
section. Vaccine type and date(s) should be recorded as concomitant medications for all 
participants who receive COVID-19 vaccination. 
An Unscheduled Visit should be conducted pre-vaccination for all participants intending to 
receive a vaccine until Sponsor notification that these visits are no longer required. Participants 
who go on to receive a vaccine will return for an Unscheduled Visit post-vaccination; this visit 
should take place approximately 2 weeks after receiving the final dose of the primary vaccine 
regimen.  
The assessments to be performed at the pre-vaccination and post-vaccination Unscheduled Visits 
specific for placebo- and ADG20-treated participants are indicated in Table 3.5. To assess 
immunogenicity of the vaccine, blood draws for sVNA titers may be performed in participants 
who are unblinded due to intent to receive a COVID-19 vaccine. Investigators will be notified by 
the Sponsor when these blood draws are no longer required. 
The Investigator should encourage these participants to remain in the study for ongoing safety 
and efficacy assessments. Participants will continue to follow the visit schedule and procedures 
as indicated on the main SoA (Table 3.3) and CLI SoA (Table 3.4) regardless of the Unscheduled 
Visits for the remainder of the study. All study procedures should be performed as indicated, 
except that placebo-treated participants will NOT have blood draws for PK and ADA performed 
at any time after the pre-vaccination visit.  
Unblinded participants will continue to be monitored for CLI symptoms as detailed in 
Section 3.5.4.1. 
Table 3.5 
Assessments to be Performed at Unscheduled Visits for Participants Intending 
to Receive COVID-19 Vaccine 
Assessment 
COVID-19 Vaccinationa 
Initial (Pre-Vaccination) Visit 
Post-Vaccination Follow-up 
Visitb 
Placebo 
ADG20 
Placebo 
ADG20 
Health status including physical examc 
X 
X 
X 
X 
Blood sample for SARS-CoV-2 sVNA 
titersd 
X 
X 
X 
Xe 
Blood sample for ADA 
 
X 
 
X 
Blood sample for PK 
 
X 
 
X 
ADA=antidrug antibodies; PK=pharmacokinetics; sVNA=serum virus neutralizing antibody 
a Participants who request to be unblinded for COVID-19 vaccination will continue to be monitored for CLI symptoms 
(Table 3.4) and will undergo assessments according to the main SoA (Table 3.3), except that placebo participants will NOT 
have any blood draws for PK and ADA performed at any time after the pre-vaccination visit through the remainder of the 
study.  
b The window for this visit is 2 to 6 weeks post-vaccination. This visit occurs after receipt of the final COVID-19 vaccination in 
the primary vaccination regimen. Record the type and date(s) of COVID-19 vaccination(s) received in the participant’s eCRF. 
c Collect only if not already done at the main study visit. 
d Samples for sVNA titers may not be collected for all participants. The Sponsor will notify Investigators when these blood draws 
are no longer required. 


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e sVNA titer assessment will include both induced and ADG20 antibodies. 
3.5.2.8. 
Hypersensitivity Reaction Assessment Unscheduled Visit 
Hypersensitivity reactions are described in Section 3.5.5.5. If a participant reports a 
hypersensitivity reaction outside of a regularly scheduled in-person visit, the Investigator may 
perform an unscheduled visit for further evaluation. The following assessments should be 
performed: 
• If occurring after Day 4: blood samples for PK and ADA 
• Local and/or central safety laboratory tests, at the discretion of the investigator (or qualified 
designee) 
• Vital signs 
• Targeted review of changes in health 
• Review of concomitant medications  
• Review of AEs 
• Collection of medically attended visit information  
3.5.2.9. 
Other Unscheduled Visits 
An unscheduled visit may be necessary per investigator (or medically qualified designee) 
judgment for assessment of an AE or SAE or an abnormal lab or procedural findings. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
3.5.3. 
CLI Period: Study Visits in the Event of COVID-19-Like Illness 
As of protocol version 6.0, monitoring for CLI symptoms and CLI visits are discontinued. 
Sections 3.5.3, 3.5.3.1, 3.5.3.2, 3.5.3.3, and 3.5.3.4 are no longer applicable. The text is 
retained in these sections for reference only.  
If at any time from Day 1 through the Month 12 Visit a participant experiences CLI qualifying 
symptoms (see Section 3.1.1.1) that are confirmed by the site, the participant will enter the CLI 
Period and follow the CLI SoA (Table 3.4). The participant should not complete study visits in 
the main SoA while in the CLI Period, and entry into the CLI Period does not affect the overall 
study duration for an individual study participant. A participant may have multiple CLI Periods 
throughout the course of the study if COVID-19 is not confirmed for a given CLI Period. 
Participants with recurrence of CLI symptoms after resolution of confirmed COVID-19 should 
be followed according to Section 3.5.3.4. 
CLI visits will not be initiated for participants reporting a CLI after the Month 12 Visit. 
3.5.3.1. 
CLI Initial Visit (CLI Day 1) 
As of protocol version 6.0, this section is not applicable. 
The CLI Day 1 Visit will be conducted in person, either at the Clinical Site or via a home visit. 
CLI Day 1 Visit requirements are outlined in the CLI SoA (Table 3.4). If a Clinical Site or home 


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visit is not possible, study assessments for the initial CLI Visit will be conducted remotely, and 
the participant will collect and submit a saliva sample for SARS-CoV-2 RT-PCR central testing. 
The site will send a saliva collection kit to the participant via courier (or other agreed 
mechanism) and the participant will return the saliva sample to the site via courier (or other 
agreed mechanism). If a sample for local SARS-CoV-2 RT-PCR testing is collected per local 
standard of care, the result should be recorded in the eCRF (see Section 3.5.4.3). 
3.5.3.2. 
CLI Home Collection Period (CLI Day 2 to Day 21) 
As of protocol version 6.0, this section is not applicable. 
After the in-person CLI Day 1 Visit, all participants will enter the CLI Home Collection Period. 
The CLI Home Collection Period procedures should be performed as indicated in the CLI SoA 
(Table 3.4) for all participants until the result of the CLI Day 1 SARS-CoV-2 central NP 
RT-qPCR test is received. Participants will continue in the CLI Period according to the CLI SoA 
(Table 3.4) regardless of symptoms unless the Day 1 CLI central NP RT-PCR result is negative. 
Participants with missing or pending results will continue in the CLI Period. Participants with a 
negative central NP RT-PCR result will exit the CLI Period when the test result is received and 
return to following the main SoA, as described in Table 3.3 and Section 3.5.2.  
Throughout the CLI Home Collection Period, daily telemedicine visits will be conducted via 
video or phone for clinical assessments as indicated in the CLI SoA (Table 3.4) and described in 
Section 3.5.4.2.3.  
Throughout the CLI Home Collection Period, participants will report their vital signs daily as 
indicated in Section 3.5.4.2.2. 
On Days 3, 5, 8, 11, 14, and 21, the participant will collect saliva samples for SARS-CoV-2 viral 
shedding test (see Section 3.5.4.3). Note: collection of these samples was discontinued with 
protocol clarification letter 6. 
3.5.3.3. 
CLI Final Visit (CLI Day 28) 
As of protocol version 6.0, this section is not applicable. 
The final CLI Visit will be conducted in-person (either at the Clinical Site or via a home visit) on 
Day 28. Assessments will be performed as indicated in the CLI SoA (Table 3.4). Following the 
visit, the Investigator will also assign an overall COVID-19 severity grade for that day based on 
the participant’s responses and according to Appendix 5 and record the severity on the eCRF. 
3.5.3.4. 
Visit for CLI Recurrence After Resolution of COVID-19 
As of protocol version 6.0, this section is not applicable. 
If at any time after achieving sustained resolution of symptoms a participant with previously 
confirmed COVID-19 reports a recurrence of COVID-19-like symptoms, the site should perform 
a CLI Recurrence Visit as indicated in Table 3.4. Only the procedures indicated for the CLI 
Recurrence Visit should be followed; the participant will not re-enter or begin a new CLI period 
(ie, CLI Day 1). The recurrence of symptoms should be recorded as an AE (or SAE if meeting 
criteria) and followed accordingly.  


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3.5.4. 
Efficacy Assessments 
Efficacy assessments will include SARS-CoV-2 testing, evaluation of signs and symptoms of 
COVID-19, and determination of health care resource utilization. Planned time points for all 
efficacy assessments are provided in the main SoA (Table 3.3) and CLI SoA (Table 3.4). 
3.5.4.1. 
Monitoring for COVID-19 Symptoms 
As of protocol clarification letter 6, the use of an e-Diary for monitoring for COVID-19 
symptoms was discontinued. As of protocol version 6.0, monitoring for COVID-19 
symptoms (Table 3.1) and CLI visits are discontinued, and this section is no longer 
applicable. Spontaneously reported CLI symptoms will be captured as AEs as per Section 
4.1.1 and Section 4.1.3 of the protocol.  
Prior to protocol clarification letter 6 and protocol version 6.0, the following procedures 
were in place and are described here for reference only:  
Participants will be instructed to monitor throughout the study for COVID-19 symptoms and will 
also be monitored via e-Diary and regular phone calls from the site to monitor for COVID-19 
symptoms, as described in Section 3.5.2.3. Participants who experience at least one COVID-19 
qualifying symptom (see guidelines in Table 3.1) must contact the study team. Symptoms of fever, 
shortness of breath, or difficulty breathing should be reported to the study team as soon as 
possible.  
Participants reporting symptoms of COVID-19 will be evaluated via phone call to confirm if 
symptoms qualify as CLI. CLI symptoms with a known alternative etiology (eg, seasonal 
allergies responsive to antihistamines) do not require a CLI visit. The results of the call should 
be recorded in the eCRF and appropriate source documentation. If CLI is confirmed by the site, 
CLI visits will be initiated as described in Section 3.5.3 and Section 3.5.4.2. Once CLI visits are 
complete, the participant will return to following the visits and assessments schedule in the main 
SoA, including continued monitoring for new or recurring CLI symptoms. 
Use of Electronic Diaries 
At the time of consent, participants must confirm they are willing to complete an e Diary in 
accordance with the main SoA (Table 3.3) and CLI SoA (Table 3.4) using an application 
downloaded to their mobile smart device (smartphone, tablet, etc.) at the time of enrollment. The 
e-Diary may also be accessed via a web browser on any device. Participants without a device 
capable of downloading the e-Diary application or accessing via a web browser will be provided 
with a device or paper back-up, as appropriate. Before dosing on Day 1, the participant will be 
instructed to download the e Diary application on their personal mobile smart device. 
This study will utilize the e Diary application for the collection of solicited ISRs, surveillance of 
signs and symptoms of CLI, and to elicit a CLI Recurrence Visit if a participant with previously 
confirmed COVID 19 is experiencing a recurrence of CLI symptoms. Information on ISR 
monitoring via e-Diary is provided in Section 3.5.5.4. 


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Surveillance of CLI Signs and Symptoms 
Participants will be instructed to record information regarding qualifying CLI symptoms (see 
Table 3.1) in the e-Diary twice weekly from Day 1 through the Month 6 Visit, then once weekly 
through the Month 12 Visit. The participant will be trained on how to complete the e-Diary at the 
Day 1 Visit and will be reminded to call the site immediately if they experience any qualifying 
CLI symptoms. If a participant does not complete the e-Diary within a 2-day window around the 
scheduled timepoint, study staff will follow-up directly with the participant via phone call or text 
message to confirm their health status and to remind the participant of the importance of 
maintaining contact via the e-Diary. 
The e-Diary will inquire about the following: 
• Changes in health since the last time completing the e-Diary or the last contact with the 
study staff. 
• Any known exposure to someone with a SARS-CoV-2 infection or COVID-19 since the last 
time completing the e-Diary or last contact with the study staff. 
• Capture of any CLI symptoms (see Table 3.1) currently being experienced or experienced 
since the last time completing the e-Diary. 
A positive response by the participant will result in a notification to both the participant and 
study staff to arrange a call for further assessment, as described above.  
3.5.4.2. 
COVID-19-Like Illness 
3.5.4.2.1. CLI Assessment 
As of protocol version 6.0, CLI assessment and CLI visits are discontinued, and this section 
is no longer applicable. Prior to protocol version 6.0, the following procedures were in 
place and are described here for reference only:  
Participants who experience site-confirmed qualifying CLI symptoms (see Table 3.1) up to the 
Month 12 Visit will visit the Clinical Site or will be visited at home by medically qualified staff 
within 48 hours of symptom confirmation for initiation of CLI assessments (CLI Day 1 Visit) as 
described in the CLI SoA (Table 3.4 and Section 3.5.3). CLI symptoms and participant/PI 
assessments of CLI severity will be recorded, and an NP swab and saliva sample will be 
collected on CLI Day 1 for detection of SARS-CoV-2 via central lab. The CLI Day 1 symptom 
severity assessment should take into account all CLI symptoms from the time they began through 
CLI Day 1, not only those present on CLI Day 1. If a Clinical Site or home visit is not possible, 
study assessments for CLI Day 1 Visit will be conducted remotely.  
Results of any local SARS-CoV-2 RT-PCR testing conducted by the site or reported by the 
participant should also be recorded. 
Following the CLI Day 1 Visit, participants will enter the CLI Home Collection Period and 
complete daily telemedicine visits until the results of the central lab SARS-CoV-2 RT-PCR NP 
swab are known. The CLI Home Collection Period begins on CLI Day 2 and continues through 
CLI Day 21. During the CLI Home Collection Period, participants will monitor their vital signs 


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(oral temperature, SpO2, and heart rate) daily (see Section 3.5.4.2.2) and attend daily 
telemedicine visits (see Section 3.5.4.2.3) as indicated in the CLI SoA (Table 3.4). Saliva samples 
will be collected by participants at home on CLI Day 3, 5, 8, 11, 14, and 21 to measure viral 
shedding over time. (Note: collection of these saliva samples was discontinued via protocol 
clarification letter 6). 
A final CLI Visit will be conducted in-person (either at the Clinical Site or via a home health 
visit) on Day 28. 
CLI visits will not be initiated for participants reporting a CLI after the Month 12 Visit. 
Participants will report any CLI at the telephone contacts conducted at Month 13 and Month 14 
as described in Section 3.5.2.5; any symptoms should be collected as AEs as described in 
Section 4.1.3 and Section 4.2. 
3.5.4.2.2. Self-Assessed Vital Signs 
As of protocol version 6.0, CLI assessments are discontinued, and this section is no longer 
applicable. Prior to protocol version 6.0, the following procedures were in place and are 
described here for reference only:  
Participants will assess and record their vital signs (oral body temperature, SpO2, and heart 
rate) daily during the CLI Home Collection Period. Participants will be provided with a memory 
aid and the necessary equipment to assess and record vital signs. Vital signs should be assessed 
at approximately the same time each day. Additional measurements may be taken at other times 
during the day if the participant feels feverish or short of breath at rest. The participant may also 
take and report their vitals during the telemedicine visit as appropriate. Participants will report 
the highest oral body temperature and heart rate, and lowest SpO2 values during daily 
telemedicine visits.  
3.5.4.2.3. Daily Telemedicine Assessments  
As of protocol version 6.0, CLI assessments are discontinued, and this section is no longer 
applicable. Prior to protocol version 6.0, the following procedures were in place and are 
described here for reference only:  
Telemedicine visits will be conducted daily beginning on CLI Day 2 through CLI Day 21. 
Telemedicine visits may be conducted by various secure virtual means (eg, telephone, telehealth, 
videoconference, etc). At each visit, the identity of the participant must be confirmed based on 
local requirements and/or institutional procedures. Telemedicine visits may be performed by 
medically qualified staff appropriately delegated by the Investigator.  
During the telemedicine visit (preferably done in the evening) the participant will be asked to 
verbally report any CLI symptom and the severity of each symptom (according to Appendix 2). 
The participant will also report their highest body temperature, lowest SpO2, and highest heart 
rate for that day; any medications taken to treat current illness/symptoms; and any new onset 
AEs. The Investigator will determine if medical attention is required due to worsening of 
COVID-19. Following the visit, the Investigator will also assign an overall COVID-19 severity 
grade for that day based on the participant’s responses and according to Appendix 5 and record 
the severity on the eCRF.  


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The participant will be reminded to collect a saliva sample and will be provided with instruction 
on where and when to return the sample. 
3.5.4.2.4. Health Care Resource Utilization 
As of protocol version 6.0, this section is no longer applicable. Prior to protocol version 6.0, 
the following procedures were in place and are described here for reference only:  
Participants will be asked to report information in relation to their health care resource 
utilization throughout the CLI Period as indicated on the CLI SoA (Table 3.4).  
The study site should make every effort to capture the dates and types of any COVID-19 related 
health-care visit, including primary care provider visits, emergency room visits, urgent care 
clinic visits, visits to other outpatient medical facilities, hospital admissions, and ICU stays. 
Information obtained will be captured in source documents and entered into the eCRF.  
In the event a participant does not enter the CLI period but is known to be hospitalized with 
COVID-19, appropriate Health Care Resource Utilization data associated with the event should 
be captured on the eCRF. 
3.5.4.2.5. Recurrence of CLI Symptoms 
As of protocol version 6.0, CLI assessment and CLI visits are discontinued, and this section 
is no longer applicable. Prior to protocol version 6.0, the following procedures were in 
place and are described here for reference only:  
If a participant with confirmed symptomatic COVID-19 achieves sustained resolution of 
symptoms and later reports a recurrence of CLI symptoms (see Table 3.3), the investigator (or 
designee) will contact the participant to confirm CLI symptoms. If a CLI is confirmed, the site 
will perform a CLI Recurrence Visit as detailed in Section 3.5.3.4.  
3.5.4.2.6. COVID-19 Confirmed Outside of a CLI Visit 
As of protocol version 6.0, this section is no longer applicable. Confirmed COVID-19 cases 
will be captured as AEs as per Section 4 of the protocol. Prior to protocol version 6.0, the 
following procedures were in and are described here for reference only:  
If a participant is diagnosed with COVID-19 outside of the study setting (eg, is hospitalized 
before a CLI visit can be performed), every effort should be made to collect and record the date 
and result of any local RT-PCR performed at the time of diagnosis. If the participant was 
hospitalized, the clinical site will complete the appropriate SAE documentation and the 
Healthcare Resource Utilization form (see Section 4.2.2 and Section 3.5.4.2.4). 
3.5.4.3. 
SARS-CoV-2 Testing and Other Virology and Serology Assessments 
As of protocol version 6.0, CLI visits are discontinued. The samples indicated by italics below 
will no longer be collected and are described for reference only.  
Samples for SARS-CoV-2 and other virology assessments will be collected during the study as 
follows: 


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• A nasopharyngeal swab for central testing will be collected by the site on Day 1 and CLI 
Day 1 and tested for SARS-CoV-2 by authorized RT-PCR assays (qualitative on Day 1, 
quantitative on CLI Day 1). A saliva sample for central RT-PCR testing may be self-collected 
on CLI Day 1 if an in-person visit with site personnel cannot be conducted.  
• A nasopharyngeal swab will also be collected and tested for respiratory pathogens other 
than SARS-CoV-2 on CLI Day 1. 
• Saliva will be collected by site personnel or by participant self-collection at home (using a kit 
provided by the site) to quantify duration and magnitude of viral shedding during the CLI 
Period as indicated in the CLI SoA (Table 3.4). 
• Nasal swabs for SARS-CoV-2 RT-qPCR will be collected from participants in Cohort A 
(PEP) on Days 1 (predose), 8, and 15 (self-collected) to detect any asymptomatic infections 
as detailed in Section 3.5.4.4. 
• Blood samples will be collected and tested for SARS-CoV-2 serology as indicated in the 
main SoA (Table 3.3) and CLI SoA (Table 3.4). A blood sample for point of care (POC) 
rapid serology testing will also be collected from participants in Cohort A (PEP) at 
Screening. 
• Any known positive local RT-PCR test result obtained during the study period, whether 
within or outside of the study, should also be recorded on the local SARS-CoV-2 eCRF.  
Evaluation of viral resistance will be conducted using genotypic characterization of viral isolates 
for reduced susceptibility to ADG20, with phenotypic evaluation as appropriate. Samples 
collected during the study will be used for these analyses. Details on viral resistance testing will 
be described in a separate bioanalytical analysis plan.  
3.5.4.4. 
Monitoring for Asymptomatic Infection 
Post-baseline blood samples will be collected according to the main SoA (see Table 3.3) for 
SARS-CoV-2 serology testing to detect antibodies to the nucleocapsid (N) protein to monitor 
participants for asymptomatic infection. 
Nasal swabs for SARS-CoV-2 -RT-qPCR will be collected from participants in Cohort A (PEP) 
on Day 1 (predose), Day 8, and Day 15 (self-collected) to detect and quantify asymptomatic 
SARS-CoV-2 infection as indicated in the main SoA (Table 3.3).  
As of protocol version 6.0, CLI assessment and CLI visits are discontinued. Prior to 
protocol version 6.0, the following procedures were in place and are described here for 
reference only:  
Asymptomatic participants who are found to test positive, or any participant with a positive 
local RT-PCR test up to the Month 12 study visit, will be instructed to monitor for onset of 
qualifying symptoms (per Table 3.3) and to report symptoms to the clinical site. Any 
participant reporting qualifying symptoms within 14 days of collection of any positive RT-
PCR test will begin a CLI period, as described in Section 3.5.3 and Section 3.5.4.2. 


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3.5.5. 
Safety Assessments 
Planned time points for all safety assessments are provided in the main SoA (Table 3.3).  
As of protocol version 6.0, CLI visits are discontinued, and safety assessments indicated in 
the CLI SoA (Table 3.4) will not be performed. References to assessments performed at 
CLI visits (indicated in italics) are retained in the sections below for information only. 
3.5.5.1. 
Physical Examinations 
A complete physical examination will be performed at Screening followed by targeted physical 
examinations as specified in the main SoA (Table 3.3) and CLI SoA (Table 3.4). 
• Complete physical examination will include, but not be limited to, assessment of height, 
weight, general appearance, head, ears, eyes, nose, throat, neck, skin, as well as 
cardiovascular, respiratory, abdominal, and nervous systems. Each clinically significant 
abnormal finding at Screening will be recorded in the medical history. 
• A targeted physical examination will be based on reported AEs or ongoing sign/symptoms of 
COVID-19 (if any). 
• All physical examinations will be performed by a licensed health care provider 
(eg, physician, physician assistant, licensed nurse practitioner, or a licensed nurse being 
directed by a physician via live telemedicine). 
3.5.5.2. 
Vital Signs 
Vital signs, including heart rate, pulse oximetry, blood pressure, respiratory rate, and body 
temperature, will be performed as specified in the main SoA (Table 3.3) and CLI SoA 
(Table 3.4). The participant should be resting before the collection of vital signs. 
Data collected through CLI telemedicine visits on heart rate, temperature, and SpO2 level will be 
recorded but should not be reported as AEs unless meeting criteria for an SAE. 
3.5.5.3. 
Clinical Laboratory Assessments 
A Laboratory Manual will be provided to the sites that specifies the procedures for collection, 
processing, storage, and shipment of samples, as well as laboratory contact information, specific 
to this clinical study. The clinical laboratory tests that will be performed on blood samples are 
listed in Appendix 6. 
For participants of childbearing potential, a urine (or serum if required by local health 
regulations) sample for pregnancy testing will be collected at Screening and other timepoints 
according to the main SoA (Table 3.3). Urine pregnancy tests for beta human chorionic 
gonadotropin (β-hCG) may be performed at the Clinical Site using a licensed test (dipstick). If 
urine pregnancy result is indeterminate at Screening, the urine test will be repeated or a 
quantitative serum β-hCG can be performed for confirmation. 
Additional safety samples may be collected if clinically indicated at the discretion of the 
Investigator. 


