Clinical trial NCT04405739
Conditions: SARS-CoV 2
Sponsor: Ridgeback Biotherapeutics, LP
Start date: 2020-06-16; Completion date: 2022-02-21
Enrollment: 71 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Designed as a multi-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of EIDD-2801 on SARS-CoV-2 Virus Shedding in Newly Hospitalized Adults with polymerase chain reaction (PCR)-Confirmed COVID-19.

Detailed description:
Phase 2a randomized, placebo-controlled, double-blinded clinical trial of EIDD-2801 (also known as MK 4482) in adult men and women who have tested positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection by polymerase chain reaction (PCR) test within 6 days (144 hours) prior to randomization and are hospitalized with a diagnosis of COVID-19. Rapid enrollment and treatment will be initiated such that the first dose of EIDD-2801 or placebo will be administered as soon as possible and within 7 days of onset of symptoms.

Arms: arm 1: EIDD-2801 orally twice daily (BID) for 5 days at Dose A, Dose B, Dose C, Dose D, Dose E, Dose F arm 2: Placebo (PBO) orally twice daily (BID) for 5 days matched for size and appearance to active IP
Interventions: intervention 1: EIDD-2801 intervention 2: Placebo
Intervention descriptions: intervention 1: Oral capsule of EIDD-2801 intervention 2: Oral placebo capsule

Protocol documents:
Prot_000.pdf: 
Long title: The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2
Short title: The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2
(The END-COVID Study)
Ridgeback Biotherapeutics Protocol #: EIDD-2801-2004
Clinical Phase: 2
ClinicalTrials.gov Identifier: NCT04405739
IND Sponsor/Principal Investigator:
Sponsor: Ridgeback Biotherapeutics LP
Principal Investigator: Ashwin Balagopal, MD
IND Number: 147734
Study Drug: EIDD-2801 and Placebo Capsules
Version/Date of Issue: Amendment 6, Version 7.0, 18 May 2021
Confidential Information: The information contained in this document is the property of 
Ridgeback Biotherapeutics LP and may not be reproduced, published, or disclosed to others 
without written authorization from Ridgeback Biotherapeutics LP.


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PROTOCOL SUMMARY
Sample Size: 84 with allowance to increase up to 15% over as needed for dropouts or logistics 
considerations.
Study Population: 
Adults aged 18 years or older who are hospitalized with a new diagnosis of coronavirus disease-2019 
(COVID-19) with a duration of symptoms 7 days. Patients requiring admission to an intensive care unit 
or mechanical ventilation are not eligible.
Study Duration:
Length of study: Approximately 10 months from First Participant First Visit to Last Participant Last Visit
Length of participation of study participants: Up to 30 days, including a 0 to 2-day screening window, 
5 days of dosing with study drug, and 23 days of post-dosing follow-up.
Locations:
Johns Hopkins Health System, The University of California, Los Angeles, and up to 5 additional sites in 
the United States
Study Design: 
Phase 2a randomized, placebo-controlled, double-blinded clinical trial of EIDD-2801 (also known as 
MK-4482) in adult men and women who have tested positive for severe acute respiratory syndrome-
coronavirus-2 (SARS-CoV-2) infection by polymerase chain reaction (PCR) test within 6 days
(144 hours) prior to randomization and are hospitalized with a diagnosis of COVID-19. Rapid enrollment 
and treatment will be initiated such that the first dose of EIDD-2801 or placebo will be administered as
soon as possible and within 7 days of onset of symptoms.
Randomization
Participants will be enrolled in up to 4 sequential study parts. During Part 1, participants will be 
randomized in a 1:1:1 ratio to: 200 mg EIDD-2801:400 mg EIDD-2801:placebo.  In Part 2 of the study, 
21 participants will be randomized in a 2:1 ratio to receive EIDD-2801 400 mg or placebo and in Part 3 of 
the study, 21 participants will be randomized in a 2:1 ratio to receive EIDD-2801 800 mg or placebo.  An 
optional Part 4 may be added during which 21 participants will be randomized in a 2:1 ratio to EIDD-
2801:placebo and the dose of EIDD-2801 may be the same or lower than doses studied in previous 
Part(s), but not to exceed 800 mg BID.
The study parts will be conducted as follows:  Enrollment into Part 1 of the study may be terminated upon 
approval and implementation of Protocol Amendment 3, and enrollment into Part 2 will be initiated 
immediately thereafter.  Enrollment into Part 3 will be initiated once Part 2 has been fully enrolled.  If 
initiated, Part 4 may begin enrolling participants as soon as Part 3 has been fully enrolled. Study Parts 2 
and 3 may be terminated prematurely based on emerging data from this and other ongoing studies of 
EIDD-2801.


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Study Drug:
Ɣ
EIDD-2801 and matching placebo
Primary Efficacy Objective: 
To test whether orally administered EIDD-2801 results in a greater proportion of clearance from 
nasopharyngeal (NP) swabs compared to placebo in hospitalized adults by achieving undetectable (below 
the limit of detection [LOD] of the assay) viral RNA by Day 5 after initiation of study drug.
Primary Efficacy Endpoint: 
Achievement of undetectable (below the LOD of the assay) SARS-CoV-2 RNA by Day 5 in NP swabs by 
quantitative reverse transcription polymerase chain reaction (qPCR). 
Primary Safety Objective:
To evaluate the safety of treatment with EIDD-2801 in participants diagnosed with COVID-19
Primary Safety Endpoints:
1. Adverse events (AEs)
2. Serious adverse events (SAEs)
3. Physical examination including vital signs
4. Safety laboratory assessments
x
complete blood counts (CBC) with differentials
- decrease in hemoglobin (Hgb) by >1 g/dL, or to <9 g/dL
- decrease in platelet count by 50,000/μL, or to <75,000/μL
x
comprehensive metabolic panels (CMP) including liver function tests
- increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase, or 
lipase to 3x the upper limit of normal (ULN)
x
urinalysis
5. Electrocardiograms (ECGs)
Secondary Virologic Objectives: 
To evaluate the efficacy of EIDD-2801 on clearance of SARS-CoV-2 RNA.
Secondary Virologic Endpoints:
1. Time to clearance of viral RNA in NP swabs
- by qPCR 
2. The decline in viral RNA by Day 3, Day 5, Day 8, Day 11, Day 15, Day 19, and Day 28 after 
initiation of study drug in NP swabs
- by qPCR 


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3. Rate of decline in viral RNA (change in log10 copies/mL per day) in NP swabs
- by qPCR  
Secondary Clinical Objective  
To evaluate the effect of EIDD-2801 on improvement of clinical symptoms and signs of COVID-19.  
Secondary Clinical Endpoints:
1. Peak stage on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement
(Appendix 1) OR clinical requirement for addition of other antivirals including but not limited to:
- Pegylated interferon alpha
- Inhaled interferon beta1 
- Ribavirin (any formulation) 
- Any interleukin (IL)-6 inhibitor
2. Number of days of supplemental oxygen  
3. Number of days of mechanical ventilation
4. Number of days in the Intensive Care Unit (ICU)
5. Death
Exploratory Virologic Objective 
To evaluate the efficacy of EIDD-2801 to clear SARS-CoV-2 RNA and infectious virus.  
Exploratory Virologic Endpoints:
1. Achievement of undetectable(below the LOD of the assay) viral titers by Day 5 in NP swabs
- by infectivity assay  
2. Time to clearance of infectious virus in NP swabs
- by infectivity assay
3. Clearance of infectious virus by Day 3 and Day 5 in NP swabs 
- by infectivity assay
4. The number of acquired single-nucleotide polymorphisms in SARS-CoV-2 genomes by Day 5 or 
Day 11 in NP swabs 
- by viral sequencing 
Exploratory Clinical Objective
To ascertain the role of EIDD-2801 in improvement of clinical symptoms and signs of COVID-19. 
Exploratory Clinical Endpoints:  
1. Days of hospitalization
2. Time until on room air without requirement for supplemental oxygen
3. Time to resolution of COVID-19 symptoms defined as: 
- Fevers OR 


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- At least one of the IROORZLQJV\PSWRPVFRXJKVKRUWQHVVRIEUHDWKUHVSLUDWRU\UDWH
radiographic evidence of pneumonia OR
- other clinical symptoms or signs of pneumonia that are not otherwise explained by 
comorbidities or co-diagnoses
4. Number of days until a 2-point decrease in stage according to the WHO Ordinal Scale for Clinical 
Improvement (Appendix 1).
5. Radiologic improvement by grading chest diagnostics (when radiography is available)
6. Change in interleukin (IL)-6 levels by Day 5 
Pharmacokinetic Objectives 
(To be conducted in a subset of participants at clinical sites that can participate, including but not limited 
to
 on Days 3 to 4 of dosing):
Secondary:
To evaluate EIDD-1931 pharmacokinetics in plasma.   
Exploratory:
To characterize the pharmacokinetics of EIDD-2061 (NHC-TP) in peripheral blood mononuclear cells 
(PBMC) in a subset of participants. 
Pharmacokinetic Endpoints: 
Secondary (plasma analysis):
1. Maximum EIDD-1931 concentration (Cmax) 
2. 1.5-hour EIDD-1931 concentration (C1.5) 
3. 3-hour EIDD-1931 concentration (C3) 
4. Area under the concentration: time curve of EIDD-1931 (AUC) 
5. Elimination half-life (t1/2) of EIDD-1931 
Exploratory (PBMC analysis):
1. Maximum EIDD-2061 concentration (Cmax) 
2. EIDD-2061 time of maximal concentration (tmax) 
3. Elimination half-life of EIDD-2061 (t1/2) 
4. Area under the concentration: time curve of EIDD-2061 (AUC0-12)  
5. Parent: metabolite (EIDD-1931:EIDD-2061) concentration ratio at each time point, in which both 
plasma and PBMC are processed for PK analysis


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TABLE OF CONTENTS
SPONSOR APPROVAL................................................................................................................. 2 
SIGNATURE PAGE....................................................................................................................... 3 
PROTOCOL SUMMARY.............................................................................................................. 4 
TABLE OF CONTENTS................................................................................................................ 8 
LIST OF APPENDICES ............................................................................................................... 11 
LIST OF FIGURES ...................................................................................................................... 11 
LIST OF ABBREVIATIONS ....................................................................................................... 12 
1. 
STUDY OBJECTIVES ......................................................................................................... 14 
1.1. 
Primary Efficacy Objective ............................................................................................ 14 
1.2. 
Primary Safety Objective ............................................................................................... 14 
1.3. 
Secondary Virologic Objective ...................................................................................... 14 
1.4. 
Secondary Clinical Objectives ....................................................................................... 15 
1.5. 
Exploratory Virologic Objective .................................................................................... 15 
1.6. 
Exploratory Clinical Objective ....................................................................................... 16 
1.7. 
Pharmacokinetic Objectives ........................................................................................... 16 
2. 
BACKGROUND AND SCIENTIFIC RATIONALE ........................................................... 18 
2.1. 
Abstract .......................................................................................................................... 18 
2.2. 
Background .................................................................................................................... 19 
2.3. 
Known Potential Risks ................................................................................................... 20 
2.3.1. 
Clinical Findings ...................................................................................................... 20 
2.3.2. 
Nonclinical Findings ................................................................................................ 21 
2.3.3. 
 ............................................................. 25 
2.4. 
Known Potential Benefits ............................................................................................... 26 
2.4.1. 
Potential Benefits of Treatment ............................................................................... 26 
2.4.2. 
Potential Benefits of Clinical Monitoring and Virologic Testing ............................ 27 
3. 
PATIENT POPULATION ..................................................................................................... 28 
3.1. 
Inclusion Criteria for Enrollment ................................................................................... 28 
3.2. 
Exclusion Criteria for Enrollment .................................................................................. 29 
4. 
INVESTIGATIONAL PLAN ................................................................................................ 32 
4.1. 
Definitions ...................................................................................................................... 32 
4.2. 
Randomization and Blinding .......................................................................................... 32 
4.3. 
Intervention..................................................................................................................... 33 
4.3.1. 
Screening .................................................................................................................. 33 


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4.3.2. 
Administration of Study Drugs ................................................................................ 33 
4.3.3. 
Virologic Assessments ............................................................................................. 33 
4.3.4. 
Clinical Assessments ................................................................................................ 34 
4.4. 
Pregnancy Testing .......................................................................................................... 34 
4.5. 
Serology .......................................................................................................................... 35 
4.6. 
Rationale for Medication Dosing ................................................................................... 35 
4.7. 
Concomitant Medications ............................................................................................... 35 
4.8. 
Study Discontinuation .................................................................................................... 35 
5. 
PHARMACEUTICAL INFORMATION ............................................................................. 37 
5.1. 
Agent Accountability ..................................................................................................... 37 
5.2. 
Mode of Action .............................................................................................................. 37 
5.3. 
Description ..................................................................................................................... 38 
5.4. 
Packaging ....................................................................................................................... 38 
5.5. 
Storage ............................................................................................................................ 38 
5.6. 
Route of Administration ................................................................................................. 38 
5.7. 
Participant Care Implications ......................................................................................... 38 
5.8. 
Returns and Reconciliations ........................................................................................... 38 
5.9. 
Pharmacokinetics ............................................................................................................ 39 
6. 
STATISTICAL CONSIDERATIONS .................................................................................. 40 
6.1. 
Sample Size and Power Considerations ......................................................................... 40 
6.2. 
Statistical Analysis ......................................................................................................... 40 
6.2.1. 
Analysis Populations ................................................................................................ 40 
6.2.2. 
Data Handling .......................................................................................................... 41 
6.2.3. 
Handling of Dropouts, Missing Data, and Outliers.................................................. 41 
6.2.4. 
Analysis of Primary Endpoint .................................................................................. 41 
6.2.5. 
Analysis of Secondary Endpoints ............................................................................ 42 
6.2.6. 
Analysis of Adverse Event Data .............................................................................. 42 
6.2.7. 
Analysis of Other Safety and Clinical Data ............................................................. 42 
6.2.8. 
Analysis of Pharmacokinetic Data ........................................................................... 43 
7. 
STUDY PROCEDURES ....................................................................................................... 44 
7.1. 
Schedule of Events ......................................................................................................... 44 
8. 
ADVERSE EVENTS, RISKS, AND BENEFITS ................................................................. 49 
8.1. 
Potential Benefits of treatment ....................................................................................... 49 
8.2. 
Potential benefits of clinical monitoring ........................................................................ 49 


