Clinical trial NCT04805671
Conditions: COVID-19
Sponsor: Invivyd, Inc.
Start date: 2021-07-26; Completion date: 2022-11-03
Enrollment: 399 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This placebo controlled study is intended to generate safety and efficacy data in order to provide a treatment option for COVID-19 in patients with a high risk of disease progression based on age or co-morbid medical conditions.

Detailed description:

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: Normal saline
Intervention descriptions: intervention 1: Single dose of ADG20 intervention 2: Single dose of normal saline

Protocol documents:
Prot_000.pdf: 
Protocol 
 
Study ID: ADG20-TRMT-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 Treatment of Ambulatory Participants with 
Mild or Moderate COVID-19 (STAMP) 
 
NCT ID: NCT04805671 
 
IND Identifier: 152327 
 
EudraCT Identifier: 2020-006082-11 
 
Date of Document: 02-March-2022 




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DOCUMENT REVISION HISTORY 
Document 
Date of Issue 
Overall Rationale 
Version 1.0 
11 January 2021 
Original Protocol. No participants were enrolled under this version 
of the protocol. 
Version 2.0 
18 February 2021 
Update the protocol objectives, endpoints, and study population 
based on US FDA feedback. No participants were enrolled under 
this version of the protocol. 
Version 3.0 
12 April 2021 
Revise the study design, sample size, and inclusion criteria based on 
evolving data. No participants were enrolled under this version of 
the protocol. 
Version 4.0 
06 May 2021 
Remove the Phase 1 lead-in and IV dosing from the study. Revise 
the planned total enrollment and clarify that enrollment would not 
pause between Phases 2 and 3 of the study. Update the SAP to 
reflect removal of Phase 1 and interim analysis modifications. 
Protocol Version 4.0 was implemented prior to enrollment of the 
first participant in the study. 
Version 5.0 
23 November 2021 
Revise the planned total enrollment to 900 participants and update 
inclusion criteria related to conditions considered high risk for 
disease progression to include a larger study population. Update the 
SAP with regards to sample size, timing of interim analysis, and to 
reflect minor adjustments to objectives/endpoints. Protocol 
Version 5.0 was submitted to the US FDA only and was not 
implemented at study sites.  
Version 6.0 
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 in the study. Update the SAP to reflect 
changes to the analysis plan due to the emergence of Omicron, 
including analysis of data collected in participants infected with a 
non-Omicron variant of SARS-CoV-2.  
Version 5.0 of the protocol was not submitted to sites/IRBs. 
Enrollment in the study has been suspended (as of 11-JAN-2022) 
and no further participants are expected to be enrolled under 
Version 6.0 of the protocol; therefore, updates to the total planned 
sample size and updates to inclusion criteria to expand the 
population for the study that were included in Version 5.0 of the 
protocol were removed in Version 6.0.  
 




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DECLARATION OF INVESTIGATOR 
I have read and understood all sections of the protocol entitled “A Phase 2/3 Randomized, 
Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of ADG20 in the 
Treatment of Ambulatory Participants with Mild or Moderate COVID-19 (STAMP)” and the 
accompanying Investigator’s Brochure. 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Final Protocol Version 6.0, dated 02 March 2022, the International Council 
for Harmonisation guideline E6(R2): Good Clinical Practice and all applicable government 
regulations. I will not make changes to the protocol before consulting with Adagio Therapeutics 
or implement protocol changes without independent ethics committee approval except to 
eliminate an immediate risk to participants. I agree to administer study treatment only to 
participants under my personal supervision or the supervision of a subinvestigator. 
I will not supply the study drug to any person not authorized to receive it. Confidentiality will be 
protected. Participant identity will not be disclosed to third parties or appear in any study reports 
or publications. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without authorization from Adagio Therapeutics, Inc. 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
Printed Name of Principal Investigator 
 
 


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CONTACT INFORMATION FOR SAE REPORTING  
Any AE that meets SAE criteria (Section 6.4.6.1.2) must be reported to 
 Pharmacovigilance 
immediately (ie, within 24 hours) after site personnel first learn of the event. The following 
contact information is to be used for SAE reporting:  
 
 
 
 
 
  
 
 
  
 
 
 
 
  
 
 
  
 
 


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TABLE OF CONTENTS 
DOCUMENT REVISION HISTORY .............................................................................................2 
PROTOCOL APPROVAL – SPONSOR SIGNATORY ................................................................3 
DECLARATION OF INVESTIGATOR .........................................................................................4 
CONTACT INFORMATION FOR SAE REPORTING .................................................................5 
TABLE OF CONTENTS .................................................................................................................6 
LIST OF TABLES .........................................................................................................................10 
LIST OF FIGURES .......................................................................................................................11 
PROTOCOL SYNOPSIS...............................................................................................................12 
LIST OF ABBREVIATIONS ........................................................................................................23 
PHARMACOKINETIC ABBREVIATIONS ................................................................................25 
1. 
INTRODUCTION ......................................................................................................26 
1.1. 
ADG20 Background ...................................................................................................26 
1.1.1. 
Nonclinical Studies of ADG20 ...................................................................................26 
1.1.2. 
Clinical Studies of ADG20 .........................................................................................26 
1.1.2.1. 
Study ADG20-1-001 ...................................................................................................27 
1.1.2.2. 
Study ADG20-PREV-001 (EVADE) .........................................................................27 
1.2. 
Background on COVID-19 .........................................................................................27 
1.3. 
Study Rationale ...........................................................................................................29 
1.3.1. 
Rationale for Use of a Monoclonal Antibody .............................................................29 
1.3.2. 
Rationale for Study Design .........................................................................................30 
1.3.2.1. 
Rationale for Dose Selection ......................................................................................32 
1.4. 
Risks and Benefits ......................................................................................................34 
1.4.1. 
Target Study Population and Risk/Benefit Assessment .............................................34 
1.4.2. 
Risks from Study Participation ...................................................................................34 
1.4.3. 
Overall Benefit-Risk Conclusion ................................................................................36 
2. 
STUDY OBJECTIVES, ENDPOINTS, AND DEFINITIONS ..................................37 
2.1. 
Objectives and Endpoints ...........................................................................................37 
2.2. 
Definitions ..................................................................................................................39 
2.2.1. 
SARS-CoV-2 Variant Determination .........................................................................39 
2.2.2. 
COVID-19 Severity Categorization ...........................................................................39 
2.2.3. 
COVID-19-Related Medically Attended Visits ..........................................................41 


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2.2.4. 
COVID-19-Related Hospitalization ...........................................................................41 
2.2.5. 
COVID-19-Related Mortality .....................................................................................41 
2.2.6. 
Time to Sustained Resolution of COVID-19 Symptoms ...........................................41 
3. 
INVESTIGATIONAL PLAN FOR ADG20-TRMT-001 PROTOCOL ....................41 
3.1. 
Study Design ...............................................................................................................41 
3.1.1. 
Study Duration ............................................................................................................42 
4. 
PARTICIPANT SELECTION AND WITHDRAWAL CRITERIA .........................43 
4.1. 
Selection of Study Participants ...................................................................................43 
4.1.1. 
Inclusion Criteria ........................................................................................................43 
4.1.2. 
Exclusion Criteria .......................................................................................................46 
4.1.3. 
Screen Failures ............................................................................................................47 
4.2. 
Discontinuation of Study Drug or Withdrawal from the Study ..................................47 
4.2.1. 
Premature Discontinuation from Study Drug .............................................................47 
4.2.2. 
Premature Withdrawal from the Study .......................................................................48 
4.2.3. 
Replacements ..............................................................................................................49 
5. 
STUDY TREATMENTS ............................................................................................49 
5.1. 
Method of Assigning Participants to Treatment Groups ............................................49 
5.2. 
Treatments Administered ............................................................................................49 
5.3. 
Identity of Study Drug ................................................................................................50 
5.4. 
Management of Clinical Supplies ...............................................................................50 
5.4.1. 
Study Drug Packaging and Labeling ..........................................................................50 
5.4.2. 
Storage and Handling Instructions ..............................................................................50 
5.4.3. 
Study Drug Accountability .........................................................................................51 
5.5. 
Blinding ......................................................................................................................51 
5.5.1. 
Breaking the Blind ......................................................................................................52 
5.6. 
Prior and Concomitant Medications and Treatments .................................................52 
5.6.1. 
Prior Therapy ..............................................................................................................52 
5.6.2. 
Concomitant Therapy .................................................................................................52 
5.6.2.1. 
Prohibited Concomitant Therapy ................................................................................53 
5.6.2.2. 
COVID-19 Vaccination ..............................................................................................54 
5.6.2.3. 
Allowed Concomitant Therapy ...................................................................................54 
6. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................55 


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6.1. 
Screening Procedures ..................................................................................................55 
6.2. 
Day 1 Procedures ........................................................................................................56 
6.3. 
Efficacy Assessments .................................................................................................57 
6.3.1. 
Participant At-Home Assessments/Collections ..........................................................57 
6.3.1.1. 
Daily COVID-19 Symptom Diary ..............................................................................57 
6.3.1.2. 
Saliva Collection for SARS-CoV-2 Quantitative RT-PCR ........................................57 
6.3.1.3. 
Daily Temperature, Blood Oxygen Saturation, and Heart Rate .................................58 
6.3.2. 
Site Clinical Assessments ...........................................................................................58 
6.3.2.1. 
COVID-19 Symptom Diary, Reported Vitals Review, and Injection Site 
Reaction Diary Review ...............................................................................................58 
6.3.2.2. 
COVID-19 Severity Assessment ................................................................................59 
6.3.2.3. 
Survival Assessment ...................................................................................................59 
6.3.2.4. 
Medically Attended Visits Assessment ......................................................................59 
6.3.2.5. 
Long-Term Health Status Assessment ........................................................................60 
6.3.2.6. 
Household Transmission Questionnaire .....................................................................60 
6.4. 
Safety Assessments .....................................................................................................60 
6.4.1. 
Safety Monitoring After Study Drug Administration .................................................61 
6.4.1.1. 
Injection Site Reaction Monitoring and Management ................................................61 
6.4.1.2. 
Injection Site Reaction Diary ......................................................................................62 
6.4.2. 
Clinical Safety Laboratory Assessments ....................................................................62 
6.4.3. 
Physical Examinations ................................................................................................63 
6.4.4. 
Targeted Review of Changes in Health ......................................................................63 
6.4.5. 
Vital Signs ..................................................................................................................63 
6.4.6. 
Adverse Events ...........................................................................................................63 
6.4.6.1. 
Definitions ..................................................................................................................63 
6.4.6.2. 
Eliciting and Documenting Adverse Events ...............................................................65 
6.4.6.3. 
Reporting Adverse Events ..........................................................................................67 
6.4.6.4. 
Follow-Up of Participants Reporting Adverse Events ...............................................70 
6.4.7. 
Pregnancy ...................................................................................................................70 
6.4.8. 
Treatment of Overdose ...............................................................................................71 
6.5. 
Blood Collection and Nasopharyngeal Swabs ............................................................71 
6.6. 
Pharmacokinetics ........................................................................................................71 


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6.7. 
Immunogenicity ..........................................................................................................72 
6.8. 
Unscheduled Visits .....................................................................................................72 
6.8.1. 
COVID-19 Unscheduled Visits (Worsening, Relapse, or Recurrence) ......................72 
6.8.2. 
Hypersensitivity Reaction Assessment Unscheduled Visit ........................................72 
6.8.3. 
Other Unscheduled Visits ...........................................................................................73 
6.9. 
Administrative Procedures ..........................................................................................73 
6.9.1. 
Visit Type Requirements ............................................................................................73 
6.9.2. 
Use of eDiary ..............................................................................................................73 
6.9.3. 
Collection and Update of Contacts .............................................................................74 
7. 
STATISTICAL CONSIDERATIONS .......................................................................74 
7.1. 
Sample Size Determination ........................................................................................74 
7.2. 
Analysis Sets ...............................................................................................................75 
7.3. 
Subgroups of Interest ..................................................................................................76 
7.4. 
Statistical Analyses .....................................................................................................76 
7.5. 
Multiplicity Adjustments ............................................................................................76 
7.6. 
Main Estimation Utilizing the Primary Efficacy Endpoint ........................................77 
7.7. 
Main Estimation Utilizing Key Secondary Efficacy Endpoints .................................77 
7.8. 
Analyses of Other Secondary Efficacy Endpoints ......................................................78 
7.9. 
Analyses of Exploratory Endpoints ............................................................................79 
7.10. 
Pharmacokinetic Analyses ..........................................................................................80 
7.11. 
Safety Analyses ..........................................................................................................80 
7.12. 
Immunogenicity ..........................................................................................................80 
7.13. 
Safety Monitoring and Interim Analyses ....................................................................80 
8. 
DATA QUALITY ASSURANCE ..............................................................................82 
8.1. 
Data Management .......................................................................................................82 
9. 
ETHICS ......................................................................................................................82 
9.1. 
Independent Ethics Committee or Institutional Review Board ..................................82 
9.2. 
Ethical Conduct of the Study ......................................................................................83 
9.3. 
Participant Information and Consent/Assent ..............................................................83 
10. 
INVESTIGATOR’S OBLIGATIONS ........................................................................84 
10.1. 
Confidentiality ............................................................................................................84 
10.2. 
Data Protection ...........................................................................................................84 


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10.3. 
Financial Disclosure and Obligations .........................................................................84 
10.4. 
Investigator Documentation ........................................................................................84 
10.5. 
Study Conduct ............................................................................................................85 
10.6. 
Adverse Events and Study Report Requirements .......................................................85 
10.7. 
Investigator’s Final Report .........................................................................................85 
10.8. 
Records Retention .......................................................................................................85 
10.9. 
Publication Policy .......................................................................................................85 
10.10. 
Study Management .....................................................................................................85 
10.11. 
Independent Data Monitoring Committee ..................................................................86 
10.12. 
Monitoring ..................................................................................................................86 
10.12.1. 
Monitoring of the Study ..............................................................................................86 
10.12.2. 
Inspection of Records .................................................................................................87 
10.13. 
Management of Protocol Amendments and Deviations .............................................87 
10.13.1. 
Modification of the Protocol .......................................................................................87 
10.13.2. 
Protocol Deviations ....................................................................................................87 
10.14. 
Study Termination ......................................................................................................88 
10.15. 
Final Report ................................................................................................................88 
11. 
REFERENCES ...........................................................................................................89 
12. 
APPENDICES ............................................................................................................95 
12.1. 
Appendix: Schedule of Assessments ..........................................................................95 
12.2. 
Appendix: COVID-19 Symptom Diary ......................................................................99 
12.3. 
Appendix: Injection Site Reaction Diary ..................................................................100 
12.4. 
Appendix: Clinical Laboratory Tests ........................................................................101 
12.5. 
Appendix: Country-Specific Requirements ..............................................................102 
12.5.1. 
Germany-Specific Requirements ..............................................................................102 
 
LIST OF TABLES 
Table 2-1: Objectives and Endpoints ...........................................................................................37 
Table 5-1: Details for Study Drug ................................................................................................50 
Table 6-1: Safety Monitoring After Study Drug Administration .................................................61 
Table 6-2 DAIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events – Systemic .......................................................................................................66 


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Table 7-1: Defined Analysis Sets and Descriptions .....................................................................75 
Table 7-2: Analyses of Other Secondary Efficacy Endpoints ......................................................78 
Table 7-2: Safety Monitoring and Interim Analyses ....................................................................81 
Table 10-1: Pausing Guidelines .....................................................................................................86 
Table 12-1: Schedule of Assessments ............................................................................................96 
 
LIST OF FIGURES 
Figure 3-1: Study Design Schematic for ADG20-TRMT-001 ......................................................42 
 


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PROTOCOL SYNOPSIS 
Sponsor: 
Adagio Therapeutics, Inc. 
Protocol No. 
ADG20-TRMT-001 
Title of Study: 
A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial 
to Evaluate the Efficacy and Safety of ADG20 in the Treatment of 
Ambulatory Participants with Mild or Moderate COVID-19 
(STAMP) 
Study Drug: 
ADG20 
Study Phase: 
2/3 
Indication 
COVID-19 
US IND No. 
152327 
EudraCT No. 
2020-006082-11 
No. of Sites/Location: 
Approximately 100 to 115 sites / global 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of ADG20 compared 
to placebo in the treatment of mild or moderate 
COVID-19 in participants at high risk of 
disease progression 
COVID-19-related hospitalization or all-cause death through 
Day 29 
To evaluate the safety and tolerability of 
ADG20 compared to placebo through Day 29 
in participants with mild or moderate 
COVID-19 and high risk of disease progression 
Assessment of safety through Day 29 based on: 
• 
The incidence of TEAEs 
• 
Incidence of solicited injection site reactions through 
Day 4  
• 
Changes from baseline in clinical laboratory tests (ie, CBC 
with differential, serum chemistry, coagulation)  
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure) 
Secondary  
To evaluate the effect of ADG20 on the 
following clinical parameters in participants 
with mild or moderate COVID-19 and high risk 
of disease progression 
• 
Severity of COVID-19 
• 
COVID-19-related emergency room visits, 
COVID-19-related hospitalizations, or 
all-cause death 
• 
Severe/critical COVID-19 or all-cause death through 
Day 29 
• 
COVID-19-related emergency room visits, COVID-19-
related hospitalization, or all-cause death through Day 29 
• 
Time to sustained resolution of COVID-19 symptoms 
through Day 29 


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Objectives 
Endpoints 
• 
Time to sustained resolution of COVID-19 
symptoms 
• 
COVID-19-related medically attended 
visits 
• 
Time to sustained recovery of COVID-19 
symptoms 
• 
All-cause mortality 
• 
COVID-19-related medically attended visit (telemedicine, 
physician office, urgent care center, emergency room, 
hospitalization) or all-cause death through Day 29 
• 
Time to sustained recovery defined as sustained 
improvement or resolution of COVID-19 symptoms 
through Day 29 
• 
All-cause death through Day 29, Day 60, and Day 90  
To evaluate the effect of ADG20 on 
SARS-CoV-2 viral load and clearance in 
participants with mild or moderate COVID-19 
and high risk of disease progression 
• 
Change from baseline in SARS-CoV-2 viral load 
(log10 copies/mL) to Day 7 (±1) assessed by RT-qPCR 
from NP samples 
• 
Viral load >5 log10 copies/mL on Day 7 (±1) based on NP 
samples 
• 
Duration of SARS-CoV-2 viral shedding from Day 1 
through Day 29 assessed by RT-qPCR from saliva 
samples 
• 
Change from baseline in SARS-CoV-2 viral load 
(log10 copies/mL) to Days 3, 5, 7, 11, and 14 assessed by 
RT-qPCR from saliva samples 
• 
SARS-CoV-2 viral clearance (Days 5, 7, 11, 14, 21, and 
29) assessed by RT-qPCR from saliva samples (and NP 
samples for Day 7) 
• 
SARS-CoV-2 viral load AUC assessed by RT-qPCR from 
saliva samples from baseline to Day 29  
To evaluate the long-term safety and 
tolerability of ADG20 compared to placebo in 
participants with mild or moderate COVID-19 
and high risk of disease progression 
Assessment of safety based on: 
• 
The incidence of TEAEs 
• 
Changes from baseline in clinical laboratory tests (ie, CBC 
with differential, serum chemistry, coagulation)  
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure) 
To evaluate the PK of ADG20 following IM 
administration 
PK parameters of ADG20: As data permit, Cmax, Tmax,  
AUC0-last, AUC0-inf, CL, Vd, and T1/2  Additional PK parameters 
may be calculated as data permit 
To evaluate the immunogenicity (ADAs) to 
ADG20 
Incidence of ADAs against ADG20 
To evaluate the emergence of resistance to 
ADG20 
Genotypic characterization of viral isolates for reduced 
susceptibility to ADG20, with phenotypic evaluation as 
appropriate 
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; CBC=complete blood count; CL=clearance; 
Cmax=maximum plasma concentration; NP=nasopharyngeal; PASC=post-acute sequelae of SARS-CoV-2 infection; 
RT-(q)PCR=(quantitative) reverse transcription-polymerase chain reaction; TEAEs=treatment-emergent adverse events; 
t½=plasma concentration half-life; Tmax=time to reach Cmax; Vd=apparent volume of distribution. 
 


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Diagnosis and Main Criteria for Inclusion and Exclusion 
The study population will include adults (aged ≥18 years) and adolescents (aged 12 to <18 years) 
in both cohorts; enrollment of adolescents will begin upon sponsor communication to the sites 
following iDMC review of safety data in each cohort, and only in regions permitted by health 
authorities and local ethics committees. Participants with laboratory confirmed mild or moderate 
COVID-19 who are at high risk for disease progression will be included.   
Inclusion Criteria: 
Each participant must meet all of the following criteria to be enrolled in this study: 
1. Age: Is an adult aged 18 years and above, or is an adolescent aged 12 to 17 years (inclusive) 
and weighing ≥40 kg at the time of screening  
Note: Adolescent enrollment will open only upon sponsor communication to sites after 
iDMC review of safety data in adults, and only if permitted by the local health authority. 
2. Has had a SARS-CoV-2 positive antigen test, or by RT-PCR, or other locally approved 
molecular diagnostic assay obtained within 5 days prior to randomization.  
Note: A historical record of a positive result from a test conducted within 5 days prior to 
randomization is acceptable. SARS-CoV-2 antibody testing cannot be used for study 
eligibility. 
3. Has had initial onset of one or more of the following self-reported COVID-19-related signs 
or symptoms within 5 days prior to randomization: 
a. measured temperature ≥38 °C (100.4 °F) 
b. subjective fever (feeling hot or feverish) 
c. chills (shivering) 
d. cough 
e. sore throat 
f. congestion (stuffy or runny nose) 
g. shortness of breath or difficulty breathing with exertion worse than usual 
h. muscle or body aches 
i. fatigue (low energy or tiredness) 
j. headache 
k. loss of taste or smell 
l. nausea or vomiting 
m. diarrhea 
4. Has mild or moderate COVID-19 (per Section 2.2.2) with one or more of the following 
COVID-19-related signs or symptoms on the day of randomization: 
a. measured temperature ≥38 °C (100.4 °F) 


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b. subjective fever (feeling hot or feverish) 
c. chills (shivering) 
d. cough 
e. sore throat 
f. congestion (stuffy or runny nose) 
g. shortness of breath or difficulty breathing with exertion worse than usual 
h. muscle or body aches 
i. fatigue (low energy or tiredness) 
j. headache 
k. loss of taste or smell 
l. nausea or vomiting 
m. diarrhea 
5. Is at high risk of disease progression defined as: 
a. Age ≥55 years 
b. Age 18 to <55 years with one or more preexisting medical conditions as follows 
i. 
Obesity (body mass index [BMI] ≥30 kg/m2) 
ii. Diabetes (Type 1 or Type 2) 
iii. 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) 
iv. Chronic lung disease (emphysema/chronic obstructive pulmonary disease, chronic 
bronchitis, interstitial lung disease [including idiopathic pulmonary fibrosis], or 
cystic fibrosis) 
v. 
Cardiac disease (heart failure, coronary artery disease, or cardiomyopathies)  
vi. Sickle cell disease or thalassemia  
vii. Solid organ or blood stem cell transplant recipients 
viii. Other immunodeficiency due to underlying illness or immunosuppressant 
medication (eg, corticosteroids ≥20 mg/day prednisone or equivalent) 
ix. Down Syndrome 
x. 
Stroke or cerebrovascular disease, which affects blood flow to the brain 
xi. Substance use disorder 
xii. Pregnant (Enrollment of participants who are pregnant may only open upon sponsor 
communication to sites after iDMC review of data, and only in regions permitted by 
the local health authority) 


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c. Age 12 to 17 years (inclusive) with one or more preexisting medical conditions as 
follows 
i. 
BMI >85th percentile for age and sex based on United States Center for Disease 
Control (CDC) growth charts 
ii. 
Diabetes (Type 1 or Type 2) 
iii. 
Chronic kidney disease 
iv. 
Sickle cell disease or thalassemia 
v. 
Congenital or acquired heart disease 
vi. 
Neurodevelopmental disorders (eg, cerebral palsy, Down syndrome) 
vii. A medically-related technological dependence (eg, tracheostomy, gastrostomy, or 
positive pressure ventilation not related to COVID-19) 
viii. Asthma, reactive airway, or other chronic respiratory disease that requires daily 
medication for control  
ix. 
Solid organ or blood stem cell transplant recipients  
x. 
Other immunodeficiency due to underlying illness or immunosuppressant 
medication  
xi. 
Substance use disorder 
xii. Pregnant (Enrollment of participants who are pregnant may only open upon sponsor 
communication to sites after iDMC review of data, and only in regions permitted by 
the local health authority) 
6. Has been assigned female sex at birth and is of nonchildbearing potential. A female 
participant who is not of reproductive potential is eligible without requiring the use of 
contraception and pregnancy testing is not required. This includes female participants who 
have not undergone menarche or who are documented to be surgically sterile (eg, 
hysterectomy, or removal of both ovaries, or tubal ligation) or postmenopausal (ie, 
amenorrhea >1 year and FSH >40 mIU/mL). Follicle-stimulating hormone is not required in 
postmenopausal females with amenorrhea for >2 years 
7. Has been assigned female sex at birth and is of childbearing potential and fulfills all the 
following criteria:  
a. Has a negative urine or serum pregnancy test at Screening 
b. Has practiced adequate contraception for or has abstained from all activities that could 
result in pregnancy for at least 28 days prior to the first dose (Day 1) 
c. Has agreed to continue adequate contraception for sexual activity that could lead to 
pregnancy through 6 months following study drug administration 
d. Is not currently breastfeeding 
Note: Enrollment of participants who are pregnant or breastfeeding may open only upon 
sponsor communication to sites after iDMC review of Phase 2 data. 


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Adequate contraception for participants assigned female sex at birth is defined as consistent 
and correct use of a highly effective locally approved contraceptive method in accordance 
with local regulations for contraceptive use in clinical trial participants. For example: 
a. Intrauterine device (hormonal or non-hormonal) 
b. Hormonal contraceptive taken or administered via oral, transdermal, intravaginal, 
implantable, or injectable method  
c. Sterilization of a female participant’s monogamous male partner prior to entry into the 
study  
d. 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 
starting at the time of consent to participate in the study 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. Has been assigned male sex at birth with partner(s) of childbearing potential and agree to use 
contraception, per local regulations, through 6 months after dosing. If their partner is 
pregnant, males must agree to use a condom. No sperm donation is permitted through 
6 months after dosing. 
9. Is able to understand and comply with study requirements/procedures (if applicable, with 
assistance by caregiver, surrogate, or guardian/LAR) based on the assessment of the 
investigator.  
10. Is able and willing to provide informed consent. An LAR may be used only in cases where 
inclusion criterion 9 is able to be fulfilled. In the case of adolescents, informed assent must 
also be obtained as required by local guidelines. 
Exclusion Criteria: 
Participants meeting any of the following criteria will be excluded from the study: 
1. Is currently hospitalized or, in the opinion of the investigator, requires urgent medical 
attention or is anticipated to require hospitalization within 48 hours of randomization. 
2. Has oxygen saturation (SpO2) ≤93% on room air at sea level or ratio of arterial oxygen 
partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) 
<300 mmHg, respiratory rate ≥30 per minute, or heart rate ≥125 per minute. 
3. Is on supplemental oxygen therapy at the time of randomization for any reason or, in the 
opinion of the investigator, has an anticipated impending need for mechanical ventilation. 
4. Has a history of a positive SARS-CoV-2 antibody serology test. Note: serology testing is not 
required for study eligibility, exclusion criterion is based on known history only. 


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5. Has participated, within the last 30 days, in a clinical study involving an investigational 
intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 
30 days, whichever is longer, should have passed. 
6. Has known allergy/sensitivity or hypersensitivity to study drug, including excipients.  
7. Has received a SARS-CoV-2 vaccine, monoclonal antibody, or plasma from a person who 
recovered from COVID-19 any time prior to participation in the study.  
8. Has a known active co-infection (eg, influenza, urinary tract infection, etc). 
9. Has any serious concomitant systemic disease, condition, or disorder that, in the opinion of 
the investigator, might confound the results of the study or pose an additional risk to the 
participant by their participation in the study including, but not limited to, any co-morbidity 
requiring surgery or conditions considered life-threatening within 29 days. 
10. Has a clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet 
disorder), or prior history of significant bleeding or bruising following IM injections or 
venipuncture. Abnormal coagulation labs or use of anticoagulant medication are not 
exclusionary in the absence of clinical findings. 
11. Is or has an immediate family member (eg, spouse, sibling, child, guardian/LAR, parent) who 
is an investigator or site or sponsor staff (or designee) directly involved with the study. 
Study Design 
This is a randomized, double-blind, placebo-controlled, multi-center adaptive study of the mAb 
ADG20 in the treatment of ambulatory participants with mild or moderate COVID-19. The study 
will evaluate the safety, efficacy, PK, and antiviral activity of ADG20 versus placebo. A total of 
approximately 1084 participants are planned to be enrolled in the study at approximately 100 to 
115 sites globally. 
Participants with laboratory confirmed mild or moderate COVID-19 with symptom duration of 5 
days or less prior to randomization and a positive SARS-CoV-2 test taken within 5 days or less 
prior to randomization will be enrolled. Participants will be randomized 1:1 to receive a single 
dose of ADG20 or placebo administered by IM injection. Randomization will be stratified by age 
(12 to 17, 18 to 65, and >65 years) and country.  
Study Design Schematic for ADG20-TRMT-001 
 
IM=intramuscular; LTFU=long-term follow-up. 
Note: Screening may be performed prior to randomization on the same day as study drug dosing. 
Study Phase 2/3: n = 1084
Adults and Adolescents
(includes 300 Phase 2 parƟcipants) 
Dosing 
(Day 1)
Day 29
Month 14
Placebo IM (N ~ 542)
ADG20 300 mg IM (N ~ 542)
Screen/
Randomize
Follow-up Period
LTFU


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This study will enroll approximately 1084 participants total in 2 phases: 
• Phase 2: Enrolling approximately 300 adult participants to evaluate initial safety, efficacy, 
PK, and antiviral activity of ADG20 300 mg IM versus placebo in adults prior to enrolling 
additional participants in Phase 3.  
• Phase 3: Enrolling an additional 784 adult and adolescent participants (to reach the total 
sample size of 1084 for Phase 2/3), to evaluate efficacy, safety, PK, and antiviral activity of 
ADG20 300 mg IM versus placebo in adults and adolescents. There is no planned enrollment 
pause between Phase 2 and 3.  
At the recommendation of the iDMC following review at approximately n=200 and upon 
sponsor communication to sites, enrollment of adolescents will open only in regions permitted by 
health authorities and local ethics committees. Pausing guidelines triggering iDMC ad hoc 
reviews are described in Section 10.11. 
Duration of Study 
The study duration for each participant will be approximately 14 months. Each participant will 
receive a single dose of study drug or placebo at the Day 1 Visit. Participants will have 
telemedicine visits (via video or phone) and in-person clinic or at-home visits through Day 29. 
Participants will continue long-term follow-up through Month 14, with additional visits for 
safety laboratory tests at Day 90 and Month 6.  
Efficacy and Virologic Assessments  
Clinical efficacy assessments will include COVID-19-related hospitalization and all-cause death; 
COVID-19 severity; COVID-19-related emergency room visits and medically attended visits; 
and daily patient-reported symptoms.  
Virologic assessments will include quantitative SARS-CoV-2 viral load, clearance and duration 
of viral shedding assessed on nasopharyngeal samples and/or participant collected saliva 
samples. 
Resistance to ADG20 in viral isolates obtained from participants will be characterized using 
genotypic methods, with phenotypic methods deployed as appropriate. The impact of host 
biomarkers, such as baseline SARS-CoV-2 antibody responses, and viral load, on selected 
outcomes, may be evaluated. 
Pharmacokinetic and Immunogenicity Assessments 
Blood samples will be collected at specified time points for assessments of PK and to evaluate 
immunogenicity (anti-drug antibodies) to ADG20. 
Safety Assessments 
Safety will be assessed in an ongoing manner. Participants will receive ADG20 or placebo. As a 
precaution for acute worsening of disease, hypersensitivity, and injection site reactions (ISRs), 
participants will be observed after study drug administration as described in Section 6.4.1 of the 
protocol. If any hypersensitivity reactions occur, the iDMC will review available safety data and 


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provide a recommendation regarding the duration of monitoring. Participants will then be 
followed via telemedicine visits, phone calls, or in-person visits as described in the Schedule of 
Assessments through Day 29 for safety assessments.  
Safety assessments will include monitoring of AEs, clinical laboratory testing, vital sign 
measurements (body temperature, heart rate, respiration rate, and systolic and diastolic blood 
pressure), and physical examinations. Any AESIs (hypersensitivity reactions through Day 4) will 
be recorded. Hypersensitivity reactions occurring after Day 4 will be recorded as AEs. 
Participants will record any ISRs using the Injection Site Reaction Diary starting after dosing on 
Day 1 through Day 4 (Appendix 12.3). Other AEs, including SAEs and medically attended 
adverse events (MAAEs) (including new onset chronic illnesses), will be collected through the 
Month 14/EOS visit. 
For the purposes of this study, worsening or sequelae of the index case of COVID-19 will not be 
recorded as AEs, unless they meet 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. 
Details of Applicable Monitoring Committee 
The iDMC will provide safety oversight for all parts of the study, including monitoring for 
potential antibody-dependent enhancement (ADE). The iDMC will meet at designated points per 
Section 7.13 and the iDMC charter 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. Pausing guidelines for iDMC ad hoc 
safety reviews are outlined in Section 10.11.  
Study Drug, Dosage, and Route of Administration 
The study drug, ADG20, is a mAb, which will be administered once on Study Day 1. 
Participants will receive either 300 mg IM injection or matching placebo (3 mL injection). 
Placebo (normal saline solution) will be administered by the same route at a matched volume. 
Number of Planned Participants 
Approximately 1084 participants are planned to be enrolled. 
Efficacy Analyses 
Enrollment in the study was suspended on 11-Jan-2022 after emergence and global spread of the 
Omicron variant in regions enrolling the trial, beginning in December 2021. Therefore, the 
primary analysis is focused on evaluating the efficacy of ADG20 300 mg IM in participants with 
a non-Omicron variant of SARS-CoV-2. With this analysis plan, the primary efficacy and short-
term safety analyses are planned 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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The primary analysis is the comparison of the ADG20 arm versus the placebo arm with respect 
to the proportion of participants infected with a non-Omicron variant of SARS-CoV-2 with a 
COVID-19-related hospitalization or all-cause death through Day 29.  
The original sample size was calculated based on assumptions obtained from a review of data 
from studies of other mAbs in participants at high risk for disease progression leading to 
hospitalization or death prior to widespread emergence of both the Delta and Omicron variants. 
The original sample size of 1084 participants was planned with 90% power, 2-sided alpha .05, 
and a 1:1 randomization ratio to detect a statistically significant risk reduction with a true 
efficacy of relative risk reduction 70% and a 5% event rate in the placebo arm.  
At the time of enrollment suspension in January 2022, a total of 399 participants were 
randomized. Of them, approximately 320 participants will be included in the primary efficacy 
population of participants with a non-Omicron variant of SARS-CoV-2. Based on blinded 
monitoring of the primary endpoint outcomes, an approximate aggregate event rate of 9% was 
observed, indicating a higher placebo event rate than previously assumed and providing 
approximately 80% power to test the primary endpoint in the primary efficacy population given 
the same efficacy assumption.  
The analysis of the primary estimand, incidence of COVID-19-related hospitalization or all-
cause death through Day 29 in the ADG20 arm versus the placebo arm in the mFAS-non-
Omicron analysis set will be analyzed using the methodology for determining a standardized 
estimator for a binary outcome as detailed in Ge 2011, with adjustment for the following 
prognostic factors: age (continuous), sex (categorical), baseline qualitative serostatus 
(categorical), BMI (continuous), and baseline viral load (continuous). The standard error of the 
standardized estimator will be estimated using the delta method based on the algorithm presented 
in Ge 2011. The risk difference (placebo minus ADG20) with CI (using the Miettinen-Nurminen 
method), standardized risk difference with CI, relative risk reduction with CI, and associated 
p-value for the standardized risk difference will be provided. A treatment policy strategy will be 
used to handle intercurrent events of interest. For example, treatment effect will be estimated 
regardless of baseline or emergence of coinfection with a non-SARS-CoV-2 pathogen, which is a 
potential intercurrent event of interest.  
The key secondary endpoints will be tested in the following order in the mFAS-non-Omicron 
analysis set: (1) Severe/critical COVID-19 or all-cause death through Day 29, (2) COVID-19-
related emergency room visits, COVID-19-related hospitalization, or all-cause death through 
Day 29, and (3) Time to sustained resolution of COVID-19 symptoms through Day 29.  
Analyses of other secondary and exploratory efficacy endpoints will be conducted to support the 
findings of the primary and key secondary efficacy endpoints. 
Safety Analyses  
Safety summaries through Day 29 and overall will be presented. 
The incidence of TEAEs (including solicited ISRs), SAEs, TEAEs related to study drug, SAEs 
related to study drug, TEAEs leading to study drug discontinuation, AESIs, and MAAEs will be 
summarized by MedDRA system organ class (SOC), preferred term (PT), and treatment group. 


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The incidence of study drug related TEAEs (including solicited ISRs) will also be summarized 
by maximum severity by SOC, PT, and treatment group.  
The incidence of solicited AEs (ISRs) will be summarized by maximum severity through Day 4. 
The maximum duration and time from injection to report of first onset of any solicited ISR will 
also be summarized. 
Descriptive statistics for clinical laboratory results and vital sign parameters and for the change 
from baseline will be presented by treatment group and time point assessed. Potentially clinically 
significant laboratory and vital sign parameters will be summarized by treatment group and time 
point assessed. 
Immunogenicity Analyses  
Immunogenicity data will be listed and summarized in tables using descriptive statistics. 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACIP 
Advisory Committee on Immunization 
ADA 
anti-drug antibodies 
ADE 
antibody-dependent enhancement (of disease) 
AE 
adverse event 
AESI 
adverse event of special interest 
ANCOVA 
analysis of covariance 
BLQ 
below the limit of quantification 
BMI 
body mass index 
CBC 
complete blood count 
CDC 
Centers for Disease Control and Prevention 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CONSORT 
Consolidated Standards of Reporting Trials 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CRO 
contract research organization 
CV% 
coefficient of variation 
DAIDS 
Division of AIDS (National Institute of Allergy and Infectious Disease) 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
eCRF 
electronic case report form 
ELF 
epithelial lining fluid 
EMA 
European Medicines Agency 
EOS 
end of study 
EU 
European Union 
EUA 
emergency use authorization 
FAS 
full analysis set 
Fc 
fraction crystallizable 
FDA 
Food and Drug Administration 
FiO2 
fractional inspired oxygen 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
IA 
interim analysis 


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Abbreviation 
Definition 
IB 
Investigator’s Brochure 
IC50 
Half-maximal inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
ICU 
intensive care unit 
iDMC 
independent data monitoring committee 
IEC 
independent ethics committee 
IgG 
immunoglobulin G 
IM 
intramuscular 
IRB 
institutional review board 
IRT 
interactive response technology 
ISR 
injection site reaction 
IV 
intravenous 
KM 
Kaplan-Meier 
LAR 
legally authorized representative 
LLOQ 
lower limit of quantitation 
LS 
least squares 
MAAE 
medically attended adverse event 
mAb 
monoclonal antibody 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
modified full-analysis set 
MMRM 
Mixed Model for Repeated Measures 
NHP 
non-human primate 
NIAID 
National Institute of Allergy and Infectious Diseases 
NOAEL 
no observed adverse effect level  
NP 
nasopharyngeal 
OTC 
over-the-counter 
PASC 
post-acute sequelae of SARS-CoV-2 infection 
PaO2 
oxygen partial pressure 
PCR 
polymerase chain reaction 
PCS 
potentially clinically significant 
PK 
pharmacokinetic 
PPS 
per-protocol set 
PT 
preferred term 


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Abbreviation 
Definition 
QSP/PBPK 
quantitative systems pharmacology/whole body physiologically based pharmacokinetic 
RBD 
receptor-binding domain 
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 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous 
SOC 
system-organ-class 
SOP 
standard operating procedure 
SpO2 
oxygen saturation 
SUSAR 
suspected unexpected serious adverse reaction 
sVNA 
serum virus neutralizing antibody 
TCR 
tissue cross reactivity 
TEAE 
treatment-emergent adverse event 
UP 
unanticipated problems involving risks and adverse events 
US 
United States 
USP 
US Pharmacopeia 
VOC 
variants of concern 
VNA 
virus neutralizing antibody 
WGS 
whole genome sequencing 
WOCBP 
women of childbearing potential 
 
PHARMACOKINETIC ABBREVIATIONS 
Abbreviation 
Definition 
AUC 
area under the concentration-time curve 
AUC0-inf 
area under the concentration-time curve from zero to an infinite time 
AUC0-last 
area under the concentration-time curve from zero up to the last concentration ≥LLOQ 
CL 
clearance 
Cmax 
observed maximum plasma or serum concentration after administration 
T1/2 
plasma concentration half-life 
Tmax 
time to reach maximum plasma or serum concentration 
Vd 
volume of distribution 


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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 healthy 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 
ADG20 is being developed for the treatment and prevention of COVID-19, the disease caused by 
SARS-CoV-2. This placebo-controlled study (ADG20-TRMT-001; STAMP) is intended to 
generate safety and efficacy data to provide treatment options for COVID-19 in patients with a 
high risk of disease progression based on age or co-morbid medical conditions. On 21-Dec-2021, 
the iDMC reviewed unblinded data from approximately 200 participants dosed with ADG20 
300 mg IM or placebo in this study and recommended that the study continue. 