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3.5.5.4. 
Injection Site Reactions 
This study will utilize an e-Diary application for the collection of solicited ISRs. At the time of 
consent, participants must confirm they are willing to complete the e-Diary in accordance with 
the main SoA (Table 3.3). The e-Diary may be accessed via an application downloaded to their 
mobile smart device (smartphone, tablet, etc.) or a web browser on any device. Participants 
without a device capable of downloading the e-Diary application or accessing via a web browser 
will be provided with a device or paper back-up, as appropriate. Before dosing on Day 1, the 
participant will be instructed to download the e-Diary application on their personal mobile smart 
device. 
Solicited ISRs will be collected in the e-Diary daily on Days 1 through 4.  
Participants will complete the e-Diary on site for evaluating any Day 1 ISRs. Study staff will 
instruct the participant on usage of the e-Diary and assist in reporting any findings on Day 1. 
Thereafter the participants will be required to self-monitor the injection site and record the 
results in the ISR e-Diary daily through Day 4. 
Participants will be provided with a ruler and instructed on the use of the ruler. Participants will 
be instructed to record the presence and severity of the following local solicited AEs at the 
injection site: pain or tenderness, erythema/redness, and induration/swelling. Severity will be 
assessed for solicited AEs (ISRs) by the participant (or, if applicable, their caregiver, surrogate, 
or legally authorized representative). Reaction severity will be graded according to FDA 
Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (2007), as described in Appendix 1. 
Any reported ISR that is graded >2 by a participant in the e-Diary will alert the site. The site will 
then contact the participant by telephone or telemedicine to determine if further evaluation or 
care is needed. Participants will be provided an emergency 24-hour telephone number and may 
contact the clinical site directly to report an ISR of concern, including those graded ≤2.  
Investigators or medically qualified designees will follow all ISRs that are ongoing beyond 
Day 4 to resolution and record the resolution date. 
3.5.5.5. 
Hypersensitivity Reactions 
All participants will be monitored closely for signs/symptoms of local or systemic 
hypersensitivity reactions for 1 to 4 hours after study drug administration (see Section 3.1.2). 
Participants in the sentinel groups will additionally be monitored for hypersensitivity reactions 
daily by telephone for 4 days after dosing. 
Study drug administration will occur in a setting where health care providers have immediate 
access to medications to treat a severe hypersensitivity reaction, such as anaphylaxis, and the 
ability to activate the emergency medical system, as necessary. It is recommended that 
participants who experience a systemic hypersensitivity reaction be treated per the local standard 
of care. 
Hypersensitivity reactions include but are not limited to anaphylaxis, anaphylactic shock, 
bronchospasm, hypotension, loss of consciousness, generalized skin rash, angioedema, 
bronchoconstriction, allergic bronchial asthma, allergic rhinitis, allergic conjunctivitis, drug 


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allergy, immune thrombocytopenia, autoimmune hemolytic anemia, rash, urticaria, and arthus 
reaction. Hypersensitivity reactions will be graded according to the DAIDS Table for Grading 
the Severity of Adult and Pediatric Adverse Events(NIAID 2017).  
If such a reaction occurs, additional details describing each symptom should be provided to the 
sponsor in the appropriate CRF page. 
Possible hypersensitivity reactions occurring within 4 days of study drug injection and after 
4 days (possible delayed hypersensitivity reactions) will be adjudicated by the Sponsor.  
3.5.5.6. 
Adverse Events 
All AEs occurring after the participant signs the ICF and up to the last study visit will be 
recorded. 
As of protocol version 6.0, any COVID-19-related event will be recorded as an AE.  
Prior to protocol version 6.0, the following procedures were in place and are described here 
for reference only: 
For the purposes of this study, the first case of COVID-19 or SARS-CoV-2 infection, 
including worsening or sequelae, will not be recorded as an AE, unless it meets SAE 
criteria. These data will be captured as efficacy assessment data as these are expected 
endpoints. Subsequent episodes of COVID-19 in the same participant will be captured 
according to standard AE processes, including the standard process for expedited reporting 
of SAEs if the event meets the definition of an SAE. A participant-reported first case of 
COVID-19 occurring after Month 12 will be captured in the eCRF detailing date of onset of 
symptoms, date of positive RT-PCR, any treatment or medical care received, and date of 
resolution (or ongoing). 
See Section 4 for additional information. 
3.5.5.7. 
Treatment of Overdose 
The definition of overdose for this study is receipt of any dose greater than the dose the 
participant was randomized to receive.  
Treatment of overdose with ADG20 or matching placebo should consist of general supportive 
measures including monitoring of vital signs and observation of the clinical status of the 
participant. There is no specific antidote for overdose of ADG20.  
The occurrence of an overdose with no associated abnormal laboratory assessments or clinical 
symptoms should be reported to the Sponsor as an overdose without adverse effect. If an 
overdose is associated with an AE, the AE term should describe the clinical symptoms or test 
result that was abnormal. 
3.5.6. 
Pharmacokinetic and Immunogenicity Assessments 
Blood samples for analyses of PK and ADA will be collected as described in the SoA 
(Table 3.3).  


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Immunogenicity may be assessed by a validated assay designed to detect ADAs in the presence 
of ADG20 at a laboratory approved by the Sponsor. Antibodies may be further characterized for 
their ability to neutralize the activity of ADG20.  
As of protocol version 6.0, CLI visits are discontinued, and PK and ADA assessments 
indicated in the CLI SoA (Table 3.4) will not be performed.  
3.5.7. 
Appropriateness of Measurements 
All assessments to be used in this study are commonly used, standard measurements frequently 
seen in mAb studies. 
4. 
ADVERSE EVENT REPORTING 
AEs will be monitored and recorded in an AE page of the eCRF, including the AE’s description, 
start, and end date, seriousness, severity, action taken, and relationship to the study drug. If AEs 
occur, the first concern will be the safety of the study participants. All AEs will be followed until 
resolved or stable and the outcome documented in the eCRF. 
4.1. 
Definitions and Criteria 
4.1.1. 
Adverse Events 
An AE is any untoward medical occurrence in a participant or clinical investigation participant 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding, for example), symptom, or disease temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. TEAEs are defined in Section 5.10.1. 
Medical interventions such as surgeries, diagnostic procedures, and therapeutic procedures are 
not AEs, but the action taken to treat the medical condition. They should be recorded as 
treatment of the AEs. 
4.1.2. 
Serious Adverse Events 
An SAE or reaction is any untoward medical occurrence that at any dose: 
• results in death. 
• is immediately life-threatening. 
• requires inpatient hospitalization or prolongation of existing hospitalization. 
• results in persistent or significant disability or incapacity 
• is a congenital anomaly or birth defect 
• Is an important medical event (eg, intensive treatment in an ER or at home for allergic 
bronchospasm; blood dyscrasias, or convulsions that do not result in hospitalization; or 


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development of drug dependency or drug abuse; malignancy tumors [histologically different 
from primary tumor]). 
“Immediately life-threatening”: report if suspected that the patient was at substantial risk of 
dying at the time of the AE or use or continued use of the medical product might have resulted in 
the death of the patient. 
“Inpatient hospitalization”: report as an SAE if admission to the hospital or prolongation of 
hospitalization was a result of an AE. 
Emergency room visits that do not result in admission to the hospital should be evaluated for one 
of the other serious outcomes (eg, life-threatening, required intervention to prevent permanent 
impairment or damage, other serious medically important event).  
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, they 
may jeopardize the participant or may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Seriousness (not severity) serves as a guide for defining regulatory reporting obligations. An 
SAE is not necessarily severe (eg, an overnight hospitalization for a diagnostic procedure must 
be reported as an SAE because it is considered serious even though the occurrence is not 
considered medically severe). Furthermore, a severe AE is not necessarily serious (eg, nausea of 
several hours’ duration may be rated as severe but may not be considered serious). 
4.1.3. 
Adverse Events Based on Signs and Symptoms 
All AEs spontaneously reported by the participant or reported in response to the open question 
from the Clinical Site staff: ‘Have you had any health problems since the previous visit/you were 
last asked?’ or revealed by observation will be collected and recorded in the eCRF. When 
collecting AEs, the recording of diagnoses is preferred (when possible) to recording a list of 
signs and symptoms. However, if a diagnosis is known and there are other signs or symptoms 
that are not generally part of the diagnosis, the diagnosis and each sign or symptom will be 
recorded separately. 
4.1.4. 
Adverse Events Based on Examinations and Tests 
Any abnormal safety assessment (eg, vital sign measurement, physical examination) that in the 
medical and scientific judgment of the investigator is considered to be clinically significant, 
including worsening from baseline, is to be recorded as an AE or SAE. The medical diagnosis 
related to the abnormal finding (eg, hypotension) should be recorded, not the examination/test 
result or parameter/measurement. For AEs associated with vital sign abnormalities, the event 
should be graded on the basis of the clinical severity in the context of the underlying conditions. 


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However, any clinically significant safety assessments that are associated with an underlying 
disease, unless judged by the investigator to be more severe than expected for the participant’s 
condition, are not to be reported as AEs or SAEs. 
4.1.5. 
Abnormal Laboratory Values 
Any abnormality in a laboratory value that is new in onset or that has worsened in severity or 
frequency from the baseline condition and meets one of the following criteria will be recorded in 
the AE pages of the eCRF: 
• Requires therapeutic intervention or diagnostic tests. 
• Has accompanying or inducing symptoms or signs. 
• Is judged by the Investigator as clinically significant. 
If the AE qualifies as serious, this would be reported as an SAE.  
The investigator must review the laboratory reports, document this review, and record any 
clinically relevant changes occurring during the study. If the laboratory reports are not 
transferred electronically, the values must be filed with the source information (including 
reference ranges).  
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator. If such values do not return to 
normal/baseline within a period of time judged reasonable by the investigator, the etiology 
should be identified, and the sponsor or designee notified. 
4.1.6. 
Solicited Adverse Events 
4.1.6.1. 
Injection Site Reactions 
Predefined solicited AEs for ISR assessments are defined in Appendix 1. Solicited AEs for ISR 
will be captured and assessed for severity as described in Section 3.5.5.4 and Appendix 1. 
Because solicited ISR AEs are expected to occur after injections, they will not be assessed for 
relationship to study drug. 
Solicited ISR AEs should be reported as SAEs or MAAEs if they fulfill the criteria (see 
Section 4.1.2 and Section 4.1.8, respectively) for seriousness. 
Solicited ISR AEs will be considered resolved on the day the participant reports “none” for a 
given symptom. If any symptom is scored higher than “none” on Day 4, the site will be notified 
and will follow the symptom until resolution.  
4.1.6.2. 
Solicited CLI Symptoms  
As of protocol version 6.0, CLI assessment and CLI visits are discontinued and CLI 
symptoms (Table 3.1) will not be solicited. Spontaneously reported CLI symptoms should be 
recorded as AEs only if these symptoms meet the AE criteria outlined in Section 4.1.1. In this 


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case, symptoms should be combined using a diagnostic term whenever possible, as described in 
Section 4.2.1. 
Prior to protocol version 6.0, the following procedures were in place for recording of 
solicited CLI symptoms and are described here for reference only: 
CLI symptoms are collected via site contact with participants throughout the study.  
• Outside of a CLI Period, solicited CLI symptoms are not captured as AEs when collected via 
telephone contacts for monitoring for CLI, including symptoms spontaneously reported by 
the participant according to self-monitoring guidelines or collected by the site during pre-
specified telephone contacts, as described in Section 3.5.4.1. 
• During the CLI Period, solicited CLI symptoms and severity, as predefined in Appendix 2 
and collected during telemedicine/in-person visits, will be captured and assessed as 
described in Section 3.5.4.2.3. 
− Solicited CLI symptoms should not be reported as AEs for participants who test positive 
for SARS-CoV-2 within 14 days of the onset of these symptoms (ie, has confirmed 
COVID-19); these symptoms will be reported as efficacy endpoints. 
− For participants who enter a CLI Period and ultimately test negative for SARS-CoV-2, 
CLI symptoms reported during CLI visits should be recorded as AEs only if these 
symptoms meet the AE criteria outlined in Section 4.1.1. In this case, symptoms should be 
combined using a diagnostic term whenever possible and as described in Section 4.2.1. 
4.1.7. 
Adverse Events of Special Interest 
AESIs are events of scientific and medical interest specific to the further understanding of study 
intervention safety profile and require close monitoring and rapid communication by the 
investigators to the Sponsor. An AESI can be serious or non-serious. All AESIs will be recorded 
in the eCRF. 
AESIs for ADG20 are hypersensitivity reactions, as defined in Section 3.5.5.5, which occur 
within 4 days of study drug administration.  
Solicited AEs related to hypersensitivity reactions will be collected via telephone through 4 days 
in sentinel group participants. 
4.1.8. 
Medically Attended Adverse Events 
MAAEs are defined as AEs leading to medically attended visits that were not routine visits for 
physical examination or vaccination, such as an ER visit, or an otherwise unscheduled visit to or 
from medical personnel (medical doctor) for any reason other than the illness under study 
(COVID-19). AEs, including abnormal vital signs, identified on a routine study visit or during 
the scheduled illness visits will not be considered MAAEs. 
4.1.9. 
Assessing Intensity and Relationship 
All AEs will be assessed on 2 descriptive parameters: intensity and relationship to the study 
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• Intensity refers to the severity of an event and references impact on a participant’s 
functioning. 
• Relationship refers to the likelihood that the event being assessed was caused by the study 
drug. 
4.1.9.1. 
Adverse Event Intensity 
The severity, or intensity, of an AE refers to the extent to which an AE affects the participant’s 
daily activities. The intensity of all AEs (with the exception of injection site reactions) will be 
graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events (NIAID 2017). The DAIDS grading table provides an AE severity grading scale ranging 
from grades 1 to 5 with descriptions for each AE based on the following general guidelines: 
• Grade 1 indicates a mild event 
• Grade 2 indicates a moderate event 
• Grade 3 indicates a severe event 
• Grade 4 indicates a potentially life-threatening event 
• Grade 5 indicates death (Note: This grade is not specifically listed on each page of the 
grading table) 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity for the experience should be noted. If the intensity category changes over a number of 
days, those changes should be recorded separately (with distinct onset dates). For SAEs, only 
one instance of the event would be reported with the highest severity grade. 
4.1.9.2. 
Adverse Event Relationship to Study Drug 
The Investigator’s assessment of an AE’s relationship to study drug is part of the documentation 
process but is not a factor in determining what is or is not reported in the study. 
The Investigator will assess causality (ie, whether there is a reasonable possibility that the study 
drug caused the event) for all AEs and SAEs. The relationship will be characterized using the 
following classification: 
Not related: There is not a reasonable possibility of a relationship to the study drug. The 
participant did not receive the study drug, temporal sequence of the AE onset relative to 
administration of the study drug is not reasonable, OR the AE is more likely explained by 
another cause than the study drug. 
Related: There is a reasonable possibility of a relationship to the study drug. There is evidence 
of exposure to the study dug. The temporal sequence of the AE onset relative to the 
administration of the study drug is reasonable. The AE is more likely explained by the study 
drug than by another cause. 
When assessing the relationship to the study drug, the following criteria will be considered: 
• Known class effect. 


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• Biological plausibility. 
• Lack of alternative explanation, ie, concomitant drug, or disease. 
4.2. 
Reporting Procedures and Requirements 
4.2.1. 
Adverse Events 
Adverse events occurring from when the participant signs the ICF until the last study event will 
be recorded. Prior to randomization, only SAEs related to a study procedure are required to be 
reported. Complaints or diagnostic findings that occur from the time the ICF is signed until 
randomization that are not study procedure-related are to be recorded as medical history. Once 
randomized/assigned to study treatment, all AEs are reported. Also, any sign, symptom, or 
disease present before starting the treatment period is only considered an AEs/SAEs if it worsens 
after administration of study drug. 
If the Investigator detects an SAE in a study participant within 3 months after the last scheduled 
follow-up visit and considers the event possibly related or related to study treatment, the 
Investigator should report it to Synteract. 
The Investigator should report all AEs in the AE page(s) of the eCRF and source documents, 
regardless of seriousness, severity, and causality. Whenever possible, an AE will be reported 
using a diagnostic term, (eg, “common cold” or “upper respiratory infection” rather than “runny 
nose, cough, mild fever”) and should be assessed for intensity and causality as described in 
Section 4.1.9.  
4.2.2. 
Serious Adverse Events 
Each AE will be assessed to determine whether it meets seriousness criteria according to the 
definition in Section 4.1.2. If the AE is considered serious, the Investigator should report this 
event to Synteract as outlined below and to the IRB/IEC according to its SOPs. 
Recording of SAEs is required on the AE eCRF and the paper SAE form within 24 hours of 
awareness. Upon collecting new information (follow up), the eCRF and the paper SAE form 
must be updated and continue to match, including, but not limited to, event term, start/stop date, 
relationship to investigational product and outcome. 
Relevant, appropriately redacted hospital records should be sent to the CRO as soon as possible, 
including but not limited to: discharge summary, COVID-19 test results, diagnostic test results 
supporting the specific SAE event, evidence of number of days in ICU, requirement for 
intubation/mechanical ventilation, medications or procedures administered for treatment or 
management of the SAE, etc. 
If the Investigator detects an SAE in a study participant after the last scheduled Follow-up Visit, 
and considers the SAE related or possibly related to prior study treatment, the Investigator 
should report it to Synteract. If this occurs after the EDC closure, this will only be captured in the 
Safety Database. 
All information about SAEs will be collected and reported via the SAE form and sent by email 
message (contact information will be contained in the Investigator site file). The Investigator 


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should send the initial report within 24 hours of becoming aware of the SAE. At a minimum, the 
initial report should include the following information: 
• Event 
• Study code 
• Participant number, initials, and date of birth 
• Study drug 
• Reporter name and contact information 
In the case of a “minimum report” (one that solely comprises the information bulleted above), a 
more detailed follow-up report should be sent as soon as more information becomes available but 
no later than 7 calendar days after the date of the initial report.  
Each SAE should be followed up until resolution or stabilization and for reported deaths, the 
Investigator should supply Synteract and the IRB/IEC with any additional requested information 
(eg, hospital discharge summary, autopsy reports and terminal medical reports). 
The original SAE form should be kept at the Clinical Site. The Investigator (or qualified 
designee) will be responsible for reviewing and signing each SAE form that is submitted. With 
each SAE form submission, the SAE from will be updated with the new SAE information. The 
Sponsor or its representative will be responsible for determining and in turn, reporting SAEs to 
regulatory authorities according to the applicable regulatory requirements. 
Serious AEs that are ongoing at the Month 14 Visit should be followed until resolved. 
4.2.3. 
Procedures for Documenting Pregnancy During Study 
All pregnancies of female participants in the study will be collected and reported on the 
Pregnancy Form. Information regarding pregnancies occurring in female partners of male study 
participants will not be solicited. 
Pregnancy in female participants is not regarded as an AE unless there is a suspicion that the 
study drug may have interfered with the effectiveness of a contraceptive medication. Pregnancies 
will not be reported as an SAE. Abnormal pregnancy outcomes, for example, spontaneous 
abortion, fetal death, stillbirth, congenital anomalies, and ectopic pregnancy, are considered 
SAEs. Any SAE occurring in association with a pregnancy, brought to the investigator’s 
attention after the participant has completed the study, and considered by the investigator as 
possibly related to the study treatment, must be promptly reported to the sponsor or designee. 
If a participant becomes pregnant during the study, the investigator will notify the Sponsor or 
designee within 72 hours following pregnancy confirmation (via urine pregnancy test, or serum 
pregnancy test if required by local regulations) using the Pregnancy Report form. These 
participants are encouraged to continue with all follow-up visits. Pregnancy outcomes for all 
participants should be followed by the site through the Month 14 or ET Visit. The investigator 
will also notify the participant’s physician that the participant may have been treated with 
ADG20, and request that any pregnancy outcomes occurring after the participant has completed 


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the study be reported to the clinical site. All pregnancy outcome information should be recorded 
on the Pregnancy Report Form and forwarded to the sponsor or designee when available. 
Any spontaneously reported information from a pregnant partner of a participant assigned male 
at birth will similarly be captured on the Pregnancy Report Form or Newborn Form as 
appropriate.  
4.2.4. 
Unanticipated Problems Involving Risks and Adverse Events 
In the United States, Investigators are required to report all unanticipated problems involving 
risks to human participants promptly to the IRB and Sponsor. This includes AEs that are 
considered unanticipated problems (21 CFR 56.108[b][1], 21 CFR 312.53[c][1][vii], and 
21 CFR 312.66).  
4.2.4.1. 
Definition of Unanticipated Problems 
An AE observed during the conduct of a study should be considered an Unanticipated Problem 
(UP) involving risk to human participants, and be reported to the IRB, only if it meets all the 
following three conditions: it is unexpected, serious, and has implications for the conduct of the 
study (eg, requiring a significant, and usually safety-related, change in the protocol, such as 
revising inclusion/exclusion criteria or including a new monitoring requirement, informed 
consent, or IB). The occurrence of such an event would suggest that the research may place study 
participants or others at a greater risk of harm. Some examples of AEs that should be considered 
UPs and must be reported to the IRB are: 
• A single occurrence of a serious, unexpected event that is uncommon and strongly associated 
with drug exposure (such as angioedema, agranulocytosis, hepatic injury, or Stevens-Johnson 
syndrome).  
• A single occurrence, or more often a small number of occurrences, of a serious, unexpected 
event that is not commonly associated with drug exposure, but uncommon in the study 
population (eg, tendon rupture, progressive multifocal leukoencephalopathy). 
• An AE that is described or addressed in the IB, protocol, or informed consent documents, but 
occurs at a specificity or severity that is inconsistent with prior observations.  
• An SAE that is described or addressed in the IB, protocol, or informed consent documents, 
but for which the rate of occurrence in the study represents a clinically significant increase in 
the expected rate of occurrence (ordinarily, reporting would only be triggered if there were a 
credible baseline rate for comparison). 
• Any other AE or safety finding (eg, based on animal or epidemiological data) that would 
cause the sponsor to modify the IB, study protocol, or informed consent documents, or would 
prompt other action by the IRB to ensure to ensure the protection of human participants.  
4.2.4.2. 
Reporting of Unanticipated Problem 
The Investigator will report UPs to their IRB and to the sponsor if required by local regulations.  
Include the following information in the UP report: protocol title and number, Investigator’s 
name, and the IRB project number; a detailed description of the event, incident, experience, or 


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outcome; and an explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP. For any additional details regarding reporting of UPs refer to the FDA 
Guidance for Clinical Investigators, Sponsors, and IRBs Adverse Event Reporting to IRBs––
Improving Human Subject Protection (https://www.fda.gov/media/72267/download). 
5. 
STATISTICAL ANALYSIS 
5.1. 
Overall Analysis Plan 
The statistical analysis will be undertaken by the Sponsor and representative. 
Each cohort will be treated independently under this master protocol. Cohorts A and B will each 
have a separate randomization list. Efficacy and safety analyses will be performed separately for 
each cohort, with each cohort allocated a 2-sided alpha of .05.  
A change to the data analysis methods described in this master protocol will require a protocol 
amendment only if it alters a principal feature of the protocol. Otherwise, any changes to the 
SAP before unblinding for the primary efficacy analyses of each cohort will be documented in an 
amendment to the SAP. Changes made to analyses in the SAP after unblinding and ad hoc 
analyses will be described in the Clinical Study Report. In addition, any deviations from the 
analyses described below will be included in the SAP and documented in the Clinical Study 
Report as appropriate. 
Enrollment in Cohort A (PEP) and in Cohort B (PrEP) was suspended on 11-Jan-2022 after 
emergence and global spread of the Omicron variant in regions enrolling the trial, beginning in 
December 2021, against which 300 mg ADG20 was not expected to have adequate efficacy due 
to decreased neutralization activity. Therefore, the primary analysis is focused on evaluating 
ADG20 300 mg IM treatment in the population randomized prior to the emergence of the 
Omicron variant.  
A preliminary efficacy and safety analysis was conducted with a data cutoff of 02-Mar-2022. 
The primary efficacy objective was to assess efficacy of ADG20 in the setting of susceptible 
variants (pre-emergence of Omicron); thus, the primary efficacy population included participants 
randomized on or prior to 30-Nov-2021 and followed for at least 2 weeks (up to 15-Dec-2021) 
when Omicron became the predominant variant in the US. The efficacy of ADG20 after the 
emergence of the Omicron variant was evaluated independently as an exploratory analysis in 
participants randomized after 30-Nov-2021. A full analysis of efficacy following a database soft 
lock (data cutoff: 11-Apr-2022) was carried out when all enrolled participants had a minimum of 
3 months follow-up or had discontinued. A 6-month safety analysis will be carried out following 
a database soft lock when all enrolled participants have a minimum of 6 months follow-up or 
have discontinued. A final safety analysis is planned after all enrolled participants have been 
followed through 14 months or have discontinued.  
5.2. 
Blinding 
This study will be double-blinded. The investigator, participant, all clinical site staff, and 
Sponsor personnel (or designees) involved in study intervention and evaluation will be blinded to 


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study drug assignment on the participant level. Investigators and participants will remain blinded 
to each participant’s assigned study treatment throughout the course of the study, except as 
described in Section 3.4.5 and Section 3.4.6. Sponsor personnel (or designees) will become 
unblinded as described below. An iDMC will review data in an unblinded manner as described 
in Section 5.12 and in the iDMC Charter. 
Efficacy and short-term safety analyses will be performed at the time of the database soft locks. 
Participants will continue to be followed through the Month 14 visit/EOS or discontinuation 
from study for the long-term safety. After the soft locks, all participants and site staff will 
continue to stay blinded to the individual study drug assignment until the final database lock; any 
unblinding of sponsor personnel (or designees) will be documented as described in the study 
unblinding plan.  
Plans for additional data locks or analyses may be revised during the study to adapt to 
unexpected issues in study execution and/or data that affect planned analyses and/or to address 
regulatory authority request, and/or to address protocol amendments.  
Further details will be included in the study unblinding plan.  
5.3. 
Analysis Sets 
The analysis sets that will be used for statistical analyses of Cohorts A and B are defined in 
Table 5.1. 
Table 5.1 
Defined Analysis Sets and Descriptions 
Defined Analysis 
Data Sets 
Description 
Full Analysis Set (FAS) 
Includes all randomized participants regardless of whether the participant received 
study drug.  
Pre-Emergence of 
Omicron Analysis Set 
Includes all participants randomized on or prior to 30-Nov-2021, allowing participants 
to be followed a minimum of 2 weeks through 15-Dec-2021 when Omicron became 
the predominant variant.  
Modified Full Analysis 
Set – RT-PCR-negative 
and seronegative 
(mFAS) 
Includes all randomized participants without prior or current SARS-CoV-2 infection at 
baseline based on central tests (RT-PCR-negative and seronegative). If either central 
RT-PCR or central serology is missing at baseline, a negative baseline status can be 
imputed for a participant if there is a post-baseline negative central serology sample 
collected at least 14 days from Day 1 and prior to any positive local/central RT-PCR. 
Modified Full Analysis 
Set – RT-PCR-negative 
(mFAS-1) 
Includes all randomized participants without current SARS-CoV-2 infection at 
baseline based on central tests (RT-PCR-negative regardless of serology status). If 
central RT-PCR is missing at baseline, a negative baseline status can be imputed for a 
participant if there is a post-baseline negative central serology sample collected at least 
14 days from Day 1 and prior to any positive local/central RT-PCR. 
Modified Full Analysis 
Set – RT-PCR-negative 
and seropositive 
(mFAS-2) 
Includes all randomized participants with prior infection but without current 
SARS-CoV-2 infection at baseline based on central tests (RT-PCR-negative and 
seropositive). No imputation is performed if any baseline test is missing. 