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8.3. 
Potential risks ................................................................................................................. 49 
8.4. 
Alternatives..................................................................................................................... 49 
8.5. 
Definitions ...................................................................................................................... 49 
8.5.1. 
Adverse Event .......................................................................................................... 49 
8.5.2. 
Serious Adverse Event ............................................................................................. 50 
8.6. 
Relationship .................................................................................................................... 51 
8.7. 
Assessment of Grade/Severity ........................................................................................ 52 
8.8. 
Expectedness .................................................................................................................. 52 
8.9. 
Handling of Expedited Safety Reports ........................................................................... 52 
8.10. Reporting ........................................................................................................................ 52 
8.10.1. Routine Adverse Event Reporting ........................................................................... 53 
8.10.2. Laboratory Test Abnormalities ................................................................................ 53 
8.10.3. Serious Adverse Event Reporting ............................................................................ 53 
8.10.4. Pregnancy and Exposure During Breastfeeding ...................................................... 55 
9. 
SAFETY OVERSIGHT ......................................................................................................... 56 
9.1. 
Monitoring Plan .............................................................................................................. 56 
9.2. 
Stopping Criteria for the Study....................................................................................... 56 
10. 
ETHICS/PROTECTION OF HUMAN SUBJECTS ......................................................... 58 
10.1. Ethical Standard.............................................................................................................. 58 
10.2. Institutional Review Board ............................................................................................. 58 
10.3. Informed Consent Process .............................................................................................. 58 
10.4. Participant Confidentiality.............................................................................................. 59 
10.5. Future Use of Stored Specimens .................................................................................... 59 
10.6. Data Management and Monitoring ................................................................................. 59 
10.6.1. Source Documents ................................................................................................... 59 
10.6.2. Data Management Plan ............................................................................................ 60 
10.6.3. Data Capture Methods ............................................................................................. 60 
10.6.4. Study Record Retention ........................................................................................... 60 
11. 
REFERENCES ................................................................................................................... 61 


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LIST OF APPENDICES
Appendix 1. 
World Health Organization Ordinal Scale for Clinical Improvement of COVID-19 
Disease ............................................................................................................................... 62 
Appendix 2. 
Contraceptive Guidance ..................................................................................................... 63 
LIST OF FIGURES
Figure 1. 
 23 


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LIST OF ABBREVIATIONS
ADR: Adverse Drug Reaction
AE: Adverse Event/Adverse Experience
ALT: Alanine aminotransferase
ARDS: Acute Respiratory Distress Syndrome
AST: Aspartate aminotransferase
AUC: Area under the curve
AUC0-12: Area under the concentration-time curve throughout 12-hour dosing interval
AUC0-24: Area under the concentration-time curve throughout 24-hour dosing interval
AUC0-8: Area under the concentration-time curve throughout 8-hour dosing interval
BID: Bis in die, or twice daily
BiPAP: Bilevel positive airway pressure
BMI: Body mass index, or weight in kilograms divided by height in meters squared
C1.5: One point five-hour concentration
C3: Three-hour concentration
CDC: United States Centers for Disease Control and Prevention
CFR: Code of Federal Regulations
CHKV: Chikungunya virus
CLIA: Clinical Laboratory Improvement Amendment of 1988
Cmax: Maximum concentration
COI: Conflict of Interest
CoV: Coronavirus
COVID-19: Coronavirus Disease 
CRF: Case Report Form
CRS: Cytokine Release Syndrome
DMC: Data Management Center
DRF: Dose range finding
ECG: Electrocardiogram
EEEV: Eastern equine encephalitis virus
EUA: Emergency Use Authorization
FDA: Food and Drug Administration
GCP: Good Clinical Practice
HBV: Hepatitis B virus
HCV: Hepatitis C virus
HIV: Human immunodeficiency virus
IB: Investigator’s Brochure
I/E: Inclusion and exclusion
ICF: Informed Consent (Informed Consent Form)
ICU: Intensive Care Unit
IEC: Independent ethics committee
IRB: Institutional review board


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IWRS: Interactive web response system
LOD: Limit of detection
MAD: Multiple ascending dose
MERS: Middle East Respiratory Syndrome 
MERS-CoV: Middle East Respiratory Syndrome Coronavirus
MTD: Maximum tolerated dose
NOAEL: No observed adverse effect level
NP: Nasopharyngeal
PFA: Plaque forming assay
PO2: Partial pressure of oxygen
QD: Quaque die, or once daily
QOD: Quaque altera die, or once every other day
qPCR: Quantitative polymerase chain reaction
RSV: Respiratory syncytial virus
RT-PCR: Reverse transcriptase polymerase chain reaction
SAD: Single ascending dose
SAE: Serious adverse event
SARS: Severe Acute Respiratory Syndrome
SARS-CoV: Severe Acute Respiratory Syndrome Coronavirus
SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2
SOC: Standard of care
SRC: Safety review committee
t1/2: half-life
VEEV: Venezuelan equine encephalitis virus 
ZIKV: Zika virus


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1. STUDY OBJECTIVES
1.1.
Primary Efficacy Objective
Primary Efficacy Objective:
To test whether orally administered EIDD-2801 results in a greater proportion of clearance from 
nasopharyngeal (NP) swabs compared to placebo in hospitalized adults by achieving undetectable (below 
the limit of detection [LOD] of the assay) viral RNA by Day 5 after initiation of study drug.
Primary Efficacy Endpoint: 
Achievement of undetectable (below the LOD of the assay) severe acute respiratory syndrome-
coronavirus-2 (SARS-CoV-2) RNA by Day 5 in NP swabs by quantitative reverse transcription 
polymerase chain reaction (qPCR). 
1.2.
Primary Safety Objective 
Primary Safety Objective:
To evaluate the safety of treatment with EIDD-2801 in participants diagnosed with COVID-19
Primary Safety Endpoints:
1. Adverse events (AEs)
2. Serious adverse events (SAE)
3. Physical examination including vital signs
4. Safety laboratory assessments:
x
complete blood counts (CBC) with differentials
-
decrease in hemoglobin (Hgb) by >1 g/dL, or to <9 g/dL
-
decrease in platelet count by 50,000/μL, or to <75,000/μL
x
comprehensive metabolic panels (CMP) including liver function tests
-
increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase,
or lipase to 3x the upper limit of normal (ULN)
x
urinalysis
5. Electrocardiograms (ECGs)
1.3.
Secondary Virologic Objective
To evaluate the efficacy of EIDD-2801 on clearance of SARS-CoV-2 RNA.


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Secondary Virologic Endpoints:
1. Time to clearance of viral RNA in NP swabs 
-
by qPCR  
2. The decline in viral RNA by Day 3, Day 5, Day 8, Day 11, Day 15, Day 19, and Day 28 after 
initiation of study drug in NP swabs
-
- by qPCR  
3. Rate of decline in viral RNA, (change in log10 copies/mL per day) in NP swabs
-
- by qPCR  
1.4.
Secondary Clinical Objectives 
To evaluate the effect of EIDD-2801 on improvement of clinical symptoms and signs of COVID-19.  
Secondary Clinical Endpoints:  
1. Peak stage on the World Health Organization (WHO) Ordinal Scale for Clinical Improvement 
(Appendix 1) OR clinical requirement for addition of other antivirals including but not limited to:
-
Pegylated interferon alpha
-
Inhaled interferon beta1
-
Ribavirin (any formulation)
-
Any interleukin (IL)-6 inhibitor
2. Number of days of supplemental oxygen  
3. Number of days of mechanical ventilation
4.
Number of days in the Intensive Care Unit (ICU)
5.
Death
1.5.
Exploratory Virologic Objective  
To evaluate the efficacy of EIDD-2801 to clear SARS-CoV-2 RNA and infectious virus .
Exploratory Virologic Endpoints:
1. Achievement of undetectable (below the LOD of the assay) viral RNA titers by Day 5 in NP 
swabs
-
by infectivity assay
2. Time to clearance of infectious virus in NP swabs 
- by infectivity assay
3. Clearance of infectious virus by Day 3 and Day 5 in NP swabs 
- by infectivity assay
4. The number of acquired single-nucleotide polymorphisms in SARS-CoV-2 genomes by Day 5 or 
Day 11 in NP swabs 
- by viral sequencing 


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1.6.
Exploratory Clinical Objective
To ascertain the role of EIDD-2801 in improvement of clinical symptoms and signs of EIDD-2801. 
Exploratory Clinical Endpoints:
1. Days of hospitalization
2. Time until on room air without requirement for supplemental oxygen 
3. Time to resolution of COVID-19 symptoms defined as: 
-
Fevers OR 
-
At least one of the following symptoms: cough, shortness of breath, respiratory rate 20,
radiographic evidence of pneumonia OR
-
other clinical symptoms or signs that are not otherwise explained by comorbidities or co-
diagnoses 
4. Number of days until a 2-point decrease in stage according to the WHO Ordinal Scale for Clinical 
Improvement (Appendix 1).
5. Radiologic improvement by grading chest diagnostics (when radiography is available) 
6. Change in IL-6 levels by Day 5 
1.7.
Pharmacokinetic Objectives
The pharmacokinetic (PK) objectives will be assessed on dosing Days 3 and 4 in participants enrolled at 
clinical sites able to conduct the collections. These sites include but are not limited to 
 
 
Secondary:
To evaluate EIDD-1931 PK in plasma in a subset of participants.   
Exploratory:
To characterize the PK of EIDD-2061 (NHC-TP) in peripheral blood mononuclear cells (PBMC) in a 
subset of participants. 
Pharmacokinetic Endpoints: 
Secondary (plasma analysis):
1. Maximum EIDD-1931 concentration (Cmax) 
2. 1.5-hour EIDD-1931 concentration (C1.5) 
3. 3-hour EIDD-1931 concentration (C3) 
4. Area under the concentration: time curve of EIDD-1931 (AUC) 
5. Elimination  half-life (t1/2) EIDD-1931 


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Exploratory (PBMC analysis):
1. Maximum EIDD-2061 concentration (Cmax)
2. EIDD-2061 time of maximal concentration (tmax)
3. Elimination half-life of EIDD-2061 (t1/2)
4. Area under the concentration: time curve of EIDD-2061 (AUC0-12)
5. Parent: metabolite (EIDD-1931:EIDD-2061) concentration ratio at each time point, in which both 
plasma and PBMC are processed for PK analysis


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2. BACKGROUND AND SCIENTIFIC RATIONALE
2.1.
Abstract
SARS-CoV-2 has infected over 5 million people worldwide since December 2019, with >300,000 
fatalities reported as of the date of this protocol (Johns Hopkins University Coronavirus Resource Center: 
https://coronavirus.jhu.edu/map.html). In this unprecedented global crisis, the medical community is 
lacking adequate tools to combat the severe outcomes of COVID-19: respiratory collapse, multi-system 
organ failure, and death. There is a desperate need for safe and effective antiviral therapies to mitigate the 
natural course of COVID-19, especially in those who are at high risk for severe disease. Currently, there 
are no approved therapeutics specific for COVID-19.  
EIDD-2801 (also known as MK-4482) is an orally bioavailable prodrug of EIDD-1931, a small molecule 
ribonucleoside analogue that was developed for respiratory viruses. EIDD-2801 has demonstrated potent 
in vitro antiviral activity against a broad array of coronaviruses including SARS-CoV-2, Severe Acute 
Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome-coronavirus 
(MERS-CoV), and it has shown in vivo activity in animal models of SARS-CoV and MERS-CoV 
(Agostini et al, 2019; Sheahan et al, 2020). EIDD-2801 is currently in Phase 1 clinical trials.  
We propose a Phase 2a randomized, placebo-controlled, double-blinded clinical trial of EIDD-2801 in 
hospitalized men and women (aged 18+ years) with PCR-confirmed SARS-CoV-2 infection who also 
have evidence of symptomatic COVID-19. We plan to enroll hospitalized patients who present within 7 
days of symptom onset for a 5-day course of twice daily (BID) dosing of EIDD-2801 or placebo. We will 
follow participants for every hospitalized day and after they are discharged, for 28 days after the first 
dose. The primary endpoint will be the achievement of undetectable (below the LOD of the assay) SARS-
CoV-2 RNA in NP swabs by Day 5 (end-of-treatment). Secondary clinical endpoints will include the time 
until virologic clearance (by RNA testing), rate of decline in viral RNA, peak stage on the WHO Ordinal 
Scale for Clinical Improvement, requirement for additional antivirals, duration of ICU stay, duration of 
mechanical ventilation, or death. Safety outcomes will include AEs, SAEs, physical examination with 
vital signs, ECGs, and laboratory measurements (including CBC, CMP, and urinalysis). We will measure 
the PK of EIDD-1931, the primary circulating form of EIDD-2801, in plasma. We will also collect 
PBMCs for measurement of EIDD-2061 (NHC-TP), as an exploratory objective.  PK sampling will be 
assessed on  dosing days 3 and 4 in participants enrolled at clinical sites able  to conduct the collections. 
These sites include but are not limited to 
 
. We anticipate enrollment of 80 participants in this trial at the following dose levels: EIDD-2801 
200 mg, EIDD-2801 400 mg, EIDD-2801 800 mg, and placebo.  In the primary analysis, we will compare 
the proportion of participants in each EIDD-2801 and placebo groups who achieve virological clearance.   