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In addition to this study, Adagio Therapeutics, Inc. 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, 24 participants across 
3 dose levels (300 mg IM, 500 mg IV, and 600 mg IM) received ADG20 (8 per dose cohort) and 
6 received placebo (2 per dose cohort). Dosing in these cohorts was initiated on 12-Feb-2021 and 
completed on 23-Mar-2021; follow-up is ongoing.  
Preliminary findings from blinded data review with a minimum of 9 months of follow-up 
showed that no SAEs, AESIs (hypersensitivity reactions or infusion-related reactions), study 
drug-related AEs, or ISRs have been reported. The observed ADG20 PK appears to be dose 
proportional, with an estimated half-life of approximately 97 days based on linear regression of 
the Days 21, 90, and 180 PK timepoints from the 300 mg IM dose.  
1.1.2.2. 
Study ADG20-PREV-001 (EVADE) 
Study ADG20-PREV-001 (EVADE) is a Phase 2/3 randomized, double-blind, placebo-
controlled study to evaluate the efficacy and safety of ADG20 in the prevention of COVID-19. 
Dosing in the study was initiated on 23-Apr-2021; follow-up is ongoing. On 24-Aug-2021, the 
iDMC reviewed the EVADE trial Phase 2 safety data, and on 30-Nov-2021, the iDMC reviewed 
the cumulative Phase 2/3 data. No safety concerns were identified, and the iDMC recommended 
that the trial continue. As of 11-Jan-2022, approximately 2471 participants had received study 
drug (ADG20 or placebo) in the study and enrollment was suspended on this date due to the 
global spread of the Omicron variant. 
1.2. 
Background on COVID-19 
Coronaviruses are ubiquitous pathogens with high pandemic potential. In recent years, 
3 pathogenic coronaviruses have crossed into the human population from zoonotic sources: 
SARS-CoV, MERS-CoV, and SARS-CoV-2. SARS-CoV-2, the most recent of these 
coronaviruses 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 (Johns 
Hopkins University & Medicine 2022). 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 World 
War II (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. Although rigorous testing, contact tracing, and 
quarantine procedures may help to temporarily slow down the spread of COVID-19 in society, 
widespread immunity is required to truly halt the 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 


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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 
2021b). A subset of individuals with initially mild to moderate symptoms may experience 
disease progression. Dyspnea developed after a median of 5 days after symptom onset with 
hospital admission occurring after a median of 7 days after 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, 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 individuals with mild disease may experience 
prolonged symptoms, with only 65% of individuals reporting return to baseline health by 14 to 
21 days after diagnosis (Tenforde 2020b). 
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 
(COPD, moderate to severe asthma), Down syndrome, heart conditions (heart failure, coronary 
artery disease, cardiomyopathies, hypertension), immunocompromised state (eg, solid organ 
transplant), obesity (BMI ≥30 kg/m2), pregnancy, sickle cell disease, smoking, and diabetes 
(CDC 2021a). 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; Starr 2021). 
To date, remdesivir is the only approved antiviral agent for the treatment of COVID-19 in the US 
(Gilead Sciences 2022a) and has conditional marketing authorization by the EMA (Gilead 
Sciences 2022b). Two other antivirals possess FDA emergency use authorization (EUA) for the 
treatment of patients with mild-to-moderate COVID-19 who are at high risk for progression to 


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severe disease: molnupiravir, which is authorized for use in adult patients only (Merck & Co 
2022) and nirmatrelvir co-packaged with ritonavir (Paxlovid), which is authorized in adult and 
pediatric (≥12 years) patients (Pfizer 2022). Paxlovid recently received conditional marketing 
authorization in the EU (Pfizer Europe MA EEIG 2022) and the EMA issued advice for the use 
of molnupiravir to support national decision making before a marketing authorization is issued 
(EMA 2021). However, the availability of these antivirals is limited. Furthermore, molnupiravir 
is not recommended for pregnant or breastfeeding women due to the risk of embryo-fetal toxicity 
and Paxlovid is not recommended for patients with severe renal or hepatic impairment and is 
contraindicated with many drugs that are highly dependent on CYP3A for clearance.  
Four monoclonal antibody (mAb) products, bamlanivimab/etesevimab, casirivimab/imdevimab, 
sotrovimab, and bebtelovimab have been granted FDA EUA for the treatment of patients with 
mild-to-moderate COVID-19 at high risk for progressing to severe COVID-19 and/or 
hospitalization (Eli Lilly and Company 2022a; Eli Lilly and Company 2022b; GlaxoSmithKline 
2022; Regeneron 2022). In the EU, casirivimab/imdevimab, sotrovimab, and regdanvimab are all 
authorized for treatment of high-risk patients (Celltrion Healthcare Hungary 2021; 
GlaxoSmithKline 2021; Roche Registration GmbH 2021). However, the availability of these 
treatments is limited at this time. Further, mAbs are susceptible to relative or absolute resistance 
to emerging variants of SARS-CoV-2, as was demonstrated with the emergence of Omicron, 
against which bamlanivimab/etesevimab, casirivimab/imdevimab, and regdanvimab have no in 
vitro activity (Planas 2021; Eli Lilly and Company 2022a; Regeneron 2022). As a result, mAb 
products may not be authorized for use in regions where the predominant variant is non-
susceptible to that product.  
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 
treatment have taken on unprecedented urgency.  
Clinical trial experience of neutralizing mAbs that target the SARS-CoV-2 spike protein supports 
a favorable risk-benefit profile for the evaluation of mAb therapies in recently diagnosed 
ambulatory patients with mild-to-moderate COVID-19 who are at high risk of disease 
progression (Celltrion Healthcare Hungary 2021; Eli Lilly and Company 2022a; Eli Lilly and 
Company 2022b; GlaxoSmithKline 2022; Regeneron 2022).  
The potential for ADG20 to provide broad protection against disease progression to a wide range 
of individuals is supported by nonclinical data, in which ADG20 displayed potent binding and 
neutralizing activity against all SARS-CoV-2 variants of concern identified prior to the 
emergence of Omicron, and retained neutralizing activity against Omicron, albeit with reduced 
potency (Liu 2021b; Planas 2021; Starr 2021; Wang 2021). In combination with the clinical 
experience with other mAbs targeting SARS-CoV-2, these data support the evaluation of 
ADG20 in ambulatory adult and adolescent participants with mild or moderate COVID-19 who 
are at high risk of disease progression. Clinical evaluation of agents such as ADG20 that possess 
broad activity against SARS-CoV-2 and additional coronaviruses with pandemic potential is 


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urgently needed to provide potential solutions for both the current and future pandemics due to 
sarbecoviruses.  
1.3.2. 
Rationale for Study Design 
This randomized, double-blind, placebo-controlled Phase 2/3 study is intended to generate safety 
and efficacy data to provide a treatment option for mild or moderate COVID-19 in patients with 
a high risk of disease progression based on age or co-morbid medical conditions. The patient 
population, placebo-control, safety monitoring, duration of follow-up, and efficacy endpoints are 
consistent with regulatory guidance (FDA 2020b; FDA 2021b).  
Phase 2/3 design: A streamlined Phase 2/3 design is being utilized due to the critical nature of 
the COVID-19 pandemic and the urgent need for effective therapies. Available Phase 1 safety 
data in healthy volunteers from Study ADG20-1-001 identified no safety concerns for ADG20 
across 3 dose levels (300 mg IM, 500 mg IV, and 600 mg IM), including no injection site or 
infusion-related reactions and no hypersensitivity reactions within 6 weeks following study drug 
administration. Additionally, healthy volunteer PK demonstrated that QSP/PBPK model 
predicted the observed ADG20 concentrations well and with relatively little bias across the 
21-day sampling interval. The study demonstrated high sVNA titers in healthy volunteers 
receiving ADG20, which were consistent with those associated with efficacy in nonhuman 
primate adoptive transfer studies (McMahan 2021). The absence of safety and tolerability 
signals, PK results that confirm prior model predictions, and high sVNA titers supported the 
initiation of ADG20-TRMT-001. Refer to the IB for additional detailed Phase 1 data from study 
ADG20-1-001.  
Participant Population: Mild or moderate COVID-19 in adults and adolescents can typically be 
managed in the outpatient/ambulatory setting. Data from other SARS-CoV-2 mAb programs 
suggest that populations at high risk for progression of COVID-19 are likely to benefit from 
treatment with a mAb (see Section 1.4.1). In order to ensure similar risk of COVID-19 disease 
progression across the two treatment groups, enrollment will be stratified based on age. Data 
from several regions have consistently shown that age is the most critical factor for risk of severe 
COVID-19 including hospitalization, ICU stay, and death (Docherty 2020; Grasselli 2020; Ko 
2020; Wu 2020; Kim 2021). Of the risk factors identified, age appears to have the most profound 
impact on outcomes, with significant increase in risk clearly evident around age 65 and a greater 
magnitude in risk than that associated with any individual co-morbidity (Kim 2021). In a cohort 
of more than 1.3 million patients diagnosed with COVID-19, of patients with no reported 
underlying health conditions, 9.6%, 15.5%, and 27.9% of patients 50-59, 60-69, and 70-79 years 
of age required hospitalization, respectively (Stokes 2020).  
Symptom Onset Within 5 Days: Symptoms of COVID-19 generally appear from 2 to 14 days 
following exposure to SARS-CoV-2. A subset of individuals with initially mild or moderate 
symptoms may experience disease progression. For example, in a study of 138 hospitalized 
patients with COVID-19 pneumonia, dyspnea, and hospitalization developed after a median of 
5 and 8 days, respectively, from symptom onset (Wang 2020). These data suggest a window for 
intervention of <7 days from onset of symptoms with a potently neutralizing antiviral mAb like 
ADG20 to prevent disease progression. Consistent with this hypothesis, experience with other 
highly potent mAbs (casirivimab/imdevimab, bamlanivimab/etesevimab, sotrovimab, 


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regdanvimab, and bebtelovimab) suggests that administration early in the course of infection (eg, 
within 5 to 7 days or less of onset of symptoms) is associated with faster resolution of symptoms 
and a reduction in the need for medically attended visits, including emergency room visits and 
hospitalizations (Celltrion Healthcare Hungary 2021; Eli Lilly and Company 2022a; Eli Lilly and 
Company 2022b; GlaxoSmithKline 2022; Regeneron 2022).  
Adolescent Population: Evidence supporting the efficacy and safety of potential therapeutic 
agents are urgently needed for the treatment of COVID-19 children and adolescents (Gotzinger 
2020). Overall, the symptoms of COVID-19 are similar in adolescents and adults, although the 
frequency of specific symptoms may vary, and disease is generally less severe in adolescents 
(Stokes 2020). Although COVID-19 in children is generally mild and the case fatality rate is 
low, some children progress to severe disease requiring intensive care admission (Gotzinger 
2020). Similar to adults, severe outcomes are more common in adolescents with underlying co-
morbidities including chronic lung disease, obesity, cardiovascular disease, 
neurologic/developmental disorders and immunosuppressive conditions (Bixler 2020; Stokes 
2020). FDA EUA for SARS-CoV-2 mAbs (bamlanivimab/etesevimab, casirivimab/imdevimab, 
sotrovimab, and bebtelovimab) and EMA marketing authorization of casirivimab/imdevimab 
include adolescent populations at high risk for progressing to severe COVID-19 despite limited 
clinical data generated for these products in adolescents, underscoring the high unmet need for 
treatment options for adolescents at risk of severe outcomes (Eli Lilly and Company 2022a; Eli 
Lilly and Company 2022b; GlaxoSmithKline 2022; Regeneron 2022).  
The dose regimens of ADG20 under evaluation in this study are expected to result in comparable 
serum exposures of ADG20 in patients 12 years of age and older and weighing at least 40 kg as 
observed in adults. For these reasons, adolescents with mild or moderate COVID-19 who are at 
increased risk for severe COVID-19 will be included in Phase 3 of the study upon sponsor 
communication to sites after iDMC review of safety data in adults, and only if permitted by the 
local health authority. 
Pregnant and Breastfeeding Women: Pregnant individuals are at an increased risk for severe 
illness from COVID-19 when compared to non-pregnant individuals and may also be at 
increased risk for other poor outcomes, such as preterm birth (CDC 2021a). As with other 
COVID-19 monoclonal antibody products (FDA 2020a; FDA 2021a), no specific risks to 
pregnant or lactating individuals have been identified based on ADG20 non-clinical safety data. 
Specifically, in a tissue cross reactivity study using human fetal tissues, no binding of clinical 
concern was detected for ADG20 (refer to the IB for details). Based on the increased risk for 
poor COVID-19 outcomes for pregnant individuals and the low assessed risk associated with 
SARS-CoV-2 mAb administration, pregnant or breastfeeding individuals may be included in the 
trial upon sponsor communication to sites after iDMC review of safety data, and only in regions 
permitted by the local health authority. No dosage adjustment of ADG20 is recommended during 
pregnancy or while lactating. 
Use of Placebo Control: In the absence of globally approved and widely available therapies 
defining a clear standard of care for the treatment of ambulatory patients with COVID-19 at high 
risk of disease progression, a placebo-controlled trial is appropriate. Despite FDA and/or EMA 
marketing authorization of bamlanivimab/etesevimab, casirivimab/imdevimab, regdanvimab, 
sotrovimab, and bebtelovimab for treatment of high-risk patients, the continued emergence of 


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variants resistant to some available monoclonal antibodies remains a concern, limiting the utility 
of these agents (see Section 1.2). Additionally, the availability of these treatments in the US and 
EU remains limited at this time. Similarly, while the antivirals Paxlovid, molnupiravir, and 
remdesivir have FDA EUA and/or EMA conditional marketing authorization, the availability of 
these treatments remains limited at this time. Potential study participants will be made aware if 
these treatments are available in their region, how to access these therapies, and the anticipated 
activity these treatments may offer against variants of SARS-CoV-2 known to be circulating in 
their region.  
Furthermore, specific designated standard of care may be provided to patients in this study, as 
appropriate, as described in Section 5.6.2.3 and the ADG20-TRMT-001 Designated Background 
Standard of Care document, which outlines prohibited and allowed concomitant medications. 
For participants who become hospitalized due to COVID-19, treatment of COVID-19 as deemed 
appropriate is acceptable. 
Safety assessment and duration of follow-up: As a precaution for acute worsening of disease, 
hypersensitivity, and ISRs, participants will be observed after study drug administration as 
described in Section 6.4.1. In-clinic monitoring post-dosing will include frequent assessment of 
vital signs and is considered appropriate for IM injection of a fully human mAb targeted to the 
spike glycoprotein of SARS-CoV-2. Study drug will only be administered in settings in which 
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. 
AESIs will include hypersensitivity reactions occurring through Day 4. Solicited AEs (ISRs) will 
be monitored through Day 4 via patient-reported diary. Long term safety follow-up will continue 
through 14 months postdose (or approximately 5 half-lives). This timeframe is considered 
appropriate due to the preliminary estimate of an extended half-life of ADG20 of approximately 
97 days.  
Efficacy Endpoints: The primary efficacy endpoint is COVID-19-related hospitalization or all-
cause death through Day 29. This endpoint evaluates clinically relevant measures for mild and 
moderate COVID-19 over a relevant duration of time. Development of severe or critical 
COVID-19, a key secondary endpoint, will be evaluated using pre-specified disease severity 
definitions and will provide a systematic estimate of disease progression from mild or moderate 
COVID-19 (required for study entry) to a worse severity. A secondary endpoint is the time to 
sustained resolution of COVID-19 symptoms through Day 29. Although recovery from 
COVID-19 is variable, Day 29 is an appropriate time period for assessment of resolution of 
COVID-19 based on published findings suggesting that resolution of mild infection occurs over 
a period of approximately 2 to 3 weeks (WHO 2020). Data from SARS-CoV-2 mAb trials 
enrolling a similar population further support the Day 29 assessment period, with the majority of 
patients experiencing symptom resolution in <14 days (Celltrion Healthcare Hungary 2021; Eli 
Lilly and Company 2022a; GlaxoSmithKline 2022; Regeneron 2022).  
1.3.2.1. 
Rationale for Dose Selection 
ADG20 will be administered IM at a dose of 300 mg in this study. This dose was selected upon 
consideration of 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 


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human PK 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 was used to support dose selection. Preliminary early PK data from the 
healthy volunteer study (Phase 1; ADG20-1-001) described in Section 1.1.2 indicate ADG20 
pharmacokinetics following IM administration of a single 300 mg dose are consistent with the 
QSP/PBPK model predictions, providing support for use of the model for dose selection.  
Three complementary modeling approaches were used to support the dose selected for study: 
1) the ability of ADG20 to attain rapid, near complete (>90%), and durable (28 days) 
SARS-CoV-2 occupancy in the lung upper airway ELF; 2) the ability of ADG20 to maintain 
serum neutralizing antibody titer >500, a value associated with therapeutic efficacy in a non-
human primate (NHP) treatment study (McMahan 2021), and 3) the ability of ADG20 to 
maintain ELF in concentrations relative to a concentration associated with 100% viral growth 
suppression in a post-infection assay. 
Following a 300 mg IM ADG20 dose, greater than 90% of simulated patient exposures are 
predicted to result in near complete SARS-CoV-2 receptor occupancy within approximately 
5 hours of ADG20 administration. High receptor occupancy is associated with efficacy for viral 
receptor antagonists, such as ADG20 (Demarest 2008; Muller 2009; Emu 2018). Moreover, with 
the 300 mg IM ADG20 dose regimen, greater than 90% of simulated patients are predicted to 
maintain serum neutralizing antibody titers >500-fold the in vitro IC50 (as a proxy for 
neutralizing antibody titers >500) for a minimum of 28 days, a target associated with efficacy in 
a nonhuman primate treatment adoptive transfer model (McMahan 2021). Finally, following a 
300 mg IM dose, over 90% of simulated patients are to maintain ADG20 concentrations 
exceeding that required for 100% viral growth suppression in a post-infection assay. For details 
regarding the modeling and simulation, refer to the IB. 
Preliminary analysis of sVNA titers from healthy volunteers receiving a single 300 mg IM dose 
of ADG20 in Study ADG20-1-001 further supports selection of this dose. Geometric mean 
(CV%) serum 80% (MN80) and 50% (MN50) neutralization titers of 130 (177%) and 346 
(122%), respectively, were achieved within 24 hours of ADG20 administration and were 569 
(43.8%) and 1382 (32.7%), respectively, at Day 13 post-injection. These data confirm the ability 
of ADG20 to rapidly attain potentially efficacious sVNA titers and to maintain them above the 
target threshold for at least 13 days post administration.  
ADG20 dose selection for treatment of ambulatory patients with mild to moderate COVID-19 
was also guided by results from Phase 2 dose ranging studies evaluating the safety and efficacy 
of casirivimab/imdevimab, a SARS-CoV-2 spike targeting mAb product with similar potency as 
ADG20, in a similar patient population (Weinreich 2021). Clinical data from this product 
suggest a favorable benefit/risk profile if administered early in the course of illness. Based on 
these data, casirivimab/imdevimab was granted EUA at a dose level of 2400 mg (1200/1200 mg) 
(Regeneron 2022). A more recent study evaluating lower dose regimens of 
casirivimab/imdevimab demonstrated similar clinical efficacy between 2400 mg (1200/1200 mg) 
and 1200 mg (600/600 mg) IV dose levels. In a separate study, the antiviral effect of several 
different casirivimab/imdevimab regimens (IV: 2400 mg, 1200 mg, 600 mg and 300 mg; SC: 
1200 mg and 600 mg) was evaluated (Roche 2021). All tested doses met the primary endpoint, 
rapidly and significantly reducing patients' viral load (log10 copies/mL) compared to placebo 


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(p<0.001) with each dose demonstrating similar efficacy, including the lowest doses tested 
(IV: 300 mg; SC: 600 mg). Similar to the modelled ADG20 300 mg IM dose regimen in 
simulated patients, the modelled imdevimab 600 mg SC regimen (as a proxy for 
casirivimab/imdevimab 300/300 mg SC given similar PK and spike protein affinity of these two 
mAbs) maintained serum neutralizing antibody concentrations >500 for greater than 28 days in 
>90% of simulated patients. 
Preliminary safety and PK data from the Phase 1 Study ADG20-1-001 further supports the 
appropriateness of the 300 mg IM dose regimen (see Section 1.1.2). Given the safety profile 
described in healthy volunteers and the prospect for benefit in the setting of acute treatment, the 
potential benefit of the 300 mg IM dose regimen outweighs the potential risk to patients.  
The dose level is fixed, with no dose adjustment recommended for body weight, renal 
impairment, or mild to moderate hepatic impairment. Similarly, no ADG20 dose adjustment is 
warranted in adolescents (12 to <18 years of age) weighing at least 40 kg. 
In conclusion, based on this analysis, a single dose level of 300 mg ADG20 administered IM will 
be evaluated in ADG20-TRMT-001. The 300 mg IM dose is supported by: 1) ability to rapidly 
achieve antibody concentrations in the respiratory compartments to result in near complete and 
durable SARS-CoV-2 spike protein receptor occupancy; 2) ability to maintain serum neutralizing 
antibody titers associated with efficacy in a NHP treatment adoptive transfer model for 28 days; 
3) ability to maintain concentrations in the respiratory compartments that are associated with 
100% viral growth suppression in vitro; 4) the ability to be safely administered as a single 
injection; and 5) the potential advantages to patients, healthcare providers and healthcare systems 
of an IM dosing formulation for outpatient therapy. For additional details regarding dose 
selection, refer to the IB. 
1.4. 
Risks and Benefits 
1.4.1. 
Target Study Population and Risk/Benefit Assessment 
The target populations for this study are ambulatory adults and adolescents with mild or 
moderate COVID-19 and at high risk of disease progression based on age (≥55 years) and/or 
preexisting medical conditions (eg, obesity, type 2 diabetes, chronic kidney or lung disease, 
immunocompromised, pregnancy, etc.) as defined in Section 4.1.1 (CDC 2021a). Enrollment of 
participants who are pregnant or breastfeeding may only open upon sponsor communication to 
sites after iDMC review of safety data, and only in regions permitted by the local health 
authority. 
These populations that are at high risk for progression of COVID-19 are likely to benefit from 
treatment with a mAb. It is notable that clinical experience with other mAbs against the 
SARS-CoV-2 spike protein suggests potential clinical benefit in ambulatory patients with mild or 
moderate COVID-19 (Celltrion Healthcare Hungary 2021; Eli Lilly and Company 2022a; Eli 
Lilly and Company 2022b; GlaxoSmithKline 2022; Regeneron 2022). 
1.4.2. 
Risks from Study Participation 
Because ADG20 targets an exogenous epitope (spike protein) that is not present in humans, 
significant safety issues due to off-target effects are not expected. No safety concerns for ADG20 


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have been identified in data generated across the ADG20 clinical development program to date 
(see 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 mAb administration-related reactions occur 
within the first 24 hours after administration. Severe reactions are rare and are more often 
associated with mAbs targeting human proteins rather than exogenous targets. As a precaution 
for acute injection reactions, study drug will only be administered in settings in which health care 
providers have immediate access to medications to treat severe injection reactions, such as 
anaphylaxis, and the ability to activate the emergency medical system, as necessary. Refer to the 
IB for further clinical safety information. 
Risks associated with large-volume IM injections include but are not limited to bleeding, nerve 
damage, hematoma, and infection. These risks will be mitigated by clear instructions regarding 
the injection site and technique as detailed in the Pharmacy Manual. 
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 administration as the target cell burden is greatest under these 
conditions. Therefore, as a precaution for acute worsening of disease, hypersensitivity, and ISRs, 
participants will be observed after study drug administration as described in Section 6.4.1.  
There is a risk that receipt of a SARS-CoV-2 mAb 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) 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 
product. 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 
2022).  
There is a theoretical risk that receipt of a mAb against SARS-CoV-2 may cause a paradoxical 
increase in 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 
respiratory syncytial virus (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 suboptimal 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 ADG20 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 early 
COVID-19 (Celltrion Healthcare Hungary 2021; Eli Lilly and Company 2022a; Eli Lilly and 
Company 2022b; GlaxoSmithKline 2022; Regeneron 2022). Of note, a warning has been 


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provided within the EUA fact sheets for bamlanivimab/etesevimab, casirivimab/imdevimab, 
sotrovimab, and bebtelovimab regarding potential clinical worsening of COVID-19 after 
administration, which may include signs or symptoms of fever, hypoxia or increased respiratory 
difficulty, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered 
mental status. It is not known if these events were related to use of the mAbs or were due to 
progression of COVID-19 (Eli Lilly and Company 2022a; Eli Lilly and Company 2022b; 
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 
The participants in this study will be included based on a diagnosis of mild or moderate 
COVID-19 and the presence of clinical factors that indicate a high risk of disease progression. 
Based on currently available data, this population is likely to derive the greatest benefit from 
early therapy designed to reduce the risk of disease progression.  
Considering the paucity of approved therapies for the treatment of COVID‑19, the limited 
availability of these treatments in many regions, the widespread emergence of SARS-CoV-2 
variants resistant to some antibody-based therapies, and the safety profile of ADG20 across the 
clinical development program to date, the overall benefit-risk assessment for this study is 
considered favorable for treatment 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 IB. 


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2. 
STUDY OBJECTIVES, ENDPOINTS, AND DEFINITIONS 
2.1. 
Objectives and Endpoints  
The objectives and endpoints are presented in Table 2-1.  
Table 2-1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of ADG20 compared 
to placebo in the treatment of mild or moderate 
COVID-19 in participants at high risk of 
disease progression 
COVID-19-related hospitalization or all-cause death through 
Day 29 
To evaluate the safety and tolerability of 
ADG20 compared to placebo through Day 29 
in participants with mild or moderate 
COVID-19 and high risk of disease progression 
Assessment of safety through Day 29 based on: 
• 
The incidence of TEAEs 
• 
Incidence of solicited injection site reactions through 
Day 4  
• 
Changes from baseline in clinical laboratory tests (ie, CBC 
with differential, serum chemistry, coagulation)  
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure) 
Secondary  
To evaluate the effect of ADG20 on the 
following clinical parameters in participants 
with mild or moderate COVID-19 and high risk 
of disease progression 
• 
Severity of COVID-19 
• 
COVID-19-related emergency room visits, 
COVID-19-related hospitalizations, or 
all-cause death 
• 
Time to sustained resolution of COVID-19 
symptoms 
• 
COVID-19-related medically attended 
visits 
• 
Time to sustained recovery of COVID-19 
symptoms 
• 
All-cause mortality 
• 
Severe/critical COVID-19 or all-cause death through 
Day 29 
• 
COVID-19-related emergency room visits, COVID-19-
related hospitalization, or all-cause death through Day 29 
• 
Time to sustained resolution of COVID-19 symptoms 
through Day 29 
• 
COVID-19-related medically attended visit (telemedicine, 
physician office, urgent care center, emergency room, 
hospitalization) or all-cause death through Day 29 
• 
Time to sustained recovery defined as sustained 
improvement or resolution of COVID-19 symptoms 
through Day 29 
• 
All-cause death through Day 29, Day 60, and Day 90  


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Objectives 
Endpoints 
To evaluate the effect of ADG20 on 
SARS-CoV-2 viral load and clearance in 
participants with mild or moderate COVID-19 
and high risk of disease progression 
• 
Change from baseline in SARS-CoV-2 viral load 
(log10 copies/mL) to Day 7 (±1) assessed by RT-qPCR 
from NP samples 
• 
Viral load >5 log10 copies/mL on Day 7 (±1) based on NP 
samples 
• 
Duration of SARS-CoV-2 viral shedding from Day 1 
through Day 29 assessed by RT-qPCR from saliva 
samples 
• 
Change from baseline in SARS-CoV-2 viral load 
(log10 copies/mL) to Days 3, 5, 7, 11, and 14 assessed by 
RT-qPCR from saliva samples 
• 
SARS-CoV-2 viral clearance (Days 5, 7, 11, 14, 21, and 
29) assessed by RT-qPCR from saliva samples (and NP 
samples for Day 7) 
• 
SARS-CoV-2 viral load AUC assessed by RT-qPCR from 
saliva samples from baseline to Day 29  
To evaluate the long-term safety and 
tolerability of ADG20 compared to placebo in 
participants with mild or moderate COVID-19 
and high risk of disease progression 
Assessment of safety based on: 
• 
The incidence of TEAEs 
• 
Changes from baseline in clinical laboratory tests (ie, CBC 
with differential, serum chemistry, coagulation)  
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure) 
To evaluate the PK of ADG20 following IM 
administration 
PK parameters of ADG20: As data permit, Cmax, Tmax,  
AUC0-last, AUC0-inf, CL, Vd, and T1/2  Additional PK parameters 
may be calculated as data permit 
To evaluate the immunogenicity (ADAs) to 
ADG20 
Incidence of ADAs against ADG20 
To evaluate the emergence of resistance to 
ADG20 
Genotypic characterization of viral isolates for reduced 
susceptibility to ADG20, with phenotypic evaluation as 
appropriate 
Exploratory  
To evaluate the effect of host or viral 
biomarkers on clinical outcomes 
Effect of baseline SARS-CoV-2 specific antibody response on 
select clinical outcomes 
To identify a persistently high viral load 
threshold for risk of adverse clinical outcomes 
The level of viral load leading to the following adverse clinical 
outcomes: 
• 
COVID-19-related hospitalization or all-cause death 
through Day 29 
• 
COVID-19-related emergency room visits, COVID-19-
related hospitalization, or all-cause death through Day 29 
• 
Severe/critical COVID-19 or all-cause death through 
Day 29 


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Objectives 
Endpoints 
To evaluate the development of symptomatic 
COVID-19 or asymptomatic infection in 
household contacts of study participants after 
participant receipt of study drug 
• 
Participants with symptomatic COVID-19 among 
household contacts 
• 
Participants with asymptomatic SARS-CoV-2 infection 
among household contacts 
To evaluate the effect of ADG20 on the 
following parameters 
• 
COVID-19-related mortality 
• 
Time to improvement of COVID-19 
symptoms 
• 
Post-acute sequelae of SARS-CoV-2 
infection  
• 
COVID-19-related death through Day 29 
• 
Time to improvement of COVID-19 symptoms through 
Day 29 
• 
Incidence of PASC at Day 60, Day 90, and Month 6 
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; CBC=complete blood count; CL=clearance; 
Cmax=maximum plasma concentration; NP=nasopharyngeal; PASC=post-acute sequelae of SARS-CoV-2 infection; 
RT-(q)PCR=(quantitative) reverse transcription-polymerase chain reaction; TEAEs=treatment-emergent adverse events; 
t½=plasma concentration half-life; Tmax=time to reach Cmax; Vd=apparent volume of distribution. 
 
2.2. 
Definitions 
2.2.1. 
SARS-CoV-2 Variant Determination 
WGS will be used to determine a participant’s SARS-CoV-2 infecting variant (Delta, Omicron, 
and others) based on the NP or saliva sample collected at baseline; if the baseline sample is 
missing, the available post-baseline NP or saliva sample will be used. Any participants with a 
missing WGS result will be classified as suspected non-Omicron or Omicron variant by 
comparing their randomization date with the date of the first WGS-confirmed Omicron 
participant enrolled from the same country. If there is no WGS-confirmed Omicron participant 
enrolled from the same country in the study, the date of emergence of Omicron in the country, 
based on publicly available epidemiology data, will be used, as detailed in the SAP. A final 
clinical and virological review (adjudication as needed) may be performed. 
2.2.2. 
COVID-19 Severity Categorization 
The following COVID-19 severity categorizations are adapted from the FDA COVID-19 
Developing Drugs and Biological Products for Prevention or treatment Guidance for Industry 
(FDA 2021b). Only participants with mild and moderate disease severity are eligible for study 
participation. Progression to severe or critical disease will be evaluated as a secondary endpoint. 
Mild COVID-19 is defined as having a positive test by standard RT-PCR assay or equivalent 
test plus the following: 
• Symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, 
malaise, headache, muscle pain, or gastrointestinal symptoms, without shortness of breath 
or dyspnea. 


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• Respiratory rate <20 breaths per minute and heart rate <90 beats per minute. 
• No clinical signs indicative of moderate, severe, or critical illness severity. 
Moderate COVID-19 is defined as having a positive test by standard RT-PCR assay or 
equivalent test plus the following: 
• Symptoms of moderate illness with COVID-19, which could include any symptom of mild 
illness or shortness of breath with exertion worse than usual. 
• Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate 
≥20 breaths per minute, with 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 is defined as having a positive test by standard RT-PCR assay or equivalent 
test plus the following: 
• 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 (PaO2/FiO2) 
<300 mm Hg. 
• No criteria for critical severity. 
Critical COVID-19 is defined as having a positive test by standard RT-PCR assay or equivalent 
test plus the following: 
• 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). 
− Shock (defined by systolic blood pressure <90 mmHg, diastolic blood pressure 
<60 mmHg, or requiring vasopressors). 
Note: Shock is per investigator diagnosis/assessment. 
− 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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2.2.3. 
COVID-19-Related Medically Attended Visits 
COVID-19-related medically attended visits include in-person or telemedicine visits not 
specified by the protocol. 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, or hospitalization 
for attention to worsening signs or symptoms attributed to COVID-19, in the opinion of the 
investigator. 
2.2.4. 
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, intensive care units, acute care facilities created for COVID-19 pandemic 
hospitalization needs, or other acute care facilities).  
2.2.5. 
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. 
2.2.6. 
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 at rest, 
shortness of breath/difficulty breathing with exertion, muscle or body aches, fatigue, headache, 
nausea, vomiting, and diarrhea. Loss of taste/smell is not considered in this analysis. 
Time to sustained resolution of COVID-19 symptoms is defined as time from the first dose date 
to the first date when all of the above symptoms are scored as absent with no symptom 
recurrence or new symptoms, except cough, fatigue, and headache which may be mild or absent, 
through Day 29. 
3. 
INVESTIGATIONAL PLAN FOR ADG20-TRMT-001 PROTOCOL 
3.1. 
Study Design 
This is a randomized, double-blind, placebo-controlled, multi-center adaptive study of the mAb 
ADG20 in the treatment of ambulatory participants with mild or moderate COVID-19. The study 
will evaluate the safety, efficacy, PK, and antiviral activity of ADG20 versus placebo. A total of 
approximately 1084 participants are planned to be enrolled in the study at approximately 100 to 
115 sites globally. 
Participants with laboratory confirmed mild or moderate COVID-19 with symptom duration of 
5 days or less prior to randomization and a positive SARS-CoV-2 test taken within 5 days or less 
prior to randomization will be enrolled. Participants will be randomized 1:1 to receive a single 


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dose of ADG20 or placebo administered by IM injection. Randomization will be stratified by age 
(12 to 17, 18 to 65, and >65 years) and country.  
Study drug will be administered at the study site. As a precaution for acute worsening of disease, 
hypersensitivity, and or ISRs, participants will be observed after study drug administration, as 
described in Section 6.4.1. The iDMC will review available safety data as described in 
Section 6.4.1 and will provide recommendations regarding the duration of monitoring, which 
will be formally communicated to sites without a protocol amendment. After Day 1, participants 
will be followed via telemedicine visits, phone calls, or in-person visits through Month 14 as 
indicated in the Schedule of Assessments (Table 12-1). See Section 6 for details on the 
assessments and procedures for this study. 
Figure 3-1: 
Study Design Schematic for ADG20-TRMT-001 
 
IM=intramuscular; LTFU=long-term follow-up 
Note: Screening may be performed prior to randomization on the same day as study drug dosing. Randomization is stratified by 
age and country. The Schedule of Assessments is presented in Table 12-1. 
 