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Defined Analysis 
Data Sets 
Description 
Modified Full Analysis 
Set – RT-PCR-negative 
and seronegative 
(mFAS-3) 
Includes all randomized participants without prior or current SARS-CoV-2 infection at 
baseline based on central tests (RT-PCR-negative and seronegative). No imputation is 
performed if any baseline test is missing. 
Per-Protocol (PP) 
All randomized participants who receive the full dose of study drug, do not have 
missing data for the primary efficacy endpoint, and have no other important protocol 
deviation, as determined and documented by the Sponsor before database lock and 
unblinding, that could impact the assessment of efficacy.  
Safety 
All participants who receive study drug.  
Immunogenicity 
All participants who received study drug and had a valid immunogenicity test result 
before the dose of study drug and at least 1 valid result after the dose of study drug. 
Pharmacokinetic 
All participants in the Safety Analysis Set who have ADG20 concentration data for at 
least 2 post-injection time points. 
 
The primary efficacy population is defined as follows for each cohort:  
• Cohort A: baseline RT-PCR-negative participants pre-emergence of Omicron (mFAS-1 pre-
Omicron). 
• Cohort B: baseline RT-PCR-negative and seronegative participants pre-emergence of 
Omicron (mFAS pre-Omicron). 
In the efficacy analysis, participants will be analyzed based on the treatment they are randomized 
to, irrespective of what they actually might have received. In the safety analysis, participants will 
be analyzed based on the study drug received. 
5.4. 
Sample Size Determination 
Cohort A (PEP): The primary endpoint is the proportion of RT-PCR-confirmed symptomatic 
COVID-19 through 28 days after randomization. The original sample size of 1078 participants 
was planned with 90% power, 2-sided alpha .05, and a 1:1 randomization ratio to detect a 
statistically significant RR when the true RR is 0.30 (70% efficacy) with an attack rate of 5% per 
28 days in the placebo group and 1.5% in the ADG20 group. A sample size of 1270 participants 
was planned to account for 15% of participants enrolled with a prior or current SARS-CoV-2 
infection at baseline.  
Enrollment was suspended in Cohort A on 11-Jan-2022 following the emergence of Omicron 
variant, against which 300 mg ADG20 was not expected to have adequate efficacy due to 
decreased neutralization activity. As such, the analysis of the primary efficacy endpoint for 
Cohort A only included events through 28 days after randomization or the emergence of 
Omicron, whichever was earlier. Prior to suspension of enrollment, 487 participants were 
randomized in Cohort A, of which approximately 377 were enrolled prior to the emergence of 
Omicron with a minimum of 2 weeks follow-up through 15-Dec-2021, and 351 were estimated 
to be eligible for inclusion in the primary efficacy analysis population (RT-PCR-negative pre-
Omicron). The primary efficacy population yielded approximately 14 events through 28 days or 


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emergence of Omicron, whichever was earlier, for the analysis. With 14 events, any observed 
efficacy >68% would be statistically significant at 2-sided α=.05. 
Cohort B (PrEP): The primary endpoint is the proportion of RT-PCR-confirmed symptomatic 
COVID-19 through 3 months. The original sample size of 4628 participants was planned with 
84% power, 2-sided alpha .05, and a 1:1 randomization ratio to detect a statistically significant 
RR when the true RR is 0.30 (70% efficacy) with an attack rate of 1% per 3 months in the 
placebo group and 0.3% in the ADG20 group. A sample size of 5142 participants was planned to 
account for 10% of participants enrolled with a prior or current SARS-CoV-2 infection at 
baseline. 
Enrollment was suspended in Cohort B on 11-Jan-2022 following the emergence of Omicron 
variant, against which 300 mg ADG20 was not expected to have adequate efficacy due to 
decreased neutralization activity. As such, the analysis of the primary efficacy endpoint for 
Cohort B only included events through 3 months after randomization or the emergence of 
Omicron, whichever was earlier. Prior to suspension of enrollment, 2094 participants were 
randomized in Cohort B, of which approximately 1639 were enrolled prior to the emergence of 
Omicron with a minimum of 2 weeks follow-up through 15-Dec-2021, and 1477 were estimated 
to be eligible for inclusion in the primary efficacy analysis population (RT-PCR-negative and 
seronegative pre-Omicron). A higher than expected aggregate attack rate resulted in a sufficient 
number of cases to enable this cohort to be a fully powered study to detect clinically meaningful 
and statistically significant treatment differences. Based on a 3.6% aggregate attack rate, 974 
participants in a 1:1 randomization ratio provides 90% power to detect a statistically significant 
treatment effect when the true RR is 0.3 with 2-sided α =.05. Therefore, the current sample size 
of 1477 provided sufficient statistical power to carry out the primary efficacy analysis, as well as 
preliminary evaluation of safety. 
The sample size calculations were performed using SAS software version 9.4 (SAS Institute).  
5.5. 
Protocol Deviations 
All protocol deviations will be assessed and documented on a case-by-case basis in a blinded 
fashion; major deviations that are considered to have an impact on the efficacy assessment will 
lead to the relevant participant being excluded from the PP Analysis Set before any unblinded 
analysis is performed. For the interim analysis, all deviations identified before the formal data 
cut will be assessed at that time. All other deviations will be assessed before unblinding of the 
data. The numbers and percentages of participants with at least one important protocol deviation 
will be presented by study drug group and overall. Important protocol deviations will also be 
summarized by deviation type. 
Examples of protocol deviation types are: 
• Randomized without meeting inclusion criteria or with meeting an exclusion criterion. 
• Received the wrong study drug or incorrect dose; and 
• Missed study visits or missed assessments. 


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5.6. 
Participant Disposition 
The number of participants screened, the number of screen failures, and the reasons for screen 
failure will be tabulated. The numbers and percentages of participants in each analysis set will be 
summarized by and across study drug groups. The numbers and percentages of participants who 
completed the study will be presented as will the numbers and percentages of participants who 
withdrew from the study and the reason for withdrawal. If the proportion of participants 
discontinuing from the Follow-up Period is high or imbalanced across study drug groups, the 
timing of withdrawal may be explored further. 
5.7. 
Demographic and Baseline Characteristics 
Demographic and baseline data will be summarized using the FAS and the primary efficacy 
population. Demographic variables include age, age group (12 to <18, 18 to <55, 55 to <75, and 
≥75 years), sex at birth, race, ethnicity, and geographic category. Baseline variables include 
weight, height, BMI, presence of comorbidities (including those that increase the risk of severe 
COVID-19 as indicated in Appendix 4), age/risk of severe COVID-19 (12 to ≤54 years and low 
risk, 12 to ≤54 years and high risk, and ≥55 years), and baseline SARS-CoV-2 status by RT-PCR 
and by serology. 
Study drug groups will be compared with respect to participant demographics and baseline 
characteristics using descriptive statistics, but no formal statistical analysis tests will be 
performed. 
5.8. 
Concomitant Medication and Medical History 
The numbers and percentages of participants receiving prior and concomitant medications will 
be summarized by World Health Organization Drug Anatomic Therapeutic Chemical 
Classification level 2 and preferred drug name. 
Medical history incidence will be summarized by MedDRA SOC and PT. 
5.9. 
Efficacy Analyses  
The analysis approach for the primary and secondary efficacy endpoints in Cohorts A and B are 
summarized in Table 5.2 and Table 5.3, respectively. Subgroup and sensitivity analysis methods 
are described as applicable. 


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Table 5.2 
Efficacy Endpoints and Statistical Analyses Methods: Cohort A (PEP) 
Endpoint (Analysis Population) – Cohort A (PEP) 
Statistical Analysis Method and Analysis Timing 
Primary Endpoint 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28 or 
emergence of Omicron, whichever is earlier 
(mFAS-1 pre-Omicron)  
Primary analysis: Logistic regression model using the 
method that computes a population-level estimates 
adjusted for covariates including treatment, baseline 
serostatus, and stratification factors (Ge 2011).  
• 
Sensitivity analyses based on multiple imputations 
will be performed on the primary estimand.  
• 
Sensitivity analysis will be performed using Per-
Protocol Analysis Set. 
• 
A supportive analysis based on the Cochran-
Mantel-Haenszel test will be performed adjusting 
for the same factors that are used in the primary 
analysis model. 
• 
Subgroup analyses by baseline serostatus or 
stratification factors will be performed. 
Analysis Timing: After the last pre-omicron participant 
is randomized and followed for 2 weeks. 
Key Secondary Endpoints  
Proportion of participants with SARS-CoV-2 
infection (asymptomatic or symptomatic) as 
determined by positive RT-PCR or serology test 
through Day 28 or emergence of Omicron, whichever 
is earlier 
(mFAS-1 pre-Omicron) 
Key Secondary Endpoints: Same method as primary 
• 
Performed sequentially if the preceding analysis is 
statistically significant at 2-sided, .05 level. 
• 
Baseline serostatus or RT-PCR status will be 
included as covariate when applicable. 
Analysis Timing: After the last pre-omicron participant 
is randomized and followed for 2 weeks. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28 or 
emergence of Omicron, whichever is earlier 
(mFAS pre-Omicron) 
Proportion of participants with SARS-CoV-2 
infection (asymptomatic or symptomatic) as 
determined by positive RT-PCR or serology test 
through Day 28 or emergence of Omicron, whichever 
is earlier 
(mFAS pre-Omicron) 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28 or 
emergence of Omicron, whichever is earlier 
(FAS pre-Omicron) 
Proportion of participants with SARS-CoV-2 
infection (asymptomatic or symptomatic) as 
determined by positive RT-PCR or serology test 
through Day 28 or emergence of Omicron, whichever 
is earlier 
(FAS pre-Omicron) 


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Endpoint (Analysis Population) – Cohort A (PEP) 
Statistical Analysis Method and Analysis Timing 
Other Secondary Endpoints  
• 
Time from randomization to first RT-PCR-
confirmed symptomatic COVID-19  
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19  
(mFAS-1/mFAS/FAS pre-Omicron)  
Methodology: Time-to-symptomatic COVID-19 plot 
and probability of cumulative incidence at 28 days and 
3 months will be summarized using Kaplan-Meier 
methodology. The stratified log-rank test will be used to 
test the treatment effect.  
Stratified Cox proportional hazard model to estimate the 
HR and its 95% CI. The model will include treatment 
and stratification factors as strata. Baseline serostatus or 
RT-PCR status will be included as covariate when 
applicable. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months or 
emergence of Omicron, whichever is earlier 
(mFAS-1/mFAS/FAS pre-Omicron) 
Methodology: Same method as primary.  
Analysis Timing: After the last pre-omicron participant 
is randomized and followed for 2 weeks. 
Proportion of participants with SARS-CoV-2 
infection (asymptomatic or symptomatic) as 
determined by positive RT-PCR or serology test 
through 3 months or emergence of Omicron, 
whichever is earlier 
(mFAS-1/mFAS/FAS pre-Omicron) 
Methodology: Same method as primary.  
Analysis Timing: After the last pre-omicron participant 
is randomized and followed for 2 weeks. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28 and 3 
months after randomization or emergence of 
Omicron, whichever is earlier 
(mFAS-2 pre-Omicron) 
Methodology: Same analysis as primary. 
Analysis Timing: After the last pre-omicron participant 
is randomized and followed for 2 weeks. 
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by positive RT-
qPCR (nasal sample) on Days 8 and 15 after 
randomization  
(mFAS-1 pre-Omicron) 
Descriptive statistics: number and frequency on Day 8 
and on Day 15  
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by serology 
through Day 28 
(mFAS-1 pre-Omicron) 
Descriptive statistics: number and frequency through 
Day 28 
Peak post-baseline SARS-CoV-2 viral load as 
measured by RT-qPCR (nasal sample) 
Descriptive statistics in participants with asymptomatic 
SARS-CoV-2 infection as determined by positive RT-
qPCR (nasal sample) on Days 8 and 15 
SARS-CoV-2 viral load assessed by RT-qPCR (nasal 
sample) change from baseline to Day 8 and Day 15 
Descriptive statistics in participants with asymptomatic 
SARS-CoV-2 infection as determined by positive RT-
qPCR (nasal sample) at baseline, Day 8, and Day 15. 
Proportion of participants with RT-PCR-confirmed 
mild, moderate, or severe/critical COVID-19 through 
CLI Day 28 
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 
All-cause mortality through CLI Day 28 
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 


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Endpoint (Analysis Population) – Cohort A (PEP) 
Statistical Analysis Method and Analysis Timing 
COVID-19-related mortality through CLI Day 28 
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 
Time from reported symptom onset to sustained 
resolution of symptomatic COVID-19 through CLI 
Day 28 
Descriptive statistics and Kaplan-Meier methodology in 
participants with laboratory-confirmed symptomatic 
COVID-19 
Viral load from CLI Day 1 sample assessed by RT-
qPCR.  
Descriptive statistics in participants with laboratory-
confirmed symptomatic COVID-19.  
Proportion of participants with at least 1 COVID-19-
related medically attended outpatient visit 
(physician’s office, telemedicine, emergency rooms, 
or urgent care centers) through CLI Day 28  
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 
Proportion of participants with COVID-19-related 
hospitalizations through CLI Day 28   
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 
 
Table 5.3 
Efficacy Endpoints and Statistical Analyses Methods: Cohort B (PrEP) 
Endpoint (Analysis Population) – Cohort B (PrEP) 
Statistical Analysis Method and Analysis Timing 
Primary Endpoint 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months or 
emergence of Omicron, whichever is earlier 
(mFAS pre-Omicron)  
Primary analysis: Logistic regression model using the 
method that computes a population-level estimates 
adjusted for covariates including treatment and 
randomization stratification factors (Ge 2011).  
• 
Sensitivity analyses based on multiple imputations 
will be performed on the primary estimand.  
• 
Sensitivity analysis will be performed using Per-
Protocol Analysis Set. 
• 
A supportive analysis based on the Cochran-Mantel-
Haenszel test will be performed adjusting for the 
same factors that are used in the primary analysis 
model. 
• 
Subgroup analyses by stratification factors will be 
performed. 
Analysis Timing: After the last pre-omicron participant 
is randomized and followed for 2 weeks. 
Key Secondary Endpoints  
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months or 
emergence of Omicron, whichever is earlier 
(mFAS-1 pre-Omicron) 
Key Secondary Endpoints: Same method as primary 
• 
Performed sequentially if the preceding analysis is 
statistically significant at 2-sided, 0.05 level. 


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Endpoint (Analysis Population) – Cohort B (PrEP) 
Statistical Analysis Method and Analysis Timing 
Proportion of participants with SARS-CoV-2 
infection (asymptomatic or symptomatic) as 
determined by positive RT-PCR or serology test 
through 3 months or emergence of Omicron, 
whichever is earlier 
(mFAS pre-Omicron) 
• 
Baseline serostatus or RT-PCR status will be 
included as covariate when applicable.  
Analysis Timing: After the last pre-omicron participant 
is randomized and followed for 2 weeks. 
Proportion of participants with SARS-CoV-2 
infection (asymptomatic or symptomatic) as 
determined by positive RT-PCR or serology test 
through 3 months or emergence of Omicron, 
whichever is earlier 
(mFAS-1 pre-Omicron) 
Other Secondary Endpoints  
• 
Time from randomization to first RT-PCR-
confirmed symptomatic COVID-19  
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 
(mFAS/mFAS-1/FAS pre-Omicron)  
Methodology: Time-to-symptomatic COVID-19 plot 
and probability of cumulative incidence at 3 months will 
be summarized using Kaplan-Meier methodology. The 
stratified log-rank test will be used to test the treatment 
effect.  
Stratified Cox proportional hazard model to estimate the 
HR and its 95% CI. The model will include treatment 
and stratification factors as strata. Baseline serostatus or 
RT-PCR status will be included as covariate when 
applicable. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months or 
emergence of Omicron, whichever is earlier 
(FAS pre-Omicron) 
Methodology: Same method as primary. Baseline 
serostatus and RT-PCR status will be included as 
covariates. 
Proportion of participants with SARS-CoV-2 
infection (asymptomatic or symptomatic) as 
determined by positive RT-PCR or serology test 
through 3 months or emergence of Omicron, 
whichever is earlier 
(FAS pre-Omicron) 
Methodology: Same method as primary. Baseline 
serostatus and RT-PCR status will be included as 
covariates. 
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by serology at 
Month 6. 
(mFAS pre-Omicron) 
Descriptive statistics: number and frequency of 
asymptomatic SARS-CoV-2 infection 
Proportion of participants with RT-PCR-confirmed 
mild, moderate, or severe/critical COVID-19 through 
CLI Day 28  
(mFAS/mFAS-1/FAS pre-Omicron) 
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 
All-cause mortality through CLI Day 28 
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 
COVID-19-related mortality through CLI Day 28 
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 


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Endpoint (Analysis Population) – Cohort B (PrEP) 
Statistical Analysis Method and Analysis Timing 
Time from reported symptom onset to sustained 
resolution of COVID-19 symptoms through 
CLI Day 28 
Descriptive statistics and Kaplan-Meier methodology in 
participants with laboratory-confirmed symptomatic 
COVID-19 
Viral load from CLI Day 1 sample assessed by 
RT-qPCR  
Descriptive statistics in participants with laboratory-
confirmed symptomatic COVID-19.  
Proportion of participants with at least 1 COVID-19-
related medically attended outpatient visit 
(physician’s office, telemedicine, emergency rooms, 
or urgent care centers) through CLI Day 28 
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 
Proportion of participants with COVID-19-related 
hospitalizations through CLI Day 28  
Descriptive statistics: number and frequency in 
participants with laboratory-confirmed symptomatic 
COVID-19 
 
5.9.1. 
Primary Efficacy Endpoint  
The primary efficacy endpoint for Cohort A (PEP) is the proportion of RT-PCR-confirmed 
symptomatic COVID-19 through Day 28 or emergence of Omicron, whichever is earlier.  
The primary efficacy endpoint for Cohort B (PrEP) is the proportion of RT-PCR-confirmed 
symptomatic COVID-19 through 3 months or emergence of Omicron, whichever is earlier.  
RT-PCR-confirmed symptomatic COVID-19 is determined by the protocol defined COVID-19 
symptoms (Section 3.1.1.2) occurring within 14 days from the sample collection date of a 
positive central or local (in the absence of central test) RT-PCR. Any COVID-19-related 
hospitalization with a positive local SARS-CoV-2 test (within 14 days) or all-cause death are 
counted toward the endpoint. The date of event is the earliest date of COVID-19 symptom onset, 
COVID-19-related hospitalization, or all-cause death. 
The analysis of the primary estimand, incidence of RT-PCR-confirmed symptomatic COVID-19 
for ADG20 versus placebo will be analyzed using the methodology for determining a 
standardized estimator for a binary outcome as detailed in (Ge 2011) with adjustment for the 
prognostic factors. The standardized risk difference, associated p-value and 95% CI, and the 
standardized relative risk reduction with 95% CI will be provided for efficacy assessment.  
A treatment policy strategy will be used to handle the intercurrent events (ICEs) of interest in the 
primary analysis. The ICEs include the use of rescue medications (eg, COVID-19 vaccine, 
COVID-19 mAb for the purposes of prevention), subject unblinding by Investigator prior to the 
primary endpoint outcome, or others as specified in the SAP. Participants with missing primary 
endpoint outcome will be imputed as not having the primary endpoint outcome in the primary 
analysis. Sensitivity analyses using multiple imputation for missing outcome and hypothetical 
strategy of handling the ICEs will be fully described in the SAP.  
5.9.2. 
Secondary Efficacy Endpoints and Analyses  
The analyses of secondary efficacy endpoints are presented for Cohort A (PEP) in Table 5.2 and 
for Cohort B (PrEP) in Table 5.3. 


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In each cohort, a hierarchical testing approach will be used to test the key secondary hypotheses 
to preserve the type I error at 2-sided .05 level. The first key secondary hypotheses will be tested 
if the null hypothesis for the primary endpoint is rejected at 2-sided .05 level. The subsequent 
key secondary hypotheses will be tested if the null hypothesis for the preceding key secondary 
endpoint is rejected at 2-sided, .05 level.  
5.9.3. 
Multiplicity 
To control for the inflation of the overall type I error rate (alpha), a hierarchical testing procedure 
will be used within each cohort as described in Section 5.9.2.  
Analyses of other secondary and exploratory endpoints will be conducted to support the findings 
of the primary and key secondary efficacy endpoints and analyzed without any procedures to 
account for multiple comparisons. Nominal p-values and 95% CIs may be computed for these 
secondary and exploratory efficacy analyses. 
5.9.4. 
Exploratory Endpoints 
Exploratory endpoint analyses will be detailed in the SAP. For Cohorts A and B, these may 
include analyses of the primary efficacy and virological endpoints in randomized participants 
regardless of SARS-CoV-2 variant. Additional subgroup or covariate adjusted analyses may be 
performed. 
5.10. 
Safety Analyses 
All safety analyses will be performed using the Safety Analysis Set in each cohort. 
Safety endpoints include: 
• AEs (including SAEs and MAAEs) 
• AESIs (hypersensitivity reactions) 
• ISRs (solicited AEs) 
• Clinical laboratory assessments 
• Vital signs 
5.10.1. 
Adverse Events 
All AEs will be coded using the latest version of MedDRA. 
A TEAE is defined as any AE that has an onset during or after the administration of study drug 
through the Month 14 Follow-up Visit, or any pre-existing condition that has worsened during or 
after the administration of study drug through the Month 14 Follow-up Visit. Because solicited 
AEs (ISRs) are expected to occur after the IM injection all solicited AEs (ISRs) will be 
considered a TEAE. 
The incidence of TEAEs (including solicited ISRs), SAEs, TEAEs related to the study drug, 
SAEs related to the study drug, and AESIs will be summarized by MedDRA SOC, PT, and study 
drug group. 