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2.2.
Background 
COVID-19 is a disease caused by the SARS-CoV-2 that was first detected in China’s Hubei province in 
December 2019. It is a systemic disease with influenza-like symptoms; a subset of patients with severe 
disease can experience respiratory decline, acute respiratory distress syndrome (ARDS), multi-system 
organ failure, and death. SARS-CoV-2 has infected over 5 million people worldwide since its emergence, 
with >300,000 fatalities reported as of the date of this study protocol (Johns Hopkins University 
Coronavirus Resource Center: https://coronavirus.jhu.edu/map.html). 
There have been suggestions that the worst consequences of SARS-CoV-2 are seen in people with the 
highest viral burden (Wolfel et al. 2020). Although numerous agents are currently being tested in clinical 
trials, the majority of these are re-purposed drugs that are not specifically developed for SARS-CoV-2 or 
other coronaviruses. There is an urgent need for direct-acting SARS-CoV-2 antiviral agents that can be 
used in patients to mitigate the worst complications of the infection. 
SARS-CoV-2 is an enveloped, positive-sense, single-strand RNA beta-coronavirus that is related to 
SARS-CoV and distantly to MERS-CoV. SARS-CoV-2 has a genome of ~30kb which comprises 4 
structural proteins and 16 non-structural proteins. Among the non-structural proteins is nsp12, the RNA-
dependent RNA polymerase (RdRp) that is required to replicate the viral genome. Many successful 
antivirals for other viruses target the RdRp: nucleos(t)ide inhibitors for Human Immunodeficiency Virus 
(HIV)-1 and hepatitis B, NS5B inhibitors for hepatitis C.  However, many nucleoside analogues fail to 
inhibit coronaviruses because of the unique coronavirus 3'-5' exoribonuclease (nsp14) that confers 
proofreading activity to the CoV RdRp. Only 2 nucleoside analogues to date have been shown to 
overcome the coronavirus proofreading activity and inhibit a broad range of coronaviruses: remdesivir 
and EIDD-2801/EIDD-1931 (Agostini et al, 2018; Agostini et al, 2019). 
EIDD-2801 (also known as MK-4482) is an oral prodrug of EIDD-1931 ([N4-HYDROXY-މ-O-(2-
METHYLPROPANOYL)CYTIDINE, NHC], a novel small molecule ribonucleoside analogue with 
potent in vitro inhibition of a broad array of coronaviruses including SARS-CoV-2, SARS-CoV, and 
MERS-CoV (Sheahan et al, 2020). EIDD-2801 is converted into its circulating intermediate form, EIDD-
1931, by non-specific esterases in plasma—this is the primary form found in systemic circulation. EIDD-
1931 is then taken up by target mononuclear cells and enzymatically converted by host kinases to the 
metabolites 5’-monophosphate EIDD-1931 and 5’-triphosphate EIDD-1931 (also called EIDD-2061, or 
NHC-TP). The 5’-triphosphate form is a competitive antagonist of the RNA-dependent RNA polymerase 
(RdRp), while the 5’-monophosphate form promotes lethal mutagenesis in the nascent viral RNA strand,
thus impacting downstream viral processes. EIDD-1931 has a median effective concentration (EC50) of 
0.3 micromolar against SARS-CoV-2 in vitro, demonstrating a 1000-fold reduction in SARS-CoV-2 viral 
titers, as well as reduced lung hemorrhage and damage in a murine model of SARS-CoV. 


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Pharmacologic aspects of EIDD-1931 and its metabolites have been evaluated in in vitro cell culture 
systems, as well as pre-clinical animal models. Anabolic PK assessments were characterized in cultured 
human bronchial tracheal epithelial cells.  Following ex vivo incubation of epithelial cells with 20 μM
EIDD-1931, there was rapid conversion to the EIDD-1931 metabolite (EIDD-Triphosphate, EIDD-TP) 
within the first 60 minutes.  Plateau concentrations of EIDD-TP (4 nmol/106 cells) were achieved within 4 
hours and remained stable for 24 hours.  Removal of drug led to persistence of the metabolite over a 24-
hour period.  The estimated intracellular half-life (t1/2) of EIDD-TP was 4 hours.  Comparable kinetics 
were observed in mouse lung tissue post-administration of an oral 500 mg/kg dose.   
The orally bioavailable isopropylester compound, EIDD-2801, has been evaluated in an ongoing, Phase 1,
randomized, double-blind, placebo-controlled single-ascending and multiple-ascending dose first in-
human study to assess its safety, tolerability, and PK.  A total of 130 healthy participants (109 males and 
21 females) received at least 1 dose of EIDD-2801 or placebo in the Phase 1 trial EIDD-2801-1001. 
Preliminary, unblinded safety data are available for all subjects. Review of these safety data indicates that 
single oral doses of up to 1600 mg EIDD-2801 or placebo and multiple oral doses of up to 800 mg EIDD-
2801 or placebo Q12H for 5.5 days have been generally well tolerated in healthy participants.  Further 
details are provided in Section 2.3.1.
The prodrug (EIDD-2801) was generally not detectable in plasma following single (50 to 1600 mg) or 
multiple doses (50 to 800 mg BID for 5.5 days) of MK-4482.  Plasma concentrations of the nucleoside 
metabolite (EIDD-1931) were detectable.  Tmax occurred approximately 1 hour post dose.  Plasma EIDD-
1931 concentrations generally declined in a monophasic manner, with a t1/2 of approximately 1 hour.  A
biphasic profile with a later, slower elimination phase (t1/2 ranging from 1.47 to 19.2 hours) was observed
in some participants (following single doses of 1200 mg and 1600 mg and following multiple doses of 
600 mg and 800 mg).  Cmax and AUC increased in an approximately dose-proportional manner across the 
range of doses tested.  No accumulation occurred following multiple dosing (Q12H for 5.5 days), and 
administration in the fed state did not meaningfully impact plasma exposure of EIDD-1931. There were 
no significant detectable concentrations of EIDD-2801; initial PK parameters were identified for EIDD-
1931 concentrations in plasma.  Following multiple doses of 100 mg BID EIDD-2801 orally in the fasted 
state, median tmax was 1.25 hours post-dose (range 1-2 hours), and concentrations declined 
monophasically and were quantifiable until the 6 to 9-hour time points. The apparent terminal half-life 
(t1/2) was 0.918 and 0.969 hours on Days 1 and 6, respectively. AUCtau was 853 ng*h/mL (%CV 19.9), 
and Cmax was 395 ng/mL (%CV 18.5). The increase in exposure between the 50 mg and 100 mg doses 
was slightly supraproportional with the 2-fold increase in dose resulting in a 2.23-fold increase in AUCtau
and 2.31-fold increase in Cmax. (EIDD-2801 Investigator’s Brochure, V3.0, 2020). 
2.3.
Known Potential Risks
2.3.1.
Clinical Findings
EIDD-2801 has been studied in a single and multiple dose escalation study in humans that includes a food 
effect cohort. All subjects have completed participation in the study and preliminary data are available. 
A total of 130 healthy volunteers were enrolled in this study. Sixty-four participants received a single 
dose between 50 and 1600 mg EIDD-2801 or placebo; 56 participants received multiple doses between 
50 and 800 mg EIDD-2801 or placebo BID for 5.5 days; and 10 participants received a single dose of 


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200 mg EIDD-2801 in the fed state followed by a single dose of 200 mg EIDD-2801 in the fasted state 
after a washout period of 14 days, or vice versa.  
Among participants who received single doses of EIDD-1801 or placebo, a greater proportion of 
participants reported AEs following administration of placebo (43.8%) than following administration of 
EIDD 2801 (35.4%). One moderate AE (headache) was reported by 1 participant following administration 
of EIDD-2801 at the 400-mg dose level, and 2 moderate AEs (nausea and headache) were reported by 1 
participant following administration of placebo. No severe AEs were reported. The most frequently 
reported AE was headache, which was reported by 18.8% of participants who were administered placebo 
and 12.5% of participants who were administered EIDD-2801.  
Among participants who received multiple ascending doses of EIDD-2801 or placebo BID over 5.5 days, 
a greater proportion reported AEs following administration of placebo (50.0%) than following 
administration of EIDD-2801 (42.9%). With the exception of 1 participant in the 200 mg BID group who 
reported moderate AEs of sore throat, aching limbs, and flu-like symptoms, all other AEs were mild in 
severity. The most frequently reported AE was diarrhea, which was reported by 7.1% of participants who 
were administered EIDD-2801 and 7.1% of participants who were administered placebo. One participant 
had an AE of mild, truncal, maculopapular, pruritic rash following multiple doses of 800-mg EIDD 2801, 
which was considered by the investigator to be related to the study drug; this AE resulted in early 
discontinuation of the study drug dosing on Day 3. The participant was administered a topical steroid and 
anti-histamines, and the AE resolved after 18 days.  
Among participants in the food-effect evaluation, 3 participants reported 1 AE each, all of which were 
mild in severity.  
There were no serious AEs reported in this study and there were no trends of increased frequency or 
severity of AEs with higher doses of EIDD-2801.  
There were no clinically significant findings in clinical laboratory, vital signs, or ECG data.  
 
(Section 2.3.2.2).  However, no 
clinically significant changes in hematological parameters were seen in the Phase 1 study.  
2.3.2.
Nonclinical Findings
 
 
 
2.3.2.1.
Effects on the Gastrointestinal Tract
 


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2.3.2.2.
 
 
 
 
 
 
 
 


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2
3.
E
r
 
 
 
 
 
 
 
 
 
 
 
 
 
 
      


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2.3.2.4.
 
 
 
 
 
 
2.3.2.5.
2.3.2.5.1.
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2.3.2.5.2.
 
 
 
2.3.2.5.3.
 
 
 
 
 
 
 
 
2.3.3.
 
 
 
 


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2.4.
Known Potential Benefits
EIDD-2801 has been administered to COVID-19 patients in ongoing studies and the safety and 
tolerability of single and multiple ascending doses has been tested in healthy adult volunteers (See 
Section 2.3.1). 
After oral delivery, EIDD-2801 is rapidly hydrolyzed by circulating esterases to produce high circulating 
(plasma) levels of EIDD-1931.  In cell culture systems, EIDD-1931 has been shown to inhibit replication 
of multiple viral pathogens from multiple RNA virus families including pathogenic CoV (e.g., SARS-
CoV-2, severe acute respiratory syndrome (SARS-CoV), and Middle East Respiratory Syndrome 
(MERS)), influenza viruses (seasonal, pandemic, and avian subtypes), respiratory syncytial virus (RSV), 
alphaviruses (e.g., Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus 
(VEEV), and Chickungunya virus (CHKV)), Filoviruses (e.g., Ebola virus (EBOV), and Zika virus 
(ZIKV)). In addition, EIDD-2801 is active against orthopox viruses probably because orthopox viruses 
encode their own unique RNA polymerase. Antiviral activity has been verified in animal models of CoV 
(MERS- and SARS-CoV), influenza, RSV, VEEV, CHKV, and EBOV. The primary mechanism of action 
of EIDD-2801 is inhibition of viral RNA replication by incorporation of EIDD-1931 monophosphate 
metabolite into the viral RNA genome resulting in induction of viral error catastrophe.  
2.4.1.
Potential Benefits of Treatment 
EIDD-2801 has demonstrated activity against SARS-CoV-2 in vitro, and SARS-CoV as well as MERS-
CoV in vitro and in vivo. EIDD-2801 has shown efficacy against CoV in animal models.  In mice, EIDD-
2801 was active in both a prophylactic and therapeutic setting (Painter et al, 2019). When EIDD-2801 was 
administered up to 24 hours after infection with SARS-CoV or up to 12 hours after infection with MERS-
CoV, a reduction in viral lung titers, protection from both lung hemorrhage and weight loss, and 
improvements in pulmonary function were seen, compared to vehicle-treated (control) animals.
Nonclinical findings suggest that it will be active against SARS-CoV-2.  More information regarding 
nonclinical activity of EIDD-2801 can be found in the Investigators’ Brochure. 


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2.4.2.
Potential Benefits of Clinical Monitoring and Virologic Testing
Participants enrolled in the study will undergo close clinical and laboratory monitoring that could 
facilitate improved management of COVID-19 with associated benefit to the individual, their family, and 
the community at large.


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3. PATIENT POPULATION
Adults aged 18 years or older who are hospitalized with a new diagnosis of COVID-19 with a duration of 
symptoms 7 days. Patients requiring admission to an intensive care unit for mechanical ventilation are 
not eligible. Persons with Low English Proficiency (LEP) and who are non-English Speakers may join. 
3.1.
Inclusion Criteria for Enrollment
Participants who meet all the following criteria will be eligible for study participation:
1. Has COVID-19 disease, defined by having one or more of the following new symptoms and signs 
(within 7 days):
-
Fevers OR 
-
At least one of the following: cough, sore throat, shortness of breath, respiratory rate 20,
radiographic evidence of pneumonia OR
-
Anosmia OR
-
other clinical symptoms or signs of COVID-19 that are not otherwise explained by 
comorbidities or co-diagnoses
2. PCR+ test for SARS-CoV-2 within 6 days prior to randomization.
3. Has new signs or symptoms of COVID-19 that began 7 days of anticipated first dose of study 
drug.
4. Persons 18 years old.
5. Is an inpatient at the time of first dose.
6. Is willing and able to comply with all study procedures including providing informed consent
firsthand or via a legally authorized representative, collection of virology samples, and any safety 
tests that are not included as part of standard of care (SOC).
7. Is willing and able to take oral medications and is anticipated to be able to take the full course of 5 
days of study drug.
Pregnancy and Contraception:
 
Therefore, treatment with EIDD-2801 is contraindicated in women who 
are pregnant or nursing and in the male partners of women who are pregnant. Extreme care must be 
taken to avoid pregnancy during the study and for 4 days after completion of EIDD-2801 dosing in
female participants and for 4 days after completion of EIDD-2801 dosing in female partners of male 
participants.
8. A female participant is eligible to participate if she is not pregnant or breastfeeding and at least 
one of the following conditions applies: 
x
Is not a woman of childbearing potential (WOCBP)
OR
x
Is a WOCBP and using a contraceptive method that is highly effective (a low user 
dependency method OR a user-dependent method in combination with a barrier method), 


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or be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long-term and persistent basis), as described in Appendix 2 during the 
intervention period and for at least 4 days after the last dose of study intervention. The 
investigator should evaluate the potential for contraceptive method failure (ie, 
noncompliance, recently initiated) in relationship to the first dose of study intervention.
x
A WOCBP must have a negative highly sensitive pregnancy test (serum test is required) 
within 24 hours before the first dose of study intervention. 
x
Additional requirements for pregnancy testing during and after study intervention are 
located in Section 4.4. 
x
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy. 
x
Contraceptive use by women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
x
Given the elevated risk of venous thrombotic events in patients hospitalized with 
COVID-19 (Benson et al 2020; Spratt et al 2020), estrogen-containing contraceptives must 
not be started to fulfill the contraceptive requirement of this study at any time during 
participant’s hospitalization. If contraceptives are interrupted as standard of care 
management of COVID-19 patients and resumed at a later time point, such as at hospital 
discharge, then abstinence must be practiced for the defined period of back-up 
contraception per the contraceptive product labeling. After this period, contraceptive use 
must adhere to Appendix 2.
9. Male participants are eligible to participate if they agree to the following during the intervention 
period and for at least 4 days after the last dose of study intervention: 
x
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent 
on a long term and persistent basis) and agree to remain abstinent 
OR
x
Must agree to use contraception unless confirmed to be azoospermic (vasectomized or 
secondary to medical cause [Appendix 2]) as detailed below:
Agree to use a male condom plus partner use of an additional contraceptive method when having 
penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a 
pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse 
or use a male condom during each episode of penile-vaginal penetration.
x
Contraceptive use by men should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
3.2.
Exclusion Criteria for Enrollment
Participants who meet any of the following criteria will not be eligible for participation
1. Is anticipated to require ICU admission for mechanical ventilation within 24 hours of enrollment. 
2. Requires more than 6 liters/minute of oxygen to maintain O2 saturation above 95%. 
3. Is not expected to survive longer than 24 hours. 