This study will enroll approximately 1084 participants total in 2 phases (Figure 3-1).  
• Phase 2: Enrolling approximately 300 adult participants to evaluate initial safety, efficacy, 
PK, and antiviral activity of ADG20 300 mg IM versus placebo in adults prior to enrolling 
additional participants in Phase 3.  
• Phase 3: Enrolling an additional 784 adult and adolescent participants (to reach the total 
sample size of 1084 for Phase 2/3), to evaluate efficacy, safety, PK, and antiviral activity of 
ADG20 300 mg IM versus placebo in adults and adolescents. There is no planned enrollment 
pause between Phase 2 and 3.  
At the recommendation of the iDMC following review at approximately n=200 and upon 
sponsor communication to sites, enrollment of adolescents will open only in regions permitted by 
health authorities and local ethics committees. Pausing guidelines triggering iDMC ad hoc 
reviews are described in Section 10.11. 
Database locks and interim analyses will occur as described in Section 5.5 and Section 7.13. 
3.1.1. 
Study Duration 
The study duration for each participant will be approximately 14 months. Each participant will 
receive a single dose of study drug or placebo at the Day 1 Visit. Participants will have 
telemedicine visits (via video or phone) and in-person clinic or at-home visits through Day 29. 
Participants will continue long-term follow-up through Month 14, with additional visits for 
safety laboratory tests at Day 90 and Month 6.  
Study Phase 2/3: n = 1084
Adults and Adolescents
(includes 300 Phase 2 parƟcipants) 
Dosing 
(Day 1)
Day 29
Month 14
Placebo IM (N ~ 542)
ADG20 300 mg IM (N ~ 542)
Screen/
Randomize
Follow-up Period
LTFU


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4. 
PARTICIPANT SELECTION AND WITHDRAWAL CRITERIA 
4.1. 
Selection of Study Participants 
The study population will include adults (aged ≥18 years) and adolescents (aged 12 to <18 years) 
in both cohorts; enrollment of adolescents will begin upon sponsor communication to the sites 
following iDMC review of safety data in each cohort, and only in regions permitted by health 
authorities and local ethics committees. Participants with laboratory confirmed mild or moderate 
COVID-19 who are at high risk for disease progression will be included. 
Participants will be assigned to study treatment only if they meet all of the inclusion criteria and 
none of the exclusion criteria. 
Deviations from the inclusion and exclusion criteria are not allowed because of their potential to 
jeopardize the scientific integrity of the study, regulatory acceptability, or participant safety. 
Therefore, adherence to the eligibility criteria as specified in the protocol is required. 
4.1.1. 
Inclusion Criteria 
Each participant must meet all of the following criteria to be enrolled in this study: 
1. Age: Is an adult aged 18 years and above, or is an adolescent aged 12 to 17 years (inclusive) 
and weighing ≥40 kg at the time of screening  
Note: Adolescent enrollment will open only upon sponsor communication to sites after 
iDMC review of safety data in adults, and only if permitted by the local health authority. 
2. Has had a SARS-CoV-2 positive antigen test, or by RT-PCR, or other locally approved 
molecular diagnostic assay obtained within 5 days prior to randomization.  
Note: A historical record of a positive result from a test conducted within 5 days prior to 
randomization is acceptable. SARS-CoV-2 antibody testing cannot be used for study 
eligibility. 
3. Has had initial onset of one or more of the following self-reported COVID-19-related signs 
or symptoms within 5 days prior to randomization: 
a. measured temperature ≥38 °C (100.4 °F) 
b. subjective fever (feeling hot or feverish) 
c. chills (shivering) 
d. cough 
e. sore throat 
f. congestion (stuffy or runny nose) 
g. shortness of breath or difficulty breathing with exertion worse than usual 
h. muscle or body aches 
i. fatigue (low energy or tiredness) 
j. headache 


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k. loss of taste or smell 
l. nausea or vomiting 
m. diarrhea 
4. Has mild or moderate COVID-19 (per Section 2.2.2) with one or more of the following 
COVID-19-related signs or symptoms on the day of randomization: 
a. measured temperature ≥38 °C (100.4 °F) 
b. subjective fever (feeling hot or feverish) 
c. chills (shivering) 
d. cough 
e. sore throat 
f. congestion (stuffy or runny nose) 
g. shortness of breath or difficulty breathing with exertion worse than usual 
h. muscle or body aches 
i. fatigue (low energy or tiredness) 
j. headache 
k. loss of taste or smell 
l. nausea or vomiting 
m. diarrhea 
5. Is at high risk of disease progression defined as: 
a. Age ≥55 years 
b. Age 18 to <55 years with one or more preexisting medical conditions as follows 
i. 
Obesity (body mass index [BMI] ≥30 kg/m2) 
ii. Diabetes (Type 1 or Type 2) 
iii. 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) 
iv. Chronic lung disease (emphysema/chronic obstructive pulmonary disease, chronic 
bronchitis, interstitial lung disease [including idiopathic pulmonary fibrosis], or 
cystic fibrosis) 
v. 
Cardiac disease (heart failure, coronary artery disease, or cardiomyopathies)  
vi. Sickle cell disease or thalassemia  
vii. Solid organ or blood stem cell transplant recipients 


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viii. Other immunodeficiency due to underlying illness or immunosuppressant 
medication (eg, corticosteroids ≥20 mg/day prednisone or equivalent) 
ix. Down Syndrome 
x. 
Stroke or cerebrovascular disease, which affects blood flow to the brain 
xi. Substance use disorder 
xii. Pregnant (Enrollment of participants who are pregnant may only open upon sponsor 
communication to sites after iDMC review of data, and only in regions permitted by 
the local health authority) 
c. Age 12 to 17 years (inclusive) with one or more preexisting medical conditions as 
follows 
i. 
BMI >85th percentile for age and sex based on United States Center for Disease 
Control (CDC) growth charts 
ii. 
Diabetes (Type 1 or Type 2) 
iii. 
Chronic kidney disease 
iv. 
Sickle cell disease or thalassemia 
v. 
Congenital or acquired heart disease 
vi. 
Neurodevelopmental disorders (eg, cerebral palsy, Down syndrome) 
vii. A medically-related technological dependence (eg, tracheostomy, gastrostomy, or 
positive pressure ventilation not related to COVID-19) 
viii. Asthma, reactive airway, or other chronic respiratory disease that requires daily 
medication for control  
ix. 
Solid organ or blood stem cell transplant recipients  
x. 
Other immunodeficiency due to underlying illness or immunosuppressant 
medication  
xi. 
Substance use disorder 
xii. Pregnant (Enrollment of participants who are pregnant may only open upon sponsor 
communication to sites after iDMC review of data, and only in regions permitted by 
the local health authority) 
6. Has been assigned female sex at birth and is of nonchildbearing potential. A female 
participant who is not of reproductive potential is eligible without requiring the use of 
contraception and pregnancy testing is not required. This includes female participants who 
have not undergone menarche or who are documented to be surgically sterile (eg, 
hysterectomy, or removal of both ovaries, or tubal ligation) or postmenopausal (ie, 
amenorrhea >1 year and FSH >40 mIU/mL). Follicle-stimulating hormone is not required in 
postmenopausal females with amenorrhea for >2 years 
7. Has been assigned female sex at birth and is of childbearing potential and fulfills all the 
following criteria:  


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a. Has a negative urine or serum pregnancy test at Screening 
b. Has practiced adequate contraception for or has abstained from all activities that could 
result in pregnancy for at least 28 days prior to the first dose (Day 1) 
c. Has agreed to continue adequate contraception for sexual activity that could lead to 
pregnancy through 6 months following study drug administration 
d. Is not currently breastfeeding 
Note: Enrollment of participants who are pregnant or breastfeeding may open only upon 
sponsor communication to sites after iDMC review of Phase 2 data. 
Adequate contraception for participants assigned female sex at birth is defined as consistent 
and correct use of a highly effective locally approved contraceptive method in accordance 
with local regulations for contraceptive use in clinical trial participants. For example: 
a. Intrauterine device (hormonal or non-hormonal) 
b. Hormonal contraceptive taken or administered via oral, transdermal, intravaginal, 
implantable, or injectable method  
c. Sterilization of a female participant’s monogamous male partner prior to entry into the 
study  
d. 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 
starting at the time of consent to participate in the study 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. Has been assigned male sex at birth with partner(s) of childbearing potential and agree to use 
contraception, per local regulations, through 6 months after dosing. If their partner is 
pregnant, males must agree to use a condom. No sperm donation is permitted through 
6 months after dosing. 
9. Is able to understand and comply with study requirements/procedures (if applicable, with 
assistance by caregiver, surrogate, or guardian/LAR) based on the assessment of the 
investigator.  
10. Is able and willing to provide informed consent. An LAR may be used only in cases where 
inclusion criterion 9 is able to be fulfilled. In the case of adolescents, informed assent must 
also be obtained as required by local guidelines. 
4.1.2. 
Exclusion Criteria 
Participants meeting any of the following criteria will be excluded from the study: 
1. Is currently hospitalized or, in the opinion of the investigator, requires urgent medical 
attention or is anticipated to require hospitalization within 48 hours of randomization. 


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2. Has oxygen saturation (SpO2) ≤93% on room air at sea level or ratio of arterial oxygen 
partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) 
<300 mmHg, respiratory rate ≥30 per minute, or heart rate ≥125 per minute. 
3. Is on supplemental oxygen therapy at the time of randomization for any reason or, in the 
opinion of the investigator, has an anticipated impending need for mechanical ventilation. 
4. Has a history of a positive SARS-CoV-2 antibody serology test. Note: serology testing is not 
required for study eligibility, exclusion criterion is based on known history only. 
5. Has participated, within the last 30 days, in a clinical study involving an investigational 
intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 
30 days, whichever is longer, should have passed. 
6. Has known allergy/sensitivity or hypersensitivity to study drug, including excipients.  
7. Has received a SARS-CoV-2 vaccine, monoclonal antibody, or plasma from a person who 
recovered from COVID-19 any time prior to participation in the study.  
8. Has a known active co-infection (eg, influenza, urinary tract infection, etc). 
9. Has any serious concomitant systemic disease, condition, or disorder that, in the opinion of 
the investigator, might confound the results of the study or pose an additional risk to the 
participant by their participation in the study including, but not limited to, any co-morbidity 
requiring surgery or conditions considered life-threatening within 29 days. 
10. Has a clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet 
disorder), or prior history of significant bleeding or bruising following IM injections or 
venipuncture. Abnormal coagulation labs or use of anticoagulant medication are not 
exclusionary in the absence of clinical findings. 
11. Is or has an immediate family member (eg, spouse, sibling, child, guardian/LAR, parent) who 
is an investigator or site or sponsor staff (or designee) directly involved with the study. 
4.1.3. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
who are not subsequently randomly assigned to treatment. A minimum set of screen failure 
information is required to ensure transparent reporting of screen failures to meet the CONSORT 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes date of informed consent (and assent where applicable for adolescents), 
reason for screen failure, and AE information. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened.  
4.2. 
Discontinuation of Study Drug or Withdrawal from the Study 
4.2.1. 
Premature Discontinuation from Study Drug 
In rare instances, it may be necessary for a participant to permanently discontinue study drug. 
Premature discontinuation does not require or represent discontinuation from the study.  


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In the event of study drug discontinuation for safety reasons or participant refusal, the participant 
should remain in the study until all protocol-specified procedures and assessments are completed 
through the EOS Visit at Month 14. If a participant was randomized but did not receive study 
drug, these assessments are not required; however, the participant must be followed for efficacy 
endpoints through Day 29, unless the participant has withdrawn from the study. The estimated 
dose of study drug received prior to discontinuation will be documented. 
Reasons for premature discontinuation from study drug administration must be recorded in the 
eCRF and may include, but are not limited to, the following: 
• Occurrence of an AE that, in the opinion of the investigator, warrants the participant’s 
permanent discontinuation from study drug administration. 
• Participant refusal to continue study drug administration. 
4.2.2. 
Premature Withdrawal from the Study 
Participants may withdraw from the study at any time and for any reason, without prejudice to 
their future medical care, by the investigator or at the study site. Every effort should be made to 
keep participants in the study.  
A participant will be considered to have completed the study when the Month 14 Follow-up Visit 
is completed. If a participant/guardian/LAR/sponsor requests a participant to be withdrawn at 
any time after randomization into the study, the investigator will make every effort to encourage 
the participant to complete the Day 29 visit assessments (if prior to Day 29), Month 6 visit 
assessments (if after the Day 29 visit but before Month 6), or the Month 14 EOS visit 
assessments (if after the Month 6 visit is completed) as shown in Table 12-1.  
As permitted by local guidelines, survival status should be reported through Month 14 for 
participants who received study drug but withdrew from study participation, including survival 
status or death available via public records (eg, death certificates or public registers), medical 
records, participant, or participant contacts, unless the participant has expressly withdrawn 
consent for survival follow up.  
If a participant/guardian/LAR/sponsor chooses to withdraw a participant from the study prior to 
completion, the investigator must be informed immediately and the reason for withdrawal is to 
be recorded in the eCRF. The primary reason for premature withdrawal from the study should be 
selected from the following standard categories: 
Death: The participant died. 
Participant’s Request: The participant is unable to continue to participate in the study but does 
not withdraw consent. If the participant gives a reason, this reason must be recorded in the eCRF.  
Withdrawal of Consent: The participant desired to withdraw from further participation in the 
study absence an investigator-determined medical need to withdraw. If the participant gave a 
reason for withdrawing, it must be recorded in the eCRF.  
Note: If the participant withdraws consent for disclosure of future information, the sponsor 
may retain, and continue to use, any data collected before such a withdrawal of consent. If a 


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participant withdraws from the study, they may request destruction of any samples taken that 
were not tested, and the investigator must document this in the site study records. 
Lost to Follow-up: The participant stopped coming for visits and study personnel were unable to 
contact the participant. 
Note: This reason for withdrawal should not be selected until the last scheduled visit for the 
participant has been missed. In the event the site is unable to contact the participant for 
telemedicine visit, or the participant fails to have an in-clinic or home health visit, site 
personnel must attempt to reschedule the visit. Site personnel must make efforts to contact 
the participant for each scheduled visit. Attempts to contact the participant must be 
documented and may include, but are not limited to, telephone calls or letters to the last 
known telephone number or address.  
Other: The participant was withdrawn from the study for a reason other than those listed above, 
such as termination of study by the sponsor. 
4.2.3. 
Replacements 
Participants who prematurely discontinue from the study will not be replaced. 
5. 
STUDY TREATMENTS 
5.1. 
Method of Assigning Participants to Treatment Groups 
After completing the screening assessments, participants will be randomly assigned at the Day 1 
visit to receive one of the following study treatments (1:1 randomization): 
• ADG20 300 mg administered IM 
• Placebo administered IM 
Randomization will be assigned in a blinded manner using an IRT in accordance with a pre-
generated randomization schedule, generated by SAS software Version 9.4 or later (SAS 
Institute Inc, Cary, North Carolina), linking sequential participant randomization numbers to 
treatment codes. Randomization will be stratified by age (12 to 17, 18 to 65, and >65 years) and 
country; it will also use an appropriate block size, known only by the statistician. A participant is 
considered randomized when a randomization transaction has been recorded in the IRT. 
5.2. 
Treatments Administered 
An unblinded pharmacist (or locally qualified designee) will prepare the study drug or placebo 
for administration. After randomization, participants will receive either a single 300 mg dose (up 
to 3 mL) of ADG20 or matching placebo administered via IM injection.  
Refer to the instructions provided in the Pharmacy Manual for preparing and administering 
ADG20 and placebo dosing solutions.  


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5.3. 
Identity of Study Drug 
ADG20 is a fully human IgG1 targeted to an epitope in the RBD of the spike glycoprotein of 
SARS-CoV-2. Details for the study drug and placebo are shown in Table 5-1. 
Table 5-1: 
Details for Study Drug 
 
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 locally or provided by sponsor 
depending on regional requirements 
Packaging and Labeling 
Provided in glass vials within a carton. 
Each carton and vial will be labeled per 
country requirement. 
Not applicable 
Formulation 
ADG20, 20 mM L-histidine, 
150 mM sodium chloride, 
0.01% polysorbate 80, pH 6.5 
0.9% (weight/volume) sodium chloride 
(normal saline) 
Dosage Form 
Solution for Injection 100 mg/mL 
Solution for Injection 
Route of Administration 
IM 
IM 
Dose and Frequency 
300 mg IM once 
Matched volume and route 
 
5.4. 
Management of Clinical Supplies 
5.4.1. 
Study Drug Packaging and Labeling 
ADG20 drug product will be supplied in glass vials as a sterile, preservative-free solution. 
ADG20 drug product vials are supplied to the study site in a tamper-evident sealed and labeled 
carton. Each carton and vial 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 labeled by study site staff according to the 
Pharmacy Manual.  
5.4.2. 
Storage and Handling Instructions 
Study drug must be stored in a secure, environmentally controlled, and monitored area in 
accordance with the storage conditions described in the Pharmacy Manual, with access limited to 
the unblinded pharmacist (or locally qualified designee) and authorized site staff.  
ADG20 will be shipped to the study site; temperature will be monitored throughout the transit 
period, and temperature tracings will be available for review upon receipt. The investigator or 
designee must confirm the appropriate temperature conditions have been maintained during 
transit for all study drug received per the Pharmacy Manual, and any discrepancies must be 


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reported and resolved before use of the study drug. ADG20 must be stored according to the 
Pharmacy Manual. 
Placebo (normal saline) will be stored and handled at the study site under conditions specified by 
the manufacturer. 
Refer to the Pharmacy Manual for preparing and administering ADG20 and placebo dosing 
solutions and any special handling instructions.  
5.4.3. 
Study Drug Accountability 
Participants will be dosed at the study site and will receive the study drug directly from the 
investigator or locally qualified designee. The date and time of each dose administered at the 
study site will be recorded in the source documents and recorded in the eCRF.  
The investigator will maintain accurate records of receipt of all study drug, including dates of 
receipt. In addition, accurate records will be kept by unblinded site personnel, including when, 
and how much, study drug is prepared and administered to 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 preparation and 
administration of study drug must also be recorded. Upon completion of the study, to satisfy 
regulatory requirements regarding drug accountability, all study drug will be reconciled and 
retained or destroyed according to applicable regulations. Further guidance and information for 
the final disposition of unused study drug are provided in the Pharmacy Manual. 
5.5. 
Blinding 
The study will be double-blind. The investigator, participant, all clinical site staff, and sponsor 
personnel or delegates (except as detailed below) involved in study drug administration and 
evaluation will be blinded to study drug assignments on the participant level. Investigators and 
participants will remain blinded to each participant’s assigned study drug throughout the study. 
Sponsor personnel (or designees) will become unblinded as described below. An iDMC will 
review data in an unblinded manner as described in Section 10.11 and in the iDMC Charter.  
The efficacy and short-term safety analyses will be performed at the time of the database soft 
lock. Participants will be followed through the Month 14 visit or discontinuation from study. 
After the soft lock, all participants, site staff, and sponsor personnel (or designees) working 
directly with the site will remain blinded to the individual study drug assignment until the final 
database lock. The final database lock will occur after all participants have been followed 
through Month 14/EOS (or if it is known that the Month 14 visit will not occur). Subsequently, 
unblinded analysis of data through Month 14/EOS will be performed. 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.  
Vials of ADG20 and normal saline (0.9% sodium chloride injection, USP) will be unblinded to 
the study pharmacist (or locally qualified designee), who will prepare the study drug and 
placebo. All other site staff, sponsor personnel (or designee) working directly with the site staff, 


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and participants will remain blinded to each participant’s assigned study treatment throughout 
the study. 
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel, including blinded sponsor personnel. 
In the event of a quality assurance audit, the auditor(s) may be permitted access to unblinded 
study treatment records at the site(s) to verify that randomization/dispensing has been done 
accurately. However, any findings will be reported in a blinded manner. 
Further details will be included in the study’s unblinding plan.  
5.5.1. 
Breaking the Blind 
A participant’s treatment assignment will not be unblinded to site staff, sponsor personnel (or 
designees) working directly with the site staff, or the participant until the end of the study, unless 
medical treatment of the participant depends on knowing the study treatment the participant 
received. In the event that the blind needs to be broken due to a medical emergency, the 
investigator may unblind an individual participant’s treatment allocation. 
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 
treatment assignment is warranted. Participant safety must always be the first consideration in 
making such a determination. To the extent possible before unblinding, the investigator should 
contact the medical monitor to discuss the medical emergency and the reason for revealing the 
actual treatment received by that participant. The treatment assignment will be unblinded 
through IRT. Reasons for treatment unblinding must be clearly explained and justified in the 
source documentation. The date on which the code was broken together with the identity of the 
person responsible must also be documented. If a participant’s study treatment assignment is 
unblinded, the sponsor or designee must be notified within 24 hours after breaking the blind 
without revealing the study treatment.  
The study specific IRT Manual will provide contact information and additional details on the use 
of the IRT system. 
5.6. 
Prior and Concomitant Medications and Treatments 
5.6.1. 
Prior Therapy 
Information about prior medications, (including any prescription or OTC medications, vaccines, 
or blood products), taken by the participant within the 30 days before dosing (Day 1) must be 
recorded at Screening and predose on Day 1. Refer to exclusion criteria (Section 4.1.2) for 
prohibited prior therapies. 
5.6.2. 
Concomitant Therapy 
All concomitant medications and treatments, defined as those taken after dosing with study drug, 
will be recorded in the participant’s eCRF.  
As a minimum requirement, drug name and the dates of administration are to be recorded. This 
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All concomitant medications will be recorded up to and including Day 60. Any concomitant 
medications related to AEs and any vaccinations received will be recorded for the entire length 
of the study (ie, through Month 14). See the Schedule of Assessments (Table 12-1). Any changes 
in concomitant medications also will be recorded in the participant’s eCRF.  
5.6.2.1. 
Prohibited Concomitant Therapy 
If a participant receives a prohibited concomitant medication, such as those listed below, the 
investigator, in consultation with the sponsor or designee, will evaluate any potential impact on 
receipt of study drug based on time the medication was administered, the medication’s 
pharmacology and PK, and whether the medication will compromise the participant’s safety or 
interpretation of the data. 
The following medications are prohibited concomitant therapy. The use of prohibited 
concomitant medications and/or vaccines will not require withdrawal of the participant from the 
study. 
The following agents are prohibited from randomization to Day 29: 
• Investigational agents or off-label use of marketed products for the treatment of 
SARS-CoV-2 or COVID-19 (eg, convalescent plasma, direct acting antivirals, etc)  
Note: Please refer to the ADG20-TRMT-001 Designated Background Standard of Care 
document for all prohibited therapies. This document will be updated in an ongoing manner 
to address changes in standard of care as additional information becomes available, such as 
from randomized controlled trials.  
• Monoclonal antibodies to SARS-CoV-2  
• Direct-acting antivirals for SARS-CoV-2 (eg, molnupiravir, nirmatrelvir/ritonavir, 
remdesivir) 
Note: For participants who become hospitalized due to COVID-19, products for the 
treatment of SARS-CoV-2 or COVID-19 and/or participation in investigational treatment 
studies is permitted. This includes other monoclonal antibody products and direct-acting 
antiviral agents. Hospitalization is defined as ≥24 hours of acute care in a hospital or acute 
care facility (includes emergency rooms, intensive care units, acute care facilities created for 
COVID-19 pandemic hospitalization needs, or other acute care facilities). Rescue therapy for 
participants who are not hospitalized may be used at the discretion of the investigator if felt 
to be in the best interest of the participant. 
• Receipt of any SARS-CoV-2 or COVID-19 vaccine prior to randomization and through 
Day 29 is prohibited. 
• Any investigational agent or device is prohibited through 90 days after study drug 
administration (see note above for participants who become hospitalized).  
The sponsor or designee must be notified as soon as possible of any instances in which 
prohibited therapies are administered. 


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5.6.2.2. 
COVID-19 Vaccination 
Receipt of any SARS-CoV-2 or COVID-19 vaccine prior to randomization and through Day 29 
is prohibited. 
Adagio and its investigators have the responsibility to inform potential participants (or 
LAR/guardian) that mAb treatment may interfere with vaccine effectiveness. The ACIP 
originally recommended that COVID-19 vaccination be delayed for 90 days post-dosing of mAb 
products. However, based on recent data (Benschop 2021), the ACIP no longer recommends 
delaying COVID-19 vaccination after receipt of a SARS-CoV-2 mAb product (CDC 2022).  
Participants should be made aware of the following: 
1. Participants are encouraged to remain in the study for the full duration even after receipt of a 
COVID-19 vaccination (regardless of blinding status). 
2. Participants will be encouraged to follow local or national guidelines regarding if and when 
they should receive a COVID-19 vaccine. 
3. Participants should notify study staff if they plan to receive a COVID-19 vaccine. The study 
staff will discuss the potential risks and benefits of vaccination after receiving ADG20.  
5.6.2.3. 
Allowed Concomitant Therapy 
The following are allowed concomitant therapies: 
• Supportive care for the management of COVID-19 signs and/or symptoms (such as anti-
inflammatory and antipyretic agents). 
• Only specific Designated Background Standard of Care therapeutics for the management of 
COVID-19 may be maintained in all treatment arms. Please refer to the ADG20-TRMT-001 
Designated Background Standard of Care document, which will be updated in an ongoing 
manner to address changes in standard of care as additional information becomes available, 
such as from randomized controlled trials.  
− If the standard of care per regional or site written guidelines or policies (that is, not just 
an individual clinician’s decision) conflict with the study Designated Background 
Standard of Care, sites should consult with the sponsor or designee.  
− See note in Section 5.6.2.1 regarding participants who become hospitalized due to 
COVID-19 or have a COVID-19-related medically attended visit. 
• Participants may take concomitant medications for the treatment of adverse events. 
• Participants may take concomitant medications prescribed by their primary care or other 
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. 
It is the responsibility of the investigator to ensure that details regarding the medication are 
recorded in full in the eCRF. 


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6. 
STUDY ASSESSMENTS AND PROCEDURES 
Before any study procedures are performed, the participant/guardian/LAR must provide written 
informed consent. In the case of adolescents, informed assent must also be obtained as required 
by local guidelines. Additional procedural details related to the ICF are provided in Section 9.3. 
The amount of blood collected from each participant over the duration of the study, including 
any extra assessments that may be required, will be no more than approximately 200 mL. Repeat 
or unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
Participants will be dosed and monitored in clinic on Day 1 as described in Section 6.4.1.  
During the Follow-Up Period, participants will be followed via telemedicine visits or in-person 
visits (in-clinic or home health) through Day 29 as outlined in the Schedule of Assessments 
(Table 12-1) for safety, PK, virology, and efficacy assessments. In the event that a participant is 
hospitalized during the Follow-Up Period, all procedures and assessments described in 
Table 12-1 should be continued if feasible. Visits or assessments that are not performed or are 
performed late due to hospitalization will not be considered protocol deviations.  
The Schedule of Assessments is provided in Table 12-1. Sections 6.1 and 6.2 describe Screening 
and Day 1 procedures. The remainder of Section 6 describes requirements related to each of the 
activities outlined in the Schedule of Assessments that are common across several visits. 
6.1. 
Screening Procedures 
Participants may be randomized on the same day as Screening. After the completion of the 
screening assessments, eligible participants will be randomized.  
Additional requirements for screening procedures are provided below.  
• Review of participant eligibility based on study inclusion/exclusion criteria (Section 4.1.1 
and Section 4.1.2) will be completed during screening. All screening assessments must be 
reviewed to confirm participant eligibility. Any inclusion criteria with laboratory values 
associated (eg, eGFR, FSH, etc) should be based on local laboratory results or most recent 
medical record.  
− Confirmation of eligibility should be conducted on the day of randomization in case 
participant eligibility changes, eg, disease severity worsens to meet exclusion criteria. 
Site personnel will document details of all reasons for screen failures. 
• Medical history documentation will include all medical conditions, surgeries, or drug 
allergies within the prior year. Participant risk factors meeting inclusion criterion 5 and the 
date of COVID-19 self-reported symptom onset will also be documented.  
• Demographic data collection will include age, sex, and race where locally permitted.  
• Complete physical exam and vital signs, including SpO2, are to be completed per 
Section 6.4.3 and Section 6.4.5. 
• A urine or serum pregnancy test (for women of childbearing potential) must be performed 
within 24 hours prior to study drug administration.  


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• Documentation of positive SARS-CoV-2 local testing result, specimen type, assay type, 
and date of the test will be recorded in the eCRF. SARS-CoV-2 positive antigen, RT-PCR, or 
other locally approved molecular diagnostic assay must have been obtained within 5 days 
prior to the date of randomization (the day of randomization is not considered in the 
calculation of 5 days). A historical record of a positive result from a test conducted within 
5 days prior to randomization is acceptable. SARS-CoV-2 antibody testing cannot be used 
for study eligibility. 
6.2. 
Day 1 Procedures 
Perform all Day 1 procedures as outlined in the Schedule of Assessments (Table 12-1). This 
section describes details regarding only the participant education and participant activities 
performed under observation on Day 1.  
On Day 1, prior to study drug dosing site staff will provide participant study supplies and 
education to participants (guardians/LARs) regarding the following procedures to be 
completed by the participants at home and information about seeking medical care:  
• Saliva collection and packaging for transport to site 
• Daily measurement and documentation of body temperature, SpO2, and heart rate using 
provided thermometer and pulse oximeter 
• Daily COVID-19 Symptom Diary (Appendix 12.2 ) 
• Injection Site Reaction Diary, including showing participants how to use the measuring 
device (Appendix 12.3) 
• Educate participants (guardians/LARs) to seek emergency medical care if emergency 
warning signs for COVID-19, such as trouble breathing, persistent pain or pressure in the 
chest, new confusion, inability to wake or stay awake, bluish lips or face, should develop.  
• Educate participants (guardians/LARs) regarding recognizing and reporting potential 
hypersensitivity reactions to site staff after study drug administration, including but not 
limited to urticaria, edema, respiratory distress, anaphylaxis, and allergic reactions. 
On Day 1, under observation by site staff, participants will: 
• Provide a saliva sample for SARS-CoV-2 testing prior to study drug dosing 
• Complete the daily COVID-19 Symptom Diary prior to study drug dosing 
• Measure and document body temperature, SpO2, and heart rate prior to study drug dosing 
using the thermometer and pulse oximeter provided for at-home use 
• Demonstrate understanding of how to use measuring device and how to document IM 
Injection Site Reaction Diary (Appendix 12.3). At the end of the postdose monitoring period 
at the site, participants will complete the Day 1 ISR prior to departing the clinical site.  


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6.3. 
Efficacy Assessments 
6.3.1. 
Participant At-Home Assessments/Collections 
6.3.1.1. 
Daily COVID-19 Symptom Diary 
Participants will be asked to complete the COVID-19 Symptom Diary (includes global 
impression questions) daily from Day 1 to Day 29 (Appendix 12.2). Site staff will educate the 
participant on the use of the COVID-19 Symptom Diary and will observe the participant 
completing the COVID-19 Symptom Diary on Day 1 prior to study drug administration. 
The diary should be completed around the same time each day documenting each symptom at its 
worst in the prior 24 hours. Targeted symptoms and overall health status questions included in 
the diary are outlined in Appendix 12.2. If a participant is unable to complete the COVID-19 
Symptom Diary on their own, a parent/guardian/LAR/family member/other caregiver may assist 
in completion of the diary and should be educated on diary completion. When asking the 
participant the Diary questions, the exact language provided in the Diary should be used and the 
person assisting should not lead the participant or elaborate. Proxy reporting by an observer (eg, 
parent) on behalf of the participant should not be used. Only participant reported symptoms 
should be captured in the diary.  
Additionally, site staff may interview the participant via telemedicine visit or in-person visit for 
diary completion and document on the paper back-up diary for entry into the eCRF. In this 
situation, when asking the participant the Diary questions, the exact language provided in the 
Diary should be used and site staff should not lead the participant or elaborate. 
Regular reminders at each visit will be provided by site staff (or delegate) to participants for 
completion of the COVID-19 Symptom Diary. The COVID-19 Symptom Diary will be reviewed 
at all telemedicine and in-person visits (Days 3, 5, 7, 11, 14, 21, and 29) and the investigator (or 
medically qualified designee) will assess the participant’s COVID-19 severity. 
In the event that a participant is hospitalized during the Follow-Up Period, the diary should be 
completed if feasible. A parent/guardian/LAR/family member/other caregiver may assist in 
completion of the Diary or site staff or local home health care provider may interview the 
participant via telemedicine visit or in-person visit for diary completion as described above per 
local regulations. Upon discharge, the participant should resume diary completion through 
Day 29. 
6.3.1.2. 
Saliva Collection for SARS-CoV-2 Quantitative RT-PCR 
Participants will be provided with saliva sample test kits and transport packaging materials for 
use on Days 3, 5, 11, 14, and 21. Site staff will educate the participant on the proper collection 
and transport procedures. Saliva samples on Day 7 and Day 29 will be collected and transported 
by site staff at the in-person visits (in-clinic or home health). 
On Day 1 prior to study drug administration, site staff will observe the participant collecting and 
packaging the saliva sample. Participants should NOT eat, drink, smoke, or chew gum for 
30 minutes before all saliva sample collections.  


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Saliva samples will be analyzed for quantitative RT-PCR for determination of viral load, viral 
clearance, and duration of viral shedding and may be used for viral sequencing.  
In the event that a participant is hospitalized during the Follow-Up Period, saliva collection 
should be continued if feasible. If access to a participant by parent/guardian/LAR/family 
member/other or site staff is not possible, engagement of a local home health care visit can be 
considered per local regulations.  
6.3.1.3. 
Daily Temperature, Blood Oxygen Saturation, and Heart Rate 
On Day 1, participants will be provided with a thermometer and a pulse oximeter. Site staff will 
educate the participant (or guardian/LAR) on the measurement of temperature, SpO2, and heart 
rate and proper documentation in the daily diary. The participant (or guardian/LAR) will be 
observed completing the measurement and documentation of temperature, SpO2, and heart rate 
on Day 1 prior to study drug administration. 
Participants (or guardians/LARs) will be asked to monitor temperature, SpO2, and heart rate 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. In the event that a 
participant is unable to complete the measurements and documentation on their own, a 
parent/guardian/LAR/family member/other caregiver may assist in measuring and documenting 
the temperature, SpO2, and heart rate. 
In the event that a participant is hospitalized, information regarding temperature, SpO2, and heart 
rate should be collected if feasible. If access to a participant by parent/guardian/LAR/family 
member/other caregiver or site staff is not possible, engagement of a local home health care visit 
can be considered per local regulations. 
6.3.2. 
Site Clinical Assessments 
6.3.2.1. 
COVID-19 Symptom Diary, Reported Vitals Review, and Injection Site Reaction 
Diary Review  
Site staff will review the COVID-19 Symptom Diary, vitals (temperature, SpO2, and heart rate), 
and ISRs reported in the diary as outlined in the Schedule of Assessments (Table 12-1). In the 
event of participant use of paper diary, the participant will provide information at telemedicine 
visits to the site staff about their diary entries to allow for monitoring and documenting 
participant COVID-19 severity (Section 6.3.2.2), and paper diaries will be collected from 
participants at all in-person visits.  
Based on investigator judgment, participants reporting worsening of signs or symptoms related 
to COVID-19 during the study may be referred to have an unscheduled study visit with site 
personnel or home health care provider. Participants will be referred to seek emergency medical 
care if emergency warning signs for COVID-19 should develop (trouble breathing, persistent 
pain or pressure in the chest, new confusion, inability to wake or stay awake, bluish lips or face). 
During the telemedicine visit, the site staff will review the body temperature, SpO2, and heart 
rate documented in the diary. The participant (or guardians/LARs) will report any medications 
taken to treat current illness/symptoms, any new onset AEs, and the investigator or medically 


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qualified designee will determine if medical attention is required due to worsening of 
COVID-19. At all visits, the participant will be reminded to complete daily COVID-19 Symptom 
Diary; daily temperature, SpO2, and heart rate; ISR diary; and saliva sample collection on the 
appropriate days. Participants will be reminded at these visits regarding the importance of 
completion of the diary. See the Schedule of Assessments (Table 12-1) for additional details. 
6.3.2.2. 
COVID-19 Severity Assessment 
The investigator (or medically qualified designee) will assign an overall COVID-19 severity 
grade for each visit through Day 29 as determined according to the severity definitions provided 
in Section 2.2.2. The Day 1 assessment should occur prior to the first dose of study drug based 
on signs/symptoms present on Day 1.  
6.3.2.3. 
Survival Assessment 
The participant’s survival status (known to be alive or dead) will be determined at the planned 
time for any missed visit through Month 14 or at any time that the participant is thought to be 
lost to follow up. In the event that the participant is not able to be reached, site staff should 
utilize primary and secondary contacts including personal contacts, health care provider, and 
local hospitals as outlined in the ICF (Section 9.3). As described in Section 6.9.3, every effort 
should be made by site staff to ascertain survival status. If survival status is not known, the date 
last known to be alive will be recorded. 
As required for SAE reporting, a death must be reported in the eCRF within 24 hours of the site 
becoming aware of the death. As permitted by local guidelines, survival status should be reported 
for participants who have withdrawn from study participation (including survival status or death 
available via public records [eg, death certificates or public registers]).  
6.3.2.4. 
Medically Attended Visits Assessment 
Medically attended visits will be solicited from participants (or guardians/LARs) as outlined in 
the Schedule of Assessments (Table 12-1). In the event that the participant is not able to be 
reached, site staff should utilize primary and secondary contacts including personal contacts, 
health care provider, and local hospitals as outlined in the ICF (Section 9.3). 
COVID-19-related medically attended visits include telemedicine visits not specified by the 
protocol, emergency rooms or urgent care center visits, hospitalization, or visits to a physician’s 
office for attention to worsening signs or symptoms attributed to COVID-19, in the opinion of 
the investigator.  
Every effort will be made to capture medical information from any medical visits (eg, visits to 
the primary care provider(s), emergency department/urgent care clinic visits, hospitalizations, 
etc) related to COVID-19 or its complications using the appropriate eCRFs. Any data relevant 
for assessment of the efficacy endpoints and ADE will also be collected. These are likely to 
include, but are not limited to, type and duration of visit(s), reason for visit(s), information on 
ICU admissions; clinical parameters, such as SpO2, respiratory rates, and vital signs; need for 
oxygen therapy; need for ventilatory support; imaging; blood tests results; and overall outcome 
(survival or death). 


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In the event that a participant is hospitalized during the Follow-Up Period, all procedures and 
assessments described in the Schedule of Assessments (Table 12-1) should be continued if 
feasible. If access to a participant by site staff is not possible, engagement of a local home health 
care visit can be considered per local regulations. If the hospital institution does not permit 
in-person visits, telemedicine visits can be performed to collect all feasible assessments in 
Table 12-1. Visits or assessments that are not performed or are performed late due to 
hospitalization will not be considered protocol deviations. Upon discharge, every effort should 
be made to ensure continued study visits occur.  
6.3.2.5. 
Long-Term Health Status Assessment 
During the long-term follow-up period, participants will be asked questions about their overall 
health status including return to usual health and usual activities and any ongoing symptoms 
associated with COVID-19.  
6.3.2.6. 
Household Transmission Questionnaire 
At the Day 29 visit, participants will be asked about household transmission of SARS-CoV-2 
and symptomatic COVID-19. Participants will be asked if any household contacts had a 
documented asymptomatic SARS-CoV-2 infection or symptomatic COVID-19 after the 
participant’s receipt of study drug. If so, participants will be asked to report the number of 
household contacts that had SARS-CoV-2 asymptomatic infection and the number of household 
contacts that had symptomatic COVID-19. 
6.4. 
Safety Assessments 
Safety will be assessed in an ongoing manner. Participants will receive a single dose of ADG20 
or placebo at the study site and will be monitored after dosing for acute worsening of disease, 
hypersensitivity, and ISRs. During Phase 2, the first 10 participants will be monitored for at least 
4 hours after dosing. If no significant hypersensitivity reactions or ISRs are identified, the 
monitoring period may be reduced as described in Section 6.4.1. If any hypersensitivity reactions 
occur, the iDMC will review available safety data and provide a recommendation regarding the 
duration of monitoring, which will be formally communicated to sites without a protocol 
amendment and included in ICF/assents. Participants will then be followed via telemedicine 
visits, phone call, or in-person visits as indicated in the Schedule of Assessments (Table 12-1) 
through Month 14.  
Safety assessments will include monitoring of AEs, clinical laboratory testing, vital sign 
measurements (body temperature, heart rate, respiration rate, and systolic and diastolic blood 
pressure), and physical examinations. AESI (hypersensitivity reactions) will be recorded through 
Day 4. Hypersensitivity reactions occurring after Day 4 will be recorded as AEs. Participants 
will record any ISRs using the Injection Site Reaction Diary starting after dosing on Day 1 
through Day 4 (Appendix 12.3). Investigators or medically qualified designees will follow all 
ISRs that are ongoing beyond Day 4 to resolution. Only ISRs that qualify as an SAE or that 
worsen or begin after Day 4 should be recorded in the eCRF AE form; all other ISRs are only to 
be recorded in the eDiary. Other AEs, including SAEs and MAAEs (including new onset chronic 
illnesses), will be collected through 14 months. 


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See Table 12-1 for the Schedule of Assessments. 
6.4.1. 
Safety Monitoring After Study Drug Administration 
Participants will be observed at the study site after study drug administration according to 
Table 6-1.  
Table 6-1: 
Safety Monitoring After Study Drug Administration 
Post-dose 
monitoring 
duration 
• 
The first 10 participants enrolled require post-dose monitoring at site for 4 hours. 
• 
If no hypersensitivity reactions are seen in the first 10 participants, monitoring will be 
reduced to 2 hoursa 
• 
If no hypersensitivity reactions are seen during the administrative interim analysis when 
200 participants have been enrolled in Phase 2, monitoring will be reduced to 1 hour for the 
remaining participants. 
• 
If hypersensitivity reactions are observed, the iDMC will make a recommendation for 
monitoring. 
Note: Changes to post-dose monitoring required at site will be formally communicated to sites 
without a protocol amendment.  
Vital signs 
Required vital sign measurements (temperature, heart rate, respiratory rate, blood pressure, and 
SpO2). 
• 
15 minutes (±15 minutes) prior to injection 
• 
30 minutes (±5 minutes) after the injection is completed 
• 
Any additional monitoring as determined by the iDMC will be communicated to sites 
without a protocol amendment 
a As of 21 Dec 2021, evaluation of safety data revealed no hypersensitivity reactions or adverse events of concern reported 
through Day 4 in the first 200 participants. Therefore, the post-dose monitoring period was reduced from 2 hours to 1 hour. 
Previously, as 07 Oct 2021, evaluation of safety data revealed no hypersensitivity reactions or adverse events of concern 
reported through Day 4 in the first 10 participants. Therefore, the post-dose monitoring period was reduced from 4 hours to 2 
hours.  
 