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The incidence of TEAEs will also be summarized by DAIDS grading of severity for unsolicited 
AEs and FDA Toxicity scale for solicited ISRs by MedDRA SOC, PT, and study drug group.  
The incidence by study drug group as well as by intensity and duration will be summarized for 
solicited ISRs. 
For all analyses of AEs, if the same AE (based on PT) is reported for the same participant more 
than once, the AE is counted only once for the PT and at the highest severity and most-related 
relationship to study drug. Safety summaries through 14 months will be presented. 
5.10.2. 
Laboratory Data 
Descriptive statistics for clinical laboratory results (hematology and chemistry) will be presented 
for each study visit by study drug group. Descriptive statistics for the change from baseline at 
each post-baseline study visit for each laboratory parameter will also be presented by study drug 
group. In addition, laboratory parameters will be defined as potentially clinically significant in 
the SAP, and shift tables from baseline will be provided for each post-baseline visit. 
5.10.3. 
Vital Signs 
Descriptive statistics of vital sign parameters will be presented by study drug group and study 
visit, as well as the change from baseline at each study visit. Potentially clinically significant 
values will be defined in the SAP, and the numbers and percentages of participants with a 
potentially clinically significant value will be summarized by study drug group for the worst 
post-baseline value. 
5.10.4. 
Immunogenicity 
Immunogenicity data will be provided in listings and summarized in tables using descriptive 
statistics, including rates, titers, and neutralization data, as appropriate. Associations between 
immunogenicity data and PK as well as safety and efficacy data will be explored. Details of 
immunogenicity analysis will be provided in the SAP. 
5.11. 
Pharmacokinetics  
Descriptive statistics of ADG20 serum concentration at each sampling time will be provided. PK 
parameters may include, but are not limited to: AUC0-inf, AUC0-last, Cmax, CL/F, t1/2, Tmax, and 
Vss/F. The calculation method will be detailed in the SAP.  


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5.12. 
Independent Data Monitoring Committee Safety Monitoring 
Table 5.4 presents the safety monitoring performed by iDMC. 
Table 5.4 
Independent Data Monitoring Committee Safety Monitoring 
Parameter 
Analysis 
Set 
Statistical Method 
Criterion  
Monitoring Plan 
Potential Harm 
Confirmed 
COVID-19 cases 
FAS 
RR significantly >1 
(ADG20 relative to 
placebo) based on an 
exact 2-sided 90% CI 
Constant CI 
monitoring 
controlling 
1-sided α at 5% 
After every event starting after 8 
cases of confirmed symptomatic 
COVID-19 across Cohorts A and 
B until the finalization of protocol 
version 6.0.  
Potential Harm 
Severe/Critical 
COVID-19 Cases 
FAS 
RR significantly >1 
(ADG20 relative to 
placebo) based on an 
exact 2-sided 90% CI 
Constant CI 
monitoring 
controlling 
1-sided α at 5% 
Routine reviews starting after 4 
cases of severe/critical 
COVID-19 across Cohorts A and 
B. 
Safety 
Safety 
Incidence of AESIs, 
unsolicited study drug-
related AEs ≥Grade 3, 
and study drug-related 
SAEs 
COVID-19a 
Safety 
guidelines 
provided in 
iDMC charter 
Real-time monitoring 
Interim analysis after the Phase 2 
population is followed for 4 
weeks 
Routine reviews across all cohorts 
a As of protocol version 6.0, surveillance for COVID-19 will no longer be performed. Thus, monitoring will be limited to 
severe/critical cases of COVID-19 as reported through routine safety follow-up. 
 
Available unblinded safety data collected through 4 weeks postdosing, including relevant data 
for confirmed COVID-19 cases, for the first 200 participants (Phase 2) enrolled across both 
cohorts will be reviewed by the iDMC. Enrollment will continue during the iDMC review. If any 
single severe or >1 moderate acute hypersensitivity reaction, single study drug-related severe 
AE, or single study drug-related SAE occurs prior to the planned iDMC analysis, enrollment will 
be paused and an ad hoc iDMC meeting called.  
After the scheduled analyses, the iDMC will review all cases of severe acute hypersensitivity 
reactions, drug-related severe AEs, or drug-related SAEs on an ongoing basis. 
The iDMC will meet routinely to review safety data, including relevant data regarding 
symptomatic COVID-19 cases. Review of COVID-19 cases will include monitoring for potential 
ADE which may present as an increase in the incidence or severity of COVID-19 in 
ADG20-treated participants compared with placebo-treated participants. In participants with 
asymptomatic/pre-symptomatic SARS-CoV-2 infection at baseline detected by positive 
SARS-CoV-2 RT-PCR, ADE also has the potential to manifest as acute worsening of disease in 
association with ADG20 as a result of antigen-antibody complex formation leading to 
pro-inflammatory cytokine release and/or complement activation/deposition. For these reasons, 
iDMC will review the incidence and severity of symptomatic COVID-19 cases as part of their 
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To aid in the detection of potential ADE, continuous safety monitoring of the incidence of 
severe/critical COVID-19 in the FAS will also be conducted by an independent unblinded 
statistician as detailed in the iDMC charter. 
6. 
STUDY MANAGEMENT 
6.1. 
Ethics and Consent 
6.1.1. 
Regulations and Guidelines 
The study will be performed in accordance with this protocol, US investigational new drug 
regulations (21 CFR 312) or local national laws (as applicable), and ICH guidelines for GCP. 
These guidelines are on file at Synteract. 
6.1.2. 
Institutional Review Board/Independent Ethics Committees and Competent 
Authorities 
The clinical trial authorization granted by the competent authority and a favorable opinion from 
the relevant IEC(s)/IRB(s) will be obtained before the start of the study. The local authorities 
will be notified about the study as required by law. 
The competent authority and the EC/IRB will be notified about the end of the trial and a report 
summarizing the study results will be sent to the competent authority and the EC within 1 year 
after the end of the trial. If the trial is terminated early, the competent authority, and the EC will 
be notified within 15 days. Favorable opinion is required for the study protocol, Investigator 
brochure, protocol amendments, ICFs, participant information sheets, and advertising materials. 
No study drug will be shipped to a Clinical Site until written IRB/IEC favorable opinion has 
been received by the Sponsor or its representative. 
6.1.3. 
Informed Consent 
For each trial participant, informed consent will be obtained before any protocol-related 
activities. As part of this procedure, the Investigator, or a designated representative must explain 
orally and in writing the nature, duration, and purpose of the study, and the action of the study 
drug in such a manner that the participant and (if applicable) appointed guardian are aware of the 
potential risks, inconveniences, or adverse effects that may occur. Participants should be 
informed that they may withdraw from the study at any time without any resulting disadvantage. 
They will receive all information that is required by local regulations and ICH guidelines.  
All participants will be insured against injury caused by their participation in the study according 
to legal requirements. They will be informed about the insurance and the resulting obligations on 
their part. 
6.2. 
Data Protection 
Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant names or 
any information that would make the participant identifiable will not be transferred. 


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The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure and use of their 
data must also be explained to the participant in the informed consent. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
6.3. 
Discontinuation of the Study by the Sponsor 
The Sponsor reserves the right to discontinue the study at this Clinical Site or at multiple sites, or 
to terminate the study at any time for safety, administrative, or other reasons. In particular, a 
Clinical Site that does not recruit at a reasonable rate may be discontinued. Should the study be 
terminated and/or the Clinical Site closed for whatever reason, all documentation, and study drug 
pertaining to the study must be returned to the Sponsor or its representative. 
6.4. 
Study Documentation 
By signing a copy of Form FDA 1572 or other country-specific regulatory forms, the principal 
Investigator acknowledges that he/she has received a copy of the IB on ADG20 and assures the 
Sponsor that he/she will comply with the protocol and the provisions stated in Form FDA 1572 
and other country-specific forms. No changes in this protocol can be made without the Sponsor’s 
written approval. 
6.5. 
Data Management and Quality Control 
6.5.1. 
Electronic Case Report Forms 
In this study, eCRF data and eSource records (if applicable) will be entered into the data 
collection platform. 
The data collection platform is compliant with all legislation relevant to EDC (FDA 21 CFR 
Part 11, GCP). 
The Investigator Clinical Site staff will enter and edit the data via a secure network, with secure 
access features (username and password). A complete electronic audit trail will be maintained. 
The Investigator will approve the data using an electronic signature (FDA 21 CFR Part 11), and 
this approval is used to confirm the accuracy of the data recorded. Electronic case report forms 
will be used for all participants. The Investigator’s data will be accessible from the Investigator’s 
Clinical Site throughout the trial. The eCRF must be kept current to reflect participant status at 
each phase during the course of the trial. The eCRF will not capture personalized data. The 
Investigator must make a separate confidential record of personalized details (name and initials) 
on the participant identification and enrollment log. All changes to data are done through the 
EDC system and approved by the Investigator. 
It is the responsibility of the Principal Investigator of the respective Clinical Site to ensure that 
all participant discontinuations or changes in study or other medications entered on the 
participant’s eCRF are also made on the participant’s medical records. The eCRFs for any 


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participant leaving the study should be completed at the time of the final visit or shortly 
thereafter. 
6.5.2. 
Data Management Considerations 
Queries will be issued for any inconsistencies, omissions, and discrepancies, and will be resolved 
by the appropriate parties. 
6.5.3. 
Study Monitoring and Quality Assurance 
This study will be monitored for quality assurance at all stages of its development by the clinical 
research personnel employed by the Sponsor or its representative. Monitoring will include 
personal visits and telephone communication to assure that the investigation is conducted 
according to the protocol, SOPs, GCP guidelines, and applicable regulatory requirements. 
Quality control procedures will be applied to each stage of data handling to ensure that all data 
are reliable and have been processed correctly. On-site and/or remote review of eCRFs will 
include a review of forms for completeness and clarity, and consistency with source documents 
available for each participant. Note that a variety of original documents, data, and records will be 
considered as source documents in this trial. Clinical sites may elect to utilize the direct data 
entry feature in the study data collection system, in which case select data that would normally 
be transcribed from source documents into the EDC system are integrated with the system, 
preventing the need for re-entry. 
Medical advisors and clinical research associates or assistants may request to witness participant 
evaluations occurring as part of this protocol. The Investigator and appropriate personnel will be 
periodically requested to attend meetings/workshops organized by the Sponsor to assure 
acceptable protocol execution. The study may be subject to audit by the Sponsor or by regulatory 
authorities. If such an audit occurs, the Investigator must agree to allow access to required 
participant records. By signing this protocol, the Investigator grants permission to personnel 
from the Sponsor, its representatives, and appropriate regulatory authorities, for on-site 
monitoring of all appropriate study documentation, as well as on-site review of the procedures 
employed in eCRF generation, where clinically appropriate. 
6.6. 
Collection and Update of Contacts 
To reduce lost to follow-up and ensure appropriate collection of medically attended visits for 
COVID-19, participants will be asked to provide primary and secondary contacts to the site staff. 
These data will not be entered into the eCRF. 
The site will capture contact information for a primary and a secondary personal contact (eg, 
family member, friend, neighbor, etc). Additionally, sites will capture contact information for the 
participant’s primary health care provider and the hospital/emergency care centers with closest 
proximity to the participant’s home. 
Primary and secondary personal contacts, health care provider contact, and hospitals will be 
reviewed with the participant (or guardian/LAR) and updated at the visits outlined in the SoA. 


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6.7. 
Retention of Records 
The Investigator must arrange for retention of study records at the Clinical Site. The nature of the 
records and the duration of the retention period must meet the requirements of the relevant 
regulatory authority. In addition, because this is an international study, the retention period must 
meet the requirements of the most stringent authority. The Investigator should take measures to 
prevent accidental or premature destruction of these documents.  
6.8. 
Use of Study Findings 
By signing the study protocol, the Investigator agrees to the use of results of the study for the 
purposes of national and international registration. If necessary, the authorities will be notified of 
the Investigator’s name, address, qualifications, and extent of involvement. Reports covering 
clinical and biometric aspects of the study will be prepared by the Sponsor or its representative. 
6.9. 
Publications 
The results of this study may be published or presented at scientific meetings. In accordance with 
standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety, and not as individual Clinical Site data. Authorship will 
be determined by mutual agreement and in line with International Committee of Medical Journal 
Editors authorship requirements. Data are the property of the sponsor and cannot be published 
without prior written authorization from the sponsor, but data and publication thereof will not be 
duly withheld. 


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World Bank (2021). Global Economic Prospects, June 2021. Washington, DC, The World Bank. 
Wu Z and McGoogan JM (2020). Characteristics of and Important Lessons From the 
Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 
Cases From the Chinese Center for Disease Control and Prevention. JAMA 323(13):1239-1242. 
doi:10.1001/jama.2020.2648. 
 


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8. 
APPENDICES 
Appendix 1. Injection Site Reaction e-Diary 
At the Day 1 study visit, participants will be given a ruler and instructed on use of the ruler and 
the Injection Site Reaction (ISR) e-Diary (or paper back-up if deemed appropriate for the 
participant) along with an emergency 24-hour telephone number, if needed.  
Participants will be instructed to record the worst severity experienced during each recording 
period (prior 24 hours) of the following local (solicited) AEs through Study Day 4, and, if 
applicable, whether medication was taken to relieve the symptoms: 
• Injection site pain or tenderness 
• Erythema/redness at the site of injection 
• Induration/swelling at the site of injection 
Severity will be assessed for solicited AEs (ISRs) by the participant (or, if applicable, their 
caregiver, surrogate, or legally authorized representative) according to the FDA Guidance for 
Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials (2007). Because solicited AEs are expected to occur after 
injections, they will not be assessed for relationship to study drug. Investigators or medically 
qualified designees will follow all ISRs that are ongoing beyond Day 4 to resolution. 
Local Reaction 
to Injectable 
Product 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
Life-Threateninga 
(Grade 4) 
Pain 
Does not interfere 
with activity  
Repeated use of 
non-narcotic pain 
reliever >24 hours or 
interferes with activity  
Any use of narcotic 
pain reliever or 
prevents daily 
activity  
Emergency room visit 
or hospitalization  
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest  
Emergency room visit 
or hospitalization  
Erythema/redness 
2.5–5 cm  
5.1–10 cm  
>10 cm  
Necrosis or exfoliative 
dermatitis  
Induration/ 
swellingb 
2.5–5 cm and does 
not interfere with 
activity  
5.1–10 cm 
or interferes with 
activity  
>10 cm 
or prevents daily 
activity  
Necrosis  
Note: In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as a 
continuous variable. 
a Pain/tenderness are not expected to be life-threatening but can still meet Grade 4 criteria based on ER visit or hospitalization  
b Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 


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Appendix 2. Collection of Coronavirus Disease 2019 Symptoms 
Please ask questions in a location where, and during a time when, the participant will not be 
distracted. 
Assessment of Common COVID-19-Related Symptoms and Global Impression Items 
“What was the severity of your [insert symptom] 
at its worst over the last 24 hours? 
Response Options and Scoring 
1) Fever (feeling hot or feverish) 
None=0 
Mild=1 
Moderate=2 
Severe=3 
2) Chills (shivering) 
3) Cough 
4) Sore throat 
5) Congestion (stuffy or runny nose) 
6) Shortness of breath (difficulty breathing) 
7) Muscle or body aches 
8) Fatigue (low energy or tiredness) 
9) Headache 
10) Nausea (feeling like you want to throw up) 
11) Loss of smell or taste 
12) Vomiting (throwing up) or diarrhea (loose or 
watery stools) 
13) In the past 24 hours, have you returned to 
your usual health (before your COVID-19 
illness)? 
Yes or No 
14) In the past 24 hours, have you returned to 
your usual activities (before your COVID-19 
illness)?  
Yes or No 
15) In the past 24 hours, what was the severity of 
your overall COVID-19-related symptoms at 
their worst?  
None, Mild, Moderate, or Severe 
Based on above response, in the Investigator's 
opinion, indicate overall COVID-19 severity per 
protocol definitions. Refer to the protocol 
Appendix 5: FDA Scale for COVID-19 Severity.  
Asymptomatic, Mild, Moderate, or Severe 
 


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Appendix 3. Worksheet for Assessment of Risk Factors for Exposure to SARS-CoV-2 
Note: This worksheet is to be used by the site at screening to determine if a potential participant 
is at high risk of exposure to SARS-CoV-2. Any affirmative answer qualifies a participant as 
being at increased risk. 
Do you work in any of the following locations/industries? 
☐ Hospital, clinic, or outpatient medical center 
☐ Long-term care, assisted-living, nursing home, or elder care home 
☐ Correctional facility 
☐ Teacher/instructor or childcare provider in an indoor setting with more than 5 children 
☐ Shelter or group home setting 
☐ Other location or facility that does not allow for physical distancing and mask-wearing 
☐ None of the above 
Do you live in any of the following? 
☐ Long-term care facility 
☐ Assisted-living facility 
☐ Dormitory, sorority/fraternity, or multi-student campus apartment 
☐ Multi-family home (eg, more than one family/generation in the same home) 
☐ Shelter 
☐ Other adult group setting (eg, employee group housing) 
☐ Home with children participating in indoor extra-curricular/social activities 
☐ No stable residence 
☐ None of the above 
Do you frequently eat/drink in an indoor restaurant/bar/pub where you and/or others might not 
be wearing masks? ☐ Yes ☐ No 
Do you frequently exercise or play sports indoors where you and/or others might not be 
wearing masks? ☐ Yes ☐ No 
Are you frequently in an indoor setting with people not from your household, where you and/or 
others might not be wearing masks? Some examples are work, church, or social gatherings. 
 ☐ Yes ☐ No 
Do you frequently travel more than 100 miles (170 kilometer) from your home and interact 
with others indoors at your destination(s)? ☐ Yes ☐ No 
Do you frequently use any form of group transportation where you and/or others might not be 
wearing masks? Some examples are taxis/rideshares, buses, trains, or airplanes. ☐ Yes ☐ No 
 


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Appendix 4. Risk Factors for Severe Coronavirus Disease 2019  
The following are examples of chronic, stable conditions or illnesses that place an individual at 
increased risk for severe COVID-19. Individuals with these illnesses should be considered 
eligible for enrollment if medically stable and deemed appropriate by the Investigator. 
Adults: 
• Obesity (BMI >30 kg/m2) 
• Diabetes (Type 1 or Type 2) 
• Chronic kidney disease (eGFR calculated by Modification of Diet in Renal Disease [MDRD] 
of 59 mL/min/1.73 m2 or less, including end-stage renal disease on hemodialysis) 
• Chronic lung disease (emphysema/chronic obstructive pulmonary disease, chronic bronchitis, 
interstitial lung disease [including idiopathic pulmonary fibrosis]), cystic fibrosis, or asthma 
requiring daily therapy) 
• Cardiac disease (heart failure, coronary artery disease, cardiomyopathies, or hypertension 
[with at least one medication prescribed or recommended]) 
• Sickle cell disease or thalassemia 
• Solid organ or blood stem cell transplant recipients 
• Other immunodeficiency due to underlying illness or immunosuppressant medication (eg, 
corticosteroids ≥20 mg/day prednisone or equivalent) 
• Down Syndrome  
• Stroke or cerebrovascular disease, which affects blood flow to the brain 
• Substance use disorder 
Adolescents: 
• BMI >85th percentile for age and sex based on CDC growth charts 
• Diabetes (Type 1 or Type 2) 
• Chronic kidney disease 
• Sickle cell disease 
• Congenital or acquired heart disease 
• Neurodevelopmental disorders (eg, cerebral palsy, Down syndrome) 
• A medically-related technological dependence (eg, tracheostomy, gastrostomy, or positive 
pressure ventilation not related to COVID-19) 
• Asthma, reactive airway, or other chronic respiratory disease that requires daily medication 
for control 
• Solid organ or blood stem cell transplant recipients  
• Other immunodeficiency due to underlying illness or immunosuppressant medication 
• Substance use disorder 


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Appendix 5. Modified FDA Scale for COVID-19-Like Illness Severity 
The following COVID-19-like illness severity categorizations are adapted from the FDA 
COVID-19 Developing Drugs and Biological Products for Prevention or Treatment Guidance for 
Industry (FDA 2021a).  
Infection Without Symptoms 
• No symptoms. 
Mild COVID-19-Like Illness 
• Symptoms of mild COVID-19-like illness that could include fever, cough, sore throat, 
malaise, headache, muscle pain, or gastrointestinal symptoms, without shortness of breath or 
dyspnea. 
• No clinical signs indicative of moderate, severe, or critical illness severity. 
Moderate COVID-19-Like Illness 
• Symptoms of moderate COVID-19-like illness, which could include any symptom of mild 
illness or shortness of breath with exertion. 
• Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate 
≥20 breaths per minute, with saturation of oxygen (SpO2) >93% on room air at sea level, or 
heart rate ≥90 beats per minute. 
• No clinical signs indicative of severe or critical illness severity. 
Severe COVID-19-Like Illness 
• Symptoms suggestive of severe systemic illness with COVID-19, which could include any 
symptom of moderate illness or shortness of breath at rest, or respiratory distress including 
the need for initiation of oxygen therapy. 
• Clinical signs suggestive of severe systemic illness with COVID-19, such as respiratory rate 
≥30 breaths per minute, heart rate ≥125 beats per minute, SpO2 ≤93% on room air at sea 
level or ratio of arterial oxygen partial pressure to fractional inspired oxygen <300. 
• No criteria for critical severity. 
Critical COVID-19-Like Illness 
• Evidence of critical illness, defined by at least one of the following: 
− Respiratory failure based on resource utilization requiring at least one of the following: 
o Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow 
nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at 
flow rates >20 L/min with fraction of delivered oxygen ≥0.5), noninvasive positive 
pressure ventilation, extracorporeal membrane oxygenation, or clinical diagnosis of 
respiratory failure (ie, clinical need for one of the preceding therapies, but the 
preceding therapies cannot be administered in setting of resource limitations). 


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o Shock (defined by systolic blood pressure <90 mmHg, diastolic blood pressure 
<60 mmHg, or requiring vasopressors). 
o Multi-organ dysfunction/failure. 
Note: A clinical diagnosis of respiratory failure (in the setting of resource limitation) in which 
the management deviates from standard of care should be recorded as part of formal data 
collection. 


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Appendix 6. Clinical Laboratory Tests 
Hematology 
(Complete Blood Count with differential): 
Chemistry Panel 
Serum Concentrations of: 
Hemoglobin 
Non-fasting glucose 
Hematocrit 
Calcium 
Erythrocyte count 
Albumin 
Mean cell volume 
Total protein 
Mean cell hemoglobin 
Sodium 
Mean cell hemoglobin concentration 
Potassium 
Leukocyte (white blood cell) count  
Bicarbonate 
Neutrophils 
Chloride 
Lymphocytes 
Urea nitrogen 
Monocytes 
Creatinine 
Eosinophils 
Alkaline phosphatase 
Basophils 
Alanine aminotransferase 
Platelets 
Aspartate aminotransferase 
Coagulation tests 
Total bilirubin 
Prothrombin time/International Normalized Ratio 
 
Partial thromboplastin 
 
Other tests 
 
Follicle-stimulating hormone 
 
Urine (or serum, if required by local regulations) pregnancy test  
 
 


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Appendix 7. 
Country-Specific Requirements 
The country-specific requirements provided in the following subsections supersedes the content 
in the indicated section of the main protocol and MUST be followed for all sites enrolling 
participants in that country.  
 
 


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Appendix 7.1 
Argentina-specific Requirements 
No adolescents will be enrolled in Argentina. All content in the protocol specific to enrollment of 
adolescents is not applicable to sites in Argentina. Specific changes related to the exclusion of 
adolescents from the study in Argentina and other changes to the protocol specific to clinical 
sites enrolling participants in Argentina are outlined in the sections below. 
Section 3.3.1 Inclusion Criterion 
Inclusion Criterion 1: 
Adult aged ≥18 years. 
Section 3.5.5.3 Clinical Laboratory Assessments 
In addition to the requirements described in this section, monthly urine pregnancy testing is 
required for all participants of childbearing potential from the time of randomization through the 
end of study. 
 