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4. Has a platelet count less than 100,000/μL, hemoglobin <9 g/dL, or has a disorder of the 
hematologic system including anemic disorder or other blood dyscrasia, cancer of the hematologic 
system, history of bone marrow transplant, or other significant hematologic disease.
5. Women who are pregnant or breastfeeding.
6. Is experiencing DAIDS AE grading scale grade 4 baseline medical conditions or laboratory 
abnormalities.
7. Has received a vaccine for COVID-19 prior to enrollment, or plans to receive a vaccine for 
COVID-19 before the end-of-study visit.
8. Has received an experimental antiviral treatment for COVID-19 prior to enrollment.
9. Has received convalescent plasma or other monoclonal antibodies prior to enrollment.
10. Is participating in another clinical study that involves pharmacologic intervention or has 
participated in another study within 30 days of 5 half-lives of the investigational agent 
(observational study participation is permitted).
11. In the opinion of the investigator, has end-organ disease as a result of relevant comorbidities: 
chronic kidney disease (reduced glomerular filtration rate [GFR] <30 mL/min by the Modification 
of Diet in Renal Disease (MDRD) study equation prior to COVID-19 symptom onset),
decompensated chronic liver disease or cirrhosis, decompensated congestive heart failure, active 
peripheral vascular disease including active diabetic ulcers, chronic pulmonary disease prior to 
COVID-19 symptom onset requiring bilevel positive airway pressure (BiPAP) or >4 L/min
supplemental oxygen at baseline; if using 4 L/min supplemental oxygen at baseline, consultation 
with and approval of the sponsor is required prior to enrollment. 
12. Has a diagnosis of cancer that is not in remission.  Noninvasive cancers, such as basal and 
squamous cell carcinoma or history of in situ tumors are allowed at the discretion of the 
investigator after discussion with the sponsor. 
13. Has received an organ transplantation.
14. Has received a bone marrow transplantation.
15. Has been on immunosuppressive medications within 1 month prior to enrollment.
16. Has any condition that would, in the opinion of the investigator, put the participant at increased 
risk for participation in a clinical trial.
17. Has known active hepatitis C (HCV RNA positive), active hepatitis B (hepatitis B surface antigen 
positive), or HIV (ELISA and confirmatory Western blotting). New screening tests not required. 
18. Is currently taking nucleos(t)ide analogues for HIV or hepatitis B, or for their prevention, within 
30 days of study enrollment.
19. Is currently taking systemic corticosteroids other than replacement doses or for treatment of 
COVID-19.
20. Has a body mass index (BMI) >50 kg/m2.
21. Is anticipated to require surgery within 48 hours after hospital admission.


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22. Is anticipated to have an NPO (nothing per mouth) order placed within 48 hours after hospital 
admission that is expected to last for 24 hours.


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4. INVESTIGATIONAL PLAN
4.1.
Definitions
I.
Enrolled: From time consented to initiation of study drug until designated as off study 
either through discontinuation or completion of the study.
II.
Randomized: when a patient identification (ID) number is assigned through randomization.
III.
Screen Failures: signed informed consent, but then determined to be ineligible or 
withdraws before initiation of study drug.
IV.
Discontinued: randomized, but then withdrawn by investigator or withdraws consent.
V.
Completed: Participants are considered completed when they are followed through to Day
28 or died before that. 
4.2.
Randomization and Blinding
This study will be conducted in up to 4 parts.  During Part 1, participants will be randomized in a 1:1:1 
ratio to EIDD-2801 200 mg BID, EIDD-2801 400 mg BID, or placebo BID; during Part 2, approximately 
21 participants will be randomized in a 2:1 ratio to EIDD-2801 400 mg BID:placebo BID; during Part 3, 
approximately 21 participants will be randomized in a 2:1 ratio to EIDD-2801 800 mg BID:placebo BID.
An optional Part 4 may be added during which approximately 21 participants will be randomized in a 2:1
ratio to EIDD-2801 BID:placebo BID and the dose of EIDD-2801 may be the same or lower than doses 
studied in previous Part(s), but not to exceed 800 mg BID.
The study parts will be conducted as follows:  Part 1 of the study may be terminated upon approval and 
implementation of Protocol Amendment 3, and Part 2 will be initiated immediately thereafter.  Part 3 will 
be initiated once Part 2 has been fully enrolled.  If initiated, Part 4 may begin enrolling participants as
soon as Part 3 has been fully enrolled.  Study Parts 2 and 3 may be terminated prematurely based on 
emerging data from this and other ongoing studies of EIDD-2801.
On Day 1, participants will be assigned a unique ID number (randomization number). The randomization 
number encodes the participant’s assignment to one of the groups of the study, according to a
randomization schedule generated prior to the start of each individual study part. Each participant will be 
dispensed blinded study drug, labeled with his/her unique randomization number, throughout the study.
In case of an emergency, the investigator has the sole responsibility for determining if unblinding of a 
participants’ study drug assignment is warranted. Participant safety must always be the first consideration 
in making such a determination. If the investigator decides that unblinding is warranted, the investigator 
should make every effort to contact the sponsor prior to unblinding a participant’s study drug assignment 
unless this could delay emergency treatment of the participant. If a participant’s study drug assignment is 
unblinded, the sponsor must be notified within 24 hours after breaking the blind. The date and reason that 
the blind was broken must be recorded in the source documentation and case report form, as applicable. If 
the investigator decides that unblinding is warranted, unblinding of a participant’s study drug assignment 
will be coordinated by the unblinded pharmacist for the study. 


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4.3.
Intervention
4.3.1.
Screening
Adult patients who are newly hospitalized with PCR-confirmed SARS-CoV-2 and evidence of 
symptomatic COVID-19 will be invited to participate in the study. Those who express interest will 
undergo the informed consent process and be given the chance to ask any questions before agreeing to 
participate. Those who consent to participate will undergo screening for study entry; the time between 
screening and study entry should be as short as possible (ideally the same day, but no longer than 48 
hours). Screening assessments will include demographics, medical history, concomitant medications, 
review of inclusion and exclusion criteria, height, weight, BMI, physical examination including vital 
signs, clinical chemistry labs (CMP), hematology (CBC with differential), high sensitivity serum beta-
human chorionic gonadotropin (HCG) (to rule out pregnancy) as applicable, urinalysis, electrocardiogram
(ECG), and pulse oximetry. It is expected that measurements/values will have been obtained as SOC, and 
medical chart extraction will be performed. Missing values will be obtained as part of study procedures. 
Any chest radiography results from hospital admission will be recorded. 
4.3.2.
Administration of Study Drugs
Upon completion of baseline assessments (including virologic assessments below), participants will then 
be administered the first dose of study drug (EIDD-2801 or placebo). Each participant will begin study 
treatment dosing with the first dose on the morning of Day 1, if possible. If the first dose is given later in 
the day, the second dose may be given at least 4 hours later on Day 1. Study drug administration will 
continue BID for a total of 5 days (10 doses). If the first dose on Day 1 is given in the late evening, the 
second dose may be taken on the morning of Day 2, in which case the final dose will be taken on the 
morning of Day 6.  
In the event of missed doses, if the total number of missed doses is 4 or fewer, the number of days of 
study drug can be extended by no more than 1 day (through Day 6) with the equivalent of missed doses 
up to 2 doses. If the participant misses more than 4 consecutive doses, or more than 5 total doses, then the 
participant will be discontinued from any further study drug administration and followed for safety for the 
remainder of the study. Missed doses and times of administration will be recorded. 
If a participant cannot ingest capsules orally during the study period, capsules will be opened, and the 
powder will be mixed with water and administered by mouth or through a nasogastric, percutaneous 
endoscopic gastrostomy (PEG) or orogastric tube.
4.3.3.
Virologic Assessments
Upon enrollment, participants will have 2 NP swabs performed, one in each nostril (R or L to be 
documented), accessing the posterior nasopharynx. The NP swabs will be collected and stored separately 
for laboratory analysis. On Days 3, 5, 8, 11, 15 (inpatients only), 19 (inpatients only), and 28, participants 
will also have 2 NP swabs performed in the same way, collected and stored identically and individually.
One swab will be sent to an infectivity lab for analysis. The other swab will be sent to 
 for PCR 
sequencing.  Detailed instructions for preparation and shipment of samples will be provided in a separate 
document. 


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In the setting of bronchoalveolar fluid lavage with sampling, or in participants who require mechanical 
ventilation who have endotracheal tube fluid sampling, we will collect a portion to perform viral RNA 
testing and the infectivity assay on the sample. If available from SOC procedures, a sample of sputum will 
also be collected if the participant has a productive cough and used to perform viral RNA testing and 
infectivity assays.  In addition, a portion of material from NP swabs will be archived and frozen for viral 
sequencing.  
4.3.4.
Clinical Assessments
On each day that virology samples are obtained, participants will be assessed for clinical endpoints and 
interim AEs (and SAEs). Chart review will occur on structured days to perform safety assessments and 
record concomitant medications (including antivirals). CMP, CBC with differential, and urinalysis will be 
recorded at regular intervals during the study as indicated in the Schedule of Events (see Section 7.1).
Any results that are not available will be obtained on the applicable chart extraction day.
Participants who are discharged from the hospital during study participation will return to the clinic for 
study visits through the Day 28 visit. Clinic visits will occur on Days 3, 5, 8, 11, and 28.  On Day 15 
(±1 day), a member of the study staff will contact the participant by telephone to query them about 
symptoms, study drug adherence, and concomitant medications. Outpatients will be seen in one of several 
locations, including but not limited to COVID-19 ambulatory pods, COVID-19 ambulatory clinics and 
clinical research units, and home visits. In all cases, visits will conform to infection control practices that 
are established by the institution. If the participant is discharged to a secondary care facility, study site
staff will take measures to meet institutional regulatory requirements of the primary site as well as the 
receiving site to continue collecting study-related samples where allowed. 
During in-clinic study visits, partial pressure of oxygen (PO2) will be measured by oximetry, and oral 
temperature will be documented. Other vital signs will be assessed, and a targeted physical examination 
will be conducted as needed.  AEs and concomitant medications will be collected that have occurred since 
the last visit/report. Safety lab assessment (CBC with differential, CMP, and urinalysis) will be 
conducted, and for women of childbearing potential, a high sensitivity serum pregnancy test will be 
performed at the end-of-study (EOS) visit or at early discontinuation. Results of a single post-dose ECG 
should be recorded.  If the participant is discharged from the hospital before a post-dose ECG is recorded, 
and recording of an outpatient ECG is not feasible, then results of the last recorded ECG before hospital 
discharged will be entered into the CRF. The results of any chest diagnostics done as part of SOC will be 
recorded. Any SAEs will be followed for 30 days after the end of study participation as detailed in 
Section 8.10.3.
Participants who are discharged from the hospital before the EOS visit will continue to take study drug at 
home for the full 5 day course, and drug accountability will be conducted at the Day 5 and/or Day 8
interim study visits, where allowed by the study institution.  Participants will be instructed on how to 
report worsening of disease, including development of any additional symptoms of pneumonia or other 
concerning illness that may require interim assessment including clinic or urgent visits. 
4.4.
Pregnancy Testing
Pregnancy testing: 


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•
Pregnancy testing requirements for study inclusion are described in Section 3.1.
•
High sensitivity pregnancy testing should be conducted at screening (a serum test is required) 
within 24 hours of the first dose of study drug and on Day 28 approximately 23 days after the
last dose of study intervention. 
•
Additional serum or urine pregnancy tests may be performed, as determined necessary by the 
investigator or required by local regulation, to establish the absence of pregnancy at any time 
during the subject's participation in the study.
4.5.
Serology 
Serology testing will be performed on plasma for IL-6 levels on Day 1 (pre-dose), Day 5, and Day 19.
Samples will be archived for further cytokine testing in the future.  
4.6.
Rationale for Medication Dosing 
 
 
 Although 3 doses were effective in influenza 
models, the prolonged viral shedding that has been described in COVID-19 indicates that a longer dosing 
period may be beneficial. Also, allowing for differences between animal models and human disease, a 
margin of exposure at the top end of the range is desirable. Doses up to 800 mg twice daily are considered 
important to study in order to allow for sufficient exposure based on the use of data extrapolated from 
other species. Exploring a range of doses will allow for the selection of the best dose(s) to carry forward 
into subsequent studies.  
Review of preliminary, unblinded data indicates that a treatment course of 5.5 days has been generally 
safe and well tolerated at multiple ascending doses (MAD) up to 800 mg, covering the doses planned for 
this efficacy/safety study.  Also, single ascending doses (SAD) up to 1600 mg were similarly well 
tolerated, and PK has been dose-proportional in all cohorts. Refer to the IB for full information regarding 
animal efficacy studies and scaling to humans. Definition of an Overdose for this Protocol 
For purposes of this protocol, an overdose is a single dose of more than 800 mg. 
4.7.
Concomitant Medications
Nucleos(t)ide analog drugs that are used for the treatment or prevention of HIV or hepatitis B virus are 
prohibited during the study, as are vaccines against COVID-19. 
Remdesivir will be permitted. Corticosteroids for the treatment of COVID-19 will be permitted.  
4.8.
Study Discontinuation 
If a participant is withdrawn from the study, the reason for withdrawal and the date the participant was 
removed will be documented in the case report form (CRF). A participant must be discontinued from the 
trial for any of the following reasons:


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x
The participant or legal representative (such as legal guardian) withdraws consent.
x
Intercurrent illness that prevents further administration of treatment. 
x
Severe or life-threatening EIDD-2801-related AE(s). 
x
If in the opinion of the Investigator, a change or temporary or permanent discontinuation of 
therapy would be in the best interest of the participant. 
x
Noncompliance with trial treatment or procedure requirements.
x
Participant is lost to follow-up. 
x
Participant becomes pregnant. 
If a randomized participant withdraws from the study and has not been administered a dose of study drug 
or placebo, they will be replaced. Additional participants may be randomized, if needed, to ensure that an 
adequate number of participants provide Day 5 efficacy data. 
Whenever possible, participants should continue to be monitored for safety through the remainder of the 
study.   
The investigator should make every effort to perform the assessments indicated for the End-of-Study visit 
(see the Schedule of Events; Section 7.1) for participants who discontinue early from the study.  