6.4.1.1. 
Injection Site Reaction Monitoring and Management 
Monitor all participants closely during and after study drug administration as outlined above as 
there is a risk of injection site reaction and hypersensitivity (including anaphylaxis) with any 
biological agent. 
Study drug will only be administered in settings in which health care providers have immediate 
access to medications to treat a severe injection or hypersensitivity reaction, such as anaphylaxis, 
and the ability to activate the emergency medical system, as necessary. The clinical site should 
have necessary equipment and medications for the management of any reactions, which may 
include but is not limited to oxygen, IV fluid, epinephrine, acetaminophen, and antihistamines. 
Symptoms and signs that may occur include, but are not limited to fever, chills, nausea, 
headache, bronchospasm, hypotension, angioedema, throat irritation, rash including urticaria, 
pruritus, myalgia, and dizziness. 
Investigators should manage reactions based on standard of care and their clinical judgment. If a 
hypersensitivity or injection reaction occurs, then supportive care should be used in accordance 
with the signs and symptoms. Hypersensitivity reaction severity will be assessed and reported 


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using the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 
(Table 6-2). In the case of mild to moderate ISRs, acetaminophen, topical steroids, cold 
compress and/or antihistamines may be provided. Participants experiencing more severe 
reactions will be referred for appropriate care (eg, dermatology evaluation or emergency care, 
depending on the severity of the reaction).  
Hypersensitivity reactions after study drug administration will be collected as AESI through 
telephone/telemedicine visits during the follow-up period per the Schedule of Assessments 
(Table 12-1). On Day 1 through Day 4, hypersensitivity reactions including but not limited to 
urticaria, edema, respiratory distress, anaphylaxis, and allergic reactions will be recorded as 
AESIs. Hypersensitivity reactions occurring after Day 4 will be recorded as AEs. Participants 
reporting a hypersensitivity reaction outside of a regularly scheduled in-person visit should have 
an unscheduled visit as described in Section 6.8.2 for evaluation of such reaction (including 
collection of PK and ADA samples). Site staff will educate participants (guardians/LARs) on 
Day 1 regarding recognizing and reporting potential hypersensitivity reactions to site staff. 
Participants will be queried regarding any ISRs (see Section 6.4.6.2.1) and the injection sites 
examined at least 1 hour following injection. Solicited ISRs will be collected in the diary from 
Day 1 through Day 4 as described in Section 6.4.1.2. Investigators or medically qualified 
designees will follow all ISRs that are ongoing beyond Day 4 to resolution.  
6.4.1.2. 
Injection Site Reaction Diary  
Solicited ISRs will be collected in the Injection Site Reaction (ISR) Diary from Day 1 through 
Day 4. Investigators or medically qualified designees will follow all ISRs that are ongoing 
beyond Day 4 to resolution. Each day, participants should document the worst pain, tenderness, 
redness, or swelling that was experienced in the last 24 hours. Participants will be provided a 
ruler by the site study team to measure redness or swelling at the injection sites. For irregular 
shapes, the widest part of the area (how much of the skin the redness or swelling covers) should 
be measured. Redness or swelling should be measured each day that it is visible. Severity will be 
assessed for solicited AEs (ISRs) by the participant (or, if applicable, with help from their 
caregiver, surrogate, or guardian/LAR) as described in Appendix 12.3.  
At the Day 1 visit, study site staff will provide information to the participant (or guardian/LAR) 
about the questions that will be asked in the diary and how to complete the ISR Diary and use the 
measuring device. At the end of the post-dose monitoring period at the site, participants will 
complete the Day 1 ISR prior to departing the clinical site. Site staff will observe the participants 
completing the diary on Day 1 and will answer any questions participants may have about the 
diary.  
Only ISRs that qualify as an SAE or that worsen or begin after Day 4 should be recorded in the 
eCRF AE form, all other ISRs are only to be recorded in the eDiary. 
6.4.2. 
Clinical Safety Laboratory Assessments 
Blood samples for safety laboratory assessments (hematology, serum chemistry, and coagulation; 
see Appendix 12.4) will be collected on the days specified in the Schedule of Assessments 
(Table 12-1).  


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6.4.3. 
Physical Examinations 
A complete physical examination during screening will include general/appearance; head, eyes, 
ears, nose, throat, and oropharynx; pulmonary; cardiovascular; gastrointestinal; screening 
neurologic exam (mental status, cranial nerves, motor, sensory, coordination, reflexes, and gait); 
extremities; and skin evaluations. Height and weight will also be measured and recorded. On 
Day 1, the complete physical exam will include review and documentation of all COVID-19-
related signs/symptoms. Investigators should pay special attention to clinical signs related to 
previous serious illnesses. Any clinically significant abnormalities should be documented as 
medical history.  
6.4.4. 
Targeted Review of Changes in Health 
A targeted, symptom-directed review of changes in health based on reported AEs or ongoing 
signs/symptoms of COVID-19 will be conducted at the visits specified in the Schedule of 
Assessments (Table 12-1). Any clinically significant abnormalities should be documented as 
AEs by site staff. 
6.4.5. 
Vital Signs 
Vital signs, including temperature, heart rate, respiratory rate, seated blood pressure, and SpO2 
will be assessed by site staff at the specified timepoints in the Schedule of Assessments 
(Table 12-1) and recorded in the eCRF. At the Day 1 Visit, vital signs will be performed as 
described in Section 6.4.1. Daily measurement of temperature, SpO2, and heart rate by 
participants is described in Section 6.3.1.3.  
6.4.6. 
Adverse Events 
Adverse events occurring from when the participant signs the ICF until the Month 14 (EOS) visit 
or withdrawal will be recorded. Only study procedure-related AEs occurring before 
randomization will be recorded. All AEs will be followed and recorded up to the Month 14 
(EOS) Visit.  
6.4.6.1. 
Definitions 
6.4.6.1.1. Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to the study drug or their clinical significance. 
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. Participants will be instructed to contact 
the investigator at any time after randomization if any symptoms develop. 
A TEAE is defined as any event not present before exposure to the study drug or any event 
already present that worsens in either intensity or frequency after exposure to the study drug.  
For the purposes of this study, worsening or sequelae of the index case of COVID-19 will not be 
recorded as AEs, unless they meet SAE criteria. These data will be captured as efficacy 
assessment data as these are expected endpoints. Subsequent episodes of COVID-19 in the same 


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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. 
Anticipated day-to-day fluctuations of preexisting diseases or conditions present or detected at 
the start of the study that do not worsen would not be considered AEs. Laboratory results of 
disease/disorders being studied and medical/surgical procedures are not considered AEs but 
rather the condition/event that leads to it are defined as an AE. 
6.4.6.1.2. 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 
Immediately life-threatening: report if suspected that the patient was at substantial risk of dying 
at the time of the adverse event, 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 adverse event. 
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. 
6.4.6.1.3. Suspected Unexpected Adverse Events 
A SUSAR is defined as an adverse reaction, the nature or severity of which is not consistent with 
the applicable product information (eg, IB for an unapproved investigational medicinal product). 
6.4.6.1.4. Adverse Events of Special Interest 
An AESI (serious or nonserious) is defined as an AE or SAE of scientific and medical concern 
specific to the sponsor’s product or program, for which ongoing monitoring and rapid 
communication by the investigator to the sponsor or designee could be appropriate (ICH E2F; 
CIOMS VI). 


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For this study, AESIs are as follows:  
• Hypersensitivity reactions occurring through Day 4 
− 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 allergy, immune thrombocytopenia, autoimmune hemolytic anemia, rash, urticaria, 
arthus reaction, etc 
6.4.6.1.5. 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 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. 
6.4.6.2. 
Eliciting and Documenting Adverse Events 
Adverse events will be assessed from the time the participant signs the ICF until exit from the 
study. 
If the investigator learns of any SAE, including a death, at any time after a participant has been 
discharged from the study, and considers the event to be reasonably related to the study drug or 
study participation, the investigator must promptly notify the sponsor or designee. 
At every study visit, participants will be asked a standard nonleading question to elicit any 
medically related changes in their well-being.  
In addition to participant observations, AEs identified from any study data (eg, clinically 
meaningful laboratory values, physical examination findings) or identified from review of other 
documents (eg, participant diaries) that are relevant to participant safety will be documented on 
the AE page in the eCRF. 
6.4.6.2.1. Assessment of Severity 
Adverse Event Severity 
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 solicited AEs of ISRs) 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 


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• Grade 5 indicates death (Note: This grade is not specifically listed on each page of the 
grading table.) 
Hypersensitivity Reactions 
All participants will be monitored closely for signs/symptoms of local or systemic 
hypersensitivity reactions. 
The site should have appropriately trained medical staff and appropriate medical equipment 
available when study participants are receiving dosing. It is recommended that participants who 
experience a systemic hypersensitivity reaction be treated per the local standard of care. 
Hypersensitivity reaction severity will be assessed and reported using the DAIDS Table for 
Grading the Severity of Adult and Pediatric Adverse Events (Table 6-2). 
Table 6-2 
DAIDS Table for Grading the Severity of Adult and Pediatric Adverse 
Events – Systemic 
Parameter 
Grade 1 
Mild 
Grade 2 
Moderate 
Grade 3 
Severe 
Grade 4 
Severe and 
Potentially 
Life-threatening 
Acute 
Allergic 
Reaction 
Localized urticaria 
(wheals) with no 
medical intervention 
indicated 
Localized urticaria 
with intervention 
indicated 
OR 
Mild angioedema with 
no intervention 
indicated 
Generalized urticaria 
OR 
Angioedema with 
intervention indicated 
OR 
Symptoms of mild 
bronchospasm 
Acute anaphylaxis 
OR 
Life-threatening 
bronchospasm 
OR 
Laryngeal edema 
Cytokine 
Release 
Syndromea 
Mild signs and 
symptoms 
AND 
Therapy interruption 
not indicated 
Therapy interruption 
indicated 
AND 
Responds promptly to 
symptomatic 
treatment 
OR 
Prophylactic 
medications indicated 
for ≤24 hours 
Prolonged severe 
signs and symptoms 
OR 
Recurrence of 
symptoms following 
initial improvement 
Life-threatening 
consequences (for 
example, requiring 
pressor or ventilator 
support) 
a A disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath. 
Source: Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 (NIAID 
2017). 
Intramuscular Injection Site Reaction Severity 
Intramuscular ISRs will be graded using the FDA Guidance for Industry: Toxicity Grading Scale 
for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 
(FDA 2007b). The Injection Site Reaction Diary is in Appendix 12.3. Because solicited AEs are 
expected to occur after injections, ISRs will not be assessed for relationship to study drug. 


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6.4.6.2.2. Assessment of Causality 
The investigator’s assessment of an AE’s relationship to the study drug is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the study. 
If there is any doubt as to whether a clinical observation is an AE, the event should be reported. 
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 
• Biological plausibility 
• Lack of alternative explanation, ie, concomitant drug, or disease 
6.4.6.3. 
Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the eCRF from 
the time of dosing until the EOS Visit. If a study procedure-related AE occurs after the execution 
of informed consent (and assent where applicable for adolescents) but prior to randomization, it 
will also be recorded. Information to be collected includes the following: 
• Event term 
• Date and time of onset 
• Investigator-specified assessment of severity and relationship to the study drug 
• Date and time of resolution of the event 
• Seriousness 
• Any required treatment or evaluations 
• Outcome 
AEs resulting from concurrent illnesses, reactions to concurrent illnesses, reactions to concurrent 
medications, or progression of disease states must also be reported. Exceptions to this reporting 
related to COVID-19 signs and symptoms are described in Section 6.4.6.1.1. All AEs will be 
followed to adequate resolution. MedDRA will be used to code all AEs. 


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Any medical condition that is present at the time that the participant is screened but does not 
deteriorate should not be reported as an AE. However, if it deteriorates at any time during the 
study, it should be recorded as an AE. 
6.4.6.3.1. Reporting Serious Adverse Events and Suspected Unexpected Serious Adverse 
Reactions 
Each AE will be assessed to determine whether it meets seriousness criteria (Section 6.4.6.1.2). 
All SAEs (related and unrelated) will be recorded from the time of dosing until the EOS Visit. If 
a study procedure-related SAE occurs after the execution of informed consent (and assent where 
applicable for adolescents) but prior to randomization, it will also be recorded. Any SAEs 
considered related to the study drug and discovered by the investigator at any time after the study 
should be reported. The investigator will report any SAE to the sponsor or designee as outlined 
below and to the IRB/IEC according to its SOPs.  
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 the sponsor or designee. If this occurs after the electronic data capture (EDC) closure, 
this will only be captured in the Safety Database. 
Any AE that meets SAE criteria (Section 6.4.6.1.2) must be reported to 
 Pharmacovigilance 
immediately (ie, within 24 hours) after site personnel first learn of the event.  
See Contact Information for Reporting SAEs. 
At a minimum, the initial report should include the following information: 
• Event 
• Study code 
• Participant number 
• Study drug (in situations where the blind had to be broken [Section 5.5.1]) 
• 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 
until resolution or stabilization and for reported deaths, the investigator should supply the 
sponsor or designee and the IRB/IEC with any additional requested information (eg, autopsy 
reports, and terminal medical reports). The investigator will be responsible for reviewing and 
signing each SAE report that is submitted.  
The original SAE report should be kept at the study site. Additional SAE follow-up information, 
if required or available, should be submitted to the sponsor or designee within 1 business day of 
receipt following the procedure described above. All supplemental documentation regarding the 
SAE shall be maintained in the investigator’s study files. The sponsor or designee will be 
responsible for determining and in turn, reporting SAEs to regulatory authorities according to the 
applicable regulatory requirements. 
SAEs that are ongoing at the Month 14 (EOS) Visit should be followed until resolved. 


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An SAE may qualify for expedited reporting to regulatory authorities if it is determined to be a 
SUSAR (Section 6.4.6.1.3). The sponsor or designee is responsible for submitting expedited 
safety reports to the appropriate regulatory agency for all confirmed SUSARs. These reports will 
comply with the applicable regulatory requirements and with the ICH Guideline for Clinical 
Safety Data Management: Definitions and Standards for Expedited Reporting (E2A). In the case 
of a fatal or life-threatening SUSAR, the sponsor or designee will notify the appropriate 
regulatory agency as soon as possible but in no case later than 7 calendar days after the sponsor 
or designee first receives the information. For a non-life-threatening SUSAR, the report will be 
submitted no later than 15 days after the sponsor or designee is made aware of the event. 
Investigators will also be notified of all unexpected, serious, drug-related events (7- or 15-Day 
Safety Reports) that occur during the clinical trial. Each investigational site is responsible for 
notifying its IRB or IEC of these additional SAEs. 
6.4.6.3.2. Exceptions 
For the purposes of this study, worsening or sequelae of the index case of COVID-19 will not be 
recorded as AEs, unless they meet 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. 
6.4.6.3.3. Unanticipated Problems Involving Risks and Adverse Events 
Investigators will report all unanticipated problems involving risk to human subjects promptly to 
the IRB and Sponsor if required by local country regulations. 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).  
Definition of Unanticipated Problems 
An AE observed during the conduct of a study should be considered an Unanticipated Problem 
(UP) involving risk to human subjects, 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) 


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• 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 subjects  
Reporting of Unanticipated Problem 
The investigators will report the UPs to their IRB and to the Sponsor if required by the local 
country 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 
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). 
6.4.6.4. 
Follow-Up of Participants Reporting Adverse Events 
All AEs must be reported in detail on the appropriate page in the eCRF and followed to 
satisfactory resolution, until the investigator deems the event to be chronic or not clinically 
significant, the event is considered to be stable, or the participant is lost to follow-up. 
6.4.7. 
Pregnancy  
If a female 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; the 
form should be sent to 
 Pharmacovigilance (see Contact Information for Reporting SAEs). 
For participants who become pregnant and have received study drug, study discontinuation is not 
required. 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/EOS visit or at 
early termination from the study. 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 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.  
Pregnancy 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 


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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.  
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.  
6.4.8. 
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 patient. 
There is no specific antidote for overdose.  
The occurrence of an overdose with no associated abnormal laboratory assessments or clinical 
symptoms should be reported 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.  
6.5. 
Blood Collection and Nasopharyngeal Swabs 
Blood will be collected as outlined in the Schedule of Assessments (Table 12-1) for exploratory 
analyses. The impact of host and viral biomarkers, such as baseline SARS-CoV-2 antibody 
responses, and viral load, on selected outcomes may be evaluated. 
Nasopharyngeal swabs will be collected as outlined in the Schedule of Assessments (Table 12-1) 
for quantitative SARS-CoV-2 RT-PCR and for genotypic and phenotypic characterization as 
appropriate of the SARS-CoV-2 isolate for evaluation of viral resistance. The presence of 
additional pathogens on Day 1 will be assessed through a respiratory pathogen panel assay on a 
nasopharyngeal swab.  
6.6. 
Pharmacokinetics 
Blood samples to provide serum for the analysis of ADG20 concentrations will be collected as 
outlined in the Schedule of Assessments (Table 12-1). The PK sampling schedule may be 
modified based on emerging PK data. 
On Day 1, one PK sample is to be collected at baseline prior to study drug administration in all 
participants. All other visits with PK sample collection will have one sample collected during the 
visit. 
In addition to samples collected at the scheduled times, an additional blood sample should be 
collected from participants experiencing hypersensitivity reactions as described in Section 6.8.2. 
The date and time of sample collection should be documented. 
All efforts will be made to obtain PK samples at the scheduled nominal time relative to dosing. 
However, samples not obtained within the protocol-specified time windows will not be captured 
as a protocol deviation, as long as the exact time of the sample collection is documented. If a 


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scheduled blood sample collection cannot be completed for any reason, the missed sample time 
may be rescheduled with agreement of the clinical investigator, patient, and sponsor or designee. 
Samples for PK analysis will be assayed for ADG20 using a validated analytical method. Details 
regarding the collection, processing, storage and shipping of the blood samples will be provided 
in the laboratory manual. 
6.7. 
Immunogenicity 
Blood samples to provide serum for detection of ADA (and neutralizing antibody) against 
ADG20 will be collected at timepoints specified in the Schedule of Assessments (Table 12-1). In 
addition to samples collected at scheduled visits, an additional blood sample should be collected 
from participants experiencing hypersensitivity reactions as described in Section 6.8.2. 
Additional instructions for sample collection, processing, storage, and shipping will be provided 
in the laboratory manual. 
Immunogenicity may be assessed by a validated assay designed to detect ADAs in the presence 
of ADG20 at a laboratory approved by the sponsor or designee. Antibodies may be further 
characterized for their ability to neutralize the activity of ADG20. The sample analysis will 
follow a tiered approach of screening, confirmation, and titer determination. 
6.8. 
Unscheduled Visits 
6.8.1. 
COVID-19 Unscheduled Visits (Worsening, Relapse, or Recurrence) 
Based on investigator’s judgment, participants reporting worsening of signs or symptoms related 
to COVID-19 during the study may be referred to have an unscheduled study visit with site 
personnel or home health care provider. Participants will be referred to seek emergency medical 
care if emergency warning signs for COVID-19 should develop (trouble breathing, persistent 
pain or pressure in the chest, new confusion, inability to wake or stay awake, bluish lips or face). 
In the case of worsening COVID-19 not warranting emergency medical care, the site should 
perform an unscheduled visit, including saliva sample collection for RT-PCR testing and 
sequencing for SARS-CoV-2, collection of local and/or central safety laboratory samples per 
investigator discretion, vital signs, targeted review of changes in health, review of concomitant 
medications and adverse events, and medically attended visits assessment. 
If at any time a participant reports a recurrence of COVID-19-like symptoms after having met 
the sustained recovery in the investigator’s judgement or in the case of suspected re-infection, 
the site should perform an unscheduled visit, including saliva sample collection for RT-PCR 
testing and sequencing for SARS-CoV-2, collection of local and/or central safety laboratory 
samples per investigator discretion, vital signs, targeted review of changes in health, review of 
concomitant medications and adverse events, and medically attended visits assessment. This 
recurrence of symptoms will be treated as an AE (or SAE, if meeting criteria). 
6.8.2. 
Hypersensitivity Reaction Assessment Unscheduled Visit 
In the event that a participant reports a hypersensitivity reaction after Day 4 and outside of a 
regularly scheduled in-person visit, an unscheduled visit for evaluation of the reaction should be 
performed. This visit should include collection of samples for PK and ADA and collection of 


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local and/or central safety laboratory samples per investigator (or qualified designee) discretion 
using the unscheduled extra tube supply. Additionally, the following assessments should be 
performed: vital signs, a targeted review of changes in health, review of concomitant 
medications and adverse events, and medically attended visits collection.  
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 
allergy, immune thrombocytopenia, autoimmune hemolytic anemia, rash, urticaria, arthus 
reaction, etc.  
6.8.3. 
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 
using the unscheduled extra supply kits. 
6.9. 
Administrative Procedures 
6.9.1. 
Visit Type Requirements 
As outlined in the Schedule of Assessments, several visit types (in-clinic, home health, or 
telemedicine) will be utilized throughout the study.  
In-person visits may be conducted in-clinic or as home health visits (where allowed by local 
regulations and as outlined in the Schedule of Assessments [Table 12-1]). Home health provider 
visits may also be combined with telemedicine contact with the site personnel, investigator, or 
medically qualified designee as needed. Home health visits will be at the location of the 
participant and may include a home health vendor to visit to a location other than the participants 
home such as a hospital or other location. 
At all in-person visits (in-clinic or home health), site personnel or home health providers will 
follow institutional or local standards to prevent transmission of SARS-CoV-2. This may include 
procedures such as use of personal protective equipment for participants (and guardians/LARs), 
site staff, and home health providers and providing designated entry locations for study 
participants/guardians/LARs for visits.  
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.  
6.9.2. 
Use of eDiary 
At the time of consent, the participants must confirm they will be willing to complete an eDiary 
(once daily through Day 29). The eDiary will be provided either through a device or an 
application downloaded to their mobile smart device (smartphone, tablet, etc) or a provided 
device (at site discretion/availability) at the time of enrollment.  


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• Before dosing on Day 1, the participant will be instructed how to access the eDiary on their 
personal mobile smart device or provided device. 
• This study will preferably use the eDiary (via device or application) for the collection of 
COVID-19 symptoms; daily temperature, SpO2, and heart rate; and ISRs. 
• Participants or sites unwilling or unable to utilize an eDiary may be provided paper diaries 
for use (at site discretion/availability). Paper diaries may be used as back-up in the event 
eDiary is unavailable due to technological or other issues. Paper diaries should be collected 
from participants at all in-person visits. 
6.9.3. 
Collection and Update of Contacts 
In order 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. This 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 
Schedule of Assessments (Table 12-1). 
7. 
STATISTICAL CONSIDERATIONS 
This section briefly describes the statistical and analytical methods to be used. An SAP will 
provide details of the statistical methods and definitions for the analysis of efficacy and safety 
data.  
Enrollment in the study was suspended on 11-Jan-2022 after emergence and global spread of the 
Omicron variant in regions enrolling the trial, beginning in December 2021. Therefore, the 
primary analysis is focused on evaluating the efficacy of ADG20 300 mg IM in participants with 
a non-Omicron variant of SARS-CoV-2. With this analysis plan, the primary efficacy and short-
term safety analyses are planned after a database soft lock. A final safety analysis will occur after 
all enrolled participants have been followed through 14 months/EOS, have discontinued, or if it 
is known that the Month 14 visit will not occur. 
7.1. 
Sample Size Determination 
The primary analysis is the comparison of the ADG20 arm versus the placebo arm with respect 
to the proportion of participants infected with a non-Omicron variant of SARS-CoV-2 with a 
COVID-19-related hospitalization or all-cause death through Day 29. 
The original sample size was calculated based on assumptions obtained from a review of data 
from studies of other mAbs in participants at high risk for disease progression leading to 
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(AstraZeneca 2022; Eli Lilly and Company 2022a; GlaxoSmithKline 2022; Regeneron 2022). 
The original sample size of 1084 participants was planned with 90% power, 2-sided alpha .05, 
and a 1:1 randomization ratio to detect a statistically significant risk reduction with a true 
efficacy of relative risk reduction 70% and a 5% event rate in the placebo arm.  
At the time of enrollment suspension in January 2022, a total of 399 participants were 
randomized. Of them, approximately 320 participants will be included in the primary efficacy 
population of participants with a non-Omicron variant of SARS-CoV-2. Based on blinded 
monitoring of the primary endpoint outcomes, an approximate aggregate event rate of 9% was 
observed, indicating a higher placebo event rate than previously assumed and providing 
approximately 80% power to test the primary endpoint in the primary efficacy population given 
the same efficacy assumption.  
7.2. 
Analysis Sets 
The analysis sets that will be used for statistical analyses are defined in Table 7-1. In the efficacy 
analyses, participants will be analyzed based on the treatment they are randomized to, 
irrespective of which treatment was actually received. In the safety analysis, participants will be 
analyzed based on the study drug received. 
Table 7-1: 
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.  
Modified Full Analysis 
Set with non-Omicron 
SARS-CoV-2 Variant 
(mFAS-non-Omicron) 
Includes all randomized participants with COVID-19 due to WGS-confirmed or 
suspected non-Omicron SARS-CoV-2 variants, regardless of whether the participant 
received study drug. The mFAS-non-Omicron is the primary efficacy population.  
 
Modified Full Analysis 
Set with Omicron 
SARS-CoV-2 Variant 
(mFAS-Omicron): 
Includes all randomized participants with COVID-19 due to WGS-confirmed or 
suspected Omicron SARS-CoV-2 variant, regardless of whether the participant 
received study drug. 
Modified Full Analysis 
Set-PCR (mFAS-PCR): 
Includes all randomized participants with a positive baseline quantitative 
SARS-CoV-2 RT-PCR based on either an NP swab or saliva sample and who received 
study drug. Two sub-populations will be defined:  
• mFAS-NP: utilizes the baseline NP swab to determine a positive SARS-CoV-2 PCR  
• mFAS-S: utilizes the baseline saliva sample to determine a positive SARS-CoV-2 
PCR. 
mFAS-non-Omicron-
PCR 
Subset of the mFAS-non-Omicron with a positive baseline SARS-CoV-2 RT-PCR. 
The subpopulations mFAS-non-Omicron-NP and mFAS-non-Omicron-S based on 
sample type used to determine a positive SARS-CoV-2 PCR (as defined above) will 
also be analyzed.  
mFAS-Omicron-PCR 
Subset of the mFAS-Omicron with a positive baseline SARS-CoV-2 RT-PCR The 
subpopulations mFAS-Omicron-NP and mFAS-Omicron-S based on sample type used 
to determine a positive SARS-CoV-2 PCR (as defined above) will also be analyzed. 


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Defined Analysis 
Data Sets 
Description 
Per-Protocol Set (PPS) 
All mFAS-non-Omicron participants included who had no significant protocol 
deviations as defined in the SAP that affect the efficacy assessments and received 
treatment. 
Safety Set 
All participants who received any amount of study drug. All safety analyses will be 
conducted in this analysis set.  
Immunogenicity Set 
All participants who received any study drug, had a valid immunogenicity test result 
before the dose of study drug, and had at least 1 valid result after the dose of study 
drug. 
PK Analysis Set 
All participants in the Safety Set who had at least one measurable ADG20 
concentration post-administration of study drug. 
 
7.3. 
Subgroups of Interest 
The primary and key secondary analyses in the mFAS-non-Omicron population will be repeated 
within subgroups of interest as defined in the SAP.  
7.4. 
Statistical Analyses 
Statistical analysis will be performed using SAS software Version 9.4 or later. Continuous 
variables will be summarized using the mean, standard deviation, median, first and the third 
quartiles, minimum value, and maximum value. Categorical variables will be summarized using 
frequency counts and percentages. Data will be listed. 
The objectives and endpoints for all study phases are shown in Table 2-1.  
Unless otherwise specified, estimations involving the primary and secondary endpoints will 
follow a treatment policy strategy for the handling of intercurrent events, which uses and 
analyzes all data for the endpoints after the intercurrent event has occurred. When a hypothetical 
strategy is used, data may be censored in the case of a time to event endpoint or imputed in the 
case of continuous or binary endpoints.  
Estimand attributes, intercurrent events of interest, and rationales for intercurrent event handling 
strategies for the primary and key secondary estimands will be fully described in the SAP. The 
main estimation for the primary efficacy and key secondary efficacy endpoints is described in 
Section 7.6 and Section 7.7. Definitions of censoring and details of imputation methodology will 
be provided in the SAP. 
7.5. 
Multiplicity Adjustments 
To control the overall type 1 error rate at .05 (2-sided), a hierarchical testing procedure will be 
used, such that testing for the key secondary analyses difference will proceed only if the 
treatment difference is statistically significant in the primary efficacy analysis. 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. 


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7.6. 
Main Estimation Utilizing the Primary Efficacy Endpoint  
The analysis of the primary estimand, incidence of COVID-19-related hospitalization or 
all-cause death through Day 29 in the ADG20 arm versus the placebo arm in the 
mFAS-non-Omicron analysis set will be analyzed using the methodology for determining a 
standardized estimator for a binary outcome as detailed in Ge 2011, with adjustment for the 
following prognostic factors: age (continuous), sex (categorical), baseline qualitative serostatus 
(categorical), BMI (continuous), and baseline viral load (continuous). The standard error of the 
standardized estimator will be estimated using the delta method based on the algorithm presented 
in Ge 2011. The risk difference (placebo minus ADG20) with CI (using the Miettinen-Nurminen 
method), standardized risk difference with CI, relative risk reduction with CI, and associated 
p-value for the standardized risk difference will be provided. A treatment policy strategy will be 
used to handle intercurrent events of interest. For example, treatment effect will be estimated 
regardless of baseline or emergence of coinfection with a non-SARS-CoV-2 pathogen, which is a 
potential intercurrent event of interest.  
Supportive estimands for the primary efficacy objective will be fully described in the SAP. 
7.7. 
Main Estimation Utilizing Key Secondary Efficacy Endpoints 
The key secondary endpoints will be tested in the following order in the mFAS-non-Omicron 
analysis set: 
1. Severe/critical COVID-19 or all-cause death through Day 29 
2. COVID-19-related emergency room visit, COVID-19-related hospitalization, or all-cause 
death through Day 29.  
3. Time to sustained resolution of COVID-19 symptoms through Day 29 
Treatment differences in the proportion of participants with severe/critical COVID-19 or 
all-cause death through Day 29 will be presented with 95% CIs and tested using the analysis 
procedure outlined for the primary efficacy outcome.  
Treatment differences in proportion of participants with COVID-19-related emergency room 
visits, COVID-19-related hospitalizations or all-cause death through Day 29 will be presented 
with 95% CIs and tested using the analysis procedure outlined for the primary outcome. 
Time to sustained resolution in COVID-19 symptoms through Day 29 will be analyzed by KM 
methodology and stratified Cox Proportional Hazard model. Survival curves between ADG20 
and placebo will be compared using a log-rank test stratified by age (categorical as 12-17, 18-65, 
and >65 years). A stratified Cox Proportional Hazard model will be used to estimate the hazard 
ratio where the model includes age (categorical as 12-17, 18-65, and >65 years) as stratification 
variable and sex (categorical), baseline serostatus (categorical), baseline BMI (continuous), and 
baseline viral load (continuous as log10 copies/mL) as covariates. Comparison of the survival 
distributions will use the score test for the hazard ratio from the Cox model. Estimand attributes 
for the key secondary objective and supportive estimands will be fully described in the SAP.  


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7.8. 
Analyses of Other Secondary Efficacy Endpoints 
Analyses of other secondary endpoints in the mFAS-non-Omicron analysis set will be conducted 
to support the findings of the primary and key secondary efficacy endpoints. Analysis 
approaches for the other secondary endpoints (ie, non-key) are summarized in Table 7-2 . 
Table 7-2: 
Analyses of Other Secondary Efficacy Endpoints  
Endpoint 
Statistical Analysis Methods 
COVID-19-related medically 
attended visits or all-cause 
death through Day 29 
Same as primary efficacy analysis (see Section 7.6).  
Time to sustained recovery in 
COVID-19 symptoms through 
Day 29  
Same as the analysis of time to sustained resolution of COVID-19 symptoms 
through Day 29.  
All-cause death through 
Day 29, Day 60, and Day 90 
KM methodology will be used to analyze all-cause deaths. The probability of 
all-cause deaths by each of these time points will be estimated, along with 95% 
CIs for differences in the probabilities. Survival curves between ADG20 and 
placebo will be compared using a log-rank test. A Cox Proportional Hazard 
model will be used to estimate the hazard ratio. The model includes age 
(continuous), sex (categorical), baseline serostatus (categorical: positive, 
negative), baseline BMI (continuous), and baseline viral load (continuous as 
log10 copies/mL) as covariates. Comparison of the survival distributions will use 
the score test for the hazard ratio from the Cox model.  
Change from baseline in 
SARS-CoV-2 viral load 
(log10 copies/mL) to Day 7 
(±1) assessed by RT-qPCR 
from NP samples  
Observed NP baseline and post-baseline values are used to calculate change 
from baseline. ANCOVA with treatment group and the prognostic factors (with 
observed NP baseline) as in the primary efficacy endpoint analyses as 
covariates will be performed. The LS mean for the point estimate in each group 
and 95% CIs will be presented. The difference in LS means between each 
ADG20 group and the placebo group and 95% CIs for the differences will be 
determined. The analysis will be performed on the mFAS-non-Omicron-NP. 
with available data at Day 7. In addition, two-sample t-test will be used to 
compare change from baseline viral load between treatment without covariate 
adjustment (unadjusted mean difference). 
If Day 7 value is missing, the earliest measurement closest to the Day 7 visit 
within 1 day (including scheduled and unscheduled visit) will be used. 
Viral load >5 
(log10 copies/mL) on Day 7 
(±1) based on NP samples 
Same as primary efficacy analysis (see Section 7.6). Analysis will be performed 
in mFAS-non-Omicron-NP with available data at Day 7. Analysis will be 
repeated using a second definition of high viral load (viral load 
>4 log10 copies/mL). 


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Endpoint 
Statistical Analysis Methods 
Duration of SARS-CoV-2 
viral shedding from Day 1 
through Day 29 assessed by 
RT-qPCR from saliva samples 
KM methodology will be used to analyze duration of viral shedding from Day 1 
through Day 29 by SARS-CoV-2 RNA defined as time from the first dose date 
to the first date the viral load is not detected, ie, below the limit of detection 
(LOD), and sustained through Day 29. KM curves will be compared between 
ADG20 and Placebo using a log-rank test stratified by age (categorical). A 
stratified Cox Proportional Hazard model will be used to estimate the hazard 
ratio where the model includes age (categorical as 12-17 years, 18-65 years and 
>65 years) as stratification variable and sex (categorical), baseline serostatus 
(categorical as positive; negative), baseline BMI (continuous) and baseline viral 
load (continuous as log10 copies/mL) as covariates. Comparison of the survival 
distributions will use the score test for the hazard ratio from this Cox model. 
Analyses will be performed on the mFAS-non-Omicron-S. Deaths occurring 
prior to achieving cessation of viral shedding will be censored at Day 30.  
Change from baseline in 
SARS-CoV-2 viral load 
(log10 copies/mL) to Days 3, 5, 
7, 11, 14, 21, and 29 assessed 
by RT-qPCR from saliva 
samples  
Observed saliva baseline and post-baseline values are used to calculate change 
from baseline. Mixed model for repeated measures with treatment group and the 
prognostic factors (with observed saliva baseline) in the primary efficacy 
endpoint analysis as covariates will be performed. The LS mean for the point 
estimate in each group and 95% CIs will be presented. The difference in LS 
means between the ADG20 group and the placebo group and the 95% CIs for 
the differences will be determined. A plot of the LS means with 95% CIs by day 
assess by treatment group will be presented. The analysis will be performed on 
the mFAS-non-Omicron-S with available data at each timepoint. In addition, a 
two-sample t-test will be used to compare change from baseline viral load 
between treatment at each time point without covariate adjustment (unadjusted 
mean difference). 
SARS-CoV-2 viral clearance 
(Days 5, 7, 11, 14, 21, and 29) 
assessed by RT-qPCR from 
saliva samples (and BLQ/not 
detected or not detected for 
NP sample for Day 7) 
In the mFAS-non-Omicron-S, the cumulative proportion of participants with 
viral clearance will be presented for each post-baseline time point. In the 
mFAS-non-Omicron-NP, the proportion of participants with viral load BLQ/ 
not detected at Day 7 will be presented. The ADG20 arm will be compared to 
placebo using the analysis procedure outlined for the primary efficacy outcome. 
In addition, these analyses will be presented for the subgroups of participants 
with observed baseline NP viral load >5 and ≤5 log10 copies/mL. Deaths before 
achieving viral clearance will be considered to have no viral clearance.  
SARS-CoV-2 viral load AUC 
(log10 copies/mL) assessed by 
RT-qPCR from saliva samples 
through Day 29  
An ANCOVA will be used to compare ADG20 and placebo where the 
prognostic factors in the primary efficacy endpoint analysis will be used as 
covariates. Participants in the mFAS-non-Omicron-S will be included in this 
analysis. The AUC from Day 1 through Day 29 will be calculated according to 
the linear trapezoidal rule using the measured SARS-CoV-2 viral load above the 
lower limit of quantification. No AUC values will be calculated when Day 1 
and/or Day 29 values are missing, or if there are more than 3 values missing in 
the profile. 
In addition, two-sample t-test will be used to compare viral load AUC between 
treatment without covariate adjustment (unadjusted mean difference). 
ANCOVA=Analysis of Covariance; BLQ=below limit of quantitation; CI=confidence interval; FAS=full analysis set; 
KM=Kaplan-Meier; LOD=limit of detection; mFAS=modified full analysis set; LS=least squares; RT-qPCR=quantitative reverse 
transcription polymerase chain reaction. 
 
7.9. 
Analyses of Exploratory Endpoints 
Exploratory endpoint analyses, including analyses performed on the mFAS-Omicron analysis 
set, will be detailed in the SAP. Additional covariate adjusted analyses may be performed. 


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7.10. 
Pharmacokinetic Analyses 
Pharmacokinetic endpoint analyses will be detailed in an SAP.  
7.11. 
Safety Analyses 
All AEs will be coded using the latest version of MedDRA. Safety summaries will be presented 
through Day 29 and overall. 
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 are expected to 
occur after the administration of study drug all solicited AEs will be considered TEAEs.  
The incidence of TEAEs (including solicited ISRs), SAEs, TEAEs related to study drug, SAEs 
related to study drug, TEAEs leading to study drug discontinuation, AESIs, and MAAEs will be 
summarized by MedDRA SOC, PT, and treatment group. The incidence of study drug related 
TEAEs (including solicited ISRs) will also be summarized by maximum severity by SOC, PT, 
and treatment group.  
The incidence of solicited AEs (ISRs) will be summarized by maximum severity through Day 4. 
The maximum duration and time from injection to report of first onset of any solicited ISR will 
also be summarized. 
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.  
Descriptive statistics for clinical laboratory test results (hematology. serum chemistry, and 
coagulation) and vital signs 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 and vital sign parameters will be summarized by treatment group. In addition, 
treatment-emergent potentially clinically significant (PCS) laboratory parameters will be 
summarized in shift tables from baseline to each post-baseline time point assessed. The number 
and percentage of participants with a PCS vital sign will be summarized by treatment group for 
each time point assessed. PCS values will be defined in the SAP. 
7.12. 
Immunogenicity 
Immunogenicity data will be listed, 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. 
7.13. 
Safety Monitoring and Interim Analyses 
The safety and interim analysis monitoring are described in Table 7-2. Additional iDMC ad hoc 
reviews may be conducted as outlined in the DMC Charter. 


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Table 7-3: 
Safety Monitoring and Interim Analyses 
Study Phase/ 
Parameter 
Analysis 
Time point  
Reviewer: 
Data Reviewed 
Criterion 
Statistical Method 
Purpose 
Phase 2/PK 
Throughout  
Unblinded 
Pharmacology Team: 
• Unblinded available 
PK data  
• Aggregate data to 
Sponsor 
NA 
PK Analyses as 
detailed in PK 
Analysis Plan 
Confirm PK in 
participants  
Phase 2/Safety 
At any time 
during Phase 2 
iDMC: Events meeting 
criterion 
If any of the pausing guidelines are met 
(Section 10.11 ), an ad hoc iDMC meeting will 
occur. 
NA 
Monitor ongoing safety 
Phase 2/Safety 
Assessment 
(administrative 
interim analysis) 
Approximately 
N=200 
participants 
enrolled  
iDMC: Safety 
assessment of 300 mg 
IM dose 
Detailed in iDMC charter 
Safety analyses as 
detailed in SAP 
Monitor ongoing safety 
profile and provide 
recommendation 
regarding enrollment of 
adolescents and pregnant 
and breastfeeding women 
in Phase 3 and post-dose 
monitoring duration per 
Section 6.4.1. 
Phase 3/Safety 
At any time 
during Phase 3 
iDMC: Events meeting 
criterion 
If any of the pausing guidelines are met 
(Section 10.11 ), an ad hoc iDMC meeting will 
occur. 
NA 
Monitor ongoing safety 
iDMC=independent data monitoring committee; IM=intramuscular; NA=not applicable; PK=pharmacokinetics; SAP=statistical analysis plan. 