 


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Appendix 7.2 
Czech Republic-specific Requirements 
No adolescents will be enrolled in the Czech Republic. All content in the protocol specific to 
enrollment of adolescents is not applicable to sites in the Czech Republic. Specific changes 
related to the exclusion of adolescents from the study in the Czech Republic and other changes 
and clarifications to the protocol specific to clinical sites enrolling participants in the Czech 
Republic are outlined in the sections below. 
Section 3.3.1 Inclusion Criterion 
Inclusion Criterion 1: 
Adult aged ≥18 years. 
Inclusion Criterion 5: 
Is able and willing to provide informed consent. A legally authorized representative may be used 
in cases where inclusion criterion 9 is able to be fulfilled. 
Inclusion Criterion 7: 
Participants assigned female sex at birth and who are of childbearing potential may be enrolled 
in the study if the participant has practiced highly effective contraception or has abstained from 
all sexual activities that could result in pregnancy for at least 28 days before the day of dosing 
(Day 1) and has agreed to continue highly effective contraception for sexual activity that could 
lead to pregnancy through 6 months following dosing. 
Highly effective contraception for participants assigned female sex at birth is defined as 
consistent and correct use of a contraceptive as described by the Clinical Trial Facilitation Group 
(CTFG) and used in accordance with the product label. For example: 
a. Bilateral tubal ligation 
b. Intrauterine device. 
c. Hormonal contraceptive taken or administered via oral (pill), transdermal (patch), 
intravaginal, implantable*, or injectable method. 
d. Sterilization of a female participant’s male partner before entry into the study. 
e. Sexual abstinence.** 
* If locally required, in accordance with CTFG guidelines, acceptable contraceptive implants are limited to 
those which inhibit ovulation 
**Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse from providing consent until 6 months after dosing. The reliability of sexual abstinence needs 
to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the 
participant. Note: periodic abstinence (eg, calendar, ovulation, symptothermal, post ovulation methods) and 
withdrawal are not acceptable methods of contraception. 


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Section 3.3.2 Exclusion Criterion 
Exclusion Criterion 3: 
Is acutely ill or febrile 72 hours before or at Screening or has other COVID-19 symptoms 
including cough, fatigue, muscle or body aches, headache, or loss of taste or smell (for guidance 
on COVID-like illness symptoms, refer to Table 3.1). Fever is defined as a body temperature 
≥38.0 °C (≥100.4 °F).  
Note: Participants meeting this criterion may be scheduled for rescreening within the relevant 
window periods. 
Exclusion Criterion 4: 
Has received or plans to receive a non-COVID-19 vaccine within 28 days before or after dosing 
(except for seasonal influenza vaccine, which is not permitted within 14 days before or after 
dosing) or a live vaccine 30 days before or 90 days after dosing. 
Section 3.5.5.3 Clinical Laboratory Assessments 
In addition to the requirements described in this section, a urine pregnancy test is required for all 
participants of childbearing potential on Day 28. 
Section 4.2.4.2 Reporting of Unanticipated Problem 
Clarification: The Investigator will report unanticipated problems to the IRB and to the Sponsor 
only if required by local country regulations. If reporting of unanticipated problems to the IRB 
and Sponsor is not required by local country regulations, this section is not applicable. 
 
 


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Appendix 7.3 
Germany-specific Requirements 
No adolescents will be enrolled in Germany. All content in the protocol specific to enrollment of 
adolescents is not applicable to sites in Germany. Specific changes related to the exclusion of 
adolescents and other changes to the protocol specific to clinical sites enrolling participants in 
Germany are outlined in the sections below. 
Section 3.3.1 Inclusion Criterion 
Inclusion Criterion 1: 
Adult aged ≥18 years. 
Inclusion Criterion 5: 
Provides written documentation of informed consent by signing a current IEC/IRB approved ICF 
at the time of screening.  
Inclusion Criterion 7: 
Participants assigned female sex at birth and who are of childbearing potential may be enrolled 
in the study if the participant has practiced highly effective contraception or has abstained from 
all sexual activities that could result in pregnancy for at least 28 days before the day of dosing 
(Day 1) and has agreed to continue highly effective contraception for sexual activity that could 
lead to pregnancy through 6 months following dosing. 
Highly effective contraception for participants assigned female sex at birth is defined as 
consistent and correct use of a contraceptive as described by the Clinical Trial Facilitation Group 
(CTFG) and used in accordance with the product label. For example: 
a. Bilateral tubal ligation 
b. Intrauterine device. 
c. Hormonal contraceptive taken or administered via oral (pill), transdermal (patch), 
intravaginal, implantable*, or injectable method. 
d. Sterilization of a female participant’s male partner before entry into the study. 
e. Sexual abstinence.** 
* If locally required, in accordance with CTFG guidelines, acceptable contraceptive implants are limited to 
those which inhibit ovulation 
**Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse from providing consent until 6 months after dosing. The reliability of sexual abstinence needs 
to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the 
participant. Note: periodic abstinence (eg, calendar, ovulation, symptothermal, post ovulation methods) and 
withdrawal are not acceptable methods of contraception. 
Inclusion Criterion 9: 
Able to understand and comply with study requirements/procedures based on the assessment of 
the Investigator. 


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Section 3.3.2 Exclusion Criterion  
Exclusion Criterion 10: 
Subjects who are legally detained in an official institution. 
Section 6.1.3 Informed Consent 
For each trial participant, informed consent will be obtained before any protocol-related 
activities. As part of this procedure, the Investigator, or a designated representative must explain 
orally and in writing the nature, duration, and purpose of the study, and the action of the study 
drug in such a manner that the participant is aware of the potential risks, inconveniences, or 
adverse effects that may occur. Participants should be informed that they may withdraw from the 
study at any time without any resulting disadvantage. They will receive all information that is 
required by local regulations and ICH guidelines.  
All participants will be insured against injury caused by their participation in the study according 
to legal requirements. They will be informed about the insurance and the resulting obligations on 
their part. 
Section 6.3 Discontinuation of the Study by the Sponsor  
The Sponsor reserves the right to discontinue the study at this Clinical Site or at multiple sites for 
safety or administrative reasons at any time. In particular, a Clinical Site that does not recruit at a 
reasonable rate may be discontinued. Should the study be terminated and/or the Clinical Site 
closed for whatever reason, all documentation and study drug pertaining to the study must be 
returned to the Sponsor or its representative. 
From a participant safety point of view, the study must be discontinued due to unacceptable 
serious adverse events.  
The study will be discontinued if the applicable evaluation or approval by the authorities is 
revoked or canceled.  
The study will also be discontinued if the insurance coverage cannot be adjusted or maintained 
accordingly. 


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Appendix 7.4 
Ukraine-specific Requirements 
No adolescents will be enrolled in Ukraine. All content in the protocol specific to enrollment of 
adolescents is not applicable to sites in Ukraine. Specific changes related to the exclusion of 
adolescents from the study in Ukraine are outlined in the sections below.  
Section 3.3.1 Inclusion Criterion 
Inclusion Criterion 1: 
Adult aged ≥18 years. 

SAP_001.pdf: 
Statistical Analysis Plan 
 
Study ID: ADG20-PREV-001 
 
Official Title of Study: A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial to 
Evaluate the Efficacy and Safety of ADG20 in the Prevention of COVID-19 (EVADE) 
 
NCT ID: NCT04859517 
 
IND Identifier: 152327 
 
EudraCT Identifier: 2020‐005598‐28 
 
Date of Document: 02-March-2022 






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TABLE OF CONTENTS 
SPONSOR APPROVAL .................................................................................................................2 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................8 
2. 
OBJECTIVES ...............................................................................................................9 
3. 
INVESTIGATIONAL PLAN .....................................................................................14 
3.1. 
Overall Study Design and Plan ...................................................................................14 
3.2. 
iDMC, Interim, and Final Analyses ............................................................................14 
3.3. 
Study Duration ............................................................................................................14 
3.4. 
Study Assessments ......................................................................................................15 
3.4.1. 
Clinical Efficacy Assessments ....................................................................................15 
3.4.2. 
Virologic Efficacy Assessments .................................................................................15 
3.4.3. 
PK and ADA Assessments .........................................................................................16 
3.4.4. 
Safety Assessments .....................................................................................................16 
3.5. 
Study Endpoints ..........................................................................................................16 
3.5.1. 
Clinical Efficacy Endpoints ........................................................................................16 
3.5.2. 
Other Clinical and Virologic Endpoints .....................................................................17 
3.6. 
Treatments ..................................................................................................................18 
4. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................18 
4.1. 
General Rules and Considerations ..............................................................................18 
4.2. 
Sample Size ................................................................................................................20 
4.3. 
Multiplicity Adjustments ............................................................................................21 
4.4. 
Analysis Sets ...............................................................................................................21 
4.4.1. 
Screen Failures ............................................................................................................21 
4.4.2. 
Full Analysis Set .........................................................................................................21 
4.4.3. 
Modified Analysis Sets ...............................................................................................21 
4.4.4. 
Pre-Emergence of Omicron Analysis Set ...................................................................22 
4.4.5. 
Post-Emergence of Omicron Analysis Set .................................................................22 
4.4.6. 
Per-Protocol Set ..........................................................................................................22 
4.4.7. 
Safety Set ....................................................................................................................22 
4.4.8. 
Immunogenicity Set ....................................................................................................22 
4.4.9. 
PK Analysis Set ..........................................................................................................23 


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5. 
STATISTICAL ANALYSES .....................................................................................23 
5.1. 
Participant Disposition ................................................................................................23 
5.1.1. 
Disposition ..................................................................................................................23 
5.1.2. 
Protocol Deviations ....................................................................................................23 
5.2. 
Demographics and Clinical Characteristics ................................................................24 
5.2.1. 
Demographics/Baseline Characteristics .....................................................................24 
5.3. 
Medical History ..........................................................................................................24 
5.4. 
Treatments and Medications .......................................................................................24 
5.4.1. 
Prior and Concomitant Medication .............................................................................24 
5.4.2. 
Study Treatments ........................................................................................................25 
5.5. 
Efficacy Analyses .......................................................................................................25 
5.5.1. 
Primary Efficacy Analysis ..........................................................................................25 
5.5.2. 
Sensitivity Analysis of Primary Estimand ..................................................................26 
5.5.3. 
Analysis of Time to First RT-PCR-confirmed Symptomatic COVID-19 ..................27 
5.5.4. 
Key Secondary Endpoints and Analyses ....................................................................28 
5.5.5. 
Subgroup Analyses .....................................................................................................28 
5.5.6. 
Additional Secondary Endpoints and Analyses ..........................................................29 
5.5.7. 
Exploratory Endpoint Analyses ..................................................................................30 
5.6. 
Safety Analysis ...........................................................................................................31 
5.6.1. 
Solicited and Unsolicited Adverse Events ..................................................................31 
5.6.1.1. 
Adverse Events ...........................................................................................................31 
5.6.1.2. 
Injection Site Reactions ..............................................................................................31 
5.6.1.3. 
Treatment Emergent Adverse Events .........................................................................33 
5.6.1.4. 
Adverse Events of Special Interest .............................................................................33 
5.6.1.5. 
Medically Attended Adverse Events ..........................................................................33 
5.6.1.6. 
Serious Adverse Events ..............................................................................................33 
5.6.1.7. 
Adverse Event Intensity ..............................................................................................34 
5.6.1.8. 
Relationship of Adverse Events to Study Drug ..........................................................34 
5.6.1.9. 
Analysis of Adverse Events and Injection Site Reactions ..........................................34 
5.6.2. 
Clinical Laboratory Evaluations .................................................................................36 
5.6.3. 
Vital Sign Measurements ............................................................................................36 
5.6.4. 
Other Safety Data .......................................................................................................37 


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6. 
PHARMACOKINETIC ANALYSES ........................................................................37 
6.1. 
Data Handling .............................................................................................................37 
6.2. 
Serum Concentrations .................................................................................................37 
6.3. 
Serum Pharmacokinetic Parameters ...........................................................................38 
7. 
IMMUNOGENICITY ANALYSIS ............................................................................39 
8. 
CHANGES IN THE PLANNED ANALYSIS ...........................................................39 
9. 
REFERENCES ...........................................................................................................40 
10. 
APPENDICES ............................................................................................................41 
APPENDIX A. IMPUTATION RULES FOR MISSING DATES OF MEDICATIONS 
AND ADVERSE EVENTS ........................................................................................42 
APPENDIX B. ALGORITHM OF LOGISTIC REGRESSION METHOD ..............................43 
 
LIST OF TABLES 
Table 1. 
Objectives and Endpoints: Cohort A (PEP) ..................................................................9 
Table 2. 
Objectives and Endpoints: Cohort B (PrEP) ..............................................................11 
Table 3. 
Exploratory Objectives and Endpoints: Cohorts A and B ..........................................13 
Table 4. 
Key Secondary Endpoints ...........................................................................................28 
Table 5. 
Additional Secondary Endpoint Analyses ..................................................................29 
Table 6. 
Exploratory Endpoint Analyses ..................................................................................30 
Table 7. 
Grading of Injection Site Reactions ............................................................................32 
Table 8. 
Injection Site Reaction Mapping to MedDRA Coding ...............................................32 
Table 9. 
PCS Criteria for Clinical Laboratory Tests Not Graded by DAIDS ..........................36 
Table 10. 
PCS Criteria for Vital Signs .......................................................................................37 
Table 11. 
Calculated PK Parameters ..........................................................................................38 
Table 12. 
PK Parameters for Data Selection ..............................................................................38 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ATC 
Anatomical Therapeutic Chemical 
BLQ 
below the limit of quantification 
BMI 
body mass index 
CBC 
complete blood count 
CI 
confidence interval 
CLI 
COVID-19 like illness 
COVID-19 
coronavirus disease 2019 
DAIDS 
Division of AIDS 
eCRF 
electronic case report form 
EOS 
end of study 
FAS 
full analysis set 
FDA 
US Food and Drug Administration 
ICF 
informed consent form 
iDMC 
independent data monitoring committee 
IM 
intramuscular(ly) 
IRT 
interactive response technology 
ISR 
injection site reaction 
KM 
Kaplan-Meier 
LLOQ 
lower limit of quantitation 
MAAE 
medically attended adverse event 
MAR 
missing at random 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
modified full analysis set 
MI 
multiple imputation 
NP 
nasopharyngeal 
PCR 
polymerase chain reaction 
PCS 
potentially clinically significant 
PK 
pharmacokinetic 
PPS 
per-protocol set 
PT 
preferred term 
RT-PCR 
reverse transcription polymerase chain reaction 
RT-qPCR 
quantitative reverse transcription polymerase chain reaction 
SAE 
serious adverse event 


Adintrevimab (ADG20) 
 
Adagio Therapeutics 
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Abbreviation 
Definition 
SAP 
statistical analysis plan 
SARS 
severe acute respiratory syndrome 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SAS 
Statistical Analysis System 
SD 
standard deviation 
SOC 
system organ class 
SpO2 
oxygen saturation 
TEAE  
treatment-emergent adverse event 
TFLs 
tables, figures, and listings 
 
 


Adintrevimab (ADG20) 
 
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-PREV-001 
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1. 
INTRODUCTION 
This SAP describes the planned analyses of study ADG20-PREV-001 (EVADE) based on the 
clinical study protocol, version 5.0, dated 02-Mar-2022. This SAP provides statistical analysis 
details/data derivations to supplement the information presented in the statistical analysis section 
of the protocol.  
The EVADE study is a phase 2/3, multicenter, double-blind, placebo-controlled, randomized 
study of the mAb ADG20 in the prevention of symptomatic COVID-19 in adults and adolescents 
with no known history of SARS-CoV-2 infection but whose circumstances place them at 
increased risk of acquiring SARS-CoV-2 infection and developing symptomatic COVID-19. 
This objective will be independently evaluated in 2 cohorts: (1) participants with reported recent 
exposure to an individual diagnosed with a SARS-CoV-2 infection (Cohort A, PEP) and (2) 
participants with no reported recent exposure to SARS-CoV-2 (Cohort B, PrEP). An iDMC will 
monitor the study to evaluate the benefit versus risk and to ensure that the scientific integrity of 
the study is maintained.  
The EVADE study was impacted by the emergence and global spread of the SARS-CoV-2 
B.1.1.529 (Omicron) variant, which was first detected in South Africa and Botswana in 
November 2021. In vitro assessments of the neutralization activity of ADG20 demonstrated 
markedly reduced activity against authentic Omicron virus compared with prior variants such 
that ADG20 is unlikely to demonstrate adequate efficacy against SARS-CoV-2 infections caused 
by the Omicron variant. As a result, enrollment in Cohort A (PEP) and Cohort B (PrEP) of the 
study was suspended on 11-Jan-2022 as Omicron had become or was likely to become the 
predominant variant in regions enrolling the trial.  
In response to this global event, the analysis plan for this study was updated to analyze data 
collected prior to the emergence of Omicron while efficacy and safety post-Omicron continue to 
be monitored in the study. Therefore, the primary efficacy analysis is focused on evaluating 
ADG20 300 mg IM treatment in the population randomized prior to the emergence of the 
Omicron variant. With this analysis plan, the primary efficacy and short-term safety analyses are 
planned for both cohorts after a database soft lock. A final safety analysis will occur after all 
enrolled participants have been followed through 14 months/EOS or have discontinued. 


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2. 
OBJECTIVES 
For Cohort A (PEP), in participants with no known history of SARS-CoV-2 infection and 
reported recent exposure to SARS-CoV-2, the following objectives and endpoints apply 
(Table 1): 
Table 1. 
Objectives and Endpoints: Cohort A (PEP) 
Objectives 
Endpoints 
Primary (Cohort A [PEP]) 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
Day 28 in all randomized participants without 
current SARS-CoV-2 infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28. 
 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through Day 28. 
To evaluate the safety and tolerability of 
ADG20 compared with placebo following 
intramuscular administration in all treated 
participants. 
Assessment of safety based on: 
• 
Incidence of treatment-emergent adverse events. 
• 
Incidence of solicited injection site reactions through 
Day 4. 
• 
Changes from baseline in clinical laboratory tests (ie, 
complete blood count with differential and serum 
chemistry). 
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic 
blood pressure). 
Secondary (Cohort A [PEP]) 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of RT-PCR-confirmed 
symptomatic COVID-19 through Day 28 in  
each of the following populations:  
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28.  
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19 diagnosis. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through Day 28. 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of SARS-CoV-2 infection (based 
on RT-PCR or serology) regardless of 
symptoms through Day 28 in each of the 
following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19) as determined by 
positive RT-PCR or serology through Day 28.  
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19). 
• 
Probability of SARS-CoV-2 infection (asymptomatic or 
symptomatic COVID-19) through Day 28. 


Adintrevimab (ADG20) 
 
Adagio Therapeutics 
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To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 3 
months in each of the following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months.  
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of SARS-CoV-2 
infection (based on RT-PCR or serology) 
regardless of symptoms through 3 months, in 
each of the following populations:  
• 
All randomized participants without current 
SARS-CoV-2 infection at baseline. 
• 
All randomized participants without prior or 
current SARS-CoV-2 infection at baseline.  
• 
All randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19) as determined by 
positive RT-PCR or serology through 3 months. 
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection 
(asymptomatic or symptomatic COVID-19). 
• 
Probability of SARS-CoV-2 infection (asymptomatic or 
symptomatic COVID-19) through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
Day 28 in all randomized participants with prior 
but not current SARS-CoV-2 infection at 
baseline.  
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through Day 28. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic 
COVID-19 through Day 28. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of asymptomatic 
SARS-CoV-2 infection, in all randomized 
participants without prior or current 
SARS-CoV-2 infection at baseline. 
• 
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by RT-qPCR 
(nasal sample) on Days 8 and 15. 
• 
Proportion of participants with asymptomatic 
SARS-CoV-2 infection as determined by serology 
through Day 28. 
To evaluate the impact of ADG20 compared 
with placebo on viral load in all randomized 
participants with asymptomatic SARS-CoV-2 
infection detected by RT-qPCR (nasal sample) 
at baseline via surveillance.  
• 
Peak post-baseline SARS-CoV-2 viral load as measured 
by RT-qPCR 
• 
SARS-CoV-2 viral load as assessed by RT-qPCR change 
from baseline to Day 8 and Day 15. 
To evaluate the effect of ADG20 on the 
following clinical and virologic parameters in 
all randomized participants with laboratory 
confirmed symptomatic COVID-19 through CLI 
Day 28: 
 
Severity of COVID-19. 
Proportion of participants with RT-PCR-confirmed mild, 
moderate, or severe/critical COVID-19 through CLI Day 28. 
Duration of COVID-19. 
Time to sustained resolution of COVID-19 symptoms through 
CLI Day 28. 


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COVID-19-related medically attended 
outpatient visits. 
Proportion of participants with at least 1 COVID-19-related 
medically attended outpatient visit (physician’s office, 
telemedicine, emergency rooms, or urgent care centers) 
through CLI Day 28. 
COVID-19-related hospitalization. 
Proportion of participants with a COVID-19-related 
hospitalization through CLI Day 28. 
COVID-19-related mortality. 
COVID-19-related mortality through CLI Day 28. 
All-cause mortality. 
All-cause mortality through CLI Day 28. 
SARS-CoV-2 viral load. 
Viral load from CLI Day 1 sample assessed by RT-qPCR. 
To evaluate the pharmacokinetics of ADG20 in 
serum. 
PK parameters of ADG20 including but not limited to: 
AUC0-inf, AUC0-last, Cmax, Tmax, CL, t1/2, and Vss. 
To evaluate the immunogenicity of ADG20. 
Incidence of ADAs against ADG20.  
ADA=antidrug antibody; AUC =area under the plasma concentration–time curve; AUC0-inf: AUC extrapolated to infinite time; 
AUC0-last=AUC from zero up to the last concentration ≥lower limit of quantification; CL=clearance; CLI=COVID-19-like illness; 
Cmax=maximum plasma concentration; PEP=post-exposure prophylaxis; RT-(q)PCR=(quantitative) reverse transcription-
polymerase chain reaction; t½=plasma concentration half-life; Tmax=time to reach Cmax; Vss=apparent volume of distribution at 
steady state. 
 
For Cohort B (PrEP), participants with no known history of SARS-CoV-2 infection and no 
known recent exposure to SARS-CoV-2, but whose circumstances put them at increased risk of 
exposure to SARS-CoV-2 and symptomatic COVID-19, the following objectives and endpoints 
apply (Table 2). 
Table 2. 
Objectives and Endpoints: Cohort B (PrEP) 
Objectives 
Endpoints 
Primary (Cohort B [PrEP]) 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
3 months in all randomized participants 
without prior or current SARS-CoV-2 
infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic COVID-19 
through 3 months. 
To evaluate the safety and tolerability of 
ADG20 compared with placebo following 
intramuscular administration. 
Assessment of safety based on: 
• 
Incidence of treatment-emergent adverse events. 
• 
Incidence of solicited injection site reactions through Day 4. 
• 
Changes from baseline in clinical laboratory tests (ie, 
complete blood count with differential and serum 
chemistry). 
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure). 


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Objectives 
Endpoints 
Secondary (Cohort B [PrEP]) 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of RT-PCR-confirmed 
symptomatic COVID-19 through 3 months in 
all randomized participants without current 
SARS-CoV-2 infection at baseline. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
Supplementary:  
• 
Time from randomization to first RT-PCR-confirmed 
symptomatic COVID-19. 
• 
Probability of RT-PCR-confirmed symptomatic COVID-19 
through 3 months. 
Key Secondary Objective: To evaluate the 
efficacy of ADG20 compared with placebo in 
the prevention of SARS-CoV-2 infection 
(based on RT-PCR or serology) regardless of 
symptoms through 3 months, in each of the 
following populations:  
• 
All randomized participants without prior 
or current SARS-CoV-2 infection at 
baseline. 
• 
All randomized participants without 
current SARS-CoV-2 infection at 
baseline.  
Proportion of participants with SARS-CoV-2 infection 
regardless of symptoms through 3 months. 
Supplementary:  
• 
Time from randomization to first SARS-CoV-2 infection.  
• 
Probability of SARS-CoV-2 infection through 3 months. 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of RT-PCR-
confirmed symptomatic COVID-19 through 
3 months in all randomized participants. 
Proportion of participants with RT-PCR-confirmed 
symptomatic COVID-19 through 3 months. 
 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of 
SARS-CoV-2 infection (based on RT-PCR or 
serology) regardless of symptoms through 
3 months in all randomized participants. 
Proportion of participants with SARS-CoV-2 infection 
regardless of symptoms through 3 months. 
 