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5. PHARMACEUTICAL INFORMATION
5.1.
Agent Accountability
The study drug will be provided by the sponsor.
The study site will acknowledge receipt of study drug supplied by the sponsor by returning the 
appropriate documentation form to confirm the shipment condition and content. Any damaged shipments 
will be replaced.
An accurate drug disposition record will be kept, specifying all study drug received, dispensed, returned 
to the sponsor, and disposed of by the study site. This drug accountability record will be available for 
inspection at any time, and at the completion of the study, the original drug accountability record will be 
available for review by the sponsor upon request.
5.2.
Mode of Action
The mechanism of antiviral activity of EIDD-2801 is ‘lethal mutagenesis’, a concept that is predicated on 
increasing the viral mutation rate beyond a biologically tolerable threshold, resulting in impairment of 
viral fitness and leading to viral extinction.
The specifics of the mechanism are as follows: EIDD-2801 is rapidly taken up by cells and the 
ƍLVRSURS\OHVWHUFOHDYHGWo liberate EIDD-1931, which is in turn phosphorylated to EIDD-2061 by host 
NLQDVHV7KHƍWULSKRVSKDWHEIDD-2061, acts as a competitive, alternative substrate for virally-encoded 
RNA-dependent RNA polymerases, and EIDD-2061 is incorporated into nascent viral RNA. Owing to the 
ability of the N4hydroxycytosine base of EIDD-1931 to tautomerize, EIDD-2061 can pair with either 
guanosine or adenosine, and consequently can substitute for either cytidine triphosphate (CTP) or uridine 
triphosphate (UTP), respectively. This results in an accumulation of mutations, which increase with each 
cycle of viral replication. The process whereby the mutation rate is increased by exposure to a drug is 
referred to as viral decay acceleration and results in viral ablation.
Significant work has gone into validating this mechanism of action for EIDD-2801/1931, and it has been 
shown for MERS-CoV, VEEV, and influenza A virus (IAV) that viruses grown in the presence of EIDD-
1931 have significantly increased levels of transition mutations. Multi-log decreases in virus yields were 
observed after treatment with EIDD-1931. Additionally, it was demonstrated for VEEV that the 
infectivity of virions formed in the presence of EIDD-1931 decreases from approximately 20% to <0.2%, 
and that the infectious virions are significantly impaired in their replication ability. As a consequence of 
this mechanism of action, the generation of drug-resistant escape mutants is practically impossible. This
same effect was demonstrated for CoV and influenza virus. Furthermore, given the unique mechanism of 
action, EIDD-2801 is expected to be active against viruses resistant to other antiviral agents which have a 
different mechanism of action. The only data generated to date regarding the activity of EIDD-1931
against viruses resistant to other nucleoside analogs found that EIDD-1931 was active against CoV 
resistant to remdesivir in cell culture assays.
As an alternative or additional mechanism of action, it has been theorized that incorporation of 
EIDD-2061 into viral genomic RNA can change the thermodynamics of RNA secondary structure and 


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thus decrease the efficiency of the promoter regions involved in RNA genome replication. Further details 
regarding the mechanism of action of EIDD-2801 are provided in the IB.
5.3.
Description
EIDD-2801 is a white to off white solid.
EIDD 2801 (100- and 200-mg capsules) and matching placebo will be supplied as dry filled capsules for 
oral administration, along with the batch/lot numbers and Certificates of Analysis. Doses of EIDD-2801
or matching placebo will be administered as combinations of 100- and 200-mg capsules in such a way as 
to preserve the study blind and as appropriate for the dose level.
5.4.
Packaging 
The study drug will be labeled in accordance with regulatory requirements and will be stored according to 
the instructions on the label, in a location that is locked with restricted access.
5.5.
Storage
Study drug should be stored in a secure, locked, restricted access facility at controlled room temperature 
defined as 15°C to 25°C (59°F to 77°F). Excursions are permitted up to 30°C (86°F) for up to 24 hours. If 
excursions occur which are outside of this range, the pharmacy staff should contact the sponsor to 
determine the course of action. Additional stability data may be available which would allow continued 
use of the study drug, or study drug may need to be replaced.
5.6.
Route of Administration
EIDD-2801 is administered orally.
5.7.
Participant Care Implications
Participants who receive EIDD-2801 during this study will be monitored for AEs and other safety 
findings.  Virology samples will be collected and SOC for COVID-19 will be administered. Participation 
in this study will not alter clinical decisions with regards to hospital treatment, discharge, or outpatient 
management. 
Participants who are admitted and enrolled at one participating site who are then transferred to another 
participating site, will continue to remain on study and will continue to receive study drug or placebo as
initially assigned.
5.8.
Returns and Reconciliations
At completion of the study, study drug will either be disposed of at the study site according to the study 
site’s standard operating procedure or will be returned to the sponsor with the appropriate 
documentation. The site’s method of destroying sponsor-supplied study drug must be agreed to by the 
sponsor. The site must obtain written authorization from the sponsor before any sponsor-supplied study 
drug is destroyed, and study drug destruction must be documented on the appropriate form.


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5.9.
Pharmacokinetics
Pharmacokinetic analysis will be performed in a subset of study participants and will be conducted based 
on local laboratory capacity.  The PK secondary (plasma) and exploratory (PBMC) objectives will be 
limited to clinical sites that are able to participate, including but not limited to 
 
Blood samples will be collected for plasma isolation and PBMC preparation to characterize EIDD-
2801/EIDD-1931 and EIDD-2061 PK parameters.  Previous studies demonstrated an EIDD-1931 PK t1/2
of 0.969 hours in healthy human subjects (EIDD-2801 Investigator’s Brochure, V3.0, 2020).  The 
calculated t1/2 of the EIDD-2061 metabolite is 4 hours, based on ex vivo incubation studies.  Based on 
currently available PK data, additional pharmacologic analyses will be conducted in a subset of SARS-
CoV-2-infected individuals. 
Post-enrollment and initiation of therapy, and after an overnight fast (i.e., no food or liquid except for 
water after midnight), PK assessment will initiate on Day 3 for participants who are still inpatients.  For 
EIDD-2801/EIDD-1931 analysis, blood will be collected on Day 3 at pre-dose, as well as 0.5 hours,
1.5 hours, 3 hours, 6 hours, 8 hours, on Day 3 and 24 hours post-Day 3 dose on Day 4 where possible. If
a participant is scheduled to be discharged, then PK samples should be collected at all scheduled time 
points up to the time of discharge. In addition, if a participant is discharged prior to the 24-hour PK 
sample, a 12-hour PK sample on Day 3 should be collected, when possible.  
Blood sampling for PBMC isolation and EIDD-2061 measurements will occur at pre-dose, as well as 
0.5 hours, 1.5 hours, 3 hours, 6 hours, 8 hours, and 24 hours post-dose on Day 3 where possible, as 
described in the previous paragraph.  Time of dose will be recorded on eCRFs.
Sparse PBMC sampling will be conducted to estimate EIDD-2061 t1/2 and AUCtau.  Cmax and tmax will be 
estimated.  PK analyses in PBMC will be conducted as an exploratory objective to understand and 
characterize parent: metabolite (EIDD-1931:EIDD-2061) ratios at each time point, as well as persistence 
of EIDD-2061 after EIDD-1931 clearance from plasma.  
Samples may be collected within a ± 15 minute window (for timepoints up to 3 hours post dose), 
±30 minutes (for timepoints 6-8 hours post dose); and ± 1 hour (for timepoints 12-24 hours post dose).  
Full processing details for plasma and PBMC PK will be provided within the study specific manual. 
Sample Analysis
Plasma PK analysis will be performed at 
 
. PBMC analysis will be performed under the control of the 
 
 
The details of sample collection and analysis will be included in the Laboratory Manual 
and standard operating procedures (SOPs). Raw data will be archived at the bioanalytical site.


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6. STATISTICAL CONSIDERATIONS
6.1.
Sample Size and Power Considerations
We will test the hypothesis that EIDD-2801 will result in a larger proportion of NP swabs from recipients 
becoming undetectable (below the LOD of the assay) for SARS-CoV-2 RNA at Day 5 of EIDD-2801 
administration compared to placebo. Participants receiving the same dose across the study parts will be 
pooled together in the final analysis.  It is expected that 14 or more participants will receive EIDD-2801 
in the higher dose groups, and at least 14 participants will receive placebo across the study parts. The 
power calculations were based on an individual dose arm versus placebo comparison, using a Fisher’s 
exact test. Based on previous data (Wolfel, Nature, 2020), if we assume that 80% of the placebo arm and 
20% of an EIDD-2801 arm are detectable at Day 5, we will have 83% power to detect a difference with 
Į 
6.2.
Statistical Analysis
6.2.1.
Analysis Populations
Screened
All patients who consent to participate and who undergo screening will be included in the Screened 
population.  
Safety
All patients treated with at least one dose of study drug will be included in the Safety population. Safety 
patients are analyzed according to their actual treatment received.
Intent-to-treat Set
The Intent-to-treat set (ITT) will consist of all randomized patients. ITT patients are analyzed according to 
their randomized treatment.
Efficacy Analysis Set
The Efficacy Analysis Set (EAS) will consist of all participants treated with at least one dose of study 
drug and with at least 1 post baseline assessment of SARS-CoV-2 RNA in NP swabs by qPCR. Efficacy 
analysis set participants are analyzed according to their actual treatment received.
Per Protocol Set 
The Per-Protocol Set (PPS) will consist of all participants in the ITT population who do not have any 
important protocol deviations leading to exclusion from the PPS.
Protocol deviations are defined as any change, divergence, or departure from the study design or 
procedures defined in the study protocol. Important protocol deviations are a subset of protocol deviations 
and may significantly impact the correctness, accuracy, and/or reliability of the study data or that may 
significantly affect a subject’s rights, safety, or well-being.  


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Only those important protocol deviations considered to have a major effect on efficacy will lead to 
complete exclusion of the participants from the PPS. Details will be provided in a Statistical Analysis 
Plan (SAP).
Pharmacokinetic 
All participants treated with at least one dose of study drug with at least 1 reportable concentration of 
EIDD-will be included in the Pharmacokinetic (PK) population.
6.2.2.
Data Handling
Day 1 is defined as the day of first dose of study drug. Relative days after Day 1 are calculated as 
(assessment date – Day 1 date) + 1. Relative days prior to Day 1 are calculated as (assessment date – Day 
1 date). The day prior to Day 1 is Day -1.
All data will be analyzed using nominal study visits as defined in the Study Schedule and eCRF. No visit 
windows will be applied for summary and analysis. Unscheduled visits will be listed but not tabulated.
Participants who received the same dose (i.e., placebo) across study parts will be combined into the same 
dose group. Data from the active treatment arms may be combined for analysis, when appropriate in 
comparison with the pooled placebo group.  
6.2.3.
Handling of Dropouts, Missing Data, and Outliers
Participants who prematurely discontinue from the study without receiving a single dose of study drug or 
placebo will be replaced. Participants who receive at least a single dose of study drug who prematurely 
discontinue study drug should continue to undergo regularly scheduled visits, including an end of study 
visit at Day 28, to evaluate clinical assessments, AEs, and SAEs for the analysis of the primary efficacy 
endpoint, if there is no swab is available for analysis then the patient’s response will be imputed to have a 
detectable level of SARS-CoV-2 RNA by qPCR (non-response). Longitudinal analyses of secondary 
endpoints, such as the rate of decline of log10 viral RNA copies/mL for each method of sample collection, 
will use mixed effect models which are robust for missing data when this is missing completely at random 
(MCAR) or missing at random (MAR). Missing safety data will generally not be imputed. Details and 
exceptions will be provided in the SAP. No rules for outlier detection are planned.
6.2.4.
Analysis of Primary Endpoint
To address the primary endpoint, we will use a Fisher’s exact test to calculate the likelihood that a 
difference in detectable SARS-CoV-2 between a given dose of study drug (EIDD-2801 400 mg up to 800 
mg) versus placebo, occurs by chance. Because the current SARS-CoV-2 RNA test is only 70% sensitive, 
we will perform 2 NP swabs at baseline and 2 NP swabs on Day 5, each analyzed separately (4 total NP 
swab measurements). Thus, an undetectable result at a given time point will be determined when neither 
NP swab has detectable (below the LOD of the assay) viral RNA at that time point. To graphically present 
the results, we will show individual points and smoothed curves to fully account for individual negative 
tests that are contemporaneously observed with positive tests. 


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6.2.5.
Analysis of Secondary Endpoints
Secondary Virologic Endpoints:
1. Time to clearance of viral RNA in NP swabs
-
by qPCR 
2. The decline in viral RNA by Day 3, Day 5, Day 8, Day 11, Day 15, Day 19, and Day 28 after 
initiation of study drug in NP swabs
-
- by qPCR 
3. Rate of decline in viral RNA (change in log10 copies/mL per day) in NP swabs
-
- by qPCR 
The time to clearance of viral RNA will be analyzed using the Kaplan-Meier method. The event time of 
median, 25th, 75th percentiles and associated 95% confidence intervals will be provided by dose group. 
The cumulative probability of BLOQ and the associated 95% confidence interval for the scheduled visit 
will also be provided by dose group.
The decline in viral RNA over time will be analyzed using a mixed effect of repeated measure model 
(MMRM). The model estimated between-group differences and associated 95% confidence intervals will 
be provided by scheduled visits. The rate of decline for each dose group will be estimated using a mixed 
effect linear model. 
Additional details will be described in a SAP and finalized before database lock. 
Details for the analyses of exploratory virologic endpoints will be described in the SAP.
6.2.6.
Analysis of Adverse Event Data
Analysis of AE data will primarily be descriptive based on the DAIDS table for Grading the Severity of 
Adult and Pediatric Adverse Events, July 2017, version 2.1. Adverse events will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). An AE is considered treatment-emergent if it 
begins or worsens in severity after the first dose of randomized study drug. The number and percentage of 
participants with treatment-emergent AEs will be tabulated by system organ class (SOC) and preferred 
term. Additional AE summaries will be provided by severity, drug related AEs, AEs leading to study drug 
discontinuation, and serious AEs.
6.2.7.
Analysis of Other Safety and Clinical Data 
Other safety and clinical endpoints will be provided descriptively by dose group and scheduled time of 
assessment where appropriate.  Details will be provided in the SAP.


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6.2.8.
Analysis of Pharmacokinetic Data 
Plasma EIDD-1931 PK Endpoints:
1. Maximum EIDD-1931 concentration (Cmax)
2. 1.5-hour EIDD-1931 concentration (C1.5)
3. 3-hour EIDD-1931 concentration (C3)
4. Area under the concentration: time curve EIDD-1931 (AUC0-8)
5. Elimination half-life (t1/2) EIDD-1931
PBMC EIDD-2061 PK Endpoints:
1. Maximum EIDD-2061 concentration (Cmax)
2. EIDD-2061 time of maximal concentration (tmax)
3. Elimination half-life of EIDD-2061 (t1/2)
4. Area under the concentration: time curve EIDD-2061 (AUC0-12)
5. Parent: metabolite (Plasma EIDD-1931:PBMC EIDD-2061) concentration ratio at each time point
PK data will be summarized by dose group and scheduled time of assessment where appropriate. If data 
permit, assessment of dose proportionality will be performed and the relationship between the exposure 
parameters and virologic endpoints will be explored. Details will be described in the SAP.