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If pausing guidelines are met at any point in the study, an ad hoc iDMC meeting will occur 
(Section 10.11).  
To evaluate the safety profile of ADG20 and make recommendations regarding enrollment of 
adolescents and pregnant and breastfeeding women in Phase 3 and post-dose monitoring 
duration, an administrative interim analysis will be reviewed by the iDMC after approximately 
200 participants are enrolled in Phase 2. Enrollment into Phase 3 will continue while the 
administrative analysis is taking place.  
8. 
DATA QUALITY ASSURANCE 
This study will be conducted according to the ICH E6(R2) risk and quality processes described 
in the applicable procedural documents. The quality management approach to be implemented in 
this study will be documented and will comply with the current ICH guidance on quality and risk 
management. The sponsor assumes accountability for actions delegated to other individuals (eg, 
CROs). 
8.1. 
Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for the participants treated as part of the research under this 
protocol. The investigator agrees to maintain accurate eCRFs and source documentation as part 
of the case histories. These source documents may include diary cards, laboratory reports, etc. 
All eCRF information is to be filled in. If an item is not available or is not applicable, this fact 
should be indicated. Blank spaces should not be present unless otherwise directed.  
Investigative site personnel will enter participant data into RAVE, via a secure network. A 
complete electronic audit trail will be maintained. The analysis data sets will be a combination of 
these data and data from other sources (eg, laboratory data). 
Clinical data management will be performed in accordance with applicable standards and data 
cleaning procedures to ensure the integrity of the data, eg, removing errors and inconsistencies in 
the data. Adverse event and medical history terms will be coded using MedDRA; prior and 
concomitant medications will be coded using a standard dictionary (eg, WHODrug). 
9. 
ETHICS 
9.1. 
Independent Ethics Committee or Institutional Review Board 
Federal regulations and the ICH guidelines require that approval be obtained from an IRB/IEC 
before human subjects participate in research studies. Before study onset, the protocol, informed 
consent (and assent where applicable for adolescents), advertisements to be used for the 
recruitment of study participants, and other written information regarding this study to be 
provided to the participant or the participant’s guardian/LAR must be approved by the IRB/IEC. 
Documentation of all IRB/IEC approvals and of the IRB/IEC compliance with ICH guideline 


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E6(R2): GCP will be maintained by the site and will be available for review by the sponsor or its 
designee. 
All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must identify 
the IRB/IEC name and address, the clinical protocol by title or protocol number or both, and the 
date approval or a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of the 
study at intervals not exceeding 1 year or otherwise specified by the IRB/IEC. The investigator 
must promptly supply the sponsor or its designee, the IRB/IEC, and, where applicable, the 
institution, with written reports on any changes significantly affecting the conduct of the study or 
increasing the risk to participants. 
9.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki, ICH GCP, and all applicable regulations. 
9.3. 
Participant Information and Consent/Assent 
A documented informed consent (and assent where applicable for adolescents) in compliance 
with regulatory authority regulations shall be obtained from each participant (or their 
guardian/LAR) before entering the study or performing any unusual or nonroutine procedure that 
involves risk to the participant. An LAR may be used in Phase 2 and 3 only in cases where 
inclusion criterion 9 is able to be fulfilled. An informed consent and/or assent template may be 
provided by the sponsor or designee to investigative sites. If any institution-specific 
modifications to study-related procedures are proposed or made by the site, the consent and/or 
assent should be reviewed by the sponsor or its designee or both before IRB/IEC submission. 
Once reviewed, the consent and/or assent will be submitted by the investigator to their IRB/IEC 
for review and approval before the start of the study. If the consent and/or assent is revised 
during the course of the study, sites will receive notification defining the participants who are 
required to reconsent/re-assent. 
Before recruitment and enrollment, each prospective participant or their guardian/LAR will be 
given a full explanation of the study, be allowed to read the approved ICF/assent, and have any 
questions answered. Once the investigator is assured that the participant/guardian/LAR 
understands the implications of participating in the study, the participant/guardian/LAR will be 
asked to give consent to participate in the study by executing the ICF/assent. The authorized 
person obtaining the informed consent (and assent where applicable for adolescents) also 
executes the ICF/assent. 
Participant medical records need to state that documented informed consent was obtained.  
The investigator shall retain the executed original ICF(s)/assent(s) and give a copy of the 
executed original form to the participant, guardian/LAR. 


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10. 
INVESTIGATOR’S OBLIGATIONS 
The following administrative items are meant to guide the investigator in the conduct of the 
study but may be subject to change based on industry and government standard operating 
procedures, working practice documents, or guidelines. Changes will be reported to the IRB/IEC 
but will not result in protocol amendments. 
10.1. 
Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain participant confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the participant (or the participant’s guardian/LAR), except as necessary for 
monitoring and auditing by the sponsor, its designee, the FDA, or the IRB/IEC. 
The investigator and all employees and coworkers involved with this study may not disclose or 
use for any purpose other than performance of the study any data, record, or other unpublished, 
confidential information disclosed to those individuals for the purpose of the study. Prior written 
agreement from the sponsor or its designee must be obtained for the disclosure of any said 
confidential information to other parties. 
10.2. 
Data Protection 
All personal data collected related to participants, Investigators, or any person involved in the 
study, which may be included in the sponsor’s databases, shall be treated in accordance with 
local data protection law.  
Data collected must be adequate, relevant, and not excessive, in relation to the purposes for 
which they are collected. Each category of data must be properly justified and in line with the 
study objective. 
10.3. 
Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow the sponsor or 
designee to submit the complete and accurate certification or disclosure statements required 
under 21 CFR 54. In addition, the investigator must provide to the sponsor or designee a 
commitment to promptly update this information if any relevant changes occur during the course 
of the investigation and for 1 year following the completion of the study. 
Neither the sponsor nor 
 is financially responsible for further testing or treatment of any 
medical condition that may be detected during the screening process. In addition, in the absence 
of specific arrangements, neither the sponsor nor 
 is financially responsible for further 
treatment of the participant’s disease. 
10.4. 
Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 
Section 8.2 and Title 21 of the CFR by providing all essential documents. 


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10.5. 
Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH 
E6(R2). The investigator will conduct all aspects of this study in accordance with all national, 
state, and local laws or regulations. Study information from this protocol will be posted on 
publicly available clinical trial registers as required under the terms of the European Medicines 
Agency (EMA) clinical trial Directive 2001/20/EC (European Commission 2001) and 2007 
FDAAA (FDA 2007a). 
The investigator agrees to conduct the study as outlined in this protocol in accordance with ICH 
E6(R2) and all applicable guidelines and regulations. 
10.6. 
Adverse Events and Study Report Requirements 
The investigator agrees to submit reports of SAEs to the sponsor or designee and/or IRB/IEC 
according to the timeline and method outlined in the protocol (see Section 6.4.6.3.1). In addition, 
the investigator agrees to submit annual reports to the study site IRB/IEC as appropriate. 
10.7. 
Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the institution; 
the investigator/institution should provide the IRB/IEC with a summary of the study’s outcome 
and the sponsor and regulatory authority(ies) with any reports required. 
10.8. 
Records Retention 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of 
clinical development of the study drug. These documents should be retained for a longer period, 
however, if required by the applicable regulatory requirements or by an agreement with the 
sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to when 
these documents no longer need to be retained. No records may be transferred to another location 
or party without written notification to the sponsor. 
10.9. 
Publication Policy  
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 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 authorization from the sponsor, but data and publication thereof will not be unduly 
withheld.  
10.10. 
Study Management 
The study administrative structure will include the iDMC, CRO, third party vendors, and 
laboratories. 


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10.11. 
Independent Data Monitoring Committee 
The iDMC will provide safety oversight for all parts of the study, including monitoring for 
potential ADE. The iDMC will meet at designated points per Section 7.13 and the iDMC charter 
and on an ad hoc basis to review cumulative safety data and other clinical study data to ensure 
the benefit/risk remains favorable. The iDMC will make recommendations to the sponsor as 
outlined Section 7.13 and the iDMC charter.  
Details regarding iDMC membership, conduct, ongoing safety monitoring, decision making and 
communication will be provided in the iDMC Charter. Thresholds for calling ad hoc meetings 
for events of special interest such as potential ADE will be provided in the iDMC Charter. 
Study enrollment will pause and an ad hoc iDMC meeting will be called based on any of the 
Pausing Guidelines being met in the ADG20 arm as presented in Table 10-1.  
Table 10-1: 
Pausing Guidelines 
Phase 
Pausing Guideline 
Phase 2 
• 
2 or more participants with a study drug-related grade 3 or higher hypersensitivity reaction 
• 
2 or more participants with a grade 3 or higher injection site reaction 
• 
Any study drug-related death  
• 
Any study drug-related serious adverse event including hypersensitivity reactions 
Phase 3  
• 
Any study drug-related death  
• 
Any study drug-related serious adverse event including hypersensitivity reactions 
10.12. 
Monitoring 
10.12.1. 
Monitoring of the Study 
This study will be monitored according to an approved monitoring plan based on the objectives, 
purpose, design, and complexity of the study. Site monitoring is conducted to ensure that the 
rights of human subjects are protected, that the study is implemented in accordance with the 
protocol and/or other operating procedures, and that the study uses high quality data collection 
processes. The monitor will evaluate study processes based on sponsor or its designee’s 
standards, ICH E6, and all applicable, regulatory guidelines.  
When on-site monitoring visits are to be conducted, the investigator is to ensure that the monitor 
or other compliance or quality assurance reviewer is given direct access to all study-related 
documents and study-related facilities (eg, pharmacy, diagnostic laboratory), phone, fax, and 
internet and has adequate space to conduct the monitoring visit.  
During the COVID-19 pandemic, planned on-site monitoring visits may not be possible due to 
restricted access making it necessary for sponsors of clinical trials to adjust how studies are 
managed.  
In situations where on-site monitoring visits are not possible (eg, the COVID-19 pandemic), 
remote monitoring will be considered as a risk-based approach to monitor the study. Guidance 
regarding the conduct of clinical trials during the COVID-19 pandemic is available from the 
FDA (FDA 2021c) and EMA (EMA 2022) and local guidance may also be available. The 


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sponsor or its designee will work with study site personnel to put in place appropriate remote 
monitoring strategies. 
10.12.2. 
Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, audits, 
IRB/IEC review, and regulatory inspections by providing direct access to all study records. In the 
event of an audit, the investigator agrees to allow the sponsor, representatives of the sponsor, or a 
regulatory agency access to all study records. 
The investigator should promptly notify the sponsor and 
 of any audits scheduled by any 
regulatory authorities and promptly forward copies of any audit reports received to the sponsor 
or designee. 
10.13. 
Management of Protocol Amendments and Deviations 
10.13.1. 
Modification of the Protocol 
Any changes in the required procedures defined in this protocol, except those necessary to 
remove an apparent, immediate hazard to the participant, must be reviewed and approved by the 
sponsor or designee. Amendments to the protocol (including emergency changes) must be 
submitted in writing to the investigator’s IRB/IEC, along with any applicable changes to the ICF, 
for approval before participants can be enrolled into an amended protocol. During emergent 
situations, a pandemic or other natural disaster(s), modifications may be necessary to protocol-
specified procedures. Central to any decision should be ensuring that the safety of clinical trial 
participants can be maintained. 
10.13.2. 
Protocol Deviations 
A deviation from the protocol is an unintended or unanticipated departure from the procedures or 
processes approved by the sponsor and the IRB/IEC and agreed to by the investigator. A 
significant deviation occurs when there is nonadherence to the protocol or to local regulations or 
ICH GCP guidelines that may or may not result in a significant, additional risk to the participant 
or impacts the integrity of study data. 
The investigator or designee must document and explain in the participant’s source 
documentation any deviation from the approved protocol. The investigator may implement a 
deviation from, or a change of, the protocol to eliminate an immediate hazard/safety risk to study 
participants without prior IRB/IEC approval. As soon as possible after such an occurrence, the 
implemented deviation or change, the reasons for it, and any proposed protocol amendments 
should be submitted to the IRB/IEC for review and approval, to the sponsor or designee for 
agreement, and to the regulatory authorities, where required. 
In order to keep deviations from the protocol to a minimum, the investigator and relevant site 
personnel will be trained in all aspects of study conduct by the sponsor/sponsor representative. 
This training will occur either as part of the investigator meeting or site initiation. Ongoing 
training may also be performed throughout the study during routine site monitoring activities. 


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10.14. 
Study Termination 
Although the sponsor has every intention of completing the study, the sponsor reserves the right 
to discontinue the study at any time for clinical or administrative reasons. 
The end of the study is defined as the date on which the last participant completes the last visit 
(includes Follow-up Visit). 
If the study is prematurely terminated or suspended, the sponsor or designee or investigator shall 
promptly inform the investigators, the IECs/IRBs, the regulatory authorities, and any contract 
research organization(s) used in the study of the reason for termination or suspension, as 
specified by the applicable regulatory requirements. The investigator shall promptly inform the 
participant and should assure appropriate participant therapy and/or follow-up. 
10.15. 
Final Report 
Whether the study is completed or prematurely terminated, the sponsor will ensure that the final 
data are summarized and provided to the regulatory agency(ies) as required by the applicable 
regulatory requirement(s). The sponsor will also ensure that the clinical study reports in 
marketing applications (as applicable) meet the standards of the ICH guideline E3: Structure and 
content of clinical study reports.  
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the opportunity 
to review the complete study results. 
Upon completion of the final report, the sponsor or designee will provide the investigator with 
the summary of the study results. The investigator is encouraged to share a summary of the 
results with the study participants, as appropriate. The study results will be posted on publicly 
available clinical trial registers. 


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of REGEN-COV (Casirivimab and imdevimab). Revised January 2022.  Retrieved 27 January 
2022, from https://www.fda.gov/media/145611/download. 
Roche. (2021). New phase III data shows investigational antibody cocktail casirivimab and 
imdevimab reduced hospitalisation or death by 70% in non-hospitalised patients with COVID-
19.  Retrieved 04 May 2021, from https://www.roche.com/media/releases/med-cor-2021-03-
23.htm. 
Roche Registration GmbH. (2021). Summary of Product Characteristics for Ronapreve 
(casirivimab and imdevimab). from https://www.ema.europa.eu/en/documents/product-
information/ronapreve-epar-product-information_en.pdf. 
Salvatore PP, Sula E, Coyle JP, et al. (2020). Recent Increase in COVID-19 Cases Reported 
Among Adults Aged 18–22 Years — United States, May 31–September 5, 2020. MMWR Morb 
Mortal Wkly Rep 69(39): 1419. doi:10.15585/mmwr.mm6939e4. 
Starr TN, Greaney AJ, Addetia A, et al. (2021). Prospective mapping of viral mutations that 
escape antibodies used to treat COVID-19. Science 371(6531): 850-854. 
doi:10.1126/science.abf9302. 
Stein-Zamir C, Abramson N, Shoob H, et al. (2020). A large COVID-19 outbreak in a high 
school 10 days after schools' reopening, Israel, May 2020. Euro Surveill 25(29): pii=2001352. 
doi:10.2807/1560-7917.ES.2020.25.29.2001352. 
Stokes EK, Zambrano LD, Anderson KN, et al. (2020). Coronavirus Disease 2019 Case 
Surveillance - United States, January 22-May 30, 2020. MMWR Morb Mortal Wkly Rep 69(24): 
759-765. doi:10.15585/mmwr.mm6924e2. 
Tenforde MW, Rose EB, Lindsell CJ, et al. (2020a). Characteristics of adult outpatients and 
inpatients with COVID-19—11 academic medical centers, United States, March–May 2020. 
MMWR Morb Mortal Wkly Rep 69(26): 841-846. doi:10.15585/mmwr.mm6926e3. 
Tenforde MW, Kim SS, Lindsell CJ, et al. (2020b). Symptom duration and risk factors for 
delayed return to usual health among outpatients with COVID-19 in a multistate health care 
systems network—United States, March–June 2020. MMWR Morb Mortal Wkly Rep 69(30): 
993-998. doi:10.15585/mmwr.mm6930e1. 
Thomas SJ and Yoon IK (2019). A review of Dengvaxia(R): development to deployment. Hum 
Vaccin Immunother 15(10): 2295-2314. doi:10.1080/21645515.2019.1658503. 
Viner RM, Mytton OT, Bonell C, et al. (2021). Susceptibility to SARS-CoV-2 Infection Among 
Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis. 
JAMA Pediatr 175(2): 143-156. doi:10.1001/jamapediatrics.2020.4573. 
Voysey M, Clemens SAC, Madhi SA, et al. (2021). Safety and efficacy of the ChAdOx1 nCoV-
19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled 
trials in Brazil, South Africa, and the UK. Lancet 397(10269): 99-111. doi:10.1016/S0140-
6736(20)32661-1. 


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Wang D, Hu B, Hu C, et al. (2020). Clinical Characteristics of 138 Hospitalized Patients With 
2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 323(11): 1061-1069. 
doi:10.1001/jama.2020.1585. 
Wang P, Nair MS, Liu L, et al. (2021). Antibody resistance of SARS-CoV-2 variants B.1.351 
and B.1.1.7. Nature 593(7857): 130-135. doi:10.1038/s41586-021-03398-2. 
Weinreich DM, Sivapalasingam S, Norton T, et al. (2021). REGN-COV2, a Neutralizing 
Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med 384(3): 238-251. 
doi:10.1056/NEJMoa2035002. 
WHO (2019). Dengue vaccine: WHO position paper, September 2018 - Recommendations. 
Vaccine 37(35): 4848-4849. doi:10.1016/j.vaccine.2018.09.063. 
WHO. (2020). WHO Director-General's opening remarks at the media briefing on COVID-19 - 
24 February 2020.  Retrieved 19 June 2021, from https://www.who.int/director-
general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-
19---24-february-2020. 
Wilson E, Donovan CV, Campbell M, et al. (2020). Multiple COVID-19 clusters on a university 
campus—North Carolina, August 2020. MMWR Morb Mortal Wkly Rep 69(39): 1416-1418. 
doi:10.15585/mmwr.mm6939e3. 
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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12. 
APPENDICES 
12.1. 
Appendix: Schedule of Assessments 


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Table 12-1: 
Schedule of Assessments 
Study Period 
Screening/ 
Treatment 
Follow-up 
Long-Term Follow-Up 
 
Day 
Day 
Day 
Month 
Day/Month 
-2 
1a 
3 
5 
7 
11 
14 
21 
29b 
60 
90 
6b 
11 
14 EOSb 
Visit Window (days) 
2 
0 
±1 
±1 
±1 
±2 
±2 
±2 
+5 
±7 
±14 
±30 
±30 
+60 
Visit Typec 
C/H 
C 
T 
T 
C/H 
T 
T 
T 
C/H 
T 
C/H 
C/H 
C/H 
T 
Assessment 
Baseline Assessments 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history (including risk factors & COVID-19 
symptom onset) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam (including weight, height, & 
COVID-19 signs/symptoms) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Local urine or serum pregnancy test (for WOCBP; must 
be performed within 24 hours of study drug 
administration) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Documentation of local positive  
SARS-CoV-2 testd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review of study inclusion/exclusion criteria 
(Day 1 re-review prior to randomization) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Central Laboratory Assessments 
Nasopharyngeal swab(s) collection for SARS-CoV-2 RT-
qPCR, SARS-CoV-2 sequencing, & respiratory panel 
(Day 1: 2 swabs, Day 7: 1 swab) 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
Blood collections for SARS-CoV-2 antibodies 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Blood collection for safety laboratory (chemistry, 
hematology, coagulation) Day 1 & Month 6 includes 
serum pregnancy for females 
 
X 
 
 
X 
 
 
 
X 
 
X 
X 
 
 
Blood collection for PKe 
 
X 
 
 
X 
 
 
 
X 
 
X 
X 
X 
 
Blood collection for ADA (immunogenicity)e 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
Site Clinical Assessments 
Prior/Concomitant medicationsf 
––––––––––––––––––––––––––––––––––––––––X––––––––––––––––––––––––––––––––––––––––– 
AEs, SAEs, MAAEsg 
––––––––––––––––––––––––––––––––––––––––X––––––––––––––––––––––––––––––––––––––––– 


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Study Period 
Screening/ 
Treatment 
Follow-up 
Long-Term Follow-Up 
 
Day 
Day 
Day 
Month 
Day/Month 
-2 
1a 
3 
5 
7 
11 
14 
21 
29b 
60 
90 
6b 
11 
14 EOSb 
Visit Window (days) 
2 
0 
±1 
±1 
±1 
±2 
±2 
±2 
+5 
±7 
±14 
±30 
±30 
+60 
Visit Typec 
C/H 
C 
T 
T 
C/H 
T 
T 
T 
C/H 
T 
C/H 
C/H 
C/H 
T 
Assessment 
Targeted review of changes in healthh 
 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
 
Educate participant on At-Home Assessments/ 
Collections (Symptom Diary, vitals, saliva collections, 
ISR Diaryi, recognizing emergency symptoms & 
hypersensitivity reactions) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study drug administration & safety monitoring (All Day 1 
assessments must occur prior to study drug 
administration) 
 
X j 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs, including SpO2 
X 
X  j 
 
 
X 
 
 
 
X 
 
X 
X 
X 
 
Review of COVID-19 Symptom Diary, reported vitals, 
ISR diary, & COVID-19 severity assessment (Day 1 
assessment should be completed prior to study drug 
administration) 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Survival assessment & Medically Attended Visits 
assessmentk 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Collect/update participant contacts 
 
X 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
 
Long-term health status assessment 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
Household transmission questionnaire 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Participant At-Home Assessments/Collections 
Day 1 assessments/collections by participant will be observed by site staff prior to study drug administration; Days 1-4: ISR diary for IM injection participants. 
Saliva sample for SARS-CoV-2 RT-qPCRl 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Daily COVID-19 Symptom Diary & ISR Diaryi 
 
X 
––––––––––––––––––X––––––––––––––––– 
 
 
 
 
 
Daily temperature, SpO2, heart ratem 
 
X 
––––––––––––––––––X––––––––––––––––– 
 
 
 
 
 
ADA=anti-drug antibodies; EOS=end-of-study; ISR=injection site reaction; RT-qPCR=quantitative reverse transcription polymerase chain reaction; SpO2=oxygen saturation; 
WOCBP=women of childbearing potential. 
a Note that screening procedures may occur on the same day of dosing on Day 1. Study Day 1 is the calendar day that study drug is administered. On Day 1, all study procedures 
except ISR diary completion and collection of participant contacts are to be performed prior to study drug administration. Adverse events occurring from when the participant 
signs the ICF until the Month 14 (EOS) visit or withdrawal will be recorded. Any screening inclusion criteria with laboratory values associated (eg, eGFR, FSH, etc) should be 
based on local laboratory results or most recent medical record. 


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b If a participant/guardian/LAR requests a participant to be withdrawn at any time after randomization into the study, the investigator will make every effort to encourage the 
participant to complete the Day 29 assessments (if prior to Day 29), Month 6 visit assessments (if after the Day 29 visit but before Month 6), or the Month 14 EOS visit 
assessments (if after the Month 6 Visit completed). 
c Visits after Day 1 may not be combined. Visit codes: C (in-clinic); C/H (in-clinic or home health); T (Telemedicine, ‘T’ visits may also be in-clinic or home health). 
d A local positive SARS-CoV-2 test (antigen, RT-PCR, or other locally approved molecular test) taken within 5 days prior to randomization is required for eligibility. The day of 
randomization is not considered in the calculation of 5 days. Historical documentation is acceptable. Local testing result, specimen type, assay type, and date of the test will be 
recorded in the eCRF. SARS-CoV-2 antibody testing is not acceptable for eligibility. Additional samples for SARS-CoV-2 testing at local laboratory for the purposes of case 
management may be collected per local standard of care. Clinical care should be delivered per local standards of care and not wait for results of central laboratory testing. 
e On Day 1, one PK sample to be collected at baseline prior to study drug administration. All other visits with PK sample collection will have one sample collected. An additional 
PK and ADA sample should be collected from participants experiencing hypersensitivity reactions as described in Section 6.8.2. 
f Record information regarding all prior and concomitant medications taken, including OTC medications and investigational agents or supportive care taken for index COVID-19 
infection under study. All concomitant medications will be recorded up to and including Day 60. Any concomitant medications related to AEs and any vaccinations received will 
be recorded for the entire length of the study (ie, through Month 14). 
g Record all AEs from when the participant signs the ICF through the Month 14 Visit. On Day 1 through Day 4, record AESIs (hypersensitivity reactions, including but not limited 
to urticaria, edema, respiratory distress, anaphylaxis, and allergic reactions) occurring through Day 4. Hypersensitivity reactions occurring after Day 4 will be recorded as AEs. 
Investigators or medically qualified designees will follow all ISRs that are ongoing beyond Day 4 to resolution. Worsening or sequelae of the index case of COVID-19 will not 
be recorded as AEs, unless they meet SAE criteria; these data will be captured as efficacy assessment data. Subsequent instances of COVID-19 in the same participant will be 
recorded as AEs. 
h Targeted review of changes in health based on reported AEs or ongoing signs/symptoms of COVID-19. 
i Participants will complete the daily COVID-19 Symptom Diary (includes global impression questions) Day 1 through Day 29. The Injection Site Reaction Diary will be 
completed Day 1 through Day 4. Site will provide a ruler along with instructions regarding completion of the Injection Site Reaction Diary (Appendix 12.3). Instruct participants 
to record any local ISRs daily through Day 4. 
 j Perform vital signs before, during, and after study drug administration per Section 6.4.1. Section 6.4.1 outlines required vital signs on Day 1, duration of monitoring post-dose, 
and ISR monitoring and management. 
k Record information regarding participant survival and participant medically attended visits (telemedicine, physician office, urgent care center, emergency room, hospitalization) 
and relationship of medically attended visits to COVID-19. During telemedicine visits, the participant will also be reminded to complete daily COVID-19 Symptom Diary, daily 
temperature, blood oxygen saturation and heart rate, and saliva sample collection on the appropriate days. 
l Participants will collect their own saliva sample using the collection materials provided on Days 3, 5, 11, 14, and 21 and return them to the study site according to provided 
instructions. Note: Day 7 and Day 29 are in-clinic or home health visits and the saliva sample will be collected and transported by site staff or delegate. Participants should NOT 
eat, drink, smoke, or chew gum for 30 minutes before sample collection. The sample will be used for SARS-CoV-2 RT-qPCR and may be used for viral sequencing. In the event 
of worsening COVID-19 or potential relapse or re-infection, a saliva sample for SARS-COV-2 RT-qPCR and sequencing should be collected as described in Section 6.8.1. 
m Participants will be asked to monitor temperature, blood oxygen saturation, and heart rate 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. 


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12.2. 
Appendix: COVID-19 Symptom Diary 
Information about COVID-19-associated symptoms (listed below [FDA 2020b]) will be 
collected in a daily COVID-19 Symptom Diary as described in protocol Section 6.3.1.1. 
Assessment of Common COVID-19-Related Symptoms and Global Impression Items: 
Items and Response Options and Scoring 
“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 
Mild 
Moderate 
Severe 
2) Chills (shivering) 
3) Cough 
4) Sore throat 
5) Congestion (stuffy or runny nose) 
6) Shortness of breath or difficulty breathing at rest 
7) Shortness of breath or difficulty breathing with 
exertion worse than usual prior to diagnosis of 
COVID-19 
8) Muscle or body aches 
9) Fatigue (low energy or tiredness) 
10) Headache 
11) Nausea (feeling like you want to throw up) 
12) Rate your sense of taste in the last 24 hours 
My sense of taste is THE SAME AS usual 
My sense of taste is LESS THAN usual  
I have NO sense of taste 
13) Rate your sense of smell in the last 24 hours 
My sense of smell is THE SAME AS usual  
My sense of smell is LESS THAN usual 
I have NO sense of smell 
14) How many times did you vomit (throw up) in the last 
24 hours? 
I did not vomit at all 
1–2 times 
3–4 times 
5 or more times 
15) How many times did you have diarrhea (loose or 
watery stools) in the last 24 hours? 
I did not have diarrhea at all 
1–2 times 
3–4 times 
5 or more times 
16) In the past 24 hours, have you returned to your usual 
health (before your COVID-19 illness)? 
Yes or No 
17) In the past 24 hours, have you returned to your usual 
activities (before your COVID-19 illness)?  
Yes or No 
18) In the past 24 hours, what was the severity of your 
overall COVID-19-related symptoms at their worst?  
None, Mild, Moderate, or Severe 


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12.3. 
Appendix: Injection Site Reaction 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 Diary 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 (injection site reactions) by the participant (or, if 
applicable, with help from their caregiver, surrogate, or guardian/LAR) according to the FDA 
Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccine Clinical Trials (FDA 2007b).  
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 
Grade 1  
Mild 
Grade 2 
Moderate 
Grade 3  
Severe 
Grade 4 Potentially 
Life-Threateninga 
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  
ER visit or 
hospitalization  
Tenderness 
Mild discomfort 
to touch 
Discomfort with 
movement 
Significant 
discomfort at rest  
ER 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  
ER=emergency room. 
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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12.4. 
Appendix: Clinical Laboratory Tests 
Hematology (CBC with differential): 
Chemistry Panel (Serum): 
Hemoglobin 
Hematocrit 
Erythrocyte count 
Mean cell volume 
Mean cell hemoglobin 
Mean cell hemoglobin concentration 
Leukocyte (white blood cell) count 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Platelets 
Glucose, non-fasting 
Calcium 
Albumin 
Total protein 
Sodium 
Potassium 
Bicarbonate 
Chloride 
Urea nitrogen 
Creatinine (and calculated eGFR) 
Alkaline phosphatase (ALP) 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST) 
Total bilirubin 
Human chorionic gonadotropin (hCG) for females 
Coagulation Tests 
ADG20 Pharmacokinetics and Immunology 
Prothrombin time (PT)/International Normalized Ratio (INR) 
Partial thromboplastin (PTT) 
ADG20 Serum PK 
Anti-Drug Antibodies (ADA, immunogenicity)  
SARS-CoV-2 and COVID-19-Related Tests 
 
SARS-CoV-2 RT-qPCR 
SARS-CoV-2 Genomic sequencing 
SARS-CoV-2 Antibodies 
Respiratory Pathogen Panel (co-infections) 
 
 


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12.5. 
Appendix: Country-Specific Requirements 
12.5.1. 
Germany-Specific Requirements 
No adolescents, pregnant women, or breastfeeding women will be enrolled in Germany. All 
content in the protocol specific to enrollment of adolescents or pregnant/breastfeeding women is 
not applicable to sites in Germany. Specific changes related to the exclusion of adolescents and 
pregnant/breastfeeding women from the study in Germany and other changes to the protocol 
specific to clinical sites enrolling participants in Germany are outlined in the sections below. 
Throughout the protocol: 
To be eligible to participate in the study in Germany, a participant must be capable of signing the 
informed consent. All references to a participant’s legally authorized representative (LAR) in the 
protocol are not applicable for participants in Germany.  
Section 4.1.1 Inclusion Criterion 
Inclusion Criterion 1:  
Is an adult aged 18 years and above. 
Inclusion Criterion 2: 
Has had SARS-CoV-2 positive RT-PCR test obtained within 5 days prior to randomization.  
Note: In the event the National Testing Strategy is updated to include additional testing methods, 
those methods will also be allowed for use in this study without a protocol amendment. A 
historical record of a positive result from a test conducted within 5 days prior to randomization is 
acceptable. SARS-CoV-2 antibody testing cannot be used for study eligibility. 
Inclusion Criterion 5b xii: 
Does not apply to participants enrolled in Germany. 
Inclusion Criterion 5c: 
Does not apply to participants enrolled in Germany. 
Inclusion Criterion 9: 
Is able to understand and comply with study requirements/procedures based on the assessment of 
the investigator. 
Inclusion Criterion 10: 
Is able and willing to provide informed consent. 

SAP_001.pdf: 
Statistical Analysis Plan 
 
Study ID: ADG20-TRMT-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 Treatment of Ambulatory Participants with 
Mild or Moderate COVID-19 (STAMP) 
 
NCT ID: NCT04805671 
 
IND Identifier: 152327 
 
EudraCT Identifier: 2020-006082-11 
 
Date of Document: 03-March-2022 


 
Adagio Therapeutics, Inc. 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
ADG20-TRMT-001 
 
A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled 
Trial to Evaluate the Efficacy and Safety of ADG20 in the 
Treatment of Ambulatory Participants 
With Mild or Moderate COVID-19 (STAMP) 
 
FINAL Version 1.0, 03 March 2022 
 
Prepared by: 
 
 
 
 
 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
INTRODUCTION ......................................................................................................10 
2. 
OBJECTIVES .............................................................................................................11 
3. 
INVESTIGATIONAL PLAN .....................................................................................13 
3.1. 
Overall Study Design and Plan ...................................................................................13 
3.2. 
iDMC, Interim, and Final Analyses ............................................................................13 
3.3. 
Study Duration ............................................................................................................14 
3.4. 
Study Assessments......................................................................................................14 
3.4.1. 
Clinical Efficacy Assessments ....................................................................................14 
3.4.2. 
Virologic Efficacy Assessments .................................................................................15 
3.4.3. 
PK and ADA Assessments .........................................................................................15 
3.4.4. 
Safety Assessments .....................................................................................................15 
3.5. 
Study Endpoints ..........................................................................................................16 
3.5.1. 
Clinical Efficacy Endpoints ........................................................................................16 
3.5.2. 
Virologic Endpoints ....................................................................................................18 
3.6. 
Treatments ..................................................................................................................19 
3.7. 
Dose Adjustment/Modifications .................................................................................19 
4. 
GENERAL STATISTICAL CONSIDERATIONS ....................................................20 
4.1. 
General Rules and Considerations ..............................................................................20 
4.2. 
Sample Size ................................................................................................................22 
4.3. 
Randomization, Stratification, and Blinding ..............................................................22 
4.4. 
Multiplicity Adjustments ............................................................................................23 
4.5. 
Analysis Sets ...............................................................................................................23 
4.5.1. 
Screen Failures ............................................................................................................23 
4.5.2. 
Full Analysis Set .........................................................................................................23 
4.5.3. 
SARS-CoV-2 Variant Specific Analysis Sets ............................................................23 
4.5.4. 
Modified Full Analysis Set-PCR ................................................................................24 
4.5.5. 
Per-Protocol Set ..........................................................................................................24 
4.5.6. 
Safety Set ....................................................................................................................24 
4.5.7. 
Immunogenicity Set ....................................................................................................24 
4.5.8. 
PK Analysis Set ..........................................................................................................25 


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5. 
STATISTICAL ANALYSES .....................................................................................25 
5.1. 
Participant Disposition ................................................................................................25 
5.1.1. 
Disposition ..................................................................................................................25 
5.1.2. 
Protocol Deviations ....................................................................................................26 
5.2. 
Demographics and Clinical Characteristics ................................................................26 
5.2.1. 
Demographics .............................................................................................................27 
5.2.2. 
Clinical Characteristics ...............................................................................................27 
5.3. 
Medical History ..........................................................................................................29 
5.4. 
Treatments and Medications .......................................................................................29 
5.4.1. 
Prior and Concomitant Medication .............................................................................29 
5.4.1.1. 
Concomitant Procedures .............................................................................................30 
5.4.1.2. 
Study Treatments ........................................................................................................30 
5.5. 
Efficacy Analyses .......................................................................................................30 
5.5.1. 
Primary Efficacy Analysis ..........................................................................................30 
5.5.1.1. 
Sensitivity Analyses of Primary Estimand .................................................................31 
5.5.2. 
Supplemental Estimand Analyses...............................................................................32 
5.5.2.1. 
Sensitivity Analyses of Supplemental Estimand ........................................................32 
5.5.3. 
Key Secondary Endpoints and Analyses ....................................................................33 
5.5.3.1. 
Sensitivity Analyses ....................................................................................................34 
5.5.4. 
Additional Secondary Endpoints and Analyses ..........................................................34 
5.5.5. 
Exploratory and Additional Efficacy Endpoints .........................................................36 
5.5.5.1. 
COVID-19-Related Duration of Hospitalization ........................................................36 
5.5.5.2. 
Exploratory Analysis of Omicron Analysis Set ..........................................................36 
5.5.6. 
Graphical Displays of Efficacy Endpoints .................................................................37 
5.5.6.1. 
Viral Load Effect on Adverse Clinical Outcomes ......................................................37 
5.5.6.2. 
Time to Sustained Improvement of COVID-19 Symptoms Through Day 29 ............38 
5.5.6.3. 
Time to Sustained Recovery of COVID-19 Symptoms Through Day 29 ..................38 
5.5.7. 
Household Contacts ....................................................................................................38 
5.5.8. 
COVID-19-Related Mortality Through Day 29 .........................................................38 
5.5.9. 
Post-Acute Sequelae of SARS-CoV-2 Infection ........................................................39 
5.6. 
Subgroup Analyses .....................................................................................................39 
5.7. 
Other Analyses ............................................................................................................40 


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5.7.1. 
Resistance ...................................................................................................................40 
5.7.2. 
Immunogenicity Analyses ..........................................................................................40 
5.8. 
Safety Analysis ...........................................................................................................40 
5.8.1. 
Adverse Events ...........................................................................................................41 
5.8.1.1. 
Unsolicited Adverse Events ........................................................................................41 
5.8.1.2. 
Injection Site Reactions ..............................................................................................41 
5.8.1.3. 
Treatment Emergent Adverse Events .........................................................................42 
5.8.1.4. 
Adverse Events of Special Interest .............................................................................42 
5.8.1.5. 
Medically Attended Adverse Events ..........................................................................43 
5.8.1.6. 
Serious Adverse Events ..............................................................................................43 
5.8.1.7. 
Severity 
43 
5.8.1.8. 
Relationship of Adverse Events to Study Drug ..........................................................44 
5.8.1.9. 
Analysis of Adverse Events and Injection Site Reactions ..........................................44 
5.8.1.10. 
Adverse Events Leading to Treatment Discontinuation .............................................46 
5.8.1.11. 
Adverse Events Leading to Study Discontinuation ....................................................46 
5.8.2. 
Death and Survival Status ...........................................................................................46 
5.8.3. 
Clinical Laboratory Evaluations .................................................................................47 
5.8.3.1. 
Hematology .................................................................................................................47 
5.8.3.2. 
Serum Chemistry ........................................................................................................48 
5.8.3.3. 
Coagulation .................................................................................................................48 
5.8.4. 
Vital Sign Measurements ............................................................................................48 
5.8.5. 
Other Safety Data .......................................................................................................49 
6. 
PHARMACOKINETIC ANALYSES ........................................................................49 
6.1. 
Data Handling .............................................................................................................49 
6.2. 
Serum Concentrations .................................................................................................49 
6.3. 
Serum Pharmacokinetic Parameters ...........................................................................50 
7. 
CHANGES IN THE PLANNED ANALYSIS ...........................................................51 
8. 
REFERENCES ...........................................................................................................52 
9. 
APPENDICES ............................................................................................................53 
APPENDIX A. STANDARDS FOR VARIABLE DISPLAY IN TFLS ....................................54 
APPENDIX B. ANALYSIS VISIT WINDOWS ........................................................................55 


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APPENDIX C. IMPUTATION RULES FOR MISSING DATES OF 
PRIOR/CONCOMITANT MEDICATIONS FLAGS ................................................56 
APPENDIX D. IMPUTATION RULES FOR MISSING DATES OF AES ..............................57 
APPENDIX E. DATES OF EMERGENCE OF OMICRON VARIANT BY 
COUNTRY .................................................................................................................58 
APPENDIX F. RULES FOR MISSING SYMPTOM DIARY DATA ......................................59 
APPENDIX G. ESTIMANDS AND INTERCURRENT EVENTS ...........................................61 
APPENDIX H. PRIMARY AND KEY SECONDARY OBJECTIVES AND 
ESTIMANDS .............................................................................................................62 
APPENDIX I. OVERVIEW OF STATISTICAL METHODS: ESTIMATIONS OF 
ESTIMANDS AND SENSITIVITY ANALYSES ....................................................65 
APPENDIX J. ALGORITHM OF LOGISTIC REGRESSION METHOD ...............................67 
APPENDIX K. CRITERIA FOR POTENTIALLY CLINICALLY SIGNIFICANT 
EVENTS .....................................................................................................................69 
APPENDIX L. SAFETY MONITORING ..................................................................................71 
APPENDIX M. SCHEDULE OF EVENTS ...............................................................................72 
 


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LIST OF TABLES 
Table 1: 
Objectives and Endpoints ......................................................................................11 
Table 2: 
Criteria for Sustained Improvement and Sustained Resolution of COVID-
19 Symptoms Through Day 29 ..............................................................................18 
Table 3:  
Programmatic Determination of COVID-19 Severity ...........................................28 
Table 4: 
Additional Secondary Endpoint Analyses .............................................................34 
Table 5: 
Grading of Injection Site Reactions .......................................................................41 
Table 6: 
Injection Site Reaction Mapping to MedDRA Coding ..........................................42 
Table 7: 
Study Pausing Guidelines ......................................................................................46 
Table 8: 
Calculated PK Parameters......................................................................................50 
Table 9: 
PK Parameters for Data Selection..........................................................................50 
Table 10: 
Analysis Windows .................................................................................................55 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ANCOVA 
analysis of covariance 
ATC 
anatomical therapeutic chemical 
AUC 
area under the concentration-time curve 
BLQ 
below the limit of quantification 
BMI 
body mass index 
CBC 
complete blood count 
CDC 
Centers for Disease Control and Prevention 
CI 
confidence interval 
CONSORT 
Consolidated Standards of Reporting Trials 
COPD 
chronic obstructive pulmonary disease 
COVID-19 
coronavirus disease 2019 
CTMS 
PPD Clinical Trial Management System 
DAIDS 
Division of Allergy and Infectious Diseases 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EOS 
end of study 
EUA 
emergency use authorization 
FAS 
full-analysis set 
FDA 
US Food and Drug Administration 
FSH 
follicle stimulating hormone 
IA 
Interim analysis 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
iDMC 
Independent Data Monitoring Committee 
IM 
intramuscular 
IRT 
interactive response technology 
ISR 
injection site reaction 