To evaluate the efficacy of ADG20 compared 
with placebo in the prevention of 
asymptomatic SARS-CoV-2 infection (based 
on serology) in all randomized participants 
without prior or current SARS-CoV-2 
infection at baseline. 
Proportion of participants with asymptomatic SARS-CoV-2 
infection as determined by serology at Month 6. 
To evaluate the effect of ADG20 on the 
following clinical and virologic parameters in 
all randomized participants with laboratory 
confirmed symptomatic COVID-19 through 
CLI Day 28: 
 
Severity of COVID-19. 
Proportion of participants with RT-PCR-confirmed mild, 
moderate, or severe/critical COVID-19 through CLI Day 28. 
Duration of COVID-19. 
Time to sustained resolution of COVID-19 symptoms through 
CLI Day 28. 
COVID-19-related medically attended 
outpatient visits. 
Proportion of participants with at least 1 COVID-19-related 
medically attended outpatient visit (physician’s office, 
telemedicine, emergency rooms, or urgent care centers) through 
CLI Day 28. 


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Objectives 
Endpoints 
COVID-19-related hospitalization. 
Proportion of participants with a COVID-19-related 
hospitalization through CLI Day 28. 
COVID-19-related mortality. 
COVID-19-related mortality through CLI Day 28. 
All-cause mortality. 
All-cause mortality through CLI Day 28. 
SARS-CoV-2 viral load. 
Viral load from CLI Day 1 sample assessed by RT-qPCR. 
To evaluate the pharmacokinetics of ADG20 
in serum. 
PK parameters of ADG20 including but not limited to: AUC0-inf, 
AUC0-last, Cmax, Tmax, CL, t1/2, and Vss. 
To evaluate the immunogenicity of ADG20. 
Incidence of ADAs against ADG20.  
ADA=antidrug antibody; AUC =area under the plasma concentration–time curve; AUC0-inf: AUC extrapolated to infinite time; 
AUC0-last=AUC from zero up to the last concentration ≥lower limit of quantification; CL=clearance; CLI=COVID-19-like illness; 
Cmax=maximum plasma concentration; PrEP=pre-exposure prophylaxis; RT-(q)PCR=(quantitative) reverse transcription-
polymerase chain reaction; t½=plasma concentration half-life; Tmax=time to reach Cmax; Vss=apparent volume of distribution at 
steady state. 
 
Exploratory endpoints for Cohort A (PEP) and Cohort B (PrEP) are provided in Table 3. 
Table 3. 
Exploratory Objectives and Endpoints: Cohorts A and B 
Objectives  
Endpoints 
To evaluate the impact of ADG20 compared 
with placebo on medically attended visits or 
death in participants with asymptomatic 
SARS-CoV-2 infection at baseline. 
Proportion of participants with asymptomatic SARS-CoV-2 
infection at baseline (defined by positive SARS-CoV-2 RT-PCR 
test and lack of symptoms of COVID-19) with medically 
attended visits (outpatient, telemedicine, or hospitalization) or 
death through Day 28.  
To evaluate the impact of ADG20 compared 
with placebo on Health Resource Utilization 
in participants with RT-PCR-confirmed 
symptomatic COVID-19. 
Health Care Resource Utilization of participants who develop 
COVID-19 (eg, incidence and duration of ICU stay and incidence 
of emergency room visits). 
To evaluate the emergence of resistance to 
ADG20. 
Genotypic characterization of viral isolates for reduced 
susceptibility to ADG20, with phenotypic evaluation as 
appropriate. 
To evaluate the impact of ADG20 compared 
with placebo on COVID-19 vaccination-
induced immune response in a subset of 
participants. 
Pre- and post-vaccination SARS-CoV-2 neutralizing antibody 
titers in participants who choose to receive COVID-19 vaccine 
during the study. 


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3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
The EVADE study is designed as a master protocol for multiple independent cohorts. Cohort A 
and B described below are the focus of this document.  
• Cohort A (PEP): Participants with reported, recent exposure to an individual testing positive 
for SARS-CoV-2 (index case) randomized 1:1 to receive a single 300 mg IM dose of ADG20 
or placebo 
• Cohort B (PrEP): Participants with no known recent exposure but whose circumstances put 
them at increased risk of exposure to SARS-CoV-2 and symptomatic COVID-19 randomized 
1:1 to receive a single 300 mg IM dose of ADG20 or placebo 
The randomization will be assigned in a blinded manner using a centralized IRT system in 
accordance with a pre-generated randomization schedule. A participant is considered randomly 
assigned when a randomization transaction is recorded in the IRT. A separate randomization list 
will be created for each cohort. The randomization will be stratified by the following factors:  
• Geographic region (United States/Western Europe, Central/Eastern Europe, and Rest of the 
World) 
• Age/risk for severe/critical COVID-19 (12 to <55 years and low risk, 12 to <55 years and 
high risk, and aged ≥55 years) 
3.2. 
iDMC, Interim, and Final Analyses 
An iDMC will provide safety oversight for all parts of the study. The iDMC will meet at 
designated timepoints and on an ad hoc basis to review cumulative safety data and other clinical 
study data to ensure the benefit/risk remains favorable. Details regarding iDMC membership, 
conduct, ongoing safety monitoring, decision-making, and communication will be provided in 
the iDMC Charter.  
Cohort A and Cohort B enrollment was suspended on 11-Jan-2022; these cohorts will not 
reopen, thus enrollment in these cohorts is complete. A database soft lock will be performed to 
evaluate the primary efficacy and short-term safety objectives. All study participants, site staff, 
and certain sponsor personnel (or designee) working directly with the site will stay blinded to the 
individual treatment assignment until the final database lock after the Month 14 visit. 
Plans for additional database locks or analyses may be revised during the study to adapt to 
unexpected issues in study execution and/or data that affect planned analyses and/or to address 
regulatory authority request, and/or to address protocol amendments. 
3.3. 
Study Duration  
The study duration for each participant enrolled in the study will be approximately 14 months.  
For Cohort A, the study consists of a Screening Period of up to 5 days, a 1-month Study Period 
(including dosing on Day 1), a 5-month follow-up period, and an 8-month long-term follow-up 
(LTFU) Period through Month 14 or withdrawal.  


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For Cohort B, the study consists of a Screening Period of up to 21 days, a 6-month Study Period 
(including dosing on Day 1), and an 8-month LTFU Period through Month 14 or withdrawal.  
3.4. 
Study Assessments 
Each participant in Cohort A and B will receive a single 300 mg IM dose of ADG20 or placebo 
at the Day 1 Visit. Participants will record any ISRs using an e-Diary (or paper back-up) daily on 
Day 1 postdose through Day 4. All participants will undergo assessments as indicated in the 
protocol Schedule of Assessments (SoA). 
3.4.1. 
Clinical Efficacy Assessments 
In each cohort, surveillance for symptomatic COVID-19 will be performed via phone calls to the 
participant by the site. Participants reporting COVID-19-like illness (CLI) symptoms will be 
contacted by the site to determine whether their symptoms meet criteria for a CLI visit. If CLI 
symptoms are confirmed by the site, the participant will enter the CLI Period and have an initial 
CLI visit within 48 hours. Participants who enter the CLI Period will be assessed as described in 
the protocol CLI SoA.  
The occurrence of RT-PCR-confirmed COVID-19 and concomitant therapies associated with 
COVID-19 will be captured for the duration of the study. Every effort will be made to capture 
information from any medical visits (eg, visits to the primary care providers, emergency 
department/urgent care clinic visits, hospitalizations) related to COVID-19 or its complications 
for the purpose of Health Care Resource Utilization analysis. 
3.4.2. 
Virologic Efficacy Assessments 
Samples for SARS-CoV-2 and other virology assessments will be collected during the study as 
follows: 
• A nasopharyngeal swab for central testing will be collected by the site on Day 1 and 
CLI Day 1. A saliva sample for central RT-PCR testing may be self-collected on CLI Day 1 
if an in-person visit with site personnel cannot be conducted.  
• Saliva will be collected by site personnel or by participant self-collection at home (using a kit 
provided by the site) to quantify viral load on CLI Day 1 as indicated in the CLI SoA. 
• Nasal swabs for central SARS-CoV-2 RT-qPCR testing will be collected from participants in 
Cohort A (PEP) on Days 1 (predose), 8, and 15 (self-collected) to detect any asymptomatic 
infections. 
• Blood samples will be collected for central SARS-CoV-2 serology testing to detect 
antibodies to the nucleocapsid (N) protein and/or the Spike (S) protein predose. Post-baseline 
blood samples will be collected for SARS-CoV-2 serology testing to detect antibodies to the 
nucleocapsid (N) protein to monitor participants for asymptomatic infection. 
• Any known positive local RT-PCR test result obtained during the study period, whether 
within or outside of the study, should also be recorded on the local SARS-CoV-2 eCRF.  


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3.4.3. 
PK and ADA Assessments 
Blood samples for analyses of PK and ADA will be collected as described in the protocol SoA. 
3.4.4. 
Safety Assessments 
Safety will be assessed in an ongoing manner. Adverse events occurring from when the 
participant signs the ICF until the Month 14 visit or withdrawal will be recorded. Only study 
procedure-related AEs occurring before randomization will be recorded. Other AEs, including 
SAEs and MAAEs will be collected through Month 14. Any AESI, as defined in Section 5.6.1.4, 
will be recorded. Participants will record ISRs using the Injection Site Reaction Diary starting 
after dosing on Day 1 through Day 4. Investigators (or designee) will follow all ISRs that are 
ongoing beyond Day 4 to resolution. Hypersensitivity reactions and ISRs that occur after Day 4 
will be recorded as AEs. 
Clinical laboratory samples will be collected at Screening (baseline), on Day 8, Day 28, Month 
6, and Month 12. For participants who enter the CLI Period, clinical laboratory samples will also 
be collected at CLI Day 1 and CLI Day 28.  
Vital signs will be collected at baseline, on Day 1 before and after dosing, Day 8, Day 28, 
Month 6, and Month 12. For participants who enter the CLI Period, vital signs will also be 
collected by site personnel on CLI Day 1 and CLI Day 28 and will be self-collected and reported 
by the participant daily on CLI Days 2 to 21. 
3.5. 
Study Endpoints 
Study endpoints and corresponding objectives are shown in Section 2. Definitions of the key 
clinical and virologic endpoints are provided below. Safety endpoints are defined in Section 5.6. 
3.5.1. 
Clinical Efficacy Endpoints 
RT-PCR-confirmed symptomatic COVID-19: laboratory-confirmed (RT-PCR) SARS-CoV-2 
infection and an onset of symptoms as defined below occurring no more than 14 days from the 
date of the positive RT-PCR test sample collection. Central or local (in the absence of central 
test) RT-PCR tests from NP, saliva, or nasal samples are acceptable. Any COVID-19-related 
hospitalization ≥24 hours with a positive local SARS-CoV-2 test (within 14 days) or all-cause 
death are also counted toward the endpoint. The date of event is the earliest date of RT-PCR-
confirmed COVID-19 symptom onset, COVID-19-related hospitalization, or all-cause death. The 
protocol defined COVID-19 symptoms are as follows: 
• At least ONE of the following respiratory signs/symptoms:  
− Clinical evidence of pneumonia (eg, SpO2 ≤94% on room air, requiring new initiation of 
supplemental oxygen or radiographic evidence of pneumonia) 
− New or worsening dyspnea/shortness of breath.  
OR 
• At least TWO of the following systemic symptoms: 
− Fever ≥38 °C (≥100.4 °F)  


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− Cough 
− Myalgia/muscle pain 
− Fatigue that interferes with activities of daily living 
− Vomiting and/or diarrhea (only one finding to be counted toward endpoint definition) 
− Anosmia and/or ageusia (only one finding to be counted toward endpoint definition) 
− Headache 
− Sore throat 
RT-PCR-confirmed SARS-CoV-2 infection: determined by positive central RT-PCR testing 
after randomization (including Day 1). The date of event is the sample collection date of the first 
positive central RT-PCR testing after randomization (including Day 1).  
Serology-confirmed SARS-CoV-2 infection: determined by positive central serology testing 
after randomization with a negative central serology at baseline. The date of event is the first 
sample collection date of positive central serology testing after randomization. 
SARS-CoV-2 infection regardless of symptoms (asymptomatic or symptomatic): determined 
by any of the following outcomes during the study. The date of event is the earliest date of these 
events. 
• RT-PCR-confirmed symptomatic COVID-19 
• RT-PCR-confirmed SARS-CoV-2 infection 
• Serology-confirmed SARS-CoV-2 infection 
3.5.2. 
Other Clinical and Virologic Endpoints 
For randomized participants with RT-PCR-confirmed symptomatic COVID-19, the following 
clinical and virologic parameters will be evaluated through CLI Day 28: 
• Maximum severity of COVID-19: mild, moderate, or severe/critical COVID-19 as assessed 
by the investigator based on the criteria outlined in Appendix 5 of the protocol. Participants 
with COVID-19-related hospitalization or COVID-19-related death through CLI Day 28 are 
included as severe/critical. 
• Duration of COVID-19: time to sustained resolution of COVID-19 symptoms. The 
following assessed COVID-19 symptoms will be included in the time to event analysis: 
fever, chills, cough, sore throat, congestion, shortness of breath/difficulty breathing, muscle 
or body aches, fatigue, headache, nausea, vomiting or diarrhea. Loss of taste/smell is not 
considered for this endpoint. Time to sustained resolution of COVID-19 symptoms is defined 
as time from the onset date of symptomatic COVID-19 to the first date when all of the above 
symptoms are scored as none with no symptom recurrence or new symptoms, except cough, 
fatigue, and headache that may be mild or none, through CLI Day 28. 
• COVID-19-related medically attended outpatient visits: includes in-person or 
telemedicine visits not specified by the protocol and lasting <24 hours. These include 
unscheduled in-person or telemedicine visits conducted by the investigator for the purposes 


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of evaluating worsening signs or symptoms attributed to COVID-19 or emergency room, 
urgent care center, or physician office visits, for attention to worsening signs or symptoms 
attributed to COVID-19, in the opinion of the investigator. 
• COVID-19-related hospitalization: includes visits for attention to worsening signs or 
symptoms attributed to COVID 19, in the opinion of the investigator. Hospitalization is 
defined as ≥24 hours of acute care in a hospital or acute care facility (includes emergency 
rooms, ICUs, acute care facilities created for COVID-19 pandemic hospitalization needs, or 
other acute care facilities). 
• COVID-19-related mortality: COVID-19-related mortality is defined as death directly due 
to COVID-19 or any death in which COVID-19 or COVID-19 complications contributed to 
the death, as determined by the investigator, a formal autopsy report or death certificate. 
• All-cause mortality: death due to any cause. 
• SARS-CoV-2 viral load (NP sample): assessed by RT-qPCR from NP sample collected on 
CLI Day 1. 
• SARS-CoV-2 viral load (saliva sample): assessed by RT-qPCR from saliva sample 
collected on CLI Day 1. 
3.6. 
Treatments 
After randomization, participants enrolled in Cohort A and B will receive a single 300 mg dose 
of ADG20 or matching placebo administered via IM injection. 
4. 
GENERAL STATISTICAL CONSIDERATIONS 
4.1. 
General Rules and Considerations 
Continuous variables will be summarized using the following descriptive summary statistics: 
the number of participants (n), mean, SD, median, first and third quartiles, minimum (min), and 
maximum (max). 
Categorical variables will be summarized using frequency counts and percentages. 
Baseline value, unless specified otherwise, is defined as the last non-missing measurement 
(scheduled or unscheduled) collected on or before the date of dosing. If the date of study dosing 
is missing, the date of randomization will be used instead.  
A row denoted “Missing” may be included in count tabulations as needed to account for 
dropouts and missing values. The denominator for all percentages will be the number of 
participants in the treatment group within the analysis set of interest, unless otherwise specified. 
Change from baseline is defined as the value at the post-baseline visit minus the value at the 
baseline visit. 
Study Day 1 is denoted the day that study drug is administered. Subsequent study days are 
calculated as: date of assessment/event – date of dosing + 1. If a participant is not dosed, the date 
of randomization is used to define Study Day rather than the date of dosing. 


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Time-to-event parameters are defined from the date of randomization.  
Unscheduled visit measurements will be included in analysis as follows: 
• In the derivation of baseline measurements. 
• In the derivation of maximum/minimum change from baseline values and worst post-baseline 
values for safety analyses. 
• In individual participant data listings as appropriate. 
Incomplete/missing data: 
Imputation rules for missing dates of medications and AEs will be used (see Appendix A). 
Data that are continuous in nature but are reported in the form of <x, >x, ≤x, or ≥x (where x is 
considered as the limit of quantitation) will be set to limit of quantitation value with the 
following exceptions: 
• For viral load data: 
− Viral load values reported as detected but BLQ of the PCR assay (<714 copies/mL) are 
imputed with half of the LLOQ of the PCR assay (ie, 357 copies/mL) 
− Viral load values reported as not detected are imputed with 1 copy/mL (ie, 
0 log10 copies/mL) 
− Viral load values reported as >7.1×107 copies/mL are imputed to 7.1×107 copies/mL 
− All viral load analyses will use both observed and the above imputed viral load data. 
Listings present observed viral load data. 
• For PK concentrations:  
− For predose samples, the sampling time will be set to zero or labelled Predose.  
− For postdose samples, the nominal (scheduled) sampling time will be used in summary 
tables and mean concentration figures and actual sampling times will be used for all 
figures of individual concentrations.  
− All concentration values below the LLOQ will be set to zero for summary tables/figures 
and missing in individual plots.  
Other incomplete/missing data will not be imputed, unless specified otherwise. 
Treatment groups: The following treatment groups will be used for summary purposes: 
ADG20, Placebo.  
All analyses and data summaries for efficacy will be provided by treatment group using the 
appropriate analysis sets, unless otherwise specified. 
All data listings and tables displaying participant data that contain an evaluation date will display 
study day. Listings will be sorted by Subject ID and treatment. 


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4.2. 
Sample Size 
Cohort A (PEP): The primary endpoint is the proportion of RT-PCR-confirmed symptomatic 
COVID-19 through 28 days after randomization. The original sample size of 1078 participants 
was planned with 90% power, 2-sided alpha 0.05, and a 1:1 randomization ratio to detect a 
statistically significant RR when the true RR is 0.30 (70% efficacy) with an attack rate of 5% per 
28 days in the placebo group and 1.5% in the ADG20 group. A sample size of 1270 participants 
was planned to account for 15% participants enrolled with a prior or current SARS-CoV-2 
infection at baseline.  
Enrollment was suspended in Cohort A on 11-Jan-2022 following the emergence of Omicron 
variant, against which 300 mg ADG20 is not expected to have adequate efficacy due to 
decreased neutralization activity. As such, the analysis of the primary efficacy endpoint for 
Cohort A will only include events through 28 days after randomization or the emergence of 
Omicron, whichever is earlier. Prior to suspension of enrollment, 487 participants were 
randomized in Cohort A, of which approximately 377 were enrolled prior to the emergence of 
Omicron with a minimum of 2 weeks follow-up through 15-Dec-2021, and 346 were estimated 
to be eligible for inclusion in the primary efficacy analysis population (RT-PCR-negative pre-
Omicron). The primary efficacy population yielded approximately 14 events through 28 days or 
emergence of Omicron, whichever is earlier, for the analysis. With 14 events, any observed 
efficacy >68% will be statistically significant at 2-sided α=0.05. 
Cohort B (PrEP): The primary endpoint is the proportion of RT-PCR-confirmed symptomatic 
COVID-19 through 3 months. The original sample size of 4628 participants was planned with 
84% power, 2-sided alpha 0.05, and a 1:1 randomization ratio to detect a statistically significant 
RR when the true RR is 0.30 (70% efficacy) with an attack rate of 1% per 3 months in the 
placebo group and 0.3% in the ADG20 group. A sample size of 5142 participants was planned to 
account for 10% participants enrolled with a prior or current SARS-CoV-2 infection at baseline. 
Enrollment was suspended in Cohort B on 11-Jan-2022 following the emergence of Omicron 
variant, against which 300 mg ADG20 is not expected to have adequate efficacy due to 
decreased neutralization activity. As such, the analysis of the primary efficacy endpoint for 
Cohort B will only include events through 3 months after randomization or the emergence of 
Omicron, whichever is earlier. Prior to suspension of enrollment, 2101 participants were 
randomized in Cohort B, of which approximately 1646 were enrolled prior to the emergence of 
Omicron with a minimum of 2 weeks follow-up through 15-Dec-2021, and 1424 were estimated 
to be eligible for inclusion in the primary efficacy analysis population (RT-PCR-negative and 
seronegative pre-Omicron). A higher than expected aggregate attack rate resulted in sufficient 
number of cases to enable this cohort to be a fully powered study to detect clinically meaningful 
and statistically significant treatment differences. Based on 3.6% aggregate attack rate, 974 
participants in a 1:1 randomization ratio provides 90% power to detect a statistically significant 
treatment effect when the true RR is 0.3 with 2-sided α = 0.05. Therefore, the current sample size 
of 1424 provides sufficient statistical power to carry out the primary efficacy analysis, as well as 
preliminary evaluation of safety. 


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4.3. 
Multiplicity Adjustments 
In each cohort, to control the overall type I error rate (alpha) at 0.05 (2-sided), a hierarchical 
testing procedure will be used for primary and key secondary efficacy endpoints, such that 
testing for the key secondary analyses difference will proceed only if the treatment difference is 
statistically significant in the primary efficacy analysis. The first key secondary hypotheses will 
be tested if the null hypothesis for the primary endpoint is rejected at 2-sided 0.05 level. The 
subsequent key secondary hypotheses will be tested if the null hypothesis for the preceding key 
secondary endpoint is rejected at 2-sided, .05 level.  
Analyses of the other secondary and exploratory endpoints will be conducted to support the 
findings of the primary and key secondary efficacy analyses without accounting for multiple 
comparisons. Nominal p-values and 95% CIs will be computed for these secondary and 
exploratory efficacy analyses. 
4.4. 
Analysis Sets 
Analysis sets used in this study are defined below. In the efficacy analysis, participants will be 
analyzed based on the treatment they are randomized to, irrespective of what they actually might 
have received. In the safety analysis, participants will be analyzed based on the study drug 
received. 
4.4.1. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the study but are not 
subsequently randomly assigned to treatment. A participant is considered enrolled once the 
participant has been randomized. 
4.4.2. 
Full Analysis Set  
The Full Analysis Set (FAS) will include all randomized participants regardless of whether the 
participant received study drug.  
4.4.3. 
Modified Analysis Sets 
The Modified Full Analysis Set (mFAS) will include all randomized participants without prior 
or current SARS-CoV-2 infection at baseline based on central tests (baseline RT-PCR-negative 
and seronegative). If either central RT-PCR or central serology is missing at baseline, a negative 
baseline status can be imputed for a participant if there is a post-baseline negative central 
serology sample collected at least 14 days from Day 1 and prior to any positive local/central 
RT-PCR.  
The modified Full Analysis Set-1 (mFAS-1) will include all randomized participants without 
current SARS-CoV-2 infection at baseline based on central tests (baseline RT-PCR-negative 
regardless of serostatus). If central RT-PCR is missing at baseline, a negative baseline status can 
be imputed for a participant if there is a post-baseline negative central serology sample collected 
at least 14 days from Day 1 and prior to any positive local/central RT-PCR.  


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The modified Full Analysis Set-2 (mFAS-2) will include all randomized participants with prior 
infection but without current SARS-CoV-2 infection at baseline based on central tests (baseline 
RT-PCR-negative and seropositive). No imputation is performed if any baseline test is missing. 
The modified Full Analysis Set-3 (mFAS-3) is similarly defined as mFAS (baseline RT-PCR-
negative and seronegative) except that no imputation is performed if any baseline test is missing. 
Select analyses of mFAS will be repeated in mFAS-3 as the sensitivity analysis. 
4.4.4. 
Pre-Emergence of Omicron Analysis Set 
The Pre-Emergence of Omicron Analysis Set (pre-Omicron) will include all participants 
randomized on or prior to 30-Nov-2021, allowing participants to be followed a minimum of 2 
weeks through 15-Dec-2021 when Omicron became the predominant variant. The pre-Omicron 
Analysis Set will be used in combination with the modified analysis sets to define the primary 
efficacy population for each cohort, as follows:  
• Cohort A (PEP): baseline RT-PCR negative participants in the pre-Omicron Analysis Set 
(mFAS-1 pre-Omicron) 
• Cohort B (PrEP): baseline RT-PCR-negative and seronegative participants in the pre-
Omicron Analysis Set (mFAS pre-Omicron)  
4.4.5. 
Post-Emergence of Omicron Analysis Set 
The Post-Emergence of Omicron analysis set (post-Omicron) will include participants 
randomized after 30-Nov-2021 until the end of enrollment (11-Jan-2022) and will be used to 
evaluate activity against the Omicron variant.  
4.4.6. 
Per-Protocol Set 
The Per-Protocol Set (PP) includes all randomized participants who receive the full dose of 
study drug, do not have missing data for the primary efficacy endpoint, and have no other 
important protocol deviation, as determined and documented by the Sponsor before database 
freeze/lock and unblinding, that could impact the assessment of efficacy. Participants will be 
analyzed based on the study drug they are randomized to. 
4.4.7. 
Safety Set 
The Safety Set will include all participants who received any amount of study drug. All safety 
analyses will be conducted in this analysis set. Participants will be analyzed based on the study 
drug actually received. 
4.4.8. 
Immunogenicity Set 
The Immunogenicity Set includes all participants who received any study drug and had a valid 
immunogenicity test result before the dose of study drug and at least 1 valid result after the dose 
of study drug. 