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7. STUDY PROCEDURES
7.1.
Schedule of Events
Inpatient
Study Procedures
Screeninga
Day -2 to 1
Day 1
Day 3
Day 4
Day 5
Day 8
Day 11
Day 15
Day 19
Day 28 (EOS)
Early 
Discontin-
uation
Informed Consent
X
Demographic data
X
Inclusion/Exclusion Criteria
X
Randomization b
X
Medical History
X
Pregnancy testc
X
X
X
Serology (plasma)d
Xe
X
X
Height, weight, BMI
X
Study residency
Visit while hospitalized for MR 
review
X
X
X
X
X
X
X
X
X
X
Prior/Concomitant medication 
review
X
X
X
X
X
X
X
X
Study drug vs. placebo
EIDD-2801 or PBO 
administrationf
BID on 
Days 1-5
BID on 
Days 1-5
BID on 
Days 1-5
BID on 
Days 1-5
Virologic endpoints
NP swabsg
Xe
X e
X e
X
X
X
X
BAL and/or sputumh
X
X
X
X
X
X
X
Clinical endpoints
WHO Ordinal Scale 
(Appendix 1)i
Xi
X
X
X
X
X
X
X
X
Clinical assessmentsj
X
X
X
X
X
X
X
X
X
Safety and tolerability
AE/SAE reporting
X
X
X
X
X
X
X
X
X
Vital signs (temperature, blood 
pressure, pulse, respiratory rate)
X
X
X
X
X
X
X
X
X
X
Pulse oximetryk
X
X
X
X
X
X
X
X
X
X
Full physical examination
X
X
Targeted physical examination l
X
X
X
X
X
X
X
X
Laboratorym
X
X
X
X
X
X


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Inpatient
Study Procedures
Screeninga
Day -2 to 1
Day 1
Day 3
Day 4
Day 5
Day 8
Day 11
Day 15
Day 19
Day 28 (EOS)
Early 
Discontin-
uation
12-lead ECGn
X
1 posttreatment ECG to be performed, as feasible n
Chest radiographyo
X
X
X
X
X
X
X
X
X
Pharmacokinetics
Plasmap
X
X
PBMCsp
X
X
Abbreviations:  AE = adverse event; BAL = bronchoalveolar lavage; BID = twice daily; CBC = complete blood count; CMP = complete metabolic 
panel; ECG = electrocardiogram; EOS = end of study; h = hours; ICU = intensive care unit; IL-6 = interleukin 6; 
 
 MR = medical record; NP = nasopharyngeal; PBMC = peripheral blood mononuclear 
cell; PBO = placebo; PK = pharmacokinetic; QD = once daily; QOD = every other day; SARS-CoV-2 = severe acute respiratory syndrome-
coronavirus-2; SOE = schedule of events; WHO = World Health Organization. 
a.
Screening and Day 1 procedures will occur on the same day whenever possible as soon as SARS-CoV-2 testing is determined to be positive.
A window of up to 6 days is allowable if the participant has not had symptoms for more than 7 days prior to dosing.
b.
Randomization can happen at Screening or Day 1
c.
For women of child-bearing potential only, high sensitivity serum pregnancy tests are required at Screening within 24 hours of the first dose 
of study drug and on Day 28.  Additional serum or urine pregnancy tests may be performed, as determined necessary by the investigator or 
required by local regulation, to establish the absence of pregnancy at any time during the subject's participation in the study. 
d.
Serology testing will be performed on plasma for immune response on Day 1 (pre-dose), Day 5, and Day 19, and specimens will be archived 
for further cytokine testing in the future.
e.
The sample should be collected pre-dose.  
f.
EIDD-2801 and PBO are to be administered BID on Days 1-5. The first dose will be administered in the morning of Day 1, if possible. If the 
first dose is given later in the day, the second dose may be given at least 4 hours later on Day 1. If the first dose on Day 1 is given in the late 
evening, the second dose may be taken on the morning of Day 2, in which case the final dose will be taken on the morning of Day 6.  In the 
event of missed doses, if the total number of missed doses is 4 or fewer, the number of days of study drug can be extended by no more than 1 
day (through Day 6) for the equivalent of missed doses up to 2 doses. If the participant misses more than 4 consecutive doses, or more than 5 
total doses, then the participant will be discontinued from any further study drug administration and followed for safety for the remainder of 
the study. 
g.
One NP swab will be collected from each nostril at each time point for a total of 2 swabs per time point.
h.
BAL and/or sputum fluid may be collected when available for viral RNA testing. No study specific interventions will be initiated for 
collection of BAL fluid and/or sputum if participant has a productive cough. If, during clinical care, BAL is performed and excess fluid is 
available, the study team will collect this fluid for testing. 
i.
Note that on Day 1, the WHO ordinal scale assessment should be performed before the first dose of EIDD-2801 is administered. 
j.
Clinical assessments will be ascertained by chart extraction and will include number of days in the hospital, maximum O2 requirements daily, 
ICU admission and number of days in the ICU, mechanical ventilation and number of days requiring mechanical ventilation, death, and 
symptom reporting.


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k.
Oxygen saturation is to be recorded twice daily (morning and evening) and may be ascertained by chart extraction; if not available in the 
participant’s chart, it should be measured by the study staff. 
l.
Targeted physical examinations should be done if indicated by an AE or as needed in the judgement of the investigator. 
m. Laboratory measurements will include CBC with differentials, CMP (including amylase and lipase), and urinalysis. 
n.
For ECGs, a single post-dosing recording should be collected. If the participant is discharged from the hospital before a post-dose ECG is 
recorded, and recording of an outpatient ECG is not feasible, then results of the last recorded ECG before hospital discharge will be entered 
into the CRF.
o.
Results of all chest radiography performed as part of routine clinical care during Study Days 1-28 should be recorded. 
p.
Plasma and PBMC samples for PK analysis will be collected from participants if they are still inpatients on Day 3.  Samples will be collected 
before the morning dose on Day 3 and at the following times after the Day 3 morning dose: 0.5 hours, 1.5 hours, 3 hours, 6 hours, 8 hours, 
and 24 hours (i.e., on the morning of Day 4). If a participant is scheduled to be discharged, then PK samples should be collected at all 
scheduled time points up to the time of discharge; in addition, if a participants is discharged prior to the 24-hour PK sample, a 12-hour PK 
sample should be collected, when possible.  PK measurements will be assessed in participants enrolled at clinical sites able to conduct the 
collections. These sites include, but are not limited to, 
  Samples may 
be collected within a ± 15 minute window (up to 3 hours), ± 30 minutes (6-8 hours), or ± 1 hour (12-24 hours).


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Outpatienta
Study Procedures
Day 3
Day 5b
Day 8
(±1 day)
Day 11
(±1 day)
Day 15
(±1 day)
Day 28 
(EOS)
(±2 days)
Early 
Discontin-
uation
Serology (plasma)c
X
X
X
Pregnancy testd
X
X
Study residency
Outpatient visit
X
X
X
X
X
X
Phone calle
X
Study drug vs. placebo
EIDD-2801 or PBO administrationf
BID on Days 
1-5
BID on 
Days 1-5
Virologic endpoints
NP swabs g, h
X
X
X
X
X
X
Clinical endpoints
WHO Ordinal Scale (Appendix 1)h
X
X
X
X
X
X
X
Safety and tolerability
Concomitant medication review
X
X
X
X
X
X
X
AE/SAE reporting h
X
X
X
X
X
X
X
Vital signs (temperature, blood pressure, pulse, 
respiratory rate) h
X
X
X
X
X
X
Pulse oximetryj
X
X
X
X
X
X
Targeted physical examinationk
X
X
X
X
X
X
Laboratory l
X
X
X
X
X
X
Chest radiographym
X
X
X
X
X
X
Abbreviations:  AE = adverse event; BAL = bronchoalveolar; BID = twice daily; CBC = complete blood count; CMP = complete metabolic panel; 
ECG = electrocardiogram; EOS = end of study; ICU = intensive care unit; IL-6 = interleukin 6; 
 
; MR = medical record; NP = nasopharyngeal; PBO = placebo; PK = pharmacokinetic; QD = once daily; 
QOD = every other day; SOE = schedule of events; WHO = World Health Organization. 
a.
For participants who are discharged from the hospital after randomization and administration of the first-dose of study drug or PBO, this 
schedule will apply. Day number will be counted from enrollment. Participants will enter the Outpatient SOE upon day of discharge. 
Outpatients will be seen in one of several locations, including but not limited to COVID-19 ambulatory pods, COVID-19 ambulatory 
clinics and clinical research units, and home visits. In all cases, visits will conform to infection control practices that are established by the
institution.
b.
If Day 5 falls on a Saturday, then a visit will occur on Day 4. If Day 5 falls on a Sunday, then a visit will occur on Day 6.


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c.
Serology testing will be performed on plasma for IL-6 levels on Day 1 (pre-dose), Day 5 and Day 28, and specimens will be archived for 
further cytokine testing in the future.
d.
Pregnancy test is required for women of childbearing potential only.  High sensitivity serum pregnancy tests are required on Day 28.  
Additional serum or urine pregnancy tests may be performed, as determined necessary by the investigator or required by local regulation, 
to establish the absence of pregnancy at any time during the subject's participation in the study.
e.
Phone calls will be used to query participants about symptoms, study drug adherence, concomitant medications and to assess WHO 
ordinal scale.
f.
EIDD-2801 and PBO are to be administered BID on Days 1-5. The first dose will be administered in the morning of Day 1, if possible. If
the first dose is given later in the day, the second dose may be given at least 4 hours later on Day 1. If the first dose on Day 1 is given in 
the late evening, the second dose may be taken on the morning of Day 2, in which case the final dose will be taken on the morning of 
Day 6.  In addition, if a participant misses up to 2 doses during Days 1 to 5, dosing may be extended into Day 6. If discharge occurs prior 
to completion of study drug dosing (prior to Day 6), study drug will be administered in the hospital on the morning of discharge, and the 
remainder of the study drug will be dispensed for administration at home by the participant. Procedures will be put into place to ensure 
study drug compliance (e.g., telephone, eCollection) and drug accountability will be assessed on Days 5 and 8.
g.
One NP swab will be collected from each nostril at each time point for a total of 2 swabs per time point.
h.
Will be obtained at least once on the indicated day AND on the day of discharge from inpatient to outpatient, at the discretion of the 
investigator in consultation with the sponsor.
i.
Clinical assessments will be ascertained by chart extraction, including number of days in the hospital, maximum O2 requirements daily, 
ICU admission and number of days in the ICU, mechanical ventilation and number of days requiring mechanical ventilation, death, and 
symptom reporting.
j.
If the oxygen saturation value is <92%, the measurement should be repeated once within 30 minutes.
k.
Targeted physical examinations should be done if indicated by an AE or as needed in the judgement of the investigator.
l.
Laboratory measurements will include CBC with differentials, CMP (including amylase and lipase), and urinalysis. 
m. Results of all chest radiography performed as part of routine clinical care during Study Days 1-28 should be recorded. 


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8. ADVERSE EVENTS, RISKS, AND BENEFITS
8.1.
Potential Benefits of treatment
Based on animal efficacy studies, it is expected that EIDD-2801 will be active against SARS-
CoV-2 infection in humans.  This study will examine virologic responses to treatment with 
EIDD-2801 and is not powered to detect clinical outcomes.  However, clinical improvement will 
be recorded for secondary/exploratory analysis.
8.2.
Potential benefits of clinical monitoring 
Benefits of participation in this study include the increased clinical monitoring of study 
participants.  Intensive virology testing will be conducted.
8.3.
Potential risks
The AE profile for EIDD-2801 is preliminary and derives from a Phase 1 study that is ongoing.
Thus far, AE that were determined to be attributable to EIDD-2801 include insomnia, headaches, 
nausea, vomiting, abdominal pain, and loose stools (see the EIDD-2801 Investigator’s Brochure,
V3.0, 2020).
 
 
Gastrointestinal events and liver enzymes will also be monitored.  
8.4.
Alternatives
The alternative to participation in this study is routine care and monitoring of COVID-19, receipt 
of a SOC treatment for SARS-CoV-2 infection if available, or participation in a different clinical 
trial, if available.
8.5.
Definitions
8.5.1.
Adverse Event
Adverse event is defined as any undesirable sign, symptom or medical condition occurring after 
starting the study drug (or therapy/intervention) even if the event is not considered to be related 
to the study. An undesirable medical condition can be symptoms (e.g., nausea, chest pain), signs 
(e.g., tachycardia, enlarged liver) or the abnormal results of an investigation (e.g., laboratory 
findings, electrocardiogram). Medical conditions/diseases present before starting the study 
treatment are only considered AEs if they worsen after starting the study treatment (any 
procedures specified in the protocol). Adverse events occurring before starting the study 
treatment but after signing the informed consent form will not be recorded. Abnormal laboratory 
values or test results constitute AEs only if they induce clinical signs or symptoms or require 
investigation or therapy (i.e., are considered to be clinically significant).
This study will use the descriptions and grading scales found in the DAIDS Adverse Event 
Grading Scale for AE reporting.  


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8.5.2.
Serious Adverse Event
An SAE is an undesirable sign, symptom or medical condition which: 
x
Results in death 
x
Is life threatening (defined as an event in which the participant was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe) 
x
Requires inpatient hospitalization or causes prolongation of existing hospitalization (see 
note below for exceptions)
x
Results in persistent or significant disability/incapacity 
x
Is a congenital anomaly/birth defect (note: reports of congenital anomalies/birth defects 
must also be reported on the Pregnancy Supplemental Form, although participants must 
have a negative pregnancy test prior to therapy and use at least 2 forms of non-hormonal
contraception.  All participants (men and women) must state that they will use 2 forms of 
contraception during the study and for 4 days after completion of EIDD-2801 dosing in
female participants and for 4 days after completion of EIDD-2801 dosing in female 
partners of male participants.
x
Is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical 
and scientific judgment, may jeopardize the participant or may require intervention [e.g., 
medical, surgical] to prevent one of the other serious outcomes listed in the definition 
above.). Examples of such events include, but are not limited to, intensive treatment in an 
emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions 
that do not result in hospitalization.)
Events not considered to be SAEs are hospitalizations for the: 
x
Admissions as per protocol for a planned medical/surgical procedure or to facilitate a 
procedure.
x
Routine health assessment requiring admission for baseline/trending of health status (e.g., 
routine colonoscopy).
x
Medical/surgical admission for purpose other than remedying ill health state and was 
planned prior to entry into the study. Appropriate documentation is required in these 
cases.
x
Admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (e.g., lack of housing, economic 
inadequacy, care-giver respite, family circumstances, administrative).