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Abbreviation 
Definition 
IV 
intravenous 
KM 
Kaplan-Meier 
LAR 
legally authorized representative 
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 
MNAR 
missing not at random 
NIAID 
National Institute of Allergy and Infectious Diseases 
NP 
nasopharyngeal 
OTC 
over-the-counter 
PASC 
post-acute sequelae of SARS-CoV-2 
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 
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 


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Abbreviation 
Definition 
WGS 
whole genome sequencing 
 
 


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1. 
INTRODUCTION 
This SAP describes the planned analyses for ADG20-TRMT-001 (STAMP) based on the clinical 
study protocol, version 6.0, dated 02-Mar-2022. In addition to the information presented in the 
statistical analysis section of the protocol (Section 7), which provides the principal features of 
analyses for the study, this SAP provides statistical analysis details/data derivations. It also 
documents modifications or additions to the analysis plan that are not principal in nature and 
result from information that was not available at the time of protocol finalization. 
The STAMP study is a randomized, double-blind, placebo-controlled, multi-center adaptive 
study of the safety, efficacy, PK, and antiviral activity of the mAb ADG20 in the treatment of 
ambulatory participants with mild or moderate COVID-19 with a high risk of disease 
progression based on age or co-morbid medical conditions. The study will be conducted in 
2 phases with data review conducted by an iDMC throughout. 
PPD Biostatistics and programming team, designee of Adagio Therapeutics, Inc., will perform 
the statistical analysis; SAS Version 9.4 or higher will be used. If the methods in this SAP differ 
from the methods described in the protocol, the SAP will prevail. Any additional analysis outside 
of the planned analysis following the Day 29 database soft lock or the final database lock that are 
not performed by PPD are not included in the SAP. 
The STAMP 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 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 efficacy 
data collected in participants with a non-Omicron variant of SARS-CoV-2 and safety data 
collected in all participants. The efficacy in participants with an Omicron variant of 
SARS-CoV-2 will be exploratory. With this analysis plan, the primary efficacy and safety 
analyses are planned 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 
The objectives and endpoints are presented in Table 1. 
Table 1: 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the efficacy of ADG20 compared 
to placebo in the treatment of mild or moderate 
COVID-19 in participants at high risk of 
disease progression 
COVID-19-related hospitalization or all-cause death through 
Day 29 
To evaluate the safety and tolerability of 
ADG20 compared to placebo through Day 29 
in participants with mild or moderate 
COVID-19 and high risk of disease progression 
Assessment of safety through Day 29 based on: 
• 
The incidence of TEAEs 
• 
Incidence of solicited injection site reactions through 
Day 4  
• 
Changes from baseline in clinical laboratory tests (ie, CBC 
with differential, serum chemistry, coagulation)  
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure) 
Secondary  
To evaluate the effect of ADG20 on the 
following clinical parameters in participants 
with mild or moderate COVID-19 and high risk 
of disease progression 
• 
Severity of COVID-19 
• 
COVID-19-related emergency room visits, 
COVID-19-related hospitalizations, or 
all-cause death 
• 
Time to sustained resolution of COVID-19 
symptoms 
• 
COVID-19-related medically attended 
visits 
• 
Time to sustained recovery of COVID-19 
symptoms 
• 
All-cause mortality 
• 
Severe/critical COVID-19 or all-cause death through 
Day 29 
• 
COVID-19-related emergency room visits, COVID-19-
related hospitalization, or all-cause death through Day 29 
• 
Time to sustained resolution of COVID-19 symptoms 
through Day 29 
• 
COVID-19-related medically attended visit (telemedicine, 
physician office, urgent care center, emergency room, 
hospitalization) or all-cause death through Day 29 
• 
Time to sustained recovery defined as sustained 
improvement or resolution of COVID-19 symptoms 
through Day 29 
• 
All-cause death through Day 29, Day 60, and Day 90  


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Objectives 
Endpoints 
To evaluate the effect of ADG20 on 
SARS-CoV-2 viral load and clearance in 
participants with mild or moderate COVID-19 
and high risk of disease progression 
• 
Change from baseline in SARS-CoV-2 viral load 
(log10 copies/mL) to Day 7 (±1) assessed by RT-qPCR 
from NP samples 
• 
Viral load >5 log10 copies/mL on Day 7 (±1) based on NP 
samples 
• 
Duration of SARS-CoV-2 viral shedding from Day 1 
through Day 29 assessed by RT-qPCR from saliva 
samples 
• 
Change from baseline in SARS-CoV-2 viral load 
(log10 copies/mL) to Days 3, 5, 7, 11, and 14 assessed by 
RT-qPCR from saliva samples 
• 
SARS-CoV-2 viral clearance (Days 5, 7, 11, 14, 21, and 
29) assessed by RT-qPCR from saliva samples (and 
BLQ/not detected or not detected for NP samples for Day 
7) 
• 
SARS-CoV-2 viral load AUC assessed by RT-qPCR from 
saliva samples from baseline to Day 29  
To evaluate the long-term safety and 
tolerability of ADG20 compared to placebo in 
participants with mild or moderate COVID-19 
and high risk of disease progression 
Assessment of safety based on: 
• 
The incidence of TEAEs 
• 
Changes from baseline in clinical laboratory tests (ie, CBC 
with differential, serum chemistry, coagulation)  
• 
Changes from baseline in vital signs (body temperature, 
heart rate, respiration rate, and systolic and diastolic blood 
pressure) 
To evaluate the PK of ADG20 following IM 
administration 
PK parameters of ADG20: As data permit, Cmax, Tmax,  
AUC0-last, AUC0-inf, CL, Vd, and T1/2. Additional PK parameters 
may be calculated  
To evaluate the immunogenicity (ADAs) to 
ADG20 
Incidence of ADAs against ADG20 
To evaluate the emergence of resistance to 
ADG20 
Genotypic characterization of viral isolates for reduced 
susceptibility to ADG20, with phenotypic evaluation as 
appropriate 
Exploratory  
To evaluate the effect of host or viral 
biomarkers on clinical outcomes 
Effect of baseline SARS-CoV-2 specific antibody response on 
select clinical outcomes 
To identify a persistently high viral load 
threshold for risk of adverse clinical outcomes 
The level of viral load leading to the following adverse clinical 
outcomes: 
• 
COVID-19-related hospitalization or all-cause death 
through Day 29 
• 
COVID-19-related emergency room visits, COVID-19-
related hospitalization, or all-cause death through Day 29 
• 
Severe/critical COVID-19 or all-cause death through 
Day 29 


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Objectives 
Endpoints 
To evaluate the development of symptomatic 
COVID-19 or asymptomatic infection in 
household contacts of study participants after 
participant receipt of study drug 
• 
Participants with symptomatic COVID-19 among 
household contacts 
• 
Participants with asymptomatic SARS-CoV-2 infection 
among household contacts 
To evaluate the effect of ADG20 on the 
following parameters 
• 
COVID-19-related mortality 
• 
Time to improvement of COVID-19 
symptoms 
• 
Post-acute sequelae of SARS-CoV-2 
infection  
• 
COVID-19-related death through Day 29 
• 
Time to improvement of COVID-19 symptoms through 
Day 29 
• 
Incidence of PASC at Day 60, Day 90, and Month 6 
 
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; CBC=complete blood count; CL=clearance; 
Cmax=maximum plasma concentration; IM=intramuscular; NP=nasopharyngeal; PASC=post-acute sequelae of SARS-CoV-2 
infection; PK=pharmacokinetic; RT-(q)PCR=(quantitative) reverse transcription-polymerase chain reaction; TEAEs=treatment-
emergent adverse events; t½=plasma concentration half-life; Tmax=time to reach Cmax; Vd=apparent volume of distribution. 
3. 
INVESTIGATIONAL PLAN 
3.1. 
Overall Study Design and Plan 
ADG20-TRMT-001 is a randomized, double-blind, placebo-controlled, multi-center adaptive 
study of the mAb ADG20 in the treatment of ambulatory participants with mild or moderate 
COVID-19. The study will evaluate the safety, efficacy, PK, and antiviral activity of ADG20 
300 mg IM versus placebo. A total of approximately 1084 participants are planned to be enrolled 
in the study at approximately 100 to 115 sites globally. 
Participants with laboratory confirmed mild or moderate COVID-19 with symptom duration of 
5 days or less prior to randomization and a positive SARS-CoV-2 test taken within 5 days or less 
prior to randomization will be enrolled. Participants will be randomized 1:1 to receive a single 
dose of ADG20 or placebo by IM injection. Randomization will be stratified by age (age 12 to 
17, 18 to 65, and >65 years) and country. 
Study drug will be administered at the study site. As a precaution for acute worsening of disease, 
hypersensitivity, and/or ISRs, participants will be observed after study drug administration, as 
described in the protocol (Section 6.4.1). Each participant will receive a single dose of study 
drug or placebo at the Day 1 Visit. After Day 1, participants will be followed via telemedicine 
visits, phone calls, or in-person visits, as indicated in the Schedule of Events (Appendix M), 
through Month 14/EOS. 
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 available safety data, and other clinical 
study data, to ensure the benefit/risk remains favorable (refer to Appendix L and below for 


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details). Details regarding iDMC membership, conduct, ongoing safety monitoring, 
decision-making, and communication will be provided in the iDMC Charter. PPD is not 
responsible for producing iDMC reports and will complete analyses after the database locks 
(Day 29 and Month 14) as detailed below. Pausing guidelines triggering iDMC ad hoc reviews 
are described in Section 5.8.1.9. 
To evaluate the safety profile of ADG20 and to make recommendations regarding enrollment of 
adolescents and pregnant and breastfeeding women in Phase 3 and postdose monitoring duration, 
an administrative IA will be reviewed by the iDMC after approximately 200 participants are 
enrolled in Phase 2.  
Following completion of enrollment and completion of the Day 29 visit for all participants (or if 
it is known that a participant will not have a Day 29 visit), the database will be frozen (soft-
locked) to conduct the primary Day 29 analysis. All decisions regarding the analysis will be 
made in a blinded fashion and the SAP will be finalized (signed) prior to unblinding. The study 
will be unblinded to Sponsor personnel not working directly with the site staff after this freeze, 
and an unblinded data analysis will be performed. All site staff, certain Sponsor personnel (or 
designee) working directly with the site staff, and participants, will remain blinded to individual 
participant study drug assignment. 
The database will be locked for the final safety analysis after all participants have been followed 
through the Month 14 visit (or if it is known that the Month 14 visit will not occur).  
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(s), and/or to address protocol amendments. 
3.3. 
Study Duration  
The study duration for each participant will be approximately 14 months. Each participant, 
regardless of study phase, will receive a single dose of ADG20 or placebo at the Day 1 visit. 
Participants will have telemedicine visits (via video or phone) and in-person clinic or at-home 
visits through Day 29. Participants will continue long-term follow-up through Month 14, with 
additional visits for safety laboratory tests at Day 90 and at Month 6. 
3.4. 
Study Assessments 
The Schedule of Assessments is provided in Appendix M. Efficacy and safety assessments will 
be conducted by site staff, and by participants with at home assessments and collections. 
3.4.1. 
Clinical Efficacy Assessments 
Participants will be asked to complete the COVID-19 Symptom Diary (includes global 
impression questions) daily from Day 1 to Day 29. The investigator (or designee) will assign an 
overall COVID-19 severity grade for each visit through Day 29. At scheduled visits on Days 3, 
5, 7, 11, 14, 21, 29, 60, 90, and at Months 6, 11, and 14, participants (or guardians/LARs) will be 
asked to report any medically attended visits. Medically attended visits include telemedicine 
visits not specified in the protocol, emergency room or urgent care center visits, hospitalization, 
or visits to a physician’s office. COVID-19-related medically attended visits include visits for 


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attention to worsening signs or symptoms attributed to COVID-19 in the opinion of the 
investigator. The participant’s survival status (known to be dead or alive) should be determined 
at the planned time for any missed visit through Month 14, or at the time that the participant is 
thought to be lost to follow-up. At Day 29, participants will be asked about household 
transmission of SARS-CoV-2 and symptomatic COVID-19. 
During the long-term follow-up period (LTFU), participants will be asked questions about their 
overall health status, including return to usual health and usual activities and any ongoing 
symptoms associated with COVID-19.  
3.4.2. 
Virologic Efficacy Assessments 
Blood will be collected on Day 1 to test for SARS-CoV-2 antibodies. Two NP swabs will be 
collected on Day 1 for SARS-CoV-2 RT-qPCR, SARS-CoV-2 sequencing, and a respiratory 
panel assessment. One NP swab will be collected on Day 7 for SARS-CoV-2 RT-qPCR and 
SARS-CoV-2 sequencing. Saliva samples for SARS-CoV-2 RT-qPCR will be collected at the 
site on Days 1, 7, and 29, and by participants at home on Days 3, 5, 11, 14, and 21.  
3.4.3. 
PK and ADA Assessments 
On Day 1, a blood sample for PK assessment will be collected prior to study drug administration. 
Blood samples for PK assessment will also be collected on Days 7, 29, 90, and at Month 6 and 
Month 11. Blood samples for determination of ADA (and neutralizing antibody) against ADG20 
will be collected on Days 1, 29, and 90, and at Months 6 and 11. 
3.4.4. 
Safety Assessments 
Safety will be assessed in an ongoing manner. Blood samples for safety laboratory assessments 
(hematology, serum chemistry, and coagulation) will be collected on Days 1, 7, 29, and 90, and 
at Month 6. A complete physical examination will be conducted at screening, and a targeted, 
symptom-directed review of changes in health based on reported AEs or ongoing 
signs/symptoms of COVID-19 will be conducted at Days 7, 29, and 90, and at Month 6 and 
Month 11. Vitals signs (including temperature, heart rate, respiratory rate, seated blood pressure, 
and SpO2 will be assessed by site staff after study drug dosing and on Days 7, 29, and 90, and at 
Month 6 and Month 11 (see Appendix M). Measurements of temperature, SpO2, and heart rate 
are to be taken by the participant daily through Day 29.  
AEs occurring from when the participant signs the ICF until the Month 14 visit, or withdrawal 
from the study, 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. AESIs (as defined in Section 5.8.1.4) will be recorded through Day 4. 
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.  


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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 5.8. 
3.5.1. 
Clinical Efficacy Endpoints 
COVID-19-related hospitalization or all-cause death through Day 29 (primary endpoint): 
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, intensive care units, acute care facilities created for COVID-19 
pandemic hospitalization needs, or other acute care facilities).  
• Through Day 29 is defined as the admission date for the hospitalization or acute care facility 
occurring from Day 1 (postdose) up to and including Day 29.  
• All-cause death is defined as death for any reason from Day 1 (postdose) through Day 29. 
Severe/critical COVID-19 or all-cause death through Day 29: All-cause death is defined as 
death for any reason from Day 1postdose) through Day 29. Severity is based on the 
investigator’s assessment of severity (eCRF COVID-19 Severity Assessment) per the following 
protocol definitions: 
• Severe COVID-19 is defined as having a positive test by standard RT-PCR assay or 
equivalent test plus the following: 
− 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 
(PaO2/FiO2) <300 mm Hg. 
− No criteria for critical severity. 
• Critical COVID-19 is defined as having a positive test by standard RT-PCR assay or 
equivalent test plus 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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− Shock (defined by systolic blood pressure <90 mmHg, diastolic blood pressure 
<60 mmHg, or requiring vasopressors). Note: Shock is per investigator 
diagnosis/assessment. 
− Multiorgan 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.  
Regardless of investigator’s assessment of severity, severe/critical COVID-19 will be imputed 
for participants who met the primary efficacy endpoint definition in the analysis. 
COVID-19-related emergency room visits, COVID-19-related hospitalization, or all-cause 
death through Day 29: Defined as any stay in a hospital or acute care facility regardless of 
duration (includes emergency rooms, intensive care units, acute care facilities created for 
COVID-19 pandemic hospitalization needs, or other acute care facilities) for attention to 
worsening signs or symptoms attributed to COVID-19 in the opinion of the investigator or all-
cause death through Day 29. 
COVID-19-related medically attended visits or all-cause death through Day 29: Defined as 
for the primary efficacy endpoint, but also includes any medically attended visits, in-person, or 
telemedicine, not specified in the protocol. These include unscheduled in-person or telemedicine 
visits conducted by the investigator for the purpose of evaluating worsening signs or symptoms 
attributed to COVID-19 or emergency room, urgent care center or physician office visits, or 
hospitalization for attention to worsening signs or symptoms attributed to COVID-19, in the 
opinion of the investigator. 
Time to sustained recovery (improvement or resolution) of COVID-19 symptoms through 
Day 29: Defined as the time from the first dose date to the earliest date when sustained 
improvement or sustained resolution of COVID-19 symptoms is met (as detailed below) through 
Day 29. COVID-19 symptoms assessed include fever, chills, cough, sore throat, congestion, 
shortness of breath/difficulty breathing at rest, shortness of breath/difficulty breathing with 
exertion, muscle or body aches, fatigue, headache, nausea, vomiting, and diarrhea. Loss of 
taste/smell is excluded from this analysis. 
Time to sustained improvement of COVID-19 symptoms through Day 29: Defined as the 
time from the first dose date to the first date when all of the above symptoms are scored as 
moderate or severe at baseline are scored as mild or absent, all of the above symptoms scored as 
mild or absent at baseline are scored as absent, and with no symptom worsening or new 
symptoms, except for cough, fatigue, and headache which may be mild or absent, through 
Day 29.  
Time to sustained resolution of COVID-19 symptoms through Day 29: Defined as time from 
the first dose date to the first date when all of the above symptoms are scored as absent with no 
symptom recurrence or new symptoms, except cough, fatigue, and headache which may be mild 
or absent, through Day 29.   
Censoring rules for time to COVID-19 symptoms through Day 29 analysis:  
• Participants who are randomized but not treated are censored at Day 1.  


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• Participants who have any COVID-19-related hospitalization (≥24 hours) or all-cause death 
through Day 29 (as defined in the primary endpoint) will be censored at Day 30.  
• Participants who have not been followed through Day 29 visit (discontinuation from study or 
incomplete follow-up at the time of analysis) will be censored at the last contact date. 
• Participants who have completed the Day 29 visit and do not experience a defined event 
through Day 29 will be censored at Day 30.  
Table 2 provides further programming details.  
Table 2: 
Criteria for Sustained Improvement and Sustained Resolution of COVID-19 
Symptoms Through Day 29 
COVID-19 Symptoms 
Baseline 
Severity  
Criteria for Sustained 
Improvement 
Criteria for Sustained 
Resolution 
Fever, chills, sore throat, 
congestion, shortness of 
breath/difficulty breathing at rest, 
shortness of breath/difficulty 
breathing with exertion, muscle 
or body aches, nausea, vomiting, 
diarrhea 
Moderate/Severe 
Mild/Absent 
  
with no worsening 
(moderate/severe) 
Absent 
 
with no recurrence or new 
symptoms 
(mild/moderate/severe) 
Mild 
Absent 
  
with no recurrence or new 
symptoms 
(mild/moderate/severe) 
Absent 
Cough, fatigue, headache 
Moderate/Severe 
Mild/Absent 
  
with no worsening 
(moderate/severe) 
Mild/Absent 
 
with no worsening 
(moderate/severe) 
Mild 
Absent 
  
All-cause mortality through Day 29, Day 60, and Day 90: Defined as death for any reason 
from Day 1 (postdose) to Day 29, Day 60, and Day 90. In the overall survival analysis, 
participants who are alive or lost to follow-up at the time of analysis will be censored at the date 
of last contact. 
COVID-19-related mortality through Day 29: Defined as death directly due to COVID-19 or 
any death for which COVID-19 or COVID-19 complications contributed to the death, as 
determined by the investigator, a formal autopsy report or death certificate, as recorded on the 
Death eCRF. 
3.5.2. 
Virologic Endpoints 
For all virologic assessments, the confirmatory retest (reflex) result should be used for analysis if 
present. If a participant has multiple assessments on the same date with different accession 
numbers, the accession number on the record with the highest viral load value should be used to 
select records for analysis.  If viral load values are the same, the accession number on the record 
with the lowest value of MBSEQ will be used to select records for analysis. 


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Change from baseline in SARS-CoV-2 viral load (log10 copies/mL) to Day 7 assessed by 
RT-qPCR from NP sample: Change from baseline is defined as the viral load at the Day 7 
assessment from NP sample minus the viral load at baseline from NP sample. 
Viral load >5 (log10 copies/mL) on Day 7 assessed by RT-qPCR from NP sample: A second 
cutoff of high viral load will also be examined: viral load >4 (log10 copies/mL) on Day 7 
assessed by RT-qPCR from NP sample. 
Duration of SARS-CoV-2 viral shedding from Day 1 through Day 29 assessed by RT-qPCR 
from saliva samples: Duration of SARS-CoV-2 viral shedding will be analyzed based on the 
time to SARS-CoV-2 viral clearance, which is defined as time from the first dose date to the first 
date the viral load is not detected, ie, below the limit of detection (LOD), and sustained through 
Day 29. Participants who do not have the defined event or who discontinue study prior to Day 29 
are censored at the earlier date of the last viral load assessment or Day 30. Deaths occurring prior 
to Day 29 will be censored at Day 30. 
Change from baseline in SARS-CoV-2 viral load (log10 copies/mL) to Days 3, 5, 7, 11, 14, 
21, and 29 assessed by RT-qPCR from saliva samples: Change from baseline is defined as the 
viral load from saliva samples at the Day 3, 5, 7, 11, 14, 21, or 29 assessment minus the viral 
load from saliva sample at baseline. 
Proportions of SARS-CoV-2 viral clearance (Days 3, 5, 7, 11, 14, 21, and 29) assessed by 
RT-qPCR from saliva samples: In the mFAS-S, the cumulative proportion of participants with 
viral clearance (viral load not detected and sustained through Day 29) at Days 3, 5, 7, 11, 14, 21, 
and 29 will be assessed by RT-qPCR from saliva samples. Participants who have died or 
discontinued study prior to Day 29 are assumed to have no viral clearance. 
Proportion of SARS-CoV-2 viral load BLQ/not detected or not detected at Day 7 assessed 
by RT-qPCR from NP samples: In the mFAS-NP, the proportion of participants with viral load 
BLQ/not detected or not detected at Day 7 assessed by RT-qPCR from NP samples. 
SARS-CoV-2 viral load AUC assessed by RT-qPCR from saliva samples through Day 29: 
Defined as AUC of SARS-CoV-2 viral load from baseline through Day 29 from saliva samples 
at Days 3, 5, 7, 11, 14, 21, and 29. AUC is calculated using the trapezoidal method. 
3.6. 
Treatments 
After randomization, participants will receive a single 300 mg dose (up to 3 mL) of ADG20, or 
matching placebo, administered via IM injection. 
3.7. 
Dose Adjustment/Modifications 
As only a single dose is administered to each participant, there are no subsequent dose 
adjustments and/or modifications. 


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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 dose of study drug. If the date of dosing is 
missing, the date of randomization will be used instead. 
Unless otherwise specified, the display precision for the summary statistics of all numerical 
variables will follow programming standards. Please see Appendix A for variable display 
standards. 
When count data are presented, the percentage will be suppressed when the count is zero in order 
to draw attention to the non-zero counts. A row denoted “Missing” will 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 the calendar day that study drug is administered. Subsequent study days are 
calculated as the date of assessment/event – date of injection + 1. If a participant is not dosed, the 
date of randomization is used to define Study Day rather than the date of injection. 
Time-to-event variables are defined from the date of dosing. If a participant is not dosed, the 
date of randomization is used. 
All summaries involving diary data will be based on distinct diary date entries.  
Unscheduled visits: Unscheduled visit measurements will be included in the analysis as follows: 
• In scheduled visit windows per specified visit windowing rules. 
• 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. 
Visit windowing rules: Assessments collected on the nominal visits per the protocol schedule 
will be included in by-visit summaries and analysis. If an assessment is missing from a nominal 
visit, available assessments from the unscheduled visits within the protocol-defined target-study-
day range may be mapped to the corresponding nominal visit. The assessment occurring closest 
to the target study day will be used. If there are multiple assessments equally distant to the target 
study day, the earliest assessment will be used. 


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All diary data will be summarized based on the actual day.  
Incomplete/missing data: 
Imputation rules for missing dates of prior/concomitant medications, including COVID-19 
vaccinations and prohibited medications, and procedures are provided in Appendix C. 
Imputation rules for missing AE are provided in Appendix D. 
Data that are continuous in nature but are reported in the form <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 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) 
− All viral load analyses will use both observed and imputed viral load data. Listings 
present both observed and imputed viral load. 
• For PK concentrations 
− Serum concentrations that are BLQ will be treated as zero for PK analyses, except for 
BLQ values observed between 2 quantifiable concentrations, which will be set to 
missing. If consecutive BLQ concentrations are followed by quantifiable concentrations 
in the terminal phase, those concentrations after BLQ concentrations will be treated as 
missing. Missing concentrations will be treated as missing in the PK parameter 
calculations. 
• Efficacy endpoint data will be imputed as detailed in Section 5.5.  
• 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/displays for efficacy will be provided by treatment group using 
the appropriate analysis population unless otherwise specified. 
Individual participant listings of all data represented on the eCRFs and laboratory data will be 
provided to facilitate the investigation of tabulated values and to allow for the clinical review of 
all efficacy and safety data. 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 
The primary analysis is the comparison of the ADG20 arm versus the placebo arm with respect 
to proportion of participants infected with a non-Omicron variant of SARS-CoV-2 with a 
COVID-19-related hospitalization or all-cause death through Day 29.  
The original required sample size was calculated based on the following assumptions obtained 
from a review of data from studies of other mAbs in participants with a high risk for disease 
progression leading to hospitalization or death prior to widespread emergence of both the Delta 
and Omicron variants (AstraZeneca 2022; Eli Lilly and Company 2022; GlaxoSmithKline 2021; 
Regeneron 2022). The original sample size of 1084 participants was planned with 90% power, 
2-sided alpha .05, and a 1:1 randomization ratio to detect a statistically significant risk reduction 
with a true efficacy of relative risk reduction 70% and a 5% event rate in the placebo arm.  
At the time of enrollment suspension in January 2022, a total of 399 participants were 
randomized. Of them, approximately 320 participants will be included in the primary efficacy 
population of participants with a non-Omicron variant of SARS-CoV-2. Based on blinded 
monitoring of the primary endpoint outcomes, an aggregate event rate of approximately 9% was 
observed, indicating a higher placebo event rate than previously assumed and providing 
approximately 80% power to test the primary endpoint in the primary efficacy population given 
an estimated placebo event rate of 12% and the same efficacy assumption. 
4.3. 
Randomization, Stratification, and Blinding 
After completing the screening assessments, participants will be randomly assigned at the Day 1 
visit to receive one of the following (1:1 randomization): 
• ADG20 300 mg administered IM  
• Placebo administered IM 
Randomization will be assigned in a blinded manner using IRT, in accordance with a pre-
generated randomization schedule, generated by SAS software Version 9.4 or later (SAS 
Institute Inc, Cary, North Carolina), linking sequential participant randomization numbers to 
treatment codes. Randomization will be stratified by age (age 12 to 17, 18 to 65, and >65 years) 
and country; it will also use an appropriate block size, known only by the statistician. A 
participant is considered randomized when a randomization transaction has been recorded in the 
IRT.  
The main goal of the stratification by country is to promote the balance in important prognostic 
and predictive factors across the two treatment groups within a country to help increase 
comparability of the two treatments rather than incorporating stratification into the analyses to 
increase the precision of the estimates. Therefore, the country term will not be included as strata 
in the statistical models.  
A participant’s treatment assignment will not be unblinded to site staff, sponsor personnel (or 
designee) working directly with the site staff, or participants until the end of the study (Month 14 
of Phase 3) unless medical treatment of the participant depends on knowing the study treatment 
the participant received. If the blind needs to be broken due to a medical emergency, the 
investigator may unblind an individual participant’s treatment allocation. 


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Details of blinding are provided in Section 5.5 of the protocol and in the PPD Work Process 
Flow for Maintaining the Blind. 
4.4. 
Multiplicity Adjustments 
To control the overall type I error rate at .05 (2-sided), a hierarchical testing procedure will be 
used, such that testing for the key secondary analyses difference will proceed only if the 
treatment difference is statistically significant in the primary analysis.  
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 when applicable. 
4.5. 
Analysis Sets 
4.5.1. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the study but who are not 
subsequently randomly assigned to treatment. Minimal information collected includes date of 
informed consent (and assent, where applicable for adolescents), reason for screen failure, and 
AE information. Individuals who do not meet the criteria for participation in this study (screen 
failure) may be rescreened. A participant is considered enrolled once the participant has been 
randomized. 
4.5.2. 
Full Analysis Set  
The Full Analysis Set (FAS) will include all randomized participants regardless of whether the 
participant received study drug. Participants will be analyzed based on the treatment they are 
randomized to, irrespective of which treatment was actually received. 
4.5.3. 
SARS-CoV-2 Variant Specific Analysis Sets 
WGS will be used to determine a participant’s SARS-CoV-2 infecting variant (Delta, Omicron, 
and others) based on the NP or saliva sample collected at baseline; if the baseline sample is 
missing, the available post-baseline NP or saliva sample will be used. Any participants with a 
missing WGS result will be classified as suspected non-Omicron or Omicron variant by 
comparing their randomization date with the date of the first WGS-confirmed Omicron 
participant enrolled from the same country. If there is no WGS-confirmed Omicron participant 
enrolled from the same country in the study, the date of emergence of Omicron in the country, 
based on publicly available epidemiology data will be used (see Appendix E). A final clinical 
and virological review (with adjudication as needed) may be performed. 
Modified Full Analysis Set with Non-Omicron SARS-CoV-2 Variant (mFAS-non-
Omicron): will include all randomized participants with COVID-19 due to WGS-confirmed or 
suspected non-Omicron SARS-CoV-2 variants, regardless of whether the participant received 
study drug. The mFAS-non-Omicron is the primary efficacy population.  


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Modified Full Analysis Set with Omicron SARS-CoV-2 Variant (mFAS-Omicron): will 
include all randomized participants with COVID-19 due to WGS-confirmed or suspected 
Omicron SARS-CoV-2 variant, regardless of whether the participant received study drug.  
4.5.4. 
Modified Full Analysis Set-PCR 
Modified Full Analysis Set-PCR (mFAS-PCR): will include all randomized participants with a 
positive baseline quantitative SARS-CoV-2 RT-PCR based on either an NP swab or saliva 
sample and who received study drug. Participants will be analyzed based on the treatment they 
are randomized to, irrespective of what treatment was actually received. 
Two sub-populations of the mFAS-PCR will be defined:  
• mFAS-NP: will utilize the baseline NP swab to determine a positive SARS-CoV-2 PCR  
• mFAS-S: will utilize the baseline saliva sample to determine a positive SARS-CoV-2 PCR.  
mFAS-non-Omicron-PCR: is the subset of the mFAS-non-Omicron with a positive baseline 
SARS-CoV-2 RT-PCR. The subpopulations mFAS-non-Omicron-NP and 
mFAS-non-Omicron-S based on sample type used to determine a positive SARS-CoV-2 PCR (as 
defined above) will also be analyzed.  
mFAS-Omicron-PCR: is the subset of the mFAS-Omicron with a positive baseline 
SARS-CoV-2 RT-PCR. The subpopulations mFAS-Omicron-NP and mFAS-Omicron-S based 
on sample type used to determine a positive SARS-CoV-2 PCR (as defined above) will also be 
analyzed. 
4.5.5. 
Per-Protocol Set 
The PPS includes all participants in the mFAS-non-Omicron who had no significant protocol 
deviations (as defined in Section 5.1.2) that affect the efficacy assessments, received the full 
dose of study drug as randomized, and for whom the primary efficacy endpoint was assessed (ie, 
it is known whether or not the participant had a COVID-19-related hospitalization or all-cause 
death through Day 29). Protocol deviations are tracked in the PPD CTMS. The Sponsor will 
perform blinded review of all significant protocol deviations prior to database lock to determine 
if the deviation excludes the participant from the PPS.  
4.5.6. 
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. 
4.5.7. 
Immunogenicity Set 
The Immunogenicity Set includes all participants who received any study drug, had a valid 
immunogenicity test result before the dose of study drug, and had at least 1 valid result after the 
dose of study drug. 


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4.5.8. 
PK Analysis Set 
The PK Analysis Set includes all participants in the Safety Set who had at least one measurable 
ADG20 concentration post-administration of study drug. Where participants experience issues 
that may affect exposure to study drug (eg, dosing errors, etc), data will be reviewed by the study 
pharmacokineticist and evaluated for exclusion from the PK analysis set on a case-by-case basis. 
All participants excluded from the PK analysis set will be documented in the data listings. 
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 and number and percentage (based on total screened) of 
screen failure participants 
• Number and percentage of participants randomized 
• Number and percentage (based on total randomized) of participants randomized and not 
treated 
Reason for screen failure will also be summarized by number and percentage of participants with 
percentage based on the number of Screen Failure participants. The possible reasons for screen 
failure are: 
• Failure to meet randomization criteria 
• Physician decision 
• Withdrawal by participant/guardian/LAR 
• Other 
The number and percentage (based on total number in the FAS) of participants randomized will 
be presented for all analysis sets. 
The following summary will be presented in the FAS, the mFAS-non-Omicron, and the mFAS-
Omicron analysis sets:  
• The number and percentage of participants completing and not completing dosing  
• The reasons for not completing dosing (ie, reasons for treatment discontinuation) as recorded 
in the eCRF and chosen from the following list: 
− Adverse Event 
− Investigator’s discretion 
− Protocol Deviation 


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− Withdrawal by parent/guardian 
− Withdrawal by participant 
− Other 
• The number and percentage of participants who completed the study through Days 29, 60, 
and 90 and through Months 6, 11, and 14  
• The number and percentage of participants who discontinued from the study (early 
termination) prior to Day 29, prior to Month 6, and prior to Month 14.  
• The reasons for early discontinuation as recorded in the eCRF and selected from the 
following list: 
− Death 
− Participant’s request 
− Withdrawal of consent 
− Lost to Follow-up 
− Other 
Participant disposition data will also be presented in listings, including a listing of participants by 
analysis set, and a listing of participants excluded from the Per Protocol Set. 
5.1.2. 
Protocol Deviations 
All protocol deviations will be assessed according to a study deviation rules document that 
indicates whether each deviation is significant or non-significant. Significant deviations are 
defined as protocol deviations that affect the primary efficacy and safety assessments, the safety 
or mental integrity of a participant, or the scientific value of the study. Non-significant deviations 
are defined as protocol deviations that are identified but do not impact the endpoints, safety or 
mental integrity of a participant, or the scientific value of the trial project. Rules for defining 
significant protocol deviations will be developed, documented in the study deviation rules 
document, and finalized in a blinded manner before database lock. 
The number and percentages of participants with at least one protocol deviation, one significant 
deviation and one non-significant deviation will be presented in the FAS by treatment group and 
overall. Significant protocol deviations will also be summarized by deviation type and subtype. 
A table will be provided for  Day 29 and Month 14. A listing of all protocol deviations will be 
provided for all FAS participants. 
5.2. 
Demographics and Clinical Characteristics  
The following summary will be presented in the FAS, the mFAS-non-Omicron, and the mFAS-
Omicron analysis sets. 


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5.2.1. 
Demographics 
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 17, 18 to 65, >65, ≥50, 
>55, >70, and >75 years), country, sex (male, female), race (White, Black or African American, 
Asian, American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, Other, and 
Multiple [if more than one race category is selected]), ethnicity (Hispanic or Latino, Not 
Hispanic or Latino), and BMI subgroups (for adults ≥25, ≥30, ≥40 kg/m2; for adolescents ≥85th 
percentile for age and sex based on CDC growth charts for adolescents) (CDC 2001).   
Participant demographics will be presented in a listing. 
5.2.2. 
Clinical Characteristics 
Risk factors for COVID-19 progression: The number and percentage of participants with each 
of the protocol-defined baseline risk factors for COVID-19 progression will be summarized 
separately for adults and adolescents. The number of participants with ≥1, ≥2 and ≥3 risk factors 
present at baseline will be summarized. Given differences in the definition of high risk for 
COVID-19 progression in this study and other mAbs that have received FDA EUA, a summary 
of the risk factors in the definition in the FDA EUA fact sheets may also be presented.  
Duration of COVID-19 symptoms: The duration of symptom onset to randomization (defined 
as the time from date of onset of self-reported symptoms to the date of randomization) will be 
summarized with descriptive statistics and the number and percentage of participants with 
duration of symptoms of 0-3 days, 4-5 days, and >5 days. The duration of symptom onset to 
study drug administration will be summarized similarly.  
COVID-19 symptoms: COVID-19 symptoms and their severity at baseline based on the 
symptom diary on Day 1 will be presented. The number and percentage of participants with at 
least 1 severe symptom, at least 1 moderate symptom and no severe symptoms, and those with 
only mild symptoms on Day 1 will be summarized. 
COVID-19 severity: In addition, investigator-assessed COVID-19 severity (SARS-CoV-2 
infection without symptoms, mild, moderate, severe, critical) will be presented as will a 
programmatic determination of baseline severity based on parameters collected in the eCRF and 
patient diary outlined in Table 3. The programmatic derived COVID-19 severity will be 
performed at baseline and for the maximum severity through Day 29. 
 


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Table 3:  
Programmatic Determination of COVID-19 Severity   
Protocol Defined 
COVID-19 Severity 
Programmatic Determination 
Critical COVID-19, as 
defined in Section 2.2.2 
of the protocol  
Positive local RT-PCR test at baseline, and one of the following:  
• Any concomitant procedure entry of: endotracheal intubation and mechanical 
ventilation, high-flow oxygen (>20 L/min with FIO2 ≥50%), noninvasive positive 
pressure ventilation, extracorporeal membrane oxygenation 
• Any AE entry of: respiratory failure, shock, multisystem organ failure/dysfunction, 
ARDS, or acute lung injury 
Severe COVID-19, as 
defined in Section 2.2.2 
of the protocol 
Positive local RT-PCR test at baseline, none of the criteria for critical COVID-19, and 
one of the following:  
• Any of the following signs/symptoms: shortness of breath at rest, RR ≥30 breaths 
per minute, HR ≥125 beats per minute, SpO2 ≤93%. 
• Concomitant procedure of oxygen therapy 
• COVID-19 related MAV hospitalization (≥24 hours) or ICU admission.  
Moderate COVID-19, 
as defined in Section 
2.2.2 of the protocol 
Positive local RT-PCR test at baseline, none of the criteria for severe or critical 
COVID-19, and any of the following signs/symptoms: shortness of breath with 
exertion worse than usual, RR ≥20 and <30 breaths per minute, heart rate ≥90 and 
<125 beats per minute  
Mild COVID-19, as 
defined in Section 2.2.2 
of the protocol 
Positive local RT-PCR test at baseline, none of the criteria for moderate, severe, or 
critical COVID-19, and any of the following symptoms: fever, chills, cough, sore 
throat, congestion, muscle or body aches, fatigue, headache, nausea, loss of taste or 
smell, vomiting, diarrhea.  
SARS-CoV-2 test: The number and percentage of participants with a local SARS-CoV-2 test 
performed, and for those with a test performed, the specimen type, assay type, and result will be 
presented. The duration from the local positive SARS-CoV-2 test (defined as the time from date 
of the test performed to the date of randomization) will be summarized with descriptive statistics 
and summarized categorically (0 days, 1-2 days, 3-5 days, >5 days). Baseline SARS-CoV-2 RT-
qPCR results from the sample collected by NP swab and from the saliva sample will be 
presented as will descriptive statistics of the baseline viral load (log10 copies/mL) from each 
sample type. Baseline qualitative serology (SARS-CoV-2 antibody) status will be summarized 
based on qualitative serology assay (positive, negative). Baseline overall serology status based 
on three serology assays (qualitative, IgA, and IgG) will be summarized (positive if at least one 
serology assay is positive, missing if all three assays are missing, negative otherwise). Results of 
the baseline MNT test assay (not detected, detected) will be summarized.  
Respiratory pathogen test: The presence of additional pathogens on Day 1 from the respiratory 
pathogen panel assay will be summarized. 
SARS-CoV-2 variant: The number and percentage of participants with baseline isolates by 
PANGO lineage and CDC classification as variant of concern, variant of interest, variant being 
monitored, or other variants identified (CDC 2021) will be summarized in the FAS based on 
SARS-CoV-2 sequencing data. If baseline sequencing data are missing, available post-baseline 
sequencing data may be used. Participants without sequencing data will be summarized by 
suspected non-Omicron or Omicron variant (see Section 4.5.3).  