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4.4.9. 
PK Analysis Set 
The PK Analysis Set includes all participants in the Safety Set who have at least two measurable 
ADG20 concentration post-administration of study drug.  
5. 
STATISTICAL ANALYSES 
5.1. 
Participant Disposition  
5.1.1. 
Disposition 
Participant disposition will be summarized for all screened participants, in the following 
categories: 
• Number of screened participants 
• Number of screen failure participants 
• Number of participants randomized (FAS) 
• Number and percentage of participants treated 
• Number and percentage of participants randomized by analysis sets 
• Number and percentage of participants by the reasons for study discontinuation 
• Number and percentage of primary cause of death  
All percentages will be based on the number of randomized participants. Participant disposition 
data will also be presented in listings. 
Cumulative follow-up time will also be summarized for randomized participants:  
• Ongoing participants: data cut-off date - randomization date + 1 
• Discontinued or completed study participants: end of study date – randomization date + 1.  
5.1.2. 
Protocol Deviations 
All protocol deviations will be assessed and documented on a case-by-case basis before any 
unblinded analysis is performed, and important deviations that are considered to have an impact 
on the efficacy assessment will lead to the relevant participant being excluded from the PP 
analysis set.  
The number and percentages of participants with important deviations will be presented in the 
FAS by treatment group and overall. Important protocol deviations will also be summarized by 
deviation category. A listing of all protocol deviations will be provided for all FAS participants. 


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5.2. 
Demographics and Clinical Characteristics  
5.2.1. 
Demographics/Baseline Characteristics 
Descriptive statistics will be calculated for the following continuous demographic and baseline 
characteristics: age (years), weight (kg), height (cm), BMI (kg/m2). BMI is calculated as (body 
weight in kilograms) / (height in meters)2. The number and percentage of participants will be 
provided for the following categorical variables: age group (age 12 to <18, 18 to <55, 55 to <75, 
and ≥75 years), sex, race, ethnicity, stratified geographic region, stratified age/risk of severe 
COVID-19 (≥12 to <55 years and low risk, ≥12 to <55 years and high risk, and ≥55 years), 
baseline SARS-CoV-2 status by central RT-PCR, baseline SARS-CoV-2 status by central 
serology, and risk factors for COVID-19 disease progression on adults and on adolescents. In 
addition, a derived baseline high risk of progression to severe COVID-19 based on eCRF 
medical history/concomitant medication will be summarized.  
Participant demographics/baseline characteristics will be presented in a listing. 
5.3. 
Medical History  
Medical history will be coded using MedDRA Version 24.0 or higher. The number and 
percentage of participants with any medical history will be summarized by treatment arm using 
SOC and PT ordered alphabetically by SOC and by descending participant count in the ADG20 
arm for PT within SOC.  
Participant medical history data including specific details will be presented in a listing. 
5.4. 
Treatments and Medications  
5.4.1. 
Prior and Concomitant Medication 
Prior medications are defined as any medication with a start date before screening (date of 
informed consent) and stop date before the date of administration of the study drug. Concomitant 
medications are defined as any medication used on or before screening and with a stop date on or 
after the date of administration of the study drug, are ongoing, or are taken on or after the date of 
administration of the study drug. 
Medications with partially missing dates will be imputed to categorize as prior or concomitant 
medication (Appendix A). If no classification to prior or concomitant can be conclusively 
determined, the medication will be considered concomitant. All medications will be coded 
according to the World Health Organization drug dictionary (WHODrug March 2021 or higher). 
The number and percentages of participants with at least one prior/concomitant medication will 
be summarized by treatment group. The number and percentages of all prior/concomitant 
medications will be summarized by treatment group, WHODrug ATC level 2, and PT. All 
summaries will be performed using the FAS. A listing of prior/concomitant medications will be 
provided.  
The number and percentages of participants with at least one prohibited concomitant medication 
for the prevention of COVID-19 or receiving a COVID-19 vaccine based on a sponsor medical 
adjudication will be summarized by treatment group in the FAS. The number and percentages of 


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these medications will also be summarized by WHODRUG ATC level 2 and PT, and a listing of 
prohibited medications will be provided. 
5.4.2. 
Study Treatments 
In Cohorts A and B, a single 300 mg dose of ADG20 or matching placebo will be administered 
by IM injection. Summaries of study treatment will be presented for the Safety Set. The number 
and percentage of participants that received a full dose (300 mg) and did not receive a full dose 
will be presented. 
A total volume of 3 mL ADG20/placebo is administrated using the 100 mg/mL formulation in 
both US and non-US study sites. The US sites switched during the study to administer a total 
volume of 2 mL ADG20/placebo using the 150 mg/mL formulation. The non-US sites continued 
to administer 3 mL using the 100 mg/mL formulation.  
Descriptive statistics of the total volume (for the 2 mL or 3 mL regimen) and dose (mg) will be 
presented; mL is converted to mg as follows: 100×dose in mL for 100 mg/mL formulation; 
150×dose in mL for 150 mg/mL formulation. A listing of study drug administration will be 
provided. 
5.5. 
Efficacy Analyses  
5.5.1. 
Primary Efficacy Analysis  
Cohort A (PEP): The primary efficacy endpoint is the proportion of participants with RT-PCR–
confirmed symptomatic COVID-19 through Day 28 after randomization or emergence of 
Omicron (designated by 15-Dec-2021), whichever is earlier, in the mFAS-1 pre-Omicron 
analysis set. 
Cohort B (PrEP): The primary efficacy endpoint is the proportion of participants with 
RT-PCR–confirmed symptomatic COVID-19 through 3 months after randomization or 
emergence of Omicron (designated by 15-Dec-2021), whichever is earlier, in the mFAS 
pre-Omicron analysis set.  
In each cohort, the null and alternative hypotheses are the following: 
Ho: P1  ̶  P0 = 0 
H1:  P1  ̶  P0 ≠ 0 
P1 and P0 are the proportion of participants with primary endpoint outcome in the ADG20 and 
placebo groups respectively. Using the methodology described below, a standardized estimator 
for a binary outcome (primary estimand) will be estimated with adjustment for the following 
stratification factors: geographic region and age/risk of severe COVID-19.  
The method described in Ge et al. (2011) computes a population-level estimate for the treatment 
difference (in terms of difference in proportion) and supports an adjustment for the predefined 
prognostic factors. The method relies on a logistic regression model, considering the 𝑖𝑖th 
participant, 𝑖𝑖= 1, … , 𝑛𝑛, where 𝑛𝑛 is the total number of participants, and let 𝑦𝑦𝑖𝑖 denote the binary 
outcome for the primary endpoint (present =1 or absent =0). The treatment indicator will be 
denoted by 𝑡𝑡𝑖𝑖, where 𝑡𝑡𝑖𝑖= 0 corresponds to the placebo arm and 𝑡𝑡𝑖𝑖= 1 corresponds to the 


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treatment (ADG20) arm. The vector of prognostic factors for the 𝑖𝑖th participant will be denoted 
by 𝒙𝒙𝑖𝑖. The model is given by:  
logit 𝑝𝑝𝑖𝑖= 𝛽𝛽0 + 𝛽𝛽1𝑡𝑡𝑖𝑖+ 𝜷𝜷2
′ 𝒙𝒙𝑖𝑖, 
where 𝑝𝑝𝑖𝑖= 𝑃𝑃(𝑦𝑦𝑖𝑖= 1), 𝛽𝛽0 and 𝛽𝛽1 are the intercept and slope, 𝜷𝜷2 is the vector of model 
parameters corresponding to the covariates and the prime denotes transposition. 
After the model has been fitted to the data, the model parameters will be estimated (the estimates 
will be denoted by 𝛽𝛽̂0, 𝛽𝛽̂1 and 𝜷𝜷෡2, respectively). After that, two potential outcomes will be 
computed from the model for each participant. These outcomes represent the participant’s 
outcomes if the participant has been assigned to the placebo and treatment arms: 
𝑝𝑝𝑖𝑖0 = 𝑃𝑃(𝑦𝑦𝑖𝑖= 1|𝑡𝑡𝑖𝑖= 0), 
𝑝𝑝𝑖𝑖1 = 𝑃𝑃(𝑦𝑦𝑖𝑖= 1|𝑡𝑡𝑖𝑖= 1). 
The population-level estimates for the incidence rates will be defined as follows: 
𝑝𝑝̂0 = 𝑛𝑛−1 ∑
𝑝𝑝𝑖𝑖0
𝑛𝑛
𝑖𝑖=1
 and 𝑝𝑝̂1 = 𝑛𝑛−1 ∑
𝑝𝑝𝑖𝑖1
𝑛𝑛
𝑖𝑖=1
. 
These estimates can be used to define an estimate for the treatment difference (difference in the 
incidence rates) or relative risk reduction in a straightforward manner, ie, 
𝑝𝑝̂1 −𝑝𝑝̂0 and 1 −𝑝𝑝̂1/𝑝𝑝̂0 
The variance of the estimated treatment difference or relative risk reduction will be estimated 
using the delta method based on the algorithm presented in Ge et al. (2011) (Appendix B). 
The primary estimand will be analyzed using treatment policy strategy to handle the intercurrent 
events (ICEs) so that all available primary endpoint outcomes will be included. The ICEs include 
the use of rescue medications (eg, COVID-19 vaccine, COVID-19 mAb for the purposes of 
prevention) and subject level unblinding by Investigator prior to the primary endpoint outcome.  
Participants with COVID-19-related hospitalization ≥24 hours with a positive local 
SARS-CoV-2 test (within 14 days) or all-cause death are counted toward the primary endpoint 
outcome (Section 3.5.1). Participants with missing primary endpoint outcome will be imputed as 
not having the primary endpoint outcome in the primary analysis. 
The prognostic factors include the stratification factors (geographic region, age/risk of severe 
COVID-19), and baseline serostatus or baseline RT-PCR status when applicable.  
The observed risk difference (placebo minus ADG20) with 95% CI (using the Miettinen-
Nurminen method), observed relative risk reduction, standardized risk difference with 95% CI 
and associated p-values, and standardized relative risk reduction with 95% CI will be provided.  
5.5.2. 
Sensitivity Analysis of Primary Estimand 
Sensitivity Analysis 1: To assess the impact of participants with missing primary endpoint 
outcome, a sensitivity analysis will utilize multiple imputation (MI) under missing at random 
(MAR) assumption. The imputation model (using SAS PROC MI) will be informed by all the 


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observed outcomes for participants including treatment and covariates used in the primary 
analysis. Participants with missing primary endpoint outcome will be imputed using monotone 
logistic regression. Missing outcomes will be imputed multiple=100 times. The seed for 
reproducibility will be set to 2022. The final analysis model applied to the complete data set will 
be the same as that for the primary analysis. Treatment effect estimates from the individual 
completed data sets will be combined using Rubin’s rules (using SAS PROC MIANALYZE).  
Sensitivity Analysis 2: To assess the impact of the ICE, a supplementary estimand will be 
defined using hypothetical strategy to handle the ICE. If the participant had the primary endpoint 
outcome after the ICE, the primary endpoint outcome will be set to missing. The analysis will be 
carried out using MI methodology as described in Sensitivity Analysis 1. 
Sensitivity Analysis 3: A sensitivity analysis based on the Cochran-Mantel-Haenszel (CMH) 
test will be performed. This test will be adjusted for the randomization stratified factors. The 
levels of stratification may be combined if deemed necessary.  
Sensitivity Analysis 4: A sensitivity analysis will repeat the primary efficacy analysis in the PP 
analysis set. 
5.5.3. 
Analysis of Time to First RT-PCR-confirmed Symptomatic COVID-19 
The time from randomization to first RT-PCR-confirmed symptomatic COVID-19 (event) will 
be analyzed by Kaplan-Meier (KM) methodology and stratified Cox Proportional Hazard model 
in each of mFAS/mFAS-1/FAS pre-Omicron analysis sets. 
Analysis events are those dated on or prior to the following censoring date: end of study date, 
date of subject unblinding, date of subject receipt of COVID-19 vaccination or other preventive 
medication, and analysis cutoff date if applicable. When analyzing pre-Omicron analysis set, 
emergence of Omicron variant (15 Dec 2021) will be used for the analysis cut-off date.  
Participants who did not meet the defined event on or prior to the above censoring date are 
censored at the earliest of each of these dates. The time from randomization to first 
RT-PCR-confirmed symptomatic COVID-19 will be calculated as date of event/censoring – date 
of randomization + 1.  
Survival curves between ADG20 and placebo will be compared using a log-rank test stratified by 
stratification factors: geographic region and age/risk category. Probability of cumulative 
incidence (1 – survival probability) will be estimated based on the survival curves at the specific 
time points.  
A stratified Cox Proportional Hazard model will be performed to estimate the hazard ratio 
adjusted for prognostic factors. The prognostic factors include the stratification factors 
(geographic region, age/risk of severe COVID-19), and baseline serostatus or baseline RT-PCR 
status when applicable. Comparison of the survival distributions will use the score test for the 
hazard ratio from the Cox model.  


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5.5.4. 
Key Secondary Endpoints and Analyses 
Analyses of the key secondary endpoints (Table 4) will be conducted sequentially following a 
hierarchical testing order within each cohort. 
For the binary endpoint, the analysis will use the same methodology as the primary efficacy 
analysis for determining a standardized estimator (standardized risk difference/standardized 
relative risk reduction) with adjustment for the prognostic factors. The prognostic factors include 
the stratification factors (geographic region, age/risk of severe COVID-19), and baseline 
serostatus or baseline RT-PCR status when applicable. 
Table 4. 
Key Secondary Endpoints 
Endpoint 
Analysis Set  
Cohort A (PEP) 
Proportion of participants with SARS-CoV-2 infection (asymptomatic or 
symptomatic) as determined by positive RT-PCR or serology test through Day 28 or 
emergence of Omicron, whichever is earlier 
mFAS-1 pre-Omicron 
Proportion of participants with RT-PCR-confirmed symptomatic COVID-19 through 
Day 28 or emergence of Omicron, whichever is earlier 
mFAS pre-Omicron 
Proportion of participants with SARS-CoV-2 infection (asymptomatic or 
symptomatic) as determined by positive RT-PCR or serology test through Day 28 or 
emergence of Omicron, whichever is earlier 
mFAS pre-Omicron 
Proportion of participants with RT-PCR-confirmed symptomatic COVID-19 through 
Day 28 or emergence of Omicron whichever is earlier 
FAS pre-Omicron 
Proportion of participants with SARS-CoV-2 infection (asymptomatic or 
symptomatic) as determined by positive RT-PCR or serology test through Day 28 or 
emergence of Omicron, whichever is earlier 
FAS pre-Omicron 
Cohort B (PrEP) 
Proportion of participants with RT-PCR-confirmed symptomatic COVID-19 through 
3 months or emergence of Omicron, whichever is earlier 
mFAS-1 pre-Omicron 
Proportion of participants with SARS-CoV-2 infection (asymptomatic or 
symptomatic) as determined by positive RT-PCR or serology test through 3 months 
or emergence of Omicron, whichever is earlier 
mFAS pre-Omicron 
Proportion of participants with SARS-CoV-2 infection (asymptomatic or 
symptomatic) as determined by positive RT-PCR or serology test through 3 months 
or emergence of Omicron, whichever is earlier 
mFAS-1 pre-Omicron 
5.5.5. 
Subgroup Analyses 
The primary endpoint and key secondary endpoints will be analyzed in the following subgroups.  
• Sex (male, female) 
• Stratified geographic region (United States and Western Europe, Central and Eastern Europe, 
Rest of the World) from IRT 
• Stratified age/risk of severe COVID-19 (aged ≥12 and <55 years and low risk, aged ≥12 and 
<55 and high risk, aged ≥55 years) from IRT  


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• Derived age/risk of severe COVID-19 (aged ≥12 and <55 years and derived low risk, aged 
≥12 and <55 and derived high risk, aged ≥55 years) from eCRF 
• Derived high risk for severe COVID-19 (yes, no): aged ≥12 and <55 and derived high risk, 
plus aged ≥55 years 
For the binary endpoint, the analysis will use the same methodology as the primary efficacy 
analysis with age (continuous) as covariate to estimate the standardized relative risk reduction 
and 95% CI for each subgroup with at least 5 total events. Subgroups with less than 5 total 
events will be summarized descriptively. A forest plot will be provided, which displays the point 
estimate and 95% CI of the estimate. Missing age will be imputed as the average of non-missing 
value at baseline in the FAS. Additional prognostic factors may be added to the model if there is 
no issue of model convergence, such as baseline serostatus or baseline RT-PCR status when 
applicable.  
5.5.6. 
Additional Secondary Endpoints and Analyses  
Analyses of other secondary endpoints (Table 5) will be conducted to support the findings of the 
primary and key secondary efficacy endpoints. The results of these analyses will be considered 
descriptive in nature and will be analyzed without any procedures to account for multiple 
comparisons. In addition to these analyses, listings will be provided. 
Table 5. 
Additional Secondary Endpoint Analyses 
Endpoint 
Analysis Set 
Cohort A (PEP) 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through 3 months or emergence of Omicron, whichever is 
earlier 
mFAS-1/mFAS/FAS pre-Omicron 
Proportion of participants with SARS-CoV-2 infection (asymptomatic or 
symptomatic) as determined by positive RT-PCR or serology test 
through 3 months or emergence of Omicron, whichever is earlier 
mFAS-1/mFAS/FAS pre-Omicron 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through Day 28 and 3 months after randomization or 
emergence of Omicron, whichever is earlier 
mFAS-2 pre-Omicron 
Proportion of participants with asymptomatic SARS-CoV-2 infection as 
determined by positive RT-qPCR (nasal sample) on Days 8 and 15 after 
randomization 
mFAS-1 pre-Omicron 
Proportion of participants with asymptomatic SARS-CoV-2 infection as 
determined by serology through Day 28 
mFAS-1 pre-Omicron 
Peak post-baseline SARS-CoV-2 viral load as measured by RT-qPCR 
(nasal sample) 
participants with asymptomatic 
SARS-CoV-2 infection as determined 
by positive RT-qPCR (nasal sample) 
on Days 8 and 15 
SARS-CoV-2 viral load assessed by RT-qPCR (nasal sample) change 
from baseline to Day 8 and Day 15 
participants with asymptomatic 
SARS-CoV-2 infection as determined 
by positive RT-qPCR (nasal sample) 
at baseline, Day 8, and Day 15 


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Endpoint 
Analysis Set 
Cohort B (PrEP) 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through 3 months or emergence of Omicron, whichever is 
earlier 
FAS pre-Omicron 
Proportion of participants with SARS-CoV-2 infection (asymptomatic or 
symptomatic) as determined by positive RT-PCR or serology test 
through 3 months or emergence of Omicron, whichever is earlier 
FAS pre-Omicron 
Proportion of participants with asymptomatic SARS-CoV-2 infection as 
determined by serology at Month 6 
mFAS pre-Omicron 
Cohort A (PEP), Cohort B (PrEP) 
Proportion of participants with RT-PCR-confirmed mild, moderate, or 
severe/critical COVID-19 through CLI Day 28 
participants with RT-PCR-confirmed 
symptomatic COVID-19 
All-cause mortality through CLI Day 28 
COVID-19-related mortality through CLI Day 28 
Time from reported symptom onset to sustained resolution of 
symptomatic COVID-19 through CLI Day 28 
Viral load from CLI Day 1 sample assessed by RT-qPCR.  
Proportion of participants with at least 1 COVID-19-related medically 
attended outpatient visit (physician’s office, telemedicine, emergency 
rooms, or urgent care centers) through CLI Day 28  
Proportion of participants with COVID-19-related hospitalizations 
through CLI Day 28   
5.5.7. 
Exploratory Endpoint Analyses 
Analyses of exploratory endpoints (Table 6) will be conducted to explore additional efficacy 
signals for hypothesis generation. 
Table 6. 
Exploratory Endpoint Analyses 
Endpoint 
Analysis Set 
Cohort A (PEP) 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through Day 28 (regardless of variant) 
mFAS-1/mFAS/FAS pre-Omicron 
Time from randomization to first RT-PCR-confirmed symptomatic 
COVID-19 (regardless of variant) 
mFAS-1/mFAS/FAS pre-Omicron 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through Day 28 (regardless of variant) 
mFAS-1/mFAS/FAS post-Omicron 
Time from randomization to first RT-PCR-confirmed symptomatic 
COVID-19 (regardless of variant) 
mFAS-1/mFAS/FAS post-Omicron 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through Day 28 (regardless of variant) 
mFAS-1/mFAS/FAS 
Time from randomization to first RT-PCR-confirmed symptomatic 
COVID-19 (regardless of variant) 
mFAS-1/mFAS/FAS 


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Endpoint 
Analysis Set 
Cohort B (PrEP) 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through 3 months (regardless of variant) 
mFAS-1/mFAS/FAS pre-Omicron 
Time from randomization to first RT-PCR-confirmed symptomatic 
COVID-19 (regardless of variant) 
mFAS-1/mFAS/FAS pre-Omicron 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through 3 months (regardless of variant) 
mFAS-1/mFAS/FAS post-Omicron 
Time from randomization to first RT-PCR-confirmed symptomatic 
COVID-19 (regardless of variant) 
mFAS-1/mFAS/FAS post-Omicron 
Proportion of participants with RT-PCR-confirmed symptomatic 
COVID-19 through 3 months (regardless of variant) 
mFAS-1/mFAS/FAS 
Time from randomization to first RT-PCR-confirmed symptomatic 
COVID-19 (regardless of variant) 
mFAS-1/mFAS/FAS 
Cohort A (PEP), Cohort B (PrEP) 
Proportion of participants with asymptomatic SARS-CoV-2 infection at 
baseline (defined by positive central SARS-CoV-2 RT-PCR test and lack 
of symptoms of COVID-19) with medically attended visits (outpatient, 
telemedicine, or hospitalization) or death through Day 28 
Descriptive summary 
Health Care Resource Utilization of participants who develop 
COVID-19: incidence and duration of ICU stay and incidence of 
emergency room visits 
Descriptive summary 
Genotypic characterization of viral isolates for reduced susceptibility to 
ADG20: proportion of participants with baseline and post-baseline 
(treatment-emergent) variations at critical amino acid positions 
associated with ADG20 resistance (≥15% and ≥50% allele frequencies) 
Descriptive summary 
Pre- and post-vaccination SARS-CoV-2 neutralizing antibody titers in 
participants who choose to receive COVID-19 vaccine during the study 
Descriptive summary 
5.6. 
Safety Analysis  
5.6.1. 
Solicited and Unsolicited Adverse Events 
5.6.1.1. 
Adverse Events  
An AE is defined as any untoward medical occurrence in a participant enrolled into this study 
regardless of its causal relationship to the study drug. AEs occurring from when the participant 
signs the ICF until the Month 14 (EOS) visit or discontinuation from study will be recorded. 
Only study procedure-related AEs occurring before randomization will be recorded. All AEs will 
be followed to adequate resolution. MedDRA Version 24 or higher will be used to code all AEs. 
5.6.1.2. 
Injection Site Reactions  
Intramuscular ISRs will be recorded in the Injection Site Reaction Diary and graded using the 
FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials (2007), as described in Appendix 1 of 
the protocol. 