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x
Escalation of care that is considered part of the disease progression of COVID-19 
(including but not limited to need for escalation in supplemental oxygen, need for 
mechanical ventilation, need for intubation, admission to the ICU, cytokine release 
syndrome [defined by an elevation in IL-6 and CRP levels], thromboembolic events) will 
not be collected as SAE.
x
Pregnancies will be reported using the SAE reporting guidelines for expedited reports 
(Section 8.10.4).
8.6.
Relationship
The relationship of an AE to the administration of the study drug is to be assessed by the 
investigator according to the following definitions:
x
No (unrelated, not related, no relation): The time course between the administration of 
study drug and the occurrence or worsening of the AE rules out a causal relationship and 
another cause (concomitant drugs, therapies, complications, etc.) is suspected.
x
Yes (related): The time course between the administration of study drug and the 
occurrence or worsening of the AE is consistent with a causal relationship and no other 
cause (concomitant drugs, therapies, complications, etc.) can be identified. 
The following factors should also be considered:
x
The temporal sequence from study drug administration - The event should occur after the 
study drug is given. The length of time from study drug exposure to event should be 
evaluated in the clinical context of the event.
x
Underlying, concomitant, intercurrent diseases - Each report should be evaluated in the 
context of the natural history and course of the disease being treated and any other 
disease the participant may have. 
x
Concomitant medication - The other medications the participant is taking or the treatment 
the participant receives should be examined to determine whether any of them might be 
recognized to cause the event in question. 
x
Known response pattern for this class of study drug - Clinical and/or preclinical data may 
indicate whether a particular response is likely to be a class effect.
x
Exposure to physical and/or mental stresses - The exposure to stress might induce 
adverse changes in the recipient and provide a logical and better explanation for the 
event. 
x
The pharmacology and PK of the study drug - The known pharmacologic properties 
(absorption, distribution, metabolism, and excretion) of the study drug should be 
considered. 


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8.7.
Assessment of Grade/Severity
The investigator will assess grade for each AE and SAE reported during the study, which will be 
recorded in the CRF. The assessment will be based on the DAIDS AE Grading Table, corrected 
Version 2.1, July 2017, which is available on the DAIDS RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.
Any AE that changes in grade during its course will be recorded in the CRF at the highest level 
experience by the participant.
8.8.
Expectedness
Unexpected adverse event: An AE, which varies in nature, intensity or frequency from 
information on the investigational drug/agent provided in the IB, package insert or safety reports. 
Any AE that is not included in the informed consent is considered “unexpected”. At the time of 
this protocol, no events are considered to be expected for safety reporting purposes.
Expected (known) adverse event: An AE, which has been reported in the package insert. An AE
is considered “expected”, only if it is included in the informed consent document as a risk.
8.9.
Handling of Expedited Safety Reports
In accordance with local regulations, the IND sponsor or designee will notify investigators of all 
SAEs that are unexpected (i.e., not previously described in the IB), and related to EIDD-2801.
This notification will be in the form of an expedited safety report (ESR) that is to be emailed to 
the investigators and the study coordinators. Upon receiving such notices, the investigator must 
review and retain the notice with the IB and where required by local regulations, the investigator 
will submit the ESR to the appropriate IRB. The investigator and IRB will determine if the 
informed consent requires revision. The investigator should also comply with the IRB 
procedures for reporting any other safety information. 
8.10.
Reporting
Information about all AEs, whether volunteered by the participant, discovered by investigator 
questioning, or detected through physical examination, laboratory test or other means, will be 
collected, recorded, and followed as appropriate. 
All AEs experienced by participants will be collected and reported from the first dose of 
EIDD-2801, throughout the study, and will only be followed for 28 days unless related to the 
investigational agent.  
Participants who have an ongoing AE related to the study procedures and/or medication(s) may 
continue to be periodically contacted by a member of the study staff until the event is resolved or 
determined to be irreversible by the investigator.


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8.10.1.
Routine Adverse Event Reporting
If an ongoing AE changes in its intensity or in its perceived relationship to investigational 
product, the maximum severity of the AE will be recorded. Adverse events should be followed to 
resolution or stabilization or reported as SAEs if they become serious. Follow-up is also required 
for AEs that cause interruption or discontinuation of investigational product, or those that are 
present at the end of study participation. Participants with AEs at study completion should 
receive post-treatment follow-up as appropriate. 
All identified non-serious AEs must be recorded and described on the appropriate Adverse Event 
Case Report Form (CRF).
8.10.2.
Laboratory Test Abnormalities 
Laboratory abnormalities present at the screening visit will be recorded as pre-treatment signs 
and symptoms. After study treatment administration, all grade 3 and 4 clinical laboratory results 
that represent an increase in severity from baseline will be reported as AEs. A grade 1 or 2 
clinical laboratory abnormality should be reported as an AE only if it is considered clinically 
significant by the investigator.
In addition, the following laboratory abnormalities should also be captured on the AE CRF page 
as appropriate: 
x
Any laboratory test result that is clinically significant or meets the definition of an SAE
x
Any laboratory abnormality that required the participant to have the investigational
product discontinued or interrupted
x
Any laboratory abnormality that required the participant to receive specific corrective
therapy
It is expected that wherever possible, the clinical, rather than the laboratory term would be used 
by the reporting investigator (e.g., anemia versus low hemoglobin value). 
8.10.3.
Serious Adverse Event Reporting
All SAEs (including deaths) occurring from the first dose of the study drug through the 28 day 
End-of-Study telephone call will be collected and recorded on the Adverse Event Case Report 
Form (CRF). 
The PI or clinical site personnel should notify 
 of all SAEs, regardless of
relationship to the investigational drug, within 24 hours of clinical site personnel becoming 
aware of the event. The PI (or designee) will provide the initial notification by sending a
completed SAE form which must include the PI’s (or designee’s) assessment of the relationship
of the event to investigational drug and must be signed by the PI. Follow-up information, or new
information regarding an ongoing SAE, must be provided promptly to 
at
or via fax.


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The SAE Form will collect data surrounding the event (e.g., the nature of the symptom[s], time 
of onset in relation to initiation of therapy, duration, intensity, and whether or not therapy was 
interrupted or discontinued). The Investigator’s assessment of the probable cause of the event 
will also be included. In addition, relevant medical history, concomitant medications, laboratory 
and diagnostic tests reports, and procedures as well as all pertinent medical information related 
to the event will also be collected.
SAEs will be reported to each participating site’s IRB per institutional guidelines by the PI.
After the initial SAE report, the investigator is required to proactively follow each participant
and provide further information regarding the participant’s condition.
All AE(s) and SAE(s) will be followed until one of the following conditions is met:
x
Resolution
x
The condition stabilizes
x
The event is otherwise explained
x
The participant is lost to follow-up
x
Death
8.10.3.1.
Expedited IND Safety Reports to the FDA
All reporting to the FDA will be completed by the IND sponsor.
7 Calendar-Day Telephone or Fax Report:  
The IND sponsor is required to notify the FDA of any fatal or life-threatening AE that is 
unexpected and assessed by the investigator to be possibly related to the investigational agent.  
Such reports are to be submitted to the FDA within 7 calendar days of first learning of the event. 
Follow-up information will be submitted to the FDA as soon as relevant information is available. 
15 Calendar-Day Written Report:  
The IND sponsor is required to notify the FDA of any SAE that is unexpected and related to the 
investigational agent in a written IND Safety Report.  
Written IND Safety Reports should include an Analysis of Similar Events in accordance with 
regulation 21 CFR § 312.32.  All safety reports previously filed with the IND concerning similar 
events should be analyzed.  The new report should contain comments on the significance of the 
new event considering the previous, similar reports.  


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Written IND safety reports with Analysis of Similar Events are to be submitted to the FDA 
within 15 calendar days of first learning of the event. Follow-up information will be submitted to 
the FDA as soon as relevant information is available.
IND Annual Reports:
In accordance with the regulation 21 CFR § 312.33, the IND sponsor shall within 60 days of the 
anniversary date that the IND went into effect submit a brief report of the AEs and progress of 
the investigation.  Please refer to Code of Federal Regulations, 21 CFR § 312.33 for a list of the 
elements required for the annual report.  All IND annual reports will be submitted to the FDA by 
the IND sponsor.
8.10.4.
Pregnancy and Exposure During Breastfeeding
If a pregnancy is reported, the investigator will record pregnancy information on the appropriate 
form and submit it to the sponsor within 24 hours of learning of the pregnancy in a female 
participant or female partner of male participant (after obtaining the necessary signed informed 
consent from the female partner).
Although pregnancy and infant exposure during breastfeeding are not considered AEs, any 
pregnancy or infant exposure during breastfeeding in a participant (spontaneously reported to the 
investigator or their designee), including the pregnancy of a male participant’s female partner, 
that occurs during the study are reportable to the Sponsor.
All reported pregnancies must be followed to the completion/termination of the pregnancy. 
Any pregnancy complication will be reported as an AE or SAE.
The medical reason (example: maternal health or fetal disease) for an elective termination of a 
pregnancy will be reported as an AE or SAE. Prenatal testing showing a fetus will be born with 
severe abnormalities/congenital anomalies that leads to an elective termination of a pregnancy 
will be reported as an SAE for the fetus.
Pregnancy outcomes of ectopic pregnancy, spontaneous abortion, missed abortion, benign 
hydatidiform mole, blighted ovum, fetal death, intrauterine death, miscarriage, and stillbirth must 
be reported as serious events (Important Medical Events). If the pregnancy continues to term, the 
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9. SAFETY OVERSIGHT
9.1.
Monitoring Plan 
1. All AE and grade 1-3 SAE will be reviewed by the protocol team twice monthly, or more 
if needed. All grade 4-5 SAEs will be reviewed by the protocol team within 24-48 hours 
of being received.   
2. A safety review committee (SRC), composed of the principal investigator for each study 
site and the medical monitor, will be established. The Committee will review blinded 
safety data at regular intervals. If the SRC identifies a potential safety issue, they may ask 
for additional safety analyses to further assess the issue, in cooperation with the sponsor.  
Details of SRC composition, responsibilities, and procedures will be provided in a SRC 
Charter.  
Additional details can be found in Section 9.2, in the Data and Safety Monitoring Plan for the 
study, and in the Study Unblinding Plan. 
9.2.
Stopping Criteria for the Study
The study enrollment and dosing will be stopped, and an ad hoc review will be performed if any 
of the specific following events occur or, if in the judgment of the study physician, participant
safety is at risk of being compromised:
I.
Unexpected death of a dosed participant.  
II.
Occurrence of a life-threatening allergic/hypersensitivity reaction (anaphylaxis), 
manifested by bronchospasm with or without urticaria or angioedema requiring 
hemodynamic support with pressor medications or mechanical ventilation.  
III.
A trend of unexpected SAEs related to the study product. 
IV.
Two participants with a Grade 3 or higher lab toxicity for the same parameter associated 
with the study product. 
V.
An overall pattern of symptomatic, clinical, or laboratory events that the SRC considers 
associated with study product and that may appear minor in terms of individual events 
but that collectively may represent a serious potential concern for safety.
VI.
Any other event(s) which is considered to be a SAE in the good clinical judgment of the 
responsible physician. This will be appropriately documented. 
Upon completion of this review, the SRC will determine if the study enrollment or study dosing 
should be interrupted or if study enrollment and study dosing may continue according to the 
protocol. Should the trial not be stopped at this time point, the final analysis would need to 
account for the number of interim analyses that were conducted. Therefore, we will use the 
O’Brien and Flemming type spending function to preserve the overall Type 1 error. This will 


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allow for stopping the trial earlier should the intervention arm be shown to be superior at an 
interim analysis.
Interim analyses: Interim analyses are planned when 25% and 50% of the final sample size 
reach Day 14 after initiation of study drug. Blinded data will be reviewed by the principal 
investigators and the sponsor.  Data to be reviewed will include blinded summaries of the 
primary efficacy endpoint (achievement of undetectable viral RNA by Day 5 in NP swabs) and 
the primary safety endpoints. For the primary safety endpoints, the cumulative incidence of each 
type of safety endpoint will be summarized by study arm in addition to the risk difference and 
95% confidence interval of the risk difference between study arms. The interim analyses will be 
used to inform sponsor decisions about whether to continue, amend, or stop the study. 


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10. ETHICS/PROTECTION OF HUMAN SUBJECTS
10.1.
Ethical Standard
The JHU and Ridgeback Biotherapeutics, LP are committed to the integrity and quality of the 
clinical studies it coordinates and implements. JHU will ensure that the legal and ethical 
obligations associated with the conduct of clinical research involving human subjects are met. 
The information provided in this section relates to all JHU sites participating in this research 
study.
As the Department of Health and Human Services continues to strengthen procedures for human 
subjects’ protections via new regulations, JHU will review these evolving standards in relation to 
the proposed activities and will advise the investigators on those that may apply.
In addition, JHU has a Federal wide Assurance (FWA) number on file with the Office for 
Human Research Protections (OHRP). The FWA number for JHU is FWA00005834.
This assurance commits a research facility to conduct all human subjects’ research in accordance 
with the ethical principles in The Belmont Report and any other ethical standards recognized by 
OHRP. Finally, per OHRP regulations, the research facility will ensure that the mandatory 
renewal of this assurance occurs at the times specified in the regulations.
10.2.
Institutional Review Board
The JHU IRB will review this protocol and all protocol-related documents and procedures as 
required by OHRP and local requirements before participant enrollment. The JHU IRB currently 
holds and will maintain a US FWA issued by OHRP for the entirety of this study.
10.3.
Informed Consent Process
The informed consent process will be initiated before a volunteer agrees to participate in the 
study and should continue throughout the individual’s study participation. The participant or the 
participant’s legally authorized representative will sign the informed consent document before 
any procedures are undertaken for the study. A copy of the signed informed consent document 
will be given to the participant for their records. The consent will explain that participants may 
withdraw consent at any time throughout the course of the trial. Extensive explanation and 
discussion of risks and possible benefits of this investigation will be provided to the participant
in understandable language. Adequate time will be provided to ensure that the participant has 
time to consider and discuss participation in the protocol. The consent will describe in detail the 
study interventions/products and risks/benefits associated with participation in the study. The 
rights and welfare of the participants will be protected by emphasizing that their access to and 
the quality of medical care will not be adversely affected if they decline to participate in this 
study. Participants with Low English Proficiency or who are Non-English-Speakers will be 
enrolled with the use of a certified interpreter who will also serve as a consent witness. 