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Participant clinical characteristics will be presented in a listing. 
5.3. 
Medical History  
Medical history documentation will include all medical conditions, surgeries, or drug allergies 
within the prior year. Also, any clinically significant abnormalities found during the Screening 
physical exam should be documented as medical history. Medical history will be coded using the 
MedDRA version 23.1 or higher. The number and percentage of participants with any medical 
history will be summarized by treatment arm using SOC and PT, with SOCs and PTs within each 
SOC sorted in descending order of frequency in the ADG20 arm. Percentages will be calculated 
based on number of participants in each treatment group in the FAS and the 
mFAS-non-Omicron. If the same medical history (based on PT) is reported for the same 
participant more than once, the medical history is counted only once for the PT. 
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 
A prior medication is defined as any medication that is taken within 30 days prior to dosing of 
study drug. A concomitant medication is defined as any medication that has a stop date that is on 
or after the date of study drug dosing or is ongoing after dosing. 
All medications used within 30 days prior to the date of randomization up to and including 
Day 60 will be collected on the CRF. In addition, any concomitant medications related to AEs 
and any vaccinations received will be recorded for the entire length of the study (ie, through 
Month 14). 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 by 
participant will be provided.  
The number and percentages of participants with at least one prohibited concomitant medication 
(refer to ADG20-TRMT-001 Designated Background Standard of Care document) for the 
treatment of COVID-19 or receiving a COVID-19 vaccine will be summarized by treatment 
group in the FAS and the mFAS-non-Omicron. The number and percentages of these 
medications will also be summarized by treatment group, WHODrug ATC level 2 and PT, and a 
listing of prohibited medications by participant will be provided. 
Medications with missing dates will follow the imputation rules in Appendix C to categorize as 
prior, concomitant, or prohibited up through Day 29. Medications are sorted by decreasing 
frequency of ATC Level 2 in the ADG20 arm, then by decreasing frequency of PT in the ADG20 
arm. 


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5.4.1.1. 
Concomitant Procedures 
A listing of concomitant procedures as collected on the eCRFs will be provided. 
5.4.1.2. 
Study Treatments 
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. Descriptive statistics of the total volume (mL) and dose (mg) will be presented; mL is 
converted to mg as follows: 100×dose in mL. A listing of study drug administration and of study 
drug exposure exceptions (study drug not administered, full dose not administered, and/or study 
drug not received as randomized) will be provided. 
5.5. 
Efficacy Analyses 
5.5.1. 
Primary Efficacy Analysis  
The primary efficacy endpoint is the incidence of COVID-19-related hospitalization or all-cause 
death through Day 29 in the mFAS-non-Omicron analysis set. 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 COVID-19-related hospitalization or all-cause 
death through Day 29 in the ADG20 and placebo groups respectively. Using the methodology as 
described below (with additional details in Appendix J), a standardized estimator for a binary 
outcome (standardized risk difference/standardized relative risk reduction) will be estimated with 
adjustment for the following prognostic factors: age (continuous), sex (categorical), baseline 
qualitative serostatus (categorical: positive, negative), BMI (continuous), and baseline viral load 
from NP sample (continuous as log10 copies/mL). For all efficacy analysis models, missing 
baseline serostatus will be imputed as positive and missing baseline BMI and viral load will be 
imputed as the average of all participants with non-missing data at baseline. Age is a 
randomization stratification factor and, thus, cannot be missing.  
Appendix I summarizes the main estimation and sensitivity analyses for the primary estimand 
(Estimand 1a). The main estimation for Estimand 1a will use available data for COVID-19 
hospitalization or all-cause death through Day 29, implemented in the mFAS-non-Omicron 
analysis set. Missing status on COVID-19-related hospitalization or all-cause death will be 
imputed as not having a COVID-19 hospitalization or all-cause death. The number and 
percentages of participants who experience and do not experience a COVID-19-related 
hospitalization or all-cause death will be summarized by treatment group, including summaries 
of missing data, COVID-19-related hospitalizations, and all-cause death. 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.  


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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 pre-defined 
prognostic factors. The method relies on a logistic regression model that includes 
COVID-19-related hospitalization or all-cause death present or absent as the dependent variable 
and treatment and prognostic factors as independent variables. To define this model, consider the 
𝑖th participant, 𝑖= 1, … , 𝑛, where 𝑛 is the total number of participants, and let 𝑦𝑖 denote the 
binary outcome for the primary endpoint (COVID-19-related hospitalization or all-cause death, 
present=1 or absent=0). The treatment indicator will be denoted by 𝑡𝑖, where 𝑡𝑖= 0 corresponds 
to the placebo arm and 𝑡𝑖= 1 corresponds to the treatment (ADG20) arm. The vector of 
prognostic factors for the 𝑖th participant will be denoted by 𝒙𝑖. The model is given by:  
logit 𝑝𝑖= 𝛽0 + 𝛽1𝑡𝑖+ 𝜷2
′ 𝒙𝑖, 
where 𝑝𝑖= 𝑃(𝑦𝑖= 1), 𝛽0 and 𝛽1 are the intercept and slope, 𝜷2 is the vector of model 
parameters corresponding to the prognostic factors 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 𝛽̂0, 𝛽̂1 and 𝜷̂2, 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: 
𝑝𝑖0 = 𝑃(𝑦𝑖= 1|𝑡𝑖= 0), 
𝑝𝑖1 = 𝑃(𝑦𝑖= 1|𝑡𝑖= 1). 
The population-level estimates for the for the incidence rates will be defined as follows: 
𝑝̂0 = 𝑛−1 ∑
𝑝𝑖0
𝑛
𝑖=1
 and 𝑝̂1 = 𝑛−1 ∑
𝑝𝑖1
𝑛
𝑖=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, i.e., 
𝑝̂1 −𝑝̂0 and 1 −𝑝̂1/𝑝̂0 
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 J).  
5.5.1.1. 
Sensitivity Analyses of Primary Estimand 
A sensitivity analysis will utilize multiple imputation (MI) under missing at random (MAR) 
assumption which uses all participants with available primary endpoint data through Day 29. The 
imputation model (using PROC MI) will be informed by the observed outcomes for participants 
through Day 29 including treatment and the prognostic factors listed above. Participants with 
missing information on the primary endpoint will be imputed using monotone logistic regression. 
Further variables will be considered for inclusion in the MI model on the basis they may inform 
missingness or be correlated with the endpoint. Missing outcomes will be imputed 
multiple=100 times. The seed for reproducibility will be set to 2020. The final analysis model 
applied to the complete data set will be the same as that for the primary analysis. Treatment 


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effect estimates from the individual completed data sets will be combined using Rubin’s rules via 
PROC MIANALYZE.  
A sensitivity analysis using control-based imputation will also be conducted. Missing primary 
endpoint status through Day 29 will be imputed using monotone logistic regression as stated 
above but informed only by the placebo group. This will be implemented by the MNAR 
statement with the option MODELOBS =(TRT=0), where TRT=0 indicates the placebo group.  
Additional sensitivity analyses include:  
• Repeat the primary efficacy analysis in the PPS analysis set. 
• Repeat the primary efficacy analysis with baseline overall serostatus (categorical as positive; 
negative) as covariate instead of baseline qualitative serostatus. Any missing baseline overall 
serostatus will be imputed as positive.  
5.5.2. 
Supplemental Estimand Analyses 
Appendix I provides an overview of the main estimation and sensitivity analyses for the 
supplementary estimand (Estimand 1b). Estimand 1b utilizes a hypothetical strategy for the 
intercurrent event of receipt of prohibited treatments (refer to ADG20-TRMT-001 Designated 
Background Standard of Care document) for COVID-19 (IcEV3).  
For participants with IcEv3, if the participant has not had a COVID-19-related hospitalization or 
death prior to the intercurrent event, the primary endpoint will be set to missing. Missing data for 
the supplementary analysis will be carried out using an MI based strategy that includes the 
following three steps: 
• Step 1. Missing outcomes will be imputed multiple times (M=100) based on the intercurrent 
event handling strategy 
• Step 2. The logistic regression analysis model presented above will be applied to each 
completed data set with terms including the prognostic factors and treatment variable and 
estimates of the treatment effect and associated standard error will be computed.  
• Step 3. The individual completed sets will be combined using Rubin’s rules to produce a 
single inferential statement (treatment effect, standard error, and p-value) via PROC 
MIANALYZE. 
The imputation model will be informed by the observed outcomes from participants who either 
did not experience the intercurrent event or met the primary endpoint prior to receiving 
prohibited medication. The imputation model will include the prognostic factors as listed in 
Section 5.5.1. Further variables will be considered for inclusion in the MI model on the basis 
they may inform missingness or be correlated with the endpoint. 
The final analysis model applied to the complete data set will be the same as that for the primary 
analysis.  
5.5.2.1. 
Sensitivity Analyses of Supplemental Estimand 
A sensitivity analysis using control-based imputation will be conducted. The analysis will impute 
the binary primary endpoint for participants who received prohibited medications to treat 


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COVID-19 using PROC MI. Missing primary endpoint status through Day 29 will be imputed 
using monotone logistic regression as stated in the sensitivity analyses for the primary analysis 
but informed only by the placebo group. This will be implemented by the MNAR statement with 
the option MODELOBS =(TRT=0), where TRT=0 indicates the placebo group.  
5.5.3. 
Key Secondary Endpoints and Analyses 
Appendix H provides an overview of the main estimation and sensitivity analyses for the key 
secondary estimands (Estimand 2 and Estimand 3). 
To control the overall type I error rate at .05 (2-sided), a hierarchical testing procedure will be 
used, such that testing for the key secondary analyses difference will proceed only if the 
treatment difference is statistically significant in the primary analysis. 
The key secondary endpoints will be tested in the following order: 
1. Severe/critical COVID-19 or all-cause death through Day 29 
2. COVID-19-related emergency room visit, COVID-19-related hospitalization, or all-cause 
death through Day 29 
3. Time to sustained resolution of COVID-19 symptoms through Day 29 
For binary endpoints, the analysis will use the same methodology as the primary efficacy 
endpoint for determining a standardized estimator for a binary outcome (standardized risk 
difference/standardized relative risk reduction) with adjustment for the following prognostic 
factors: age (continuous), sex (categorical), baseline serostatus (categorical as positive; 
negative), BMI (continuous) and baseline viral load (continuous as log10 copies/mL) and will be 
conducted on the mFAS-non-Omicron analysis set. Similar to the primary analysis, the standard 
error of the standardized estimator will be estimated using the delta method.  
For the first key secondary endpoint, if the determination of investigator assessment of 
COVID-19 severity is missing at a visit, it will be imputed as not severe/critical COVID-19 (or 
all-cause death) unless the participant is hospitalized due to COVID-19 at the time of the visit. In 
this case, the assessment of COVID-19 severity will be imputed as severe/critical COVID-19. 
For the second key secondary endpoint, missing data will be imputed as not having a 
COVID-19-related emergency room visit, COVID-19-related hospitalization, or all-cause death 
through Day 29. The number and percentages of participants who experience the event and do 
not experience the event will be summarized by treatment group, including summaries of 
missing data, and each component of the endpoint. The observed risk difference (placebo minus 
ADG20) with 95% CI (using the Miettinen-Nurminen method), observed relative risk reduction, 
standardized risk difference between the ADG20 arm and placebo arm with 95% CI and 
associated p-values, and standardized relative risk reduction with 95% CI will be provided.  
Time to sustained resolution in COVID-19 symptoms through Day 29 will be analyzed by KM 
methodology and stratified Cox Proportional Hazard model. Survival curves between ADG20 
and placebo will be compared using a log-rank test stratified by age (categorical as 12-17, 18-65, 
and >65 years). A stratified Cox Proportional Hazard model will be used to estimate the hazard 
ratio where the model includes age (categorical as 12-17, 18-65, and >65 years) as stratification 
variable and sex (categorical), baseline serostatus (categorical), baseline BMI (continuous), and 


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baseline viral load (continuous as log10 copies/mL) as covariates. Comparison of the survival 
distributions will use the score test for the hazard ratio from the Cox model. 
5.5.3.1. 
Sensitivity Analyses 
For each of the two binary key secondary endpoints, sensitivity analyses will include MI under 
MAR, which uses all participants with available key secondary endpoint status through Day 29. 
The imputation model (using PROC MI) will be informed by the observed outcomes for 
participants through Day 29 including treatment and prognostic factors. Participants with missing 
information on each key secondary endpoint through Day 29 will be imputed using monotone 
logistic regression. Further variables will be considered for inclusion in the MI model on the 
basis that they may inform missingness or be correlated with the endpoint. 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 via PROC MIANALYZE.  
An additional sensitivity analysis will repeat the key secondary efficacy analyses in the PPS 
analysis set. 
5.5.4. 
Additional Secondary Endpoints and Analyses  
Analyses of other secondary endpoints in the mFAS-non-Omicron analysis set 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, except as specifically noted. Analysis approaches for the other 
secondary endpoints (ie, non-key) are summarized in Table 4. In addition to these analyses, 
listings of viral load based on nasopharyngeal samples; viral load, viral clearance status, viral 
load AUC, and time to viral clearance based on saliva samples; and medically attended visits will 
be provided. 
Table 4: 
Additional Secondary Endpoint Analyses 
Endpoint 
Statistical Analysis Methods 
COVID-19-related medically 
attended visits and all-cause 
death through Day 29  
The methods for the primary efficacy endpoint will be used except without 
applying multiplicity adjustments (see Section 5.5.1).  
Time to sustained recovery in 
COVID-19 symptoms through 
Day 29  
The methods for the analysis of time to sustained resolution of COVID-19 
symptoms through Day 29 will be used (see Section 5.5.3) 
All-cause death through 
Day 29, Day 60, and Day 90 
KM methodology will be used to analyze all-cause deaths. The probability of all-
cause deaths by each of these time points will be estimated, along with 95% CIs 
for differences in the probabilities. Survival curves between ADG20 and placebo 
will be compared using a log-rank test. A Cox Proportional Hazard model will be 
used to estimate the hazard ratio. The model includes age (continuous), sex 
(categorical), baseline serostatus (categorical: positive, negative), baseline BMI 
(continuous), and baseline viral load (continuous as log10 copies/mL) as 
covariates. Comparison of the survival distributions will use the score test for the 
hazard ratio from this Cox model.  


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Endpoint 
Statistical Analysis Methods 
Change from baseline in 
SARS-CoV-2 viral load (log10 
copies/mL) to Day 7 (±1) 
assessed by RT-qPCR from 
NP samples 
Observed NP baseline and post-baseline values are used to calculate change from 
baseline. ANCOVA with treatment group and the prognostic factors (with 
observed NP baseline) as in the primary efficacy endpoint analysis as covariates. 
The LS mean for the point estimate in each group and 95% CIs will be presented. 
The difference in LS means between the ADG20 group and the placebo group 
and 95% CIs for the differences will be determined. The analysis will be 
performed on the mFAS-non-Omicron-NP with available data at Day 7. In 
addition, two-sample t-test will be used to compare change from baseline viral 
load between treatment without covariate adjustment (unadjusted mean 
difference). 
If Day 7 value is missing, the earliest measurement closest to the Day 7 visit 
within 1 day (including scheduled and unscheduled visit) will be used. 
Viral load >5 (log10 
copies/mL) on Day 7 (±1) 
based on NP samples 
The methods for the primary efficacy endpoint will be used. Analysis will be 
performed on the mFAS-non-Omicron-NP with available data at Day 7. Analysis 
will be repeated using a second definition of high viral load (viral load 
>4 log10 copies/mL). 
Duration of SARS-CoV-2 
viral shedding from Day 1 
through Day 29 assessed by 
RT-qPCR from saliva samples 
KM methodology will be used to analyze duration of viral shedding from Day 1 
through Day 29 of SARS-CoV-2 RNA. KM curves, the number and percentage 
of censored observations and the median, 25th and 75th percentiles will be 
provided. Survival distributions will be compared between ADG20 and placebo 
using a log rank test stratified by age (categorical) and baseline serostatus. A 
stratified Cox Proportional Hazard model will be used to estimate the hazard 
ratio where the model includes age (categorical as 12-17 years, 18-65 years and 
>65 years) as a stratification variable and sex (categorical), baseline serostatus 
(categorical as positive; negative), baseline BMI (continuous) and baseline viral 
load (continuous as log10 copies/mL) as covariates. Comparison of the survival 
distributions will use the score test for the hazard ratio from this Cox model. 
Analyses will be performed on the mFAS-non-Omicron-S. 
Change from baseline in 
SARS-CoV-2 viral load (log10 
copies/mL) to Days 3, 5, 7, 11, 
14, 21, and 29 assessed by 
RT-qPCR from saliva samples  
Observed saliva baseline and post-baseline values are used to calculate change 
from baseline. Mixed model for repeated measures with treatment group and the 
prognostic factors (with observed saliva baseline) in the primary efficacy 
endpoint analysis as covariates. The LS mean for the point estimate in each 
group and 95% CIs will be presented. The difference in LS means between the 
ADG20 group and the placebo group and the 95% CIs for the differences will be 
determined. A plot of the LS means with 95% CIs by Day assessed by treatment 
group will be presented. The analysis will be performed on the mFAS-Non-
Omicron-S with available data at each timepoint. In addition, a two-sample t-test 
will be used to compare change from baseline viral load between treatment at 
each time point without covariate adjustment (unadjusted mean difference).  
SARS-CoV-2 viral clearance 
(Days 3, 5, 7, 11, 14, 21, and 
29) assessed by RT-qPCR 
from saliva samples (and 
BLQ/not detected or not 
detected for NP sample for 
Day 7) 
In the mFAS-non-Omicron-S, the cumulative proportion of participants with 
viral clearance will be presented for each post-baseline time point. In the mFAS-
non-Omicron-NP, the proportion of participants with viral load BLQ/not 
detected or not detected at Day 7 will be presented. The ADG20 arm will be 
compared to placebo using the analysis procedure outlined for the primary 
efficacy outcome.  
In addition, these analyses will be presented for the subgroups of participants 
with observed baseline NP viral load >5 and ≤5 log10 copies/mL. 


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Endpoint 
Statistical Analysis Methods 
SARS-CoV-2 viral load AUC 
(log10 copies/mL) assessed by 
RT-qPCR from saliva samples 
through Day 29  
An ANCOVA will be used to compare ADG20 and placebo where the 
prognostic factors in the primary efficacy endpoint analysis will be used as 
covariates. Participants in the mFAS-non-Omicron-S will be included in this 
analysis. The AUC from Day 1 through Day 29 will be calculated according to 
the linear trapezoidal rule using the measured SARS-CoV-2 viral load above the 
lower limit of quantification. No AUC values will be calculated when Day 1 
and/or Day 29 values are missing, or if there are more than 3 values missing in 
the profile. 
In addition, two-sample t-test will be used to compare viral load AUC between 
treatment without covariate adjustment (unadjusted mean difference). 
5.5.5. 
Exploratory and Additional Efficacy Endpoints 
To facilitate review of the composite endpoints in the mFAS-non-Omicron analysis set, tables 
will be provided summarizing medically attended visits and all-cause death, both before and after 
Day 29, and summarizing COVID-19-related hospital and ICU stays.  
To explore efficacy and virological endpoints in the mFAS-Omicron analysis set, summary 
tables will be provided.  
5.5.5.1. 
COVID-19-Related Duration of Hospitalization  
For participants who did not die through Day 29, the sum of the duration of all COVID-19-
related hospital stays through Day 29 will be summarized by category (>0 to <24 hours, 1-8 
days, 9-15 days, 16-22 days, 23-29 days, >29 days) for each treatment group. The mean total 
number of days and standard deviation will also be presented. For purposes of the continuous 
summary, a hospital stay of less than 24 hours will be imputed as 0.5 days. A similar categorical 
and continuous summary will be presented for the subset of ICU stays.  
The number and percentage of participants who died on or prior to Day 29 will be presented by 
treatment group. 
5.5.5.2. 
Exploratory Analysis of Omicron Analysis Set 
Given the expected smaller sample size of the mFAS-Omicron analysis set, the following clinical 
endpoints will be summarized descriptively:  
• COVID-19-related hospitalization or all-cause death through Day 29 
• Severe/critical COVID-19 or all-cause death through Day 29 
• COVID-19-related emergency room visits, COVID-19-related hospitalization, or all-cause 
death through Day 29 
• Time to sustained resolution of COVID-19 symptoms through Day 29 
• COVID-19-related medically attended visit (telemedicine, physician office, urgent care 
center, emergency room, hospitalization) or all-cause death through Day 29 
The following virological endpoints will be summarized descriptively unless otherwise specified:  


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• Change from baseline in SARS-CoV-2 viral load (log10 copies/mL) to Day 7 (±1) assessed 
by RT-qPCR from NP samples, apply the same methodology in Table 4.  
• Viral load >5 log10 copies/mL on Day 7 (±1) based on NP samples 
• Duration of SARS-CoV-2 viral shedding from Day 1 through Day 29 assessed by RT-qPCR 
from saliva samples 
• Change from baseline in SARS-CoV-2 viral load (log10 copies/mL) to Days 3, 5, 7, 11, 14, 
21, and 29 assessed by RT-qPCR from saliva samples, apply the same methodology in Table 
4.  
• SARS-CoV-2 viral clearance (Days 3, 5, 7, 11, 14, 21, and 29) assessed by RT-qPCR from 
saliva samples (and BLQ/not detected or not detected for NP samples for Day 7) 
• SARS-CoV-2 viral load AUC assessed by RT-qPCR from saliva samples from baseline to 
Day 29 
5.5.6. 
Graphical Displays of Efficacy Endpoints 
Forest plots for the standardized relative risk reduction for the primary and two binary key 
secondary endpoints will be provided. Additionally, adjusted, and unadjusted mean change from 
baseline in viral load will be depicted with forest plots, box and whisker plots and line plots. 
Duration of viral shedding, time to sustained recovery of symptoms, time to symptom 
improvement, and time to symptom resolution will be presented using Kaplan-Meier plots and 
forest plots. Finally, a Kaplan-Meier plot for all-cause death will be provided. 
5.5.6.1. 
Viral Load Effect on Adverse Clinical Outcomes 
In order to identify a persistently high viral load threshold for risk of adverse clinical outcomes, 
the level of viral load leading to the following adverse clinical outcomes will be assessed in the 
mFAS-non-Omicron analysis set: 
• COVID-19-related hospitalization or all-cause mortality through Day 29 
• COVID-19-related emergency room visits, COVID-19-related hospitalization, or all cause 
death through Day 29 
• Severe/critical COVID-19 or all-cause mortality through Day 29 
An association between viral load (log10 copies/mL) and the adverse clinical outcome will be 
examined graphically. The viral load for participants with the adverse clinical outcome and box 
plot of viral loads for participants without the adverse clinical outcome will be presented for 
Days 3, 5, 7, 11, 14, 21, and 29. The number and percentage of participants with and without the 
adverse clinical outcome will be summarized by viral load categories at Days 3, 5, 7, 11, 14, 21,  
and 29. Viral load from saliva samples will be used for Days 3, 5, 7, 11, 14, 21, and 29, and also 
from NP swabs for Day 7. 


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5.5.6.2. 
Time to Sustained Improvement of COVID-19 Symptoms Through Day 29 
KM methodology will be used to analyze time to sustained symptom improvement through 
Day 29 (Section 3.5.1) with respect to the mFAS-non-Omicron analysis set. Median time-to 
improvement by treatment group and 95% CIs will be reported. Survival curves between ADG20 
and placebo will be compared using a log-rank test stratified by age (categorical as 12-17, 18-65, 
and >65 years). A stratified Cox Proportional Hazard model will be used to estimate the hazard 
ratio where the model includes age (categorical as 12-17, 18-65, and >65 years) as a stratification 
variable and sex (categorical), baseline serostatus (categorical: positive, negative), baseline BMI 
(continuous) and baseline viral load (continuous as log10 copies/mL) as covariates. Comparison 
of the survival distributions will use the score test for the hazard ratio from the Cox model. Refer 
to Appendix F for rules for missing symptom diary data. 
5.5.6.3. 
Time to Sustained Recovery of COVID-19 Symptoms Through Day 29 
KM methodology will be used to analyze time to sustained symptom recovery (improvement or 
resolution) through Day 29 (Section 3.5.1) with respect to the mFAS-non-Omicron analysis set. 
Median time to recovery by treatment group and 95% CIs will be reported. Survival curves 
between ADG20 and placebo will be compared using a log-rank test stratified by age 
(categorical as 12-17, 18-65, and >65 years). A stratified Cox Proportional Hazard model will be 
used to estimate the hazard ratio where the model includes age (categorical as 12-17, 18-65, and 
>65 years) as a stratification variable and sex (categorical), baseline serostatus (categorical: 
positive, negative), baseline BMI (continuous) and baseline viral load (continuous as log10 
copies/mL) as covariates. Comparison of the survival distributions will use the score test for the 
hazard ratio from the Cox model. A forest plot of median time to sustained symptom recovery by 
selected subgroups will be presented. Refer to Appendix F for rules for missing symptom diary 
data. 
5.5.7. 
Household Contacts 
The number and percentage of participants with any documented asymptomatic SARS-CoV-2 or 
symptomatic COVID-19 infection in one or more household contacts as of Day 29 will be 
summarized by treatment group in the mFAS-non-Omicron analysis set. Among those 
participants with household contacts with asymptomatic and symptomatic infection, descriptive 
summary statistics for the number of household contacts with each type of infection will be 
summarized using percentages based on the number of participants with household contacts with 
documented asymptomatic or symptomatic COVID-19 infection. 
These data will also be presented in a listing. 
5.5.8. 
COVID-19-Related Mortality Through Day 29 
The number and percentage of participants with a COVID-19 related death, with COVID-19 as 
the primary cause of death, and with COVID-19 or COVID-19 complications contributory to 
death will be summarized in the mFAS-non-Omicron by treatment group.  
The listing of deaths will include a column for primary cause of death and if COVID-19 or 
COVID-19 complications were contributory to death.  


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5.5.9. 
Post-Acute Sequelae of SARS-CoV-2 Infection 
During the long-term follow-up period, participants will be asked questions about their overall 
health status including return to usual health and usual activities and any ongoing symptoms 
associated with COVID-19 at the visits specified in the Schedule of Events (Appendix M). 
Symptoms reported on the Long-term Health Status Assessment eCRF will be considered PASC 
events. The number and percentage of participants with any PASC will be summarized by 
treatment group and in those participants with and without a COVID-19-related hospitalization 
through Day 29 with respect to the mFAS-non-Omicron. The number and percentage of 
participants reporting each symptom thought to be related to COVID-19 and the number and 
percentage of participants returning and not returning to usual health and usual activities will be 
summarized by treatment arm. The number of participants in each arm reporting no symptoms, 1 
ongoing symptom and >1 ongoing symptom will be summarized at Day 60, Day 90, and 
Month 6. The overall severity of PASC symptoms will be presented (absent, mild, moderate, 
severe) by treatment arm and time point (Day 60, Day 90, and Month 6).  
These data will also be presented in a listing. 
5.6. 
Subgroup Analyses  
The primary (Estimand 1a) and key secondary (Estimands 2 and 3) analyses will be repeated 
within the subgroups listed below in the mFAS-non-Omicron analysis set. Analyses of virologic 
endpoints will be repeated within selected subgroups as detailed below.  
• age group (12-17, 18-65, >65, ≥50, >55, and >75 years)  
• sex (male, female) 
• race (White, Black or African American, Asian, American Indian or Alaska Native, Native 
Hawaiian or Other Pacific Islander, Other, Multiple) 
• time from symptom onset to the date of study drug administration (0-3, 4-5, >5 days) 
• time from SARS-CoV-2 test to the date of study drug administration (0, 1-2, 3-5, >5 days) 
• baseline SARS-CoV-2 status by RT-qPCR from NP swab (positive, negative).  
• baseline viral load from NP swab (>5, ≤5 log10 copies/mL); viral load >5 
and >4 log10 copies/mL) on Day 7 based on the NP sample will also be analyzed in these 
subgroups  
• baseline qualitative serologic status (positive, negative) from the assay of antibodies to 
SARS-CoV-2 N antigen.  
• baseline overall serologic status (positive, negative) from three assays: antibodies to 
N antigen, IgA to S (spike) trimer, IgG to S trimer; viral load >5 and >4 log10 copies/mL on 
Day 7 based on the NP sample will also be analyzed in these subgroups 
• COVID-19 severity (mild, moderate)  


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• BMI (≥30 and ≥40 kg/m2 for adults and ≥85th percentile by age and sex based on CDC 
growth charts for adolescents, <30 kg/m2 for adults and <85th percentile by age and sex based 
on CDC growth charts for adolescents) (CDC 2001) 
• Diabetes as collected on COVID-19 Risk Factors eCRF (yes, no) 
• Cardiac disease as collected on COVID-19 Risk Factors eCRF (yes, no) 
• WGS confirmed non-Omicron variant (Delta/Delta-like, etc) 
Given the various sample sizes by subgroup, the standardized relative risk reduction will be 
estimated using the same methodology in Ge et al. (2011) from a logistic regression model fit to 
the binary endpoint with age (continuous) as covariate for each subgroup with at least 5 total 
events. Subgroups with less than 5 total events will be summarized descriptively.  
5.7. 
Other Analyses  
5.7.1. 
Resistance  
Resistance to ADG20 in viral isolates obtained from participants will be characterized using 
genotypic methods, with phenotypic methods deployed as appropriate. Plans for analysis of 
resistance data will be provided in the Resistance Monitoring Plan. A summary of participants 
with baseline and post-baseline (treatment-emergent) variations at critical amino acid positions 
associated with ADG20 resistance (≥15% and ≥50% allele frequencies) and their associated 
virologic and clinical outcomes will be provided in the FAS. 
5.7.2. 
Immunogenicity Analyses 
Analyses will be conducted in the Immunogenicity Set. ADA status will be defined as positive or 
negative based on the confirmatory cut-off point. ADA results will be summarized by treatment 
arm at baseline (predose Day 1), Days 29 and 90, and Months 6 and 11. ADA status (positive or 
negative) is determined based on the confirmatory assay results.  
Treatment-emergent ADA is defined as participants who had a negative ADA measurement at 
baseline (predose Day 1) and positive ADA post-baseline (Day 29, Day 90, Month 6, or Month 
11) 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 patients with treatment-emergent ADA will be summarized by treatment arm. The 
frequency of neutralizing antibodies (if assessed) may also be summarized.  
5.8. 
Safety Analysis  
The primary safety objective of the study is to evaluate the safety and tolerability of ADG20 
compared to placebo through Day 29 in participants with mild or moderate COVID-19 and high 
risk of disease progression. A secondary objective is to evaluate safety through Month 14. Safety 
assessments will include monitoring of AEs, clinical laboratory testing, and vital sign 
measurements.  


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5.8.1. 
Adverse Events 
5.8.1.1. 
Unsolicited 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. AEs 
resulting from concurrent illnesses, reactions to concurrent illnesses, reactions to concurrent 
medications, or progression of disease states must also be reported. Exceptions to this reporting 
related to COVID-19 signs and symptoms are described in the protocol (Section 6.4.6.3.2). All 
AEs will be followed to adequate resolution. MedDRA version 24 or higher will be used to code 
all AEs. 
5.8.1.2. 
Injection Site Reactions  
Intramuscular ISRs will be recorded in the Injection Site Reaction Diary (refer to the protocol, 
Appendix 12.3) and graded using the FDA Guidance for Industry: Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA 
2007). 
Participants will be instructed to record the worst severity (Table 5) experienced during each 
recording period (prior 24 hours) of the following local (solicited) AEs  through Day 4, and 
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 5: 
Grading of Injection Site Reactions 
Local Reaction to 
Injectable Product 
Grade 1  
Mild 
Grade 2 
Moderate 
Grade 3  
Severe 
Grade 4 Potentially 
Life-Threateninga 
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  
ER visit or 
hospitalization  
Tenderness 
Mild discomfort 
to touch 
Discomfort with 
movement 
Significant 
discomfort at rest  
ER 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  
ER=emergency room. 
Note: In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
recorded as a continuous variable. 


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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. 
 
Erythema/redness and induration/swelling reported as <2.5 cm in greatest diameter will be 
classified as Non-Graded. 
For summaries combining ISRs and other AEs, ISRs will be mapped to MedDRA SOC and PT 
as shown in Table 6. 
Table 6: 
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 with an end date defined as the date the ISR is reported as 
not occurring (ie, none) in the diary or the date of resolution for the ISR Resolution eCRF. 
Maximum severity will be assigned. 
 
5.8.1.3. 
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. 
5.8.1.4. 
Adverse Events of Special Interest 
An AESI, which can be serious or nonserious, is defined as an AE or SAE of scientific and 
medical concern specific to the sponsor’s product or program, for which ongoing monitoring and 
rapid communication by the investigator to the sponsor or designee could be appropriate (ICH 
E2F; CIOMS VI). 
For this study, AESIs are specified in the protocol as follows: Hypersensitivity reactions 
occurring through Day 4. 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 


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conjunctivitis, drug allergy, immune thrombocytopenia, autoimmune hemolytic anemia, rash, 
urticaria, arthus reaction, etc. 
Determination of hypersensitivity reactions will be based on a sponsor medical adjudication 
based on the narrow and broad terms of the 3 SMQs hypersensitivity, anaphylactic reaction, and 
angioedema. 
All hypersensitivity reactions will be summarized through Day 4, through Day 29, and through 
Month 14/EOS. However, only those reactions occurring through Day 4 will be considered 
AESIs. 
5.8.1.5. 
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. 
5.8.1.6. 
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 
5.8.1.7. 
Severity 
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.) 
Missing severity is not imputed. 
Grading criteria for ISRs are provided in Section 5.8.1.2. 


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5.8.1.8. 
Relationship of Adverse Events 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 relatedness is missing for an event, the event will be categorized as Related. 
All ISRs are considered related to study drug. 
5.8.1.9. 
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/ISR, if 
the same AE/ISR (based on PT) is reported for the same participant more than once, the AE/ISR 
is counted only once for the PT and at the highest severity and by relationship to study drug. 
Percentages will be calculated based on the number of participants in each treatment group in the 
Safety Set. Missing and incomplete dates of AEs will be imputed as described in Appendix D. In 
addition to safety summaries, listings of AEs (with TEAE designated by *), SAEs, and ISRs will 
be presented.  
Safety summaries will be presented through Day 29 and overall. All summaries will be sorted by 
decreasing frequency 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 
− ≥Grade 3 TEAE 
− an SAE 
− a study drug related SAE 
− a TEAE leading to death 


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− a study drug related TEAE leading to death 
− a TEAE leading to treatment discontinuation 
− 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 PT sorted by descending frequency of PT in the ADG20 arm 
• Incidence of MAAE 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) and by maximum severity based on the FDA toxicity scale 
through Day 4 (only for Day 29 analysis) 
• Incidence of SAEs by SOC, PT, and treatment group 
• Incidence of SAEs excluding COVID-19 SAEs associated with the primary endpoint by 
SOC, PT, and treatment group; COVID-19-related PTs include COVID-19, COVID-19 
pneumonia.  
• Incidence of study drug related SAEs by SOC, PT, and treatment group 
• For the Day 29 analysis only: incidence of solicited AEs (ISRs) summarized by maximum 
duration (defined as the end date-start date +1) of 1, 2, 3, 4, and >4 days for participants with 
any ISR and for each ISR type. Time from injection to report of first onset of any solicited 
ISR (in days) will also be summarized. 
• Overall summary of hypersensitivity reactions including number and percentage of 
participants with: 
− any hypersensitivity reaction 
− a study drug related hypersensitivity reaction 
− a severe (≥Grade 3) hypersensitivity reaction 
− a serious hypersensitivity reaction 
− any hypersensitivity reaction by onset day category of first reaction (Day 1, 2, 3, 4, 5-8, 
9-14, 15-21, 22-29, >29). Time from study drug administration to first onset of 


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hypersensitivity reaction and the duration of the hypersensitivity reaction for participants 
with hypersensitivity reactions (longest duration if multiple) will also be summarized.  
• Incidence of hypersensitivity reactions by SOC, PT, and treatment group through Day 4, 
through Day 29, and through Month 14/EOS.  
• Incidence of hypersensitivity reactions by SOC, PT, maximum severity, and treatment group, 
through Day 4, through Day 29, and through Month 14/EOS.  
• Overall summary of AEs and the incidence of AEs (including solicited ISRs) by SOC and 
PT, by age group (12-17, 18-65, >65 years). 
A listing will be provided of participants meeting any pausing guideline in the ADG20 arm, as 
described in Table 7. 
Table 7: 
Study Pausing Guidelines 
Phase 
Pausing Guideline 
Phase 2 
• 
2 or more participants with a study drug-related ≥Grade 3 hypersensitivity reaction 
• 
2 or more participants with a ≥Grade 3 injection site reaction 
• 
Any study drug-related death  
• 
Any study drug-related SAE, including hypersensitivity reactions 
Phase 3 
• 
Any study drug-related death  
• 
Any study drug-related SAE, including hypersensitivity reactions 
5.8.1.10. Adverse Events Leading to Treatment Discontinuation 
Treatment discontinuation is collected on the End of Treatment eCRF. If the reason for treatment 
discontinuation is AE, the relevant AE number is also collected, and AEs recorded should match 
the cases on the AE eCRF where Action Taken is Drug Withdrawn. In the event of disagreement 
between these data sources, AE tables/listing will present data from the AE eCRF and 
disposition tables will present data from the End of Treatment eCRF. Given study treatment is a 
single dose, the incidence of AEs leading to treatment discontinuation is expected to be 
none/minimal. 
5.8.1.11. Adverse Events Leading to Study Discontinuation 
Study discontinuation is collected on the End of Study eCRF. Adverse Event is not collected as a 
possible reason for study discontinuation because the study only involves one dose of study drug, 
and the remainder of the study collects follow-up data (though an AE may lead to treatment 
discontinuation which the leads the participant/investigator to remove the participant from 
study). Therefore, no incidence table for TEAE leading to study discontinuation will be 
provided. 
5.8.2. 
Death and Survival Status 
Death status may derive from the Adverse Event, Survival Status, End of Treatment, or End of 
Study eCRFs. In each case, details are collected on the Death eCRF. In the event of data 
inconsistency, the Death eCRF data will be used. The number and percentage (based on the 
Safety Set) of participants who died will be summarized for primary cause of death (COVID-19, 


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Other Adverse Event, Unknown) and whether COVID-19 or COVID-19 complications 
contributed to the death by treatment group. Percentages of primary cause of death and whether 
COVID-19 contributed to the death will be based on the number of participants who died. A 
summary of AEs leading to death will also be provided by SOC and PT for the Safety Set. 
A listing of death details as well as a listing of survival status for participants who discontinued 
the study early will also be provided.  
5.8.3. 
Clinical Laboratory Evaluations 
Blood samples for safety laboratory assessments (hematology, serum chemistry, and 
coagulation) will be collected on the days specified in the Schedule of Events (Appendix M). 
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 
Appendix K. Refer to Appendix B for handling of unscheduled and multiple in-window values. 
All clinical laboratory values for participants with PCS will be provided in listings. 
5.8.3.1. 
Hematology 
The following hematology parameters (CBC with differential) will be assessed per the Schedule 
of Events (Appendix M): 
• Hemoglobin 
• Hematocrit 
• Erythrocyte count 
• Mean cell volume 
• Mean cell hemoglobin 
• Mean cell hemoglobin concentration 
• Leukocyte (white blood cell) count 
• Neutrophils 


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• Lymphocytes 
• Monocytes 
• Eosinophils 
• Basophils 
• Platelets 
5.8.3.2. 
Serum Chemistry 
The following serum chemistry parameters will be assessed per the Schedule of Events 
(Appendix M):  
• Glucose, non-fasting 
• Calcium 
• Albumin 
• Total protein 
• Sodium 
• Potassium 
• Bicarbonate 
• Chloride 
• Urea nitrogen 
• Creatinine (and calculated eGFR) 
• Alkaline phosphatase (ALP) 
• Alanine aminotransferase (ALT) 
• Aspartate aminotransferase (AST) 
• Total bilirubin 
• Human chorionic gonadotropin (hCG) for females  
5.8.3.3. 
Coagulation 
The following coagulation parameters will be assessed per the Schedule of Events 
(Appendix M):  
• Prothrombin time (PT)/International Normalized Ratio (INR) 
• Partial thromboplastin time (PTT)/activated Partial thromboplastin time (aPTT) 
5.8.4. 
Vital Sign Measurements 
Vital signs, including temperature, heart rate, respiratory rate, seated blood pressure, and SpO2 
will be summarized using the site staff assessment.  