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Participants will be instructed to record the worst severity experienced (Table 7) during each 
recording period (prior 24 hours) of the following local (solicited) AEs through Study Day 4, 
and, if applicable, whether medication was taken to relieve the symptoms: 
• Injection site pain or tenderness 
• Erythema/redness at the site of injection 
• Induration/swelling at the site of injection 
Table 7. 
Grading of Injection Site Reactions 
Local Reaction to 
Injectable Product 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
Life-Threateninga 
(Grade 4) 
Pain 
Does not 
interfere with 
activity  
Repeated use of 
non-narcotic pain 
reliever >24 hours or 
interferes with activity  
Any use of narcotic 
pain reliever or 
prevents daily 
activity  
Emergency room 
visit or 
hospitalization  
Tenderness 
Mild discomfort 
to touch 
Discomfort with 
movement 
Significant 
discomfort at rest  
Emergency room 
visit or 
hospitalization  
Erythema/redness 
2.5–5 cm  
5.1–10 cm  
>10 cm  
Necrosis or 
exfoliative dermatitis  
Induration/swellingb 
2.5–5 cm and 
does not interfere 
with activity  
5.1–10 cm 
or interferes with 
activity  
>10 cm or prevents 
daily activity  
Necrosis  
Note: In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded as a 
continuous variable. 
a Pain/tenderness are not expected to be life-threatening but can still meet Grade 4 criteria based on ER visit or hospitalization  
b Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
For summaries combining ISRs and other AEs, ISRs will be mapped to MedDRA SOC and PT 
as shown in Table 8. 
Table 8. 
Injection Site Reaction Mapping to MedDRA Coding 
Injection Site 
Reaction Term 
System Organ Class 
Preferred Term 
Pain 
General disorders and administration site conditions 
Injection site pain 
Tenderness 
General disorders and administration site conditions 
Injection site pain 
Erythema 
General disorders and administration site conditions 
Injection site erythema 
Redness 
General disorders and administration site conditions 
Injection site erythema 
Induration  
General disorders and administration site conditions 
Injection site induration 
Swelling 
General disorders and administration site conditions 
Injection site swelling 
Necrosis 
General disorders and Administration site conditions 
Injection site necrosis 
Exfoliative dermatitis 
Skin and subcutaneous tissue disorders 
Dermatitis exfoliative 
An ISR that is reported on multiple days will be considered one ISR with the start date defined as 
the date the ISR was first reported, and the end date defined as the date the ISR is reported as not 


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occurring (ie, none) in the diary or the date of resolution for the ISR Resolution eCRF. 
Maximum severity will be assigned. 
5.6.1.3. 
Treatment Emergent Adverse Events 
A TEAE is defined as any AE that has an onset during or after the administration of study drug 
through the Month 14 visit, or any preexisting condition that has worsened during or after the 
administration of study drug through the Month 14 Visit. Because solicited AEs (ISRs in 
participants receiving IM injection) are expected to occur after the administration of study drug, 
all solicited AEs will be considered study drug related TEAEs. 
5.6.1.4. 
Adverse Events of Special Interest 
For this study, AESIs are specified in the protocol as follows: Hypersensitivity reactions 
occurring within 4 days of study drug administration including, but not limited to, anaphylaxis, 
anaphylactic shock, bronchospasm, hypotension, loss of consciousness, generalized skin rash, 
angioedema, bronchoconstriction, allergic bronchial asthma, allergic rhinitis, allergic 
conjunctivitis, drug allergy, immune thrombocytopenia, autoimmune hemolytic anemia, rash, 
urticaria, and arthus reaction.  
Hypersensitivity reactions will be graded according to the DAIDS Table for Grading the Severity 
of Adult and Pediatric Adverse Events (NIAID 2017). 
Determination of hypersensitivity reactions for participants throughout the study will be based on 
a sponsor medical adjudication based on the narrow and broad terms of the SMQs 
hypersensitivity, anaphylactic reaction, and angioedema. 
All hypersensitivity reactions will be summarized through Day 4 and through Month 14. 
5.6.1.5. 
Medically Attended Adverse Events  
MAAEs are defined as AEs leading to medically attended visits that are not routine visits for 
physical examination or vaccination, such as an emergency room visit, or an otherwise 
unscheduled visit to or from medical personnel (medical doctor) for any reason other than the 
illness under study (COVID-19). AEs, including abnormal vital signs, identified on a routine 
study visit or during the scheduled illness visits will not be considered MAAEs. 
5.6.1.6. 
Serious Adverse Events 
An SAE is defined as any event that: 
• results in death 
• is immediately life-threatening 
• requires inpatient hospitalization or prolongation of existing hospitalization 
• results in persistent or significant disability/incapacity 
• is a congenital anomaly/birth defect 
• is an important medical event (eg, intensive treatment in an ER or at home for allergic 
bronchospasm; blood dyscrasias, or convulsions that do not result in hospitalization; or 


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development of drug dependency or drug abuse; malignancy tumors [histologically different 
from primary tumor]). 
5.6.1.7. 
Adverse Event Intensity 
The severity, or intensity, of an AE refers to the extent to which an AE affects the participant’s 
daily activities. The intensity of all unsolicited AEs will be graded by the investigator according 
to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 
(NIAID 2017). The DAIDS grading table provides an AE severity grading scale ranging from 
grades 1 to 5 with descriptions for each AE based on the following general guidelines: 
• Grade 1 indicates a mild event 
• Grade 2 indicates a moderate event 
• Grade 3 indicates a severe event 
• Grade 4 indicates a potentially life-threatening event 
• Grade 5 indicates death (Note: This grade is not specifically listed on each page of the 
grading table.) 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity for the experience should be noted. If the intensity category changes over a number of 
days, those changes should be recorded separately (with distinct onset dates). For SAEs, only 
one instance of the event would be reported with the highest severity grade. 
Missing severity is not imputed. 
5.6.1.8. 
Relationship of Adverse Events to Study Drug 
All ISRs (solicited AEs) are considered related to study drug. 
The investigator will assess causality (ie, whether there is a reasonable possibility that the study 
drug caused the event) for all unsolicited AEs. The relationship will be characterized using the 
following classification: 
• Not related: There is not a reasonable possibility of a relationship to the study drug. The 
participant did not receive the study drug, temporal sequence of the AE onset relative to 
administration of the study drug is not reasonable, OR the AE is more likely explained by 
another cause than the study drug. 
• Related: There is a reasonable possibility of a relationship to the study drug. There is 
evidence of exposure to the study dug. The temporal sequence of the AE onset relative to the 
administration of the study drug is reasonable. The AE is more likely explained by the study 
drug than by another cause. 
If relationship is missing for an event, the event will be categorized as Related. 
5.6.1.9. 
Analysis of Adverse Events and Injection Site Reactions  
All AE and ISR analyses will be performed using the Safety Set. For all analyses of AEs/ISRs, if 
the same AE/ISR (based on PT) is reported for the same participant more than once, the AE/ISR 


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is counted only once for the PT and at the highest severity and by relationship to study drug. 
Percentages will be calculated out of the number of participants in the Safety Set. Missing and 
incomplete dates of AEs will be imputed as described in Appendix A. In addition to safety 
summaries, listings of AEs (with TEAE designated by *), SAEs, and ISRs will be presented.  
Safety summaries through Month 14 will be presented. All summaries by SOC and PT will be 
sorted by descending participant count of SOC/PT in the ADG20 arm.  
The AE/ISR summaries listed below will be provided: 
• Overall summary of AEs (solicited and unsolicited) including the number/percentage of 
participants with:  
− a pre-treatment AE 
− a TEAE (and separately for unsolicited and solicited TEAEs)  
− a study drug related TEAE 
− a ≥Grade 3 TEAE 
− an SAE 
− a study drug related SAE 
− a TEAE leading to death  
− an MAAE 
− any hypersensitivity reaction (and separately for any hypersensitivity reaction through 
Day 4 [AESI]) 
• Incidence of TEAEs (including solicited ISRs) by SOC, PT, and treatment group  
• Incidence of TEAEs (including solicited ISRs) occurring in >2% of participants in either arm 
by SOC, PT, and treatment group 
• Incidence of MAAEs by SOC, PT, and treatment group 
• Incidence of study drug related TEAEs (including solicited ISRs) by SOC, PT, and treatment 
group 
• Incidence of TEAEs (including solicited ISRs) by maximum severity by SOC, PT, and 
treatment group 
• Incidence of study drug related TEAEs (including solicited ISRs) by maximum severity by 
SOC, PT, and treatment group 
• Incidence of solicited AEs (ISRs) by maximum severity based on the FDA toxicity scale 
through Day 4  
• Incidence of SAEs by SOC, PT, and treatment group 
• Incidence of hypersensitivity reactions by SOC, PT, and treatment group  
• Incidence of hypersensitivity reactions by maximum severity by SOC, PT, and treatment 
group 


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5.6.2. 
Clinical Laboratory Evaluations 
Laboratory assessments will be performed by a central laboratory and results will be graded at 
the laboratory according to DAIDS criteria, if applicable.  
Descriptive statistics (based on SI units) for clinical laboratory test results (hematology, serum 
chemistry, and coagulation) will be presented by treatment group and time point assessed. 
Descriptive statistics for the change from baseline to each post-baseline time point for the 
laboratory parameters will also be summarized by treatment group. In addition, the number and 
percentage of participants with potentially clinically significant (PCS) laboratory parameters will 
be summarized for any time post-baseline and by time point assessed.  
A shift table of the DAIDS toxicity grading from baseline to worst post-baseline will be 
provided. For tests with both high and low DAIDS toxicity criteria, shift will be summarized 
separately for the high and low direction. A PCS value is defined as any DAIDS grade 4 post-
baseline or any increase of 2 or more DAIDS grades post-baseline, except for PCS low creatinine 
clearance, which is defined as any DAIDS Grade 4 post-baseline or any DAIDS grade shift from 
0 to 3. Laboratory parameters not graded by DAIDS will be defined as PCS based on the criteria 
in Table 9. 
Table 9. 
PCS Criteria for Clinical Laboratory Tests Not Graded by DAIDS 
Parameter 
SI Unit 
PCS Low Limit 
PCS High Limit 
Basophils percent 
% 
— 
>4.0 × ULN 
Eosinophils percent 
% 
— 
>4.0 × ULN 
Monocytes percent 
% 
— 
>4.0 × ULN 
Hematocrit 
% 
<0.6 × baseline 
>1.3 × ULN 
Blood urea nitrogen 
mmol/L 
— 
>1.3 × ULN 
Chloride 
mmol/L 
<0.8 × LLN 
>1.1 × ULN 
Protein, total 
g/L 
<0.8 × LLN 
>1.2 × ULN 
LLN=lower limit of normal; PCS=potentially clinically significant; ULN=upper limit of normal. 
All clinical laboratory values for participants with PCS will be provided in listings. 
5.6.3. 
Vital Sign Measurements 
Descriptive statistics for vital signs and for the change from baseline to each post-baseline time 
point will be presented by treatment group. The number and percentage of participants with a 
PCS vital sign parameter will be provided for any time post-baseline and by time point assessed. 
A PCS value is defined as meeting both criterion value and change from baseline provided in 
Table 10. 


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Table 10. 
PCS Criteria for Vital Signs 
Vital Sign Parameter (Unit) 
Flag 
Criterion Value 
Change from Baseline 
Systolic blood pressure 
(mmHg) 
High (CH) 
≥180 
Increase of ≥20 mmHg 
Low (CL) 
≤90 
Decrease of ≥20 mmHg 
Diastolic blood pressure 
(mmHg) 
High (CH) 
≥105 
Increase of ≥15 mmHg 
Low (CL) 
≤50 
Decrease of ≥15 mmHg 
Heart Rate (bpm) 
High (CH) 
≥120 
Increase of ≥15 bpm 
Low (CL) 
≤50 
Decrease of ≥15 bpm 
Temperature (°C) 
High (CH) 
≥38 °C 
Increase of ≥1 °C  
Low (CL) 
<35 °C 
Decrease of ≥1 °C  
Respiratory Rate (breaths/min) 
High (CH) 
≥30 breaths/min 
Increase of ≥10 breaths/min 
Low (CL) 
≤8 breaths/minute 
Decrease of ≥4 breaths/minute 
Oxygen Saturation (SpO2) 
Low (CL) 
≤93% 
Decrease of ≥3% 
bpm=beats per minute; CH=clinically high; CL=clinically low. 
All vital sign data by participant for in-person visit will be presented in a listing. 
5.6.4. 
Other Safety Data 
Physical examination results will be included in data listings. Pregnancy testing data will be 
provided in a listing for all female participants. 
6. 
PHARMACOKINETIC ANALYSES 
All PK listings, individual concentration-time profiles, PK tables and figures, and all statistical 
analyses will be presented using the PK analysis set.  
6.1. 
 
Data Handling 
Data rounding specifications for PK data are documented in the PK TLF shells. Handling of 
missing data is detailed in Section 4.1.  
6.2. 
 
Serum Concentrations  
Serial blood samples will be collected at the following time points (with collection window) for 
PK assessment: 
• Day 1 at baseline (predose) 
• Day 8 (±2 days), Day 28 (+5 days), 6 months (±2 weeks), 12 months (±2 weeks) 
Individual serum concentrations of ADG20 will be presented in data listings and summarized 
separately using descriptive statistics (number of observations, arithmetic mean, SD, CV, 
geometric mean, geometric mean CV%, median, minimum, and maximum) by time point. 


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Individual serum concentrations will be plotted by actual time on both linear and 
semi-logarithmic scales. Mean (SD) serum concentrations will be plotted by part, treatment, 
nominal time on both linear and semi-logarithmic scales. 
6.3. 
Serum Pharmacokinetic Parameters 
Serum concentration-time data will be analyzed by non-compartmental analysis using Phoenix® 
WinNonlin® Version 8.3 or higher (Certara USA, Inc., Princeton, NJ). The PK parameters to be 
calculated for ADG20, where data permit, are listed in Table 11. 
Table 11. 
Calculated PK Parameters 
Parameter 
Definition 
Cmax 
Maximum observed concentration. 
Tmax 
Time of maximum observed concentration. 
AUC0-last 
AUC from time 0 to the last measurable observed concentration (Ct), calculated using the linear 
trapezoidal rule. 
AUC0-inf 
AUC from time 0 extrapolated to infinity, calculated as [AUC0-last + (Ct / λz)]. 
T1/2 
Apparent terminal elimination half-life, calculated as: ln (2) / λz. 
CL/F 
Apparent total body clearance, calculated as: Dose / AUC0-inf. 
Vd/F 
Apparent volume of distribution during the terminal phase (for IM dose), calculated as:  
Dose / [λz × AUC0-inf]. 
In addition to the PK parameters shown in Table 11, which will be listed and summarized, the 
parameters in Table 12 will also be listed to document the selection of data points used to 
estimate T1/2 using non-compartmental procedures.  
Table 12. 
PK Parameters for Data Selection 
Parameter 
Definition 
λz 
Apparent terminal elimination rate constant, where λz is the magnitude of the slope of the linear 
regression of the log concentration versus time profile during the terminal phase 
Number 
points 
Number of data points used to estimate λz; a minimum of 3 data points must be used, and Cmax 
must not be included 
λz lower 
Lower bound used for the estimation of λz 
λz upper 
Upper bound used for the estimation of λz 
Rsq (R2) 
R2, the coefficient of determination (goodness of fit statistic); λz and all associated parameters will 
only be reported where R2 ≥0.80 
%AUCext 
Percentage of AUC0-inf due to extrapolation; AUC0-inf, CL/F and Vd/F values will be flagged and 
excluded from summary statistics where %AUCext >20% 
Actual sampling times will be used for the estimation of all serum PK parameters, and all 
concentrations will be included in the analysis (including concentrations collected outside 
predefined collection windows). 
Serum PK parameters will be presented in data listings and summarized separately using 
descriptive statistics (number of observations, arithmetic mean, SD, CV, geometric mean, 


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geometric CV, median, minimum, and maximum) by part, treatment. Tmax will be summarized 
using number of observations, median, minimum, and maximum only. 
7. 
IMMUNOGENICITY ANALYSIS 
Immunogenicity analysis will be conducted in the Immunogenicity Set. ADA status will be 
defined as positive or negative based on the confirmatory assay. Baseline (predose Day 1) and 
Day 28, Month 6, and Month 12 ADA results will be summarized by treatment arm. 
Treatment emergent ADA is defined as participants who had a negative ADA measurement at 
baseline (predose Day 1) and positive ADA post-baseline or participants who had a positive 
ADA measurement at baseline and a positive ADA measurement post-baseline with an ADA 
titer ≥4 times the baseline ADA titer. The number and percentage of participants with treatment-
emergent ADA will be summarized by treatment group. 
8. 
CHANGES IN THE PLANNED ANALYSIS 
There are no changes to the analyses presented in the protocol. 


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9. 
REFERENCES 
Ge M, Durham LK, Meyer D, et al. (2011). Covariate-Adjusted Difference in Proportions from 
Clinical Trials Using Logistic Regression and Weighted Risk Differences. Drug Inf J. 45(4): 
481-493. doi:10.1177/009286151104500409. 
NIAID. (2017). Division of AIDS (DAIDS) Table for Grading the Severity of Adult and 
Pediatric Adverse Events. Version 2.1 July 2017.  Retrieved 18 December 2020, from 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf. 
 


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10. 
APPENDICES 


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APPENDIX A. IMPUTATION RULES FOR MISSING DATES OF 
MEDICATIONS AND ADVERSE EVENTS 
For missing dates of medications or AEs, the most conservative approach will be systematically 
considered. If the AE onset date is missing/incomplete, it is assumed to have occurred during the 
treatment or follow-up phase (ie, considered a TEAE) except if the partial onset date or other 
data, such as the stop date, indicates differently. Similarly, a medication with partial start and 
stop dates could be considered either a prior or concomitant treatment. 
The following algorithms will be applied to missing and incomplete start and stop dates: 
Start Dates 
• If the day portion of the start date is missing, then the start date will be estimated to be equal 
to the date of the first dose of study drug, provided the start month and year are the same as 
the first dose of study drug and the stop date is either after the first dose of study drug or 
completely missing. Otherwise, the missing day portion will be estimated as “01.” 
• If both the day and month portions of the start date are missing, then the start date will be 
estimated to be equal to the date of the first dose of study drug, provided the start year is the 
same as the first dose of study drug and the stop date is either after the first dose of study 
drug or completely missing. Otherwise, the event will be assumed to start on the first day of 
the given year (eg, xx-xxx-2013 is estimated as 01-JAN-2013). 
• If the start date is completely missing and the stop date is either after the first dose of study 
drug or completely missing, then the start date will be estimated to be equal to the date of the 
first dose of study drug. Otherwise, the start date will be estimated to be the first day of the 
same year as the stop date. 
Stop Dates 
• If only the day of resolution is unknown, the day will be assumed to be the last of the month 
(eg, xx-JAN-2013 will be treated as 31-JAN-2013).  
• If both the day and month of resolution are unknown, the event will be assumed to have 
ceased on the last day of the year (eg, xx-xxx-2013 will be treated as 31-DEC-2013).  
• If the stop date is completely missing or the event is continuing, the event will be assumed to 
be after first dose of study drug, and the stop date will not be imputed. 
• Missing or partial end dates will not be imputed for AEs. 
 


Adintrevimab (ADG20) 
 
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-PREV-001 
Confidential 
Version 1.0, 02 March 2022 
Page 43 of 44 
APPENDIX B. ALGORITHM OF LOGISTIC REGRESSION METHOD 
The method described in Ge et al. (2011) computes a population-level estimate for the treatment 
difference (in terms of risk difference in proportions) and supports an adjustment for the pre-
defined prognostic factors.  
With a data set of n participants,  
binary response vector Y = (y1, y2, ..., yn)’,  
covariate matrix X = (x1, x2, …, xn)’,  
a logistic regression model assumes logit[P(yi = 1 | xi)] = β’xi, where logit(p) = ln[p/(l - p)].  
Let b denote the maximum likelihood estimate (MLE) of β, and its estimated variance-
covariance matrix is V. The proportions of responders to both treatment and control, and their 
risk difference are estimated as follows.  
First, create the new covariate matrix Xt from X by adjusting the column corresponding to 
treatment assignment such that all participants are in the treated group. Then calculate the vector 
of estimated probabilities of response to treatment P෡t from Xt and b, P෡t = logit -1 (Xt b)]. Similarly, 
assume each participant is assigned to control and redo the above steps to get Xc and P෡c.  
Estimate Risk Difference (RD):  
𝑅𝑅𝑅𝑅= ෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛−෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
𝑛𝑛
𝑖𝑖=1
 
where 𝑃𝑃෠𝑡𝑡𝑡𝑡 and 𝑃𝑃෠𝑐𝑐𝑐𝑐 are the ith elements of 𝑃𝑃෠𝑡𝑡 and 𝑃𝑃෠𝑐𝑐 respectively.  
The variance of the estimated risk difference:  
𝑉𝑉𝑉𝑉𝑉𝑉(𝑅𝑅𝑅𝑅) = 𝑉𝑉𝑉𝑉𝑉𝑉(෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛) −
𝑛𝑛
𝑖𝑖=1
 2𝑐𝑐𝑐𝑐𝑐𝑐൭෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
, ෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൱+ 𝑉𝑉𝑉𝑉𝑉𝑉(෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛)
𝑛𝑛
𝑖𝑖=1
 
The delta method can be used to estimate each component of the variance estimation.  
Define At as a vector with elements Ati = P෡ti൫1 −P෡ti൯.  
Similarly define Ac as a vector with elements Aci = P෡ci൫1 −P෡ci൯.  
dt = (At’Xt)/n 
dc = (Ac’Xc)/n 
SE = √(dtVdt’ + dcVdc’ - 2 dcVdt’) 
The confidence interval of RD is RD ± Z(1-α/2) SE 


Adintrevimab (ADG20) 
 
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-PREV-001 
Confidential 
Version 1.0, 02 March 2022 
Page 44 of 44 
Estimate Log Risk Ratio (RR):  
𝛿𝛿1 =  log (𝑅𝑅𝑅𝑅) = 𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛−𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
𝑛𝑛
𝑖𝑖=1
 
where 𝑃𝑃෠𝑡𝑡𝑡𝑡 and 𝑃𝑃෠𝑐𝑐𝑐𝑐 are the ith elements of 𝑃𝑃෠𝑡𝑡 and 𝑃𝑃෠𝑐𝑐 respectively.  
The variance of the estimated log risk ratio:  
𝑉𝑉𝑉𝑉𝑉𝑉(𝛿𝛿1) = 𝑉𝑉𝑉𝑉𝑉𝑉(𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛) −
𝑛𝑛
𝑖𝑖=1
 2𝑐𝑐𝑐𝑐𝑐𝑐൭𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
, 𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൱+ 𝑉𝑉𝑉𝑉𝑉𝑉(𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛)
𝑛𝑛
𝑖𝑖=1
 
Since,  
𝑉𝑉𝑉𝑉𝑉𝑉൭𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൱≈൮
1
∑
𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൲
2
𝑉𝑉𝑉𝑉𝑉𝑉൭෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൱≈൮
1
∑
𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൲
2
𝑑𝑑𝑡𝑡𝑉𝑉𝑉𝑉𝑡𝑡
′ 
𝑉𝑉𝑉𝑉𝑉𝑉൭𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൱≈൮
1
∑
𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൲
2
𝑉𝑉𝑉𝑉𝑉𝑉൭෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൱≈൮
1
∑
𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൲
2
𝑑𝑑𝑐𝑐𝑉𝑉𝑉𝑉𝑐𝑐
′ 
2𝑐𝑐𝑐𝑐𝑐𝑐൭𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
, 𝑙𝑙𝑙𝑙𝑙𝑙෍𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൱≈2 ൮
1
∑
𝑃𝑃෠𝑡𝑡𝑡𝑡
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൲൮
1
∑
𝑃𝑃෠𝑐𝑐𝑐𝑐
𝑛𝑛
𝑛𝑛
𝑖𝑖=1
൲𝑑𝑑𝑐𝑐𝑉𝑉𝑉𝑉𝑡𝑡
′ 
 
SE(δ1) = √Var(δ1) 
The confidence interval of logRR is δ1± Z(1-α/2) SE(δ1).  
The confidence interval of RR is exp(δ1± Z(1-α/2) SE(δ1)). 
The relative risk reduction and its confidence interval is  
(1 – exp(δ1)) and [1 - exp(δ1+ Z(1-α/2) SE(δ1)), 1 - exp(δ1– Z(1-α/2) SE(δ1))].