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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 separately for the time 
period of intensive monitoring post-study drug administration. PCS values are provided in 
Appendix K. Refer to Appendix B for handling of unscheduled and multiple in-window values.  
All vital sign data by participant will also be presented in listings separately for in-person visit 
and eDiary. Vital Sign listings will include participant recordings and will list data by visit, date 
and timepoint. 
5.8.5. 
Other Safety Data 
Pregnancy testing data will be provided in a listing for all female participants whose fertility 
status (as collected on the Screening Fertility Status eCRF) is Child-Bearing Potential or 
Unknown. 
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 7 (±1 day), Day 29 (+5 days), Day 90 (±14 days), Month 6 (±30 days), Month 11 (±30 
days)  
• Unscheduled 
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. 
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. 
In addition, individual serum concentrations of ADG20 will be presented in data listings and 
summarized by ADA status (positive/negative). Individual and mean concentration plots will 
also be presented by ADA status (treatment emergent ADA positive/negative). 


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6.3. 
Serum Pharmacokinetic Parameters 
Serum concentration-time data will be analyzed by non-compartmental analysis using Phoenix® 
WinNonlin® Version 8.0 or higher (Certara USA, Inc., Princeton, NJ). The PK parameters to be 
calculated for ADG20, where data permit, as listed in Table 8. 
Table 8: 
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 8, which will be listed and summarized, the 
parameters in Table 9 will also be listed to document the selection of data points used to estimate 
T1/2 using non-compartmental procedures. 
Table 9: 
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, 
geometric CV, median, minimum, and maximum) by part, treatment. Tmax will be summarized 
using number of observations, median, minimum, and maximum only. 
In addition, serum PK parameters will be presented in data listings and summarized by ADA 
status (treatment emergent ADA positive/negative). 


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7. 
CHANGES IN THE PLANNED ANALYSIS 
There are no changes to the analyses presented in the protocol. 


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8. 
REFERENCES 
AstraZeneca. (2022). Fact Sheet for Health Care Providers: Emergency Use Authorization for 
EVUSHELD (tixagevimab co-packaged with cilgavimab). February 2022. Retrieved  28 
February 2022, from https://www.fda.gov/media/154701/download. 
CDC. (2001). Data table of BMI-for-age charts. Updated August 23, 2001. Available at: 
https://www.cdc.gov/growthcharts/html_charts/bmiagerev.htm 
CDC. (2021). SARS-CoV-2 variant classifications and definitions. Updated December 1, 2021. 
Available at https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html 
Eli Lilly and Company. (2022a). Fact Sheet for Health Care Providers: Emergency Use 
Authorization (EUA) of Bamlanivimab and Etesevimab. Revised Jan. 24, 2022. Retrieved 27 
January 2022, from https://www.fda.gov/media/145802/download. 
FDA. (2007). Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials. Accessed 27 February 2022 from: 
https://www.fda.gov/media/73679/download. 
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. 
GlaxoSmithKline. (2021). Fact Sheet for Healthcare Providers: Emergency Use Authorization 
(EUA) of Sotrovimab. Revised December 2021. Retrieved 27 January 2022, from 
https://www.fda.gov/media/149534/download. 
National Institute of Allergy and Infectious Diseases (NIAID). (2017). Division of AIDS 
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events. Version 2.1 July 
2017. Available at: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf. 
Regeneron. (2022). Fact Sheet for Health Care Providers: Emergency Use Authorization (EUA) 
of REGEN-COV (Casirivimab and Imdevimab). Revised January 2022. Retrieved 27 January 
2022, from https://www.fda.gov/media/145611/download. 
 


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9. 
APPENDICES 


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APPENDIX A.  STANDARDS FOR VARIABLE DISPLAY IN TFLS 
Continuous Variables: The precision for continuous variables will be based on the precision of 
the data itself. The mean, median, 25th percentile, and 75th percentile will be presented to one 
more significant figure than the original results; the SD will be presented to two more significant 
figures than the original results; the minimum and maximum will be presented to the same level 
of precision as the original results. P-values should be presented to 4 decimal places, unless 
otherwise specified. 
Categorical Variables: Percentages will be presented to 1 decimal place. If the count is 0, the 
percentage will not be displayed. If the count equals the denominator, the percentage will be 
displayed as 100. 


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APPENDIX B.  ANALYSIS VISIT WINDOWS 
Assessments collected at scheduled or unscheduled visits will be mapped using the analysis visit 
windows listed in Table 10. All diary data will be analyzed using the actual day. Refer also to 
Section 4.1. 
Table 10: 
Analysis Windows  
AVISIT 
AVISITN 
Range of Trial Day 
Target Day 
If more than one value, which value is used 
for analyses 
Screening 
1 
Day -2 to 1 
  
Last value prior to administration of study 
drug 
Day 1 
2 
Day 1 
Day 1 
Day 1 
Day 3 
4 
Day 2 to Day 4 
Day 3 
Nominal visit. If none exist, then closest to 
target day. 
Day 5 
6 
Day 4 to Day 6 
Day 5 
Nominal visit. If none exist, then closest to 
target day. 
Day 7 
8 
Day 6 to Day 8 
Day 7 
Nominal visit. If none exist, then closest to 
target day. 
Day 11 
12 
Day 9 to Day 13 
Day 11 
Nominal visit. If none exist, then closest to 
target day. 
Day 14 
15 
Day 12 to Day 16 
Day 14 
Nominal visit. If none exist, then closest to 
target day. 
Day 21 
22 
Day 18 to Day 23 
Day 21 
Nominal visit. If none exist, then closest to 
target day. 
Day 29 
30 
Day 24 to Day 34 
Day 29 
Nominal visit. If none exist, then closest to 
target day. 
Day 60 
31 
Day 53 to Day 67 
Day 60 
Nominal visit. If none exist, then closest to 
target day. 
Day 90 
32 
Day 76 to Day 104 
Day 90 
Nominal visit. If none exist, then closest to 
target day. 
Month 6 
33 
Day 150 to Day 210 
Day 180 
Nominal visit. If none exist, then closest to 
target day. 
Month 11 
34 
Day 300 to Day 360 
Day 330 
Nominal visit. If none exist, then closest to 
target day. 
Month 14 
35 
Day 360 to Day 480 
Day 420 
Nominal visit. If none exist, then closest to 
target day. 


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APPENDIX C. IMPUTATION RULES FOR MISSING DATES OF 
PRIOR/CONCOMITANT MEDICATIONS FLAGS 
For inclusion in prior and/or concomitant medication tables, incomplete medication start and 
stop dates will be imputed as follows: 
• If it cannot be determined whether the start date of a medication is prior to the administration 
of study drug, it will be assumed that the medication was received prior to the administration 
of study drug. 
• If it cannot be determined whether the stop date of a medication is after administration of 
study drug, it will be assumed that the medication was received after the administration of 
study drug. 
For medications that are prohibited from randomization to Day 29, incomplete start and stop 
dates will be imputed as follows: 
• If year is missing, day and month are missing, or the date is completely missing, no 
imputation will be done. 
• If year and month are present and day is missing, if the month is the same as the month of 
randomization and/or the Day 29 visit, then assume the medication was received from 
randomization to Day 29. Otherwise, the prohibited medication will be assumed to not have 
been received from randomization to Day 29. 
• If year and day are present and month is missing, then assume the medication was received 
from randomization to Day 29. 


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APPENDIX D.  IMPUTATION RULES FOR MISSING DATES OF AES 
Imputation rules for missing or partial start dates and end dates of AEs are defined below: 
Missing or partial start date: 
• If only Day is missing, use the first day of the month, unless: 
− The AE end date is on/after the date of study drug administration or is missing/partial 
AND the start month and year of the AE coincide with the start month and year of study 
drug administration. In this case, use the date and time of study drug administration, even 
if AE time was collected. 
• If Day and Month are both missing, use the first day of the year, unless: 
− The AE end date is on/after the date of study drug administration or is missing/partial 
AND the start year of the AE coincides with the start year of study drug administration. 
In this case, use the date and time of study drug administration, when time is available. 
• If Day, Month, and Year are all missing, the date will not be imputed. However, if the AE 
end date is prior to the date of administration of study drug, then the AE will be considered a 
pre-treatment AE. Otherwise, the AE will be considered treatment-emergent. 
Missing or partial end date:  Missing or partial end dates will not be imputed. 
Missing start time: If the AE occurs on the date of dosing and time is missing, the AE should be 
assumed to be treatment emergent. 
 


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APPENDIX E.  DATES OF EMERGENCE OF OMICRON VARIANT BY 
COUNTRY  
Country 
Date of First Participant With 
WGS-Confirmed Omicron Variant 
from the Same Country 
Epidemiology Date of the Emergence 
of Omicron from the Same Countrya 
Brazil 
n/a 
14-Dec-21 
Bulgaria 
21-Dec-21 
 
South Africa 
10-Nov-21 
 
Germany 
25-Nov-21 
 
Greece 
29-Dec-21 
 
Poland 
n/a 
29-Dec-21 
Ukraine 
5-Jan-22 
 
Romania 
28-Dec-21 
 
a Source: Date of reaching 10% Omicron of samples tested in a country. 
For Brazil: Latif AA, Mullen JL, Alkuzweny M, et al. (2022a). BA.1 Lineage Report – Brazil. outbreak.info. 
Retrieved 1 March 2022 from: https://outbreak.info/situation-reports?xmin=2021-10-20&xmax=2022-01-
21&loc=BRA&pango=BA.1&selected=BRA.  
For Poland: Latif AA, Mullen JL, Alkuzweny M, et al. (2022b). BA.1 Lineage Report – Poland. outbreak.info. 
Retrieved 1 March 2022 from: https://outbreak.info/situation-reports?pango=BA.1&loc=POL&selected=POL. 
  
   
 


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APPENDIX F.  RULES FOR MISSING SYMPTOM DIARY DATA 
Information about COVID-19 associated symptoms is collected in a daily COVID-19 Symptom 
Diary as described in the protocol (Section 6.3.1.1). Participants are asked to rate the severity 
over the last 24 hours as None, Mild, Moderate, or Severe for the following 11 symptoms: fever, 
chills, cough, sore throat, congestion, shortness of breath at rest, shortness of breath with 
exertion, muscle or body aches, fatigue, headache, and nausea. In addition, there are two 
questions regarding senses of taste and smell (same as usual, less than usual, none), two 
questions regarding frequency of vomiting or diarrhea (none, 1-2, 3-4, ≥5 times), two general 
status questions (yes, no), and one question regarding overall severity of symptoms.  
All diary data will be listed. For analysis, the answers to the questions regarding taste and smell 
are mapped as following: absent/none=same as usual, mild/moderate=less than usual, 
severe=none and the two questions regarding frequency of vomiting diarrhea are mapped as 
following: absent/none=none, mild=1-2 times, moderate=3-4 times, and severe= ≥5 times. 
The following algorithms for imputing missing data (none/mild/moderate/severe) will be 
applied. These algorithms apply independently to individual symptom assessments. 
a. If a participant is hospitalized on or before Day 29 for a COVID-19-related hospitalization: 
• All existing data will be utilized (as the protocol indicates that the diary should be 
completed if feasible during hospitalization). 
• If a participant has no assessments during the hospitalization: for symptoms that were 
present prior to the hospitalization, the missing data are imputed as severe. If the 
symptom was not present at baseline or returned to absent (none) prior to the 
hospitalization, the symptom will be imputed as absent (none). Otherwise, if a participant 
has partial data available during the hospitalization: missing values are imputed as the 
maximum (worse) of the last observed or imputed value prior to the missing assessment 
and the next observed or imputed value after the missing assessment.  
b. If a participant is hospitalized on or before Day 29 for a non-COVID-19-related 
hospitalization, missing values during hospitalization are imputed as the maximum (worse) 
of the last observed or imputed value prior to the missing assessment and the next observed 
or imputed value after the missing assessment. 
c. If a participant discontinues from the study, is lost to follow up (LFU), or dies on or before 
Day 29, symptom ratings will not be imputed beyond the date of discontinuation/LFU/death.  
d. If diary data are missing when a participant is not COVID-related hospitalized and remains 
on study (through Day 29), data will be imputed as follows: 
• The Day 1 assessment is baseline and is performed on-site prior to study drug dosing, so 
the assessment is not likely to be missing. If data are present for Day 1 and is missing for 
a sequence of consecutive days from Day 1 but with at least one subsequent score, impute 
the missing values through to the first available score with the value of the first available 
score (provided by the participant or imputed due to hospitalization). This is a 
conservative assumption, so that symptom improvement or resolution is less likely to be 
indicated early.  


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• If only the Day 1 assessment is missing (for a given symptom), the value will be imputed 
as the Day 2 value.  
• For intermittent missingness during follow-up, impute the missing values as the worse of 
the last available value (actually provided by the participant or imputed due to 
hospitalization) before the missing value and the first available value (actually provided 
by the participant or imputed due to hospitalization) after the missing value, irrespective 
of length of sequence of missing values. If the last prior and the first subsequent value are 
equal, then symptom improvement or resolution is based on the assumption that the 
situation remained stable during the missing duration. If the last prior value is worse than 
the first subsequent one, then symptom improvement/resolution is delayed over the 
missing duration until improvement/resolution is confirmed. If the last prior assessment is 
better than the first subsequent value, then symptom improvement/resolution is reversed 
earlier.  
e. If a participant has no period(s) of hospitalization and all post-Day 1 data are missing (for a 
given symptom) or all data, including Day1, are missing (for a given symptom), the symptom 
will not be imputed. If all data are missing for all symptoms, the participant will be excluded 
in the time-to-event analyses for improvement/resolution/sustained recovery. 
f. Missing data for the questions regarding sense of taste and smell, frequency of vomiting or 
diarrhea, will be imputed using the values mapped to none/mild/moderate/severe.  
g. Missing data will not be imputed for general status questions and overall severity of 
symptoms. 
 


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APPENDIX G. ESTIMANDS AND INTERCURRENT EVENTS 
Label 
Description 
IcEv1 (Co-infection) 
Co-infection with respiratory pathogens other than SARS-CoV-2 from 
administration of drug through Day 29 
IcEv2 (Prohibited COVID-19 vaccine) 
COVID-19 vaccine through Day 29 from administration of drug  
IcEv3 (Prohibited treatments for 
COVID-19) 
Use of prohibited treatments for COVID-19 from administration of 
drug through Day 29  
 


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APPENDIX H. PRIMARY AND KEY SECONDARY OBJECTIVES AND ESTIMANDS 


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Objective 
Primary: To evaluate the 
efficacy of ADG20 compared to 
placebo in the treatment of mild 
or moderate COVID-19 in 
participants at high risk of 
disease progression 
Primary: To evaluate the 
efficacy of ADG20 compared 
to placebo in the treatment of 
mild or moderate COVID-19 in 
participants at high risk of 
disease progression 
Key Secondary: To evaluate the 
effect of ADG20 on the following 
clinical parameters in participants 
with mild or moderate COVID-19 
and high risk of disease 
progression 
Key Secondary: To evaluate 
the effect of ADG20 on the 
following clinical parameters 
in participants with mild or 
moderate COVID-19 and high 
risk of disease progression 
Estimand Label 
Estimand 1a 
(Primary) 
Estimand 1b 
(Supplementary to Primary) 
Estimand 2 
(Key Secondary 1) 
Estimand 3 
(Key Secondary 2) 
Estimand 
Description 
(with Endpoint) 
Treatment difference (ADG20 – 
Placebo) in proportion of 
COVID-19-related 
hospitalization or all-cause 
death through Day 29 regardless 
of co-infection with respiratory 
pathogens other than 
SARS-CoV-2, use of prohibited 
COVID-19 vaccine, or 
prohibited treatments for 
COVID-19 
Treatment difference (ADG20 
– Placebo) in proportion of 
COVID-19-related 
hospitalization or all-cause 
death through Day 29 
regardless of co-infection with 
respiratory pathogens other 
than SARS-CoV-2 or use of 
COVID-19 vaccine and 
assuming no intake of 
prohibited treatments for 
COVID-19 
Treatment difference (ADG20 – 
Placebo) in proportion of 
participants experiencing 
severe/critical COVID-19 or all-
cause death through Day 29 
regardless of co-infection with 
respiratory pathogens other than 
SARS-CoV-2, use of prohibited 
COVID-19 vaccine, or prohibited 
treatments for COVID-19 
Treatment difference (ADG20 
– Placebo) in proportion of 
participants experiencing 
COVID-19-related emergency 
room visits, hospitalization, or 
all-cause death through Day 
regardless of co-infection with 
respiratory pathogens other 
than SARS-CoV-2, use of 
prohibited COVID-19 
vaccine, or prohibited 
treatments for COVID-19 
Target 
Population 
Adult and adolescent 
participants with laboratory 
confirmed mild or moderate 
COVID-19 who are at high risk 
of disease progression 
Same as Estimand 1a 
Same as Estimand 1a 
Same as Estimand 1a 
Endpoint 
Incidence of COVID-19-related 
hospitalization or all-cause death 
through Day 29 
Same as Estimand 1a 
Incidence of severe/critical 
COVID-19 or all-cause death 
through Day 29 
Incidence of COVID-19-
related emergency room visits, 
hospitalizations, or all-cause 
death through Day 29 
Treatment 
Conditions 
IM ADG20, IM Placebo  
Same as Estimand 1a 
Same as Estimand 1a 
Same as Estimand 1a 
Population-
Level Summary 
Difference in proportion of 
COVID-19-related 
hospitalization or all-cause death 
through Day 29 
Difference in proportion of 
COVID-19-related 
hospitalization or all-cause 
death through Day 29 
Difference in proportion of 
severe/critical COVID-19 or 
all-cause death through Day 29 
Difference in proportion of 
COVID-19-related emergency 
room visits, hospitalization, or 
all-cause death through 
Day 29 


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Objective 
Primary: To evaluate the 
efficacy of ADG20 compared to 
placebo in the treatment of mild 
or moderate COVID-19 in 
participants at high risk of 
disease progression 
Primary: To evaluate the 
efficacy of ADG20 compared 
to placebo in the treatment of 
mild or moderate COVID-19 in 
participants at high risk of 
disease progression 
Key Secondary: To evaluate the 
effect of ADG20 on the following 
clinical parameters in participants 
with mild or moderate COVID-19 
and high risk of disease 
progression 
Key Secondary: To evaluate 
the effect of ADG20 on the 
following clinical parameters 
in participants with mild or 
moderate COVID-19 and high 
risk of disease progression 
Estimand Label 
Estimand 1a 
(Primary) 
Estimand 1b 
(Supplementary to Primary) 
Estimand 2 
(Key Secondary 1) 
Estimand 3 
(Key Secondary 2) 
IcEv1  
(Co-Infection) 
Treatment policy 
Treatment policy 
Treatment policy 
Treatment policy 
IcEv2 
(Prohibited 
COVID-19 
vaccine) 
Treatment policy 
Treatment policy 
Treatment policy 
Treatment policy 
IcEv3 
(Prohibited 
treatments for 
COVID-19) 
Treatment policy 
Hypothetical  
Treatment policy 
Treatment policy 
Rationale for 
Strategies 
Given the trial’s confirmatory 
setting, interest lies in estimating 
treatment effects in participants 
who have access to prohibited 
concomitant therapy such as 
COVID-19 vaccines or 
treatments and regardless of 
co-infection with respiratory 
pathogens other than 
SARS-CoV-2, since this 
scenario reflects general clinical 
practice and the continuously 
evolving setting for preventing 
and treating COVID-19.  
Interest lies in estimating the 
effectiveness of ADG20 
against hospitalization or 
all-cause death without the 
influences of prohibited 
treatments for COVID-19. 
Similar to Estimand 1a 
 Similar to Estimand 1a 
 


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APPENDIX I. OVERVIEW OF STATISTICAL METHODS: ESTIMATIONS OF ESTIMANDS AND 
SENSITIVITY ANALYSES 
Estimand 
Label 
Estimand Description 
Main Estimation 
Sensitivity Analysis 
Analysis Set 
Imputation/Data Handling Rules Analysis Model/Method 
Estimand 1a Treatment difference 
(ADG20 – Placebo) in 
proportion of COVID-19-
related hospitalization or all-
cause death through Day 29 
regardless of intake of 
prohibited treatments for 
COVID-19 
FAS 
The endpoint will incorporate all 
available information through 
Day 29. Where participants have 
missing primary endpoint through 
Day 29, the status will be imputed 
as not having COVID-19-related 
hospitalization or all-cause death 
(ie, responder)  
The endpoint will be analyzed 
using the methodology for 
determining a standardized 
estimator for a binary outcome, 
with adjustment for prognostic 
factors. The standard error of 
the standardized estimator will 
be estimated using the delta 
method (refer to Appendix K) 
Multiple imputation under MAR 
assumption followed by calculation of 
standardized risk difference and 95% 
CI using Rubin’s method.  
 
Control based imputation 
 
Per-protocol Set analysis 
Estimand 1b  Treatment difference 
(ADG20 – Placebo) in 
proportion of COVID-19-
related hospitalization or all-
cause death through Day 29 
assuming no intake of 
prohibited treatments for 
COVID-19 
FAS 
In case of prohibited treatments for 
COVID-19, the primary endpoint 
will utilize multiple imputation 
under MAR assumption. The 
imputation model will be informed 
by the observed outcomes from 
participants who did not receive 
such medication (or received it after 
meeting the primary endpoint). The 
logistic model will include the 
prognostic factors. 
Same as Estimand 1a 
Hypothetical strategy of handling the 
ICEs. 
Estimand 2 
Treatment difference 
(ADG20 – Placebo) in 
proportion of participants 
experiencing severe/critical 
COVID-19 or all-cause death 
through Day 29 in the target 
population  
FAS 
Same as Estimand 1a 
Treatment difference in the 
proportion of participants with 
severe/critical COVID-19 or 
all-cause death through Day 29 
will be presented and tested 
using the main analysis method 
outlined for Estimand 1a 
 


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Estimand 
Label 
Estimand Description 
Main Estimation 
Sensitivity Analysis 
Analysis Set 
Imputation/Data Handling Rules Analysis Model/Method 
Estimand 3 
Treatment difference 
(ADG20 – Placebo) in 
proportion of participants 
experiencing COVID-19-
related emergency room 
visits, COVID-19-related 
hospitalization, or all-cause 
death through Day 29 in the 
target population  
FAS 
Same as Estimand 1a 
Treatment difference in 
proportion of participants with 
COVID-19-related emergency 
room visits, COVID-19-related 
hospitalizations or all-cause 
death through Day 29 will be 
presented and tested using the 
main analysis method for 
Estimand 1a. 
 
 


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APPENDIX J. 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 𝑃̂𝑡 from Xt and b, 𝑃̂𝑡 = logit -1 (Xt b)]. 
Similarly, assume each participant is assigned to control and redo the above steps to get Xc and 
𝑃̂𝑐.  
Risk difference (RD) in proportions:  
𝑅𝐷= ∑𝑃̂𝑡𝑖
𝑛−∑𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
𝑛
𝑖=1
 
where 𝑃̂𝑡𝑖 and 𝑃̂𝑐𝑖 are the ith elements of 𝑃̂𝑡 and 𝑃̂𝑐 respectively.  
The variance of the estimated risk difference:  
𝑉𝑎𝑟(𝑅𝐷) = 𝑉𝑎𝑟(∑𝑃̂𝑡𝑖
𝑛) −
𝑛
𝑖=1
 2𝑐𝑜𝑣(∑𝑃̂𝑡𝑖
𝑛
𝑛
𝑖=1
, ∑𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
) + 𝑉𝑎𝑟(∑𝑃̂𝑐𝑖
𝑛)
𝑛
𝑖=1
 
The delta method can be used to estimate each component of the variance estimation.  
Define At as a vector with elements Ati = 𝑃̂𝑡𝑖(1 −𝑃̂𝑡𝑖). Similarly define Ac as a vector with 
elements Aci = 𝑃̂𝑐𝑖(1 −𝑃̂𝑐𝑖).  
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 


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Adagio Therapeutics 
Statistical Analysis Plan, ADG20-TRMT-001 
Confidential 
FINAL Version 1.0, 03 March 2022 
Page 68 of 74 
 
Log risk ratio (RR) in proportions:  
𝛿1 =  log (𝑅𝑅) = 𝑙𝑜𝑔∑𝑃̂𝑡𝑖
𝑛−𝑙𝑜𝑔∑𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
𝑛
𝑖=1
 
where 𝑃̂𝑡𝑖 and 𝑃̂𝑐𝑖 are the ith elements of 𝑃̂𝑡 and 𝑃̂𝑐 respectively.  
The variance of the estimated log risk ratio:  
𝑉𝑎𝑟(𝛿1) = 𝑉𝑎𝑟(𝑙𝑜𝑔∑𝑃̂𝑡𝑖
𝑛) −
𝑛
𝑖=1
 2𝑐𝑜𝑣(𝑙𝑜𝑔∑𝑃̂𝑡𝑖
𝑛
𝑛
𝑖=1
, 𝑙𝑜𝑔∑𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
) + 𝑉𝑎𝑟(𝑙𝑜𝑔∑𝑃̂𝑐𝑖
𝑛)
𝑛
𝑖=1
 
Consider,  
𝑉𝑎𝑟(𝑙𝑜𝑔∑𝑃̂𝑡𝑖
𝑛
𝑛
𝑖=1
) ≈(
1
∑
𝑃̂𝑡𝑖
𝑛
𝑛
𝑖=1
)
2
𝑉𝑎𝑟(∑𝑃̂𝑡𝑖
𝑛
𝑛
𝑖=1
) ≈(
1
∑
𝑃̂𝑡𝑖
𝑛
𝑛
𝑖=1
)
2
𝑑𝑡𝑉𝑑𝑡
′ 
𝑉𝑎𝑟(𝑙𝑜𝑔∑𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
) ≈(
1
∑
𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
)
2
𝑉𝑎𝑟(∑𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
) ≈(
1
∑
𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
)
2
𝑑𝑐𝑉𝑑𝑐
′ 
2𝑐𝑜𝑣(𝑙𝑜𝑔∑𝑃̂𝑡𝑖
𝑛
𝑛
𝑖=1
, 𝑙𝑜𝑔∑𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
) ≈2 (
1
∑
𝑃̂𝑡𝑖
𝑛
𝑛
𝑖=1
) (
1
∑
𝑃̂𝑐𝑖
𝑛
𝑛
𝑖=1
) 𝑑𝑐𝑉𝑑𝑡
′ 
 
SE(𝛿1) = √Var(𝛿1) 
The confidence interval of log(RR) 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))]. 
 


Adintrevimab (ADG20)  
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-TRMT-001 
Confidential 
FINAL Version 1.0, 03 March 2022 
Page 69 of 74 
 
APPENDIX K. CRITERIA FOR POTENTIALLY CLINICALLY SIGNIFICANT EVENTS 
Non-DAIDS Criteria for Clinical Laboratory Tests 
Parameter 
SI Unit 
PCS Low Limit 
PCS High Limit 
Basophils Percent 
% 
— 
>4.00 × ULN 
Eosinophils Percent 
% 
— 
>4.0 × ULN 
Monocytes percent 
% 
— 
>4.00 × ULN 
Hematocrit 
% 
<0.6 × baseline 
>1.3 × ULN 
Blood urea nitrogen 
mmol/L 
— 
>1.3 × ULN 
Chloride 
mmol/L 
<0.80 × LLN 
>1.1 × ULN 
Protein, total 
g/L 
<0.8 × LLN 
>1.2 × ULN 
LLN=lower limit of normal (value provided by the laboratory); PCS=potentially clinically significant; SI=International System of Units; ULN=upper limit of 
normal (value provided by the laboratory). 
 
Vital Sign Parameter 
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 
SpO2 
Low (CL) 
≤93% 
Decrease of ≥3% 
Note: PCS is meeting either criterion value or change from baseline. 
CH=clinically high; CL=clinically low. 


Adintrevimab (ADG20)  
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-TRMT-001 
Confidential 
FINAL Version 1.0, 03 March 2022 
Page 70 of 74 
 
• For temperature decreases, the participants baseline value should be accounted for. Scenarios to account for: 
− Participants with fever (≥38°C [100.4°F]) at baseline on Day 1 will not be reported as a PCS value unless an increase of 1 °C 
is met post-baseline. 
− Participants with fever (≥38°C [100.4°F]) at baseline on Day 1 will not be reported as a PCS value for a decrease in 
temperature after Day 1 unless to <35 °C, as this represents clinical improvement in a participant with COVID-19. 
• For respiratory rate, the participants baseline value should be accounted for. Scenarios to account for: 
− Participants with a RR >20 breaths/minute at baseline on Day 1 will not be reported as a PCS value for a decrease in RR after 
Day 1 unless to 8 breaths/minute, as this represents clinical improvement in a participant with COVID-19. 
• For heart rate, the participants baseline value should be accounted for. Scenarios to account for: 
− Participants with a HR >120 bpm at baseline on Day 1 will not be reported as a PCS value for a decrease in HR after Day 1 
unless 50 bpm, as this may represent clinical improvement in a participant with COVID-19. 
• Specific values for adolescents may be considered as appropriate. 
 


Adintrevimab (ADG20)  
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-TRMT-001 
Confidential 
FINAL Version 1.0, 03 March 2022 
Page 71 of 74 
 
APPENDIX L. SAFETY MONITORING 
Study Phase/ 
Parameter 
Analysis 
Time point  
Reviewer/ 
Data Reviewed 
Criterion 
Statistical Method Purpose 
Phase 2/PK 
Throughout  
Unblinded 
Pharmacology Team: 
• Unblinded available 
PK data to be 
reviewed 
• Aggregate data to 
Sponsor 
NA 
PK Analyses as 
detailed in PK 
Analysis Plan 
Confirm PK in participants  
Phase 2/Safety At any time 
during Phase 2 
iDMC: 
Events meeting 
criterion 
If any of the following pausing guidelines are met, 
an ad hoc iDMC meeting will occur: 
• 2 or more participants with a study-drug-related 
grade 3 or higher hypersensitivity reaction  
• 2 or more participants with a grade 3 or higher 
injection site reaction  
• Any study-drug-related death 
• Any study-drug-related SAE including 
hypersensitivity reactions 
NA 
Monitor ongoing  
safety 
Phase 2/Safety 
Assessment 
(administrative 
interim 
analysis) 
Approximately 
N=200 
participants 
enrolled 
iDMC: 
Safety assessment  of 
300 mg IM dose 
 
Detailed in iDMC charter 
Safety analyses as 
detailed in SAP 
Monitor ongoing safety profile  
and provide recommendation 
regarding enrollment of 
adolescents and pregnant and 
breastfeeding women in Phase 
3 and post-dose monitoring 
duration per Section 6.4.1 of 
the protocol. 
Phase 3/Safety At any time 
during Phase 3 
iDMC: 
Events meeting 
criterion 
If any of the following pausing guidelines are met, 
an ad hoc iDMC meeting will occur: 
• Any study-drug-related death  
• Any study-drug-related SAE including 
hypersensitivity reactions 
NA 
Monitor ongoing safety 
NA=not applicable.


Adintrevimab (ADG20)  
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-TRMT-001 
Confidential 
FINAL Version 1.0, 03 March 2022 
Page 72 of 74 
 
APPENDIX M. SCHEDULE OF EVENTS 
Study Period 
Screening/ 
Treatment 
Follow-up 
Long-Term Follow-Up 
 
Day 
Day 
Day 
Month 
Day/Month 
-2 
1a 
3 
5 
7 
11 
14 
21 
29b 
60 
90 
6b 
11 
14 EOSb 
Visit Window (days) 
2 
0 
±1 
±1 
±1 
±2 
±2 
±2 
+5 
±7 
±14 
±30 
±30 
+60 
Visit Typec 
C/H 
C 
T 
T 
C/H 
T 
T 
T 
C/H 
T 
C/H 
C/H 
C/H 
T 
Assessment 
Baseline Assessments 
Informed consent/assent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history (including risk factors & COVID-19 
symptom onset) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical exam (including weight, height, & 
COVID-19 signs/symptoms) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Local urine or serum pregnancy test (for WOCBP; must 
be performed within 24 hours of study drug 
administration) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Documentation of local positive  
SARS-CoV-2 testd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Review of study inclusion/exclusion criteria 
(Day 1 re-review prior to randomization) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Central Laboratory Assessments 
Nasopharyngeal swab(s) collection for SARS-CoV-2 RT-
qPCR, SARS-CoV-2 sequencing, & respiratory panel 
(Day 1: 2 swabs, Day 7: 1 swab) 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
Blood collections for SARS-CoV-2 antibodies 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Blood collection for safety laboratory (chemistry, 
hematology, coagulation) Day 1 & Month 6 includes 
serum pregnancy for females 
 
X 
 
 
X 
 
 
 
X 
 
X 
X 
 
 
Blood collection for PKe 
 
X 
 
 
X 
 
 
 
X 
 
X 
X 
X 
 
Blood collection for ADA (immunogenicity)e 
 
X 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
Site Clinical Assessments 
Prior/Concomitant medicationsf 
––––––––––––––––––––––––––––––––––––––––X––––––––––––––––––––––––––––––––––––––––– 
AEs, SAEs, MAAEsg 
––––––––––––––––––––––––––––––––––––––––X––––––––––––––––––––––––––––––––––––––––– 


Adintrevimab (ADG20)  
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-TRMT-001 
Confidential 
FINAL Version 1.0, 03 March 2022 
Page 73 of 74 
 
Study Period 
Screening/ 
Treatment 
Follow-up 
Long-Term Follow-Up 
 
Day 
Day 
Day 
Month 
Day/Month 
-2 
1a 
3 
5 
7 
11 
14 
21 
29b 
60 
90 
6b 
11 
14 EOSb 
Visit Window (days) 
2 
0 
±1 
±1 
±1 
±2 
±2 
±2 
+5 
±7 
±14 
±30 
±30 
+60 
Visit Typec 
C/H 
C 
T 
T 
C/H 
T 
T 
T 
C/H 
T 
C/H 
C/H 
C/H 
T 
Assessment 
Targeted review of changes in healthh 
 
 
 
 
X 
 
 
 
X 
 
X 
X 
X 
 
Educate participant on At-Home Assessments/ 
Collections (Symptom Diary, vitals, saliva collections, 
ISR Diaryi, recognizing emergency symptoms & 
hypersensitivity reactions) 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Study drug administration & safety monitoring (All Day 1 
assessments must occur prior to study drug 
administration) 
 
X j 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs, including SpO2 
X 
X  j 
 
 
X 
 
 
 
X 
 
X 
X 
X 
 
Review of COVID-19 Symptom Diary, reported vitals, 
ISR diary, & COVID-19 severity assessment (Day 1 
assessment should be completed prior to study drug 
administration) 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Survival assessment & Medically Attended Visits 
assessmentk 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Collect/update participant contacts 
 
X 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
 
Long-term health status assessment 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
Household transmission questionnaire 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Participant At-Home Assessments/Collections 
Day 1 assessments/collections by participant will be observed by site staff prior to study drug administration; Days 1-4: ISR diary for IM injection participants. 
Saliva sample for SARS-CoV-2 RT-qPCRl 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Daily COVID-19 Symptom Diary & ISR Diaryi 
 
X 
––––––––––––––––––X––––––––––––––––– 
 
 
 
 
 
Daily temperature, SpO2, heart ratem 
 
X 
––––––––––––––––––X––––––––––––––––– 
 
 
 
 
 
ADA=anti-drug antibodies; EOS=end-of-study; ISR=injection site reaction; RT-qPCR=quantitative reverse transcription polymerase chain reaction; SpO2=oxygen saturation; 
WOCBP=women of childbearing potential. 
a Note that screening procedures may occur on the same day of dosing on Day 1. Study Day 1 is the calendar day that study drug is administered. On Day 1, all 
study procedures except ISR diary completion and collection of participant contacts are to be performed prior to study drug administration. Adverse events 
occurring from when the participant signs the ICF until the Month 14 (EOS) visit or withdrawal will be recorded. Any screening inclusion criteria with 
laboratory values associated (eg, eGFR, FSH, etc) should be based on local laboratory results or most recent medical record. 


Adintrevimab (ADG20)  
Adagio Therapeutics 
Statistical Analysis Plan, ADG20-TRMT-001 
Confidential 
FINAL Version 1.0, 03 March 2022 
Page 74 of 74 
 
b If a participant/guardian/LAR requests a participant to be withdrawn at any time after randomization into the study, the investigator will make every effort to 
encourage the participant to complete the Day 29 assessments (if prior to Day 29), Month 6 visit assessments (if after the Day 29 visit but before Month 6), or 
the Month 14 EOS visit assessments (if after the Month 6 Visit completed). 
c Visits after Day 1 may not be combined. Visit codes: C (in-clinic); C/H (in-clinic or home health); T (Telemedicine, ‘T’ visits may also be in-clinic or home 
health). 
d A local positive SARS-CoV-2 test (antigen, RT-PCR, or other locally approved molecular test) taken within 5 days prior to randomization is required for 
eligibility. The day of randomization is not considered in the calculation of 5 days. Historical documentation is acceptable. Local testing result, specimen type, 
assay type, and date of the test will be recorded in the eCRF. SARS-CoV-2 antibody testing is not acceptable for eligibility. Additional samples for SARS-
CoV-2 testing at local laboratory for the purposes of case management may be collected per local standard of care. Clinical care should be delivered per local 
standards of care and not wait for results of central laboratory testing. 
e On Day 1, one PK sample to be collected at baseline prior to study drug administration. All other visits with PK sample collection will have one sample 
collected. An additional PK and ADA sample should be collected from participants experiencing hypersensitivity reactions as described in protocol Section 
6.8.2. 
f Record information regarding all prior and concomitant medications taken, including OTC medications and investigational agents or supportive care taken for 
index COVID-19 infection under study. All concomitant medications will be recorded up to and including Day 60. Any concomitant medications related to 
AEs and any vaccinations received will be recorded for the entire length of the study (ie, through Month 14). 
g Record all AEs from when the participant signs the ICF through the Month 14 Visit. On Day 1 through Day 4, record AESIs (hypersensitivity reactions, 
including but not limited to urticaria, edema, respiratory distress, anaphylaxis, and allergic reactions) occurring through Day 4. Hypersensitivity reactions 
occurring after Day 4 will be recorded as AEs. Investigators or medically qualified designees will follow all ISRs that are ongoing beyond Day 4 to resolution. 
Worsening or sequelae of the index case of COVID-19 will not be recorded as AEs, unless they meet SAE criteria; these data will be captured as efficacy 
assessment data. Subsequent instances of COVID-19 in the same participant will be recorded as AEs. 
h Targeted review of changes in health based on reported AEs or ongoing signs/symptoms of COVID-19. 
i Participants will complete the daily COVID-19 Symptom Diary (includes global impression questions) Day 1 through Day 29. The Injection Site Reaction 
Diary will be completed Day 1 through Day 4. Site will provide a ruler along with instructions regarding completion of the Injection Site Reaction Diary 
(protocol Appendix 12.3). Instruct participants to record any local ISRs daily through Day 4. 
 j Perform vital signs before, during, and after study drug administration per protocol Section 6.4.1. Protocol Section 6.4.1 outlines required vital signs on Day 1, 
duration of monitoring post-dose, and ISR monitoring and management. 
k Record information regarding participant survival and participant medically attended visits (telemedicine, physician office, urgent care center, emergency 
room, hospitalization) and relationship of medically attended visits to COVID-19. During telemedicine visits, the participant will also be reminded to complete 
daily COVID-19 Symptom Diary, daily temperature, blood oxygen saturation and heart rate, and saliva sample collection on the appropriate days. 
l Participants will collect their own saliva sample using the collection materials provided on Days 3, 5, 11, 14, and 21 and return them to the study site according 
to provided instructions. Note: Day 7 and Day 29 are in-clinic or home health visits and the saliva sample will be collected and transported by site staff or 
delegate. Participants should NOT eat, drink, smoke, or chew gum for 30 minutes before sample collection. The sample will be used for SARS-CoV-2 RT-
qPCR and may be used for viral sequencing. In the event of worsening COVID-19 or potential relapse or re-infection, a saliva sample for SARS-COV-2 RT-
qPCR and sequencing should be collected as described in protocol Section 6.8.1. 
m Participants will be asked to monitor temperature, blood oxygen saturation, and heart rate 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.