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10.4.
Participant Confidentiality
Participant confidentiality is strictly held in trust by the participating investigators and their staff. 
No information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of the IND Sponsor. The results of the research study may be 
published, but participants’ names or identifiers will not be revealed. Records will remain 
confidential. To maintain confidentiality, the PI will be responsible for keeping records in a 
locked area and results of tests coded to prevent association with participants’ names.  Data 
entered into computerized files will be accessible only by authorized personnel directly involved 
with the study and will be coded.  Participants’ records will be available to the FDA, the NIH, 
the manufacturer of the study product and their representatives, investigators at the site involved 
with the study, and the IRB.
10.5.
Future Use of Stored Specimens
Participants will be asked for consent to use their samples for future testing before the sample is 
obtained. The confidentiality of the participant will be maintained. There will be no plans to re-
contact them for consent or to inform them of results. The risk of collection of the sample will be 
the small risk of bruising or fainting associated with phlebotomy. However, these samples will 
be taken at the same time as other protocol required samples. No human genetic testing will be 
performed on the samples.
Samples would not be shared with investigators other than investigators at 
 unless outside 
investigators had relevant assays or expertise not available to the study investigators. The 
specimens would remain linked and at 
. Any use of these specimens not specified in the 
current protocol will be reviewed by the 
 IRB.
10.6.
Data Management and Monitoring
10.6.1.
Source Documents
The primary source documents for this study will be the participants’ medical records. If the 
investigators maintain separate research records, both the medical record and the research 
records will be considered the source documents for the purposes of auditing the study. The 
investigator will retain a copy of source documents. The investigator will permit monitoring and 
auditing of these data and will allow the IRB and regulatory authorities access to the original 
source documents. The investigator is responsible for ensuring that the data collected are 
complete, accurate, and recorded in a timely manner. Source documentation (the point of initial 
recording of information) should support the data collected and entered into the study 
database/case report form and must be signed and dated by the person recording and/or 
reviewing the data. All data submitted should be reviewed by the site investigator and signed as 
required with written or electronic signature, as appropriate. Data entered into the study database 
will be collected directly from participants during study visits or will be abstracted from 
participants’ medical records. The participants’ medical records must record their participation in 
the clinical trial and what medications (with doses and frequency) or other medical interventions 
or treatments were administered, as well as any AEs experienced during the trial.


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10.6.2.
Data Management Plan
Study data will be collected at the study site(s) and entered into the study database. Data entry is 
to be completed on an ongoing basis during the study.
10.6.3.
Data Capture Methods
Sites will collect and enter the minimum necessary study data required by the electronic Case 
Report Forms (eCRFs) into the study base, which will be contained on the Medidata Rave 
platform. Medidata Rave has been validated to comply with 21 CFR Part 11 and HIPAA. Study 
personnel designated on the Delegation of Authority log to enter data will be required to 
complete training to access the database. Each study site will only have access to data collected 
at their site, and data captured will be isolated from all other study sites. All actions taken in 
relation to the database will be tracked via an audit trail. The data system includes password 
protection and internal quality checks to identify data that appear inconsistent, incomplete, or 
inaccurate.
10.6.4.
Study Record Retention
The site investigator is responsible for retaining all essential documents listed in the ICH GCP 
Guidelines. The FDA requires study records to be retained for up to 2 years after marketing 
approval or disapproval (21 CFR 312.62), or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational agent for a specific indication. 
These records are also to be maintained in compliance with IRB/IEC, state, and federal medical 
records retention requirements, whichever is longest. All stored records are to be kept 
confidential to the extent provided by federal, state, and local law. It is the site investigator’s 
responsibility to retain copies of source documents.
No study document should be destroyed without prior approval from the Principal Investigator. 
Should the investigator wish to assign the study records to another party and/or move them to 
another location, the site investigator must provide written notification of such intent to sponsor 
with the name of the person who will accept responsibility for the transferred records and/or their 
new location. The sponsor must be notified in writing and written permission must be received 
by the site prior to destruction or relocation of research records.


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11. REFERENCES
Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng 
JY, Jordan R, Ray AS, Cihlar T, Siegel D, Mackman RL, Clarke MO, Baric RS, Denison MR.  
Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral 
Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2). pii: e00221-18. doi: 
10.1128/mBio.00221-18.
Agostini ML, Pruijssers AJ, Chappell JD, Gribble J, Lu X, Andres EL, Bluemling GR, 
Lockwood MA, Sheahan TP, Sims AC, Natchus MG, Saindane M, Kolykhalov AA, Painter GR, 
Baric RS, Denison MR. Small-0ROHFXOH$QWLYLUDOȕ-d-N 4-Hydroxycytidine Inhibits a 
Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance. J Virol. 2019 Nov 
26;93(24). pii: e01348-19. doi: 10.1128/JVI.01348-19. PMID: 31578288.
Benson LS, Madden T, Tarleton J, Micks EA. Society of Family Planning interim clinical 
recommendations: contraceptive provision when healthcare access is restricted due to pandemic 
response. Society of Family Planning. 28 May 2020. https://doi.org/10.46621/UYGR2287 
Painter GR, Bowen RA, Bluemling GR, DeBergh J, Edpuganti V, Gruddanti PR, et al. The 
prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model 
of intranasal venezuelan equine encephalitis virus infection. Antiviral Res [Internet]. 
2019;171(September):104597. Available from: https://doi.org/10.1016/j.antiviral.2019.104597
Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijssers AJ, Agostini ML, Leist SR, Schäfer A, 
Dinnon KH 3rd, Stevens LJ, Chappell JD, Lu X, Hughes TM, George AS, Hill CS, Montgomery 
SA, Brown AJ, Bluemling GR, Natchus MG, Saindane M, Kolykhalov AA, Painter G, Harcourt 
J, Tamin A, Thornburg NJ, Swanstrom R, Denison MR, Baric RS. An orally bioavailable broad-
spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple 
coronaviruses in mice. Sci Transl Med. 2020 Apr 6. pii: eabb5883. doi: 
10.1126/scitranslmed.abb5883. PMID: 32253226. 
Spratt DI, Buchsbaum RJ. COVID-19 and Hypercoagulability: Potential Impact on Management 
with Oral Contraceptives, Estrogen Therapy and Pregnancy [published online ahead of print, 
2020 Jul 29]. Endocrinology. 2020;bqaa121. doi:10.1210/endocr/bqaa121
Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, Niemeyer D, Jones 
TC, Vollmar P, Rothe C, Hoelscher M, Bleicker T, Brünink S, Schneider J, Ehmann R, 
Zwirglmaier K, Drosten C, Wendtner C. Virological Assessment of Hospitalized Patients With 
COVID-2019. Nature. 2020 Apr 1. doi: 10.1038/s41586-020-2196-x. 32235945
Yoon JJ, Toots M, Lee S, Lee ME, Ludeke B, Luczo JM, et al. Orally efficacious broad-
spectrum ribonucleoside analog inhibitor of influenza and respiratory syncytial viruses. 
Antimicrob Agents Chemother. 2018;62(8):1–18. 


Protocol EIDD-2801-2004
Ridgeback Biotherapeutics LP 
Version: 7.0
18 May 2021
Page 62 of 64
Appendix 1. World Health Organization Ordinal Scale for Clinical Improvement of 
COVID-19 Disease


Protocol EIDD-2801-2004
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Version: 7.0
18 May 2021
Page 63 of 64
Appendix 2. Contraceptive Guidance
Definition of Women of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below):
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Women in the following categories are not considered WOCBP:
x
Premenarchal
x
Premenopausal female with 1 of the following:
o
Documented hysterectomy
o
Documented bilateral salpingectomy
o
Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the 
above (eg, Mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview.
x
Postmenopausal female
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.
o
A high follicle stimulating hormone (FSH) level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormone replacement therapy (HRT).  However, in the absence 
of 12 months of amenorrhea, confirmation with two FSH measurements in the
postmenopausal range is required.
Females on HRT and whose menopausal status is in doubt will be required to use one of 
the nonhormonal highly effective contraception methods if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment.


Protocol EIDD-2801-2004
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Version: 7.0
18 May 2021
Page 64 of 64
Contraception Requirements
CONTRACEPTIVES ALLOWED DURING THE STUDY INCLUDEa:
Highly Effective Methods That Have Low User Dependency 
Failure rate of <1% per year when used consistently and correctly.
x
Progesterone-only subdermal contraceptive implantb
x
Intrauterine hormone-releasing system (IUS)c
x
Non-hormonal intrauterine device (IUD)
x
Bilateral tubal occlusion
x
Azoospermic partner (vasectomized or secondary to a medical cause)
This is a highly effective contraceptive method provided that the partner is the sole male sexual partner of the 
WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days.
Note: documentation of azoospermia for a male participant can come from the site personnel’s review of the 
participant’s medical records, medical examination, or medical history interview.
Sexual Abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and lifestyle of the 
participant.
Highly Effective Contraceptive Methods That Are User Dependentd (must be used in combination with a 
barrier method)
Combined (estrogen- and progestogen-containing ) hormonal contraception 

Oral

Intravaginal

Transdermal

Injectable
Progestogen-only hormone contraceptionb

Oral

Injectable
Barrier methods to be used with hormonal contraceptives above (male condoms are preferred method)
x Male or female condom with or without spermicide
x Cervical cap, diaphragm, or sponge with spermicide
x A combination of male condom with either cervical cap, diaphragm, or sponge with spermicide (double
barrier methods)
Footnotes: 
a)
Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive 
methods for participants of clinical studies.
b)
If locally required, in accordance with CTFG guidelines, acceptable contraceptive implants are limited to those which 
inhibit ovulation.
c)
IUS is a progestin-releasing IUD
d)
Failure rate of <1% per year when used consistently and correctly (and not in combination with barrier method). Typical 
use failure rates are higher than perfect-use failure rates (i.e., when used consistently and correctly).
Note: The following are not acceptable methods of contraception alone or in combination:
 Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides 
only, and lactational amenorrhea method.
 Male and female condom should not be used together (due to risk of failure with friction).

SAP_001.pdf: 
 
 
Statistical Analysis Plan 
 
Ridgeback Biotherapeutics LP 
EIDD-2801-2004 
 
 
 
Document Version: Final v3.0 
Document Date: 24-Mar-2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Statistical Analysis Plan 
Sponsor Name: Ridgeback Biotherapeutics LP 
Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
Page 2 of 44 
Document Date:24-Mar-21 
 
 
 
 
Table of Contents 
1. 
Source Documents ................................................................................. 9 
2. 
Protocol Details ..................................................................................... 9 
2.1 
Study Objectives................................................................................. 9 
2.2 
Overall Study Design ........................................................................... 9 
2.3 
Sample Size and Power ..................................................................... 10 
2.4 
Randomization .................................................................................. 11 
3. 
Efficacy and Safety Variables................................................................. 11 
3.1 
Primary Efficacy Endpoint .................................................................. 11 
3.2 
Secondary Efficacy Endpoints ............................................................. 11 
3.3 
Exploratory Efficacy Endpoints ............................................................ 11 
3.4 
Primary Safety Endpoints ................................................................... 11 
3.5 
Secondary Clinical Endpoints .............................................................. 12 
3.6 
Exploratory Clinical Endpoints ............................................................. 12 
3.7 
Pharmacokinetic Endpoints ................................................................. 13 
4. 
Analysis populations ............................................................................. 13 
4.1 
Screened ......................................................................................... 13 
4.2 
Randomized ..................................................................................... 13 
4.3 
Safety ............................................................................................. 13 
4.4 
Intent-to-treat Set ............................................................................ 13 
4.5 
Efficacy Analysis Set .......................................................................... 13 
4.6 
Per Protocol Set ................................................................................ 13 
4.6.1 
Important Protocol Deviations Potentially Leading to Exclusion from the PPS Analysis .... 14 
4.7 
Pharmacokinetic ............................................................................... 15 
5. 
DataHandling ...................................................................................... 15 
5.1 
Time points and Visit Windows ........................................................... 15 
5.2 
Handling of Dropouts, Missing Data, and Outliers .................................. 16 
6. 
Statistical Methods ............................................................................... 18 
6.1 
General Principles ............................................................................. 18 
6.2 
Subject Disposition and Data Sets Analyzed ......................................... 19 


Statistical Analysis Plan 
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Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
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Document Date:24-Mar-21 
 
 
 
6.3 
Protocol Deviations ........................................................................... 19 
6.4 
Demographics and Other Baseline Characteristics ................................. 20 
6.4.1 
Medical History ................................................................................................................... 20 
6.4.2 
Previous and Concomitant Medications ............................................................................. 21 
6.5 
Efficacy ............................................................................................ 21 
6.5.1 
Primary Efficacy Analysis ..................................................................................................... 21 
6.5.2 
Secondary Efficacy Analyses ............................................................................................... 22 
6.5.3 
Subgroup Analysis ............................................................................................................... 23 
6.5.4 
Exploratory Efficacy Analysis ............................................................................................... 24 
6.5.5 
Secondary Clinical Analyses ................................................................................................ 24 
6.5.6 
ExploratoryClinical Analyses ............................................................................................... 25 
6.5.7 
Pharmacokinetic Analyses .................................................................................................. 26 
6.6 
Safety ............................................................................................. 32 
6.6.1 
Extent of Exposure .............................................................................................................. 32 
6.6.2 
Adverse Events .................................................................................................................... 32 
6.6.3 
Laboratory Evaluations ....................................................................................................... 34 
6.6.4 
Vital Signs ............................................................................................................................ 35 
6.6.5 
Electrocardiograms ............................................................................................................. 35 
6.6.6 
Physical Examination ........................................................................................................... 36 
6.6.7 
Other Safety Variables – Not Applicable ............................................................................. 36 
6.7 
Interim Analysis................................................................................ 36 
7. 
Changes in Planned Analysis ................................................................. 36 
8. 
Data Issues......................................................................................... 37 
9. 
References .......................................................................................... 37 
10. 
Appendices ......................................................................................... 38 
Appendix 1: Document History ............................................................ 38 
Appendix 2: Table of Contents for SAP Shells - Tables ............................ 38 
Appendix 2: Table of Contents for SAP Shells - Figures ........................... 43 
Appendix 3: Table of Contents for SAP Shells - Listings .......................... 43 
 
 
 


Statistical Analysis Plan 
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Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
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Document Date:24-Mar-21 
 
 
 
Glossary of Abbreviations 
Abbreviation 
Term 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
ATC 
Anatomical therapeutic chemical 
AUC 
Area under the curve 
AUCt 
Area under the plasma concentration-time curve from time 
zero to time t 
BID 
Bis in die (Twice a day) 
BMI 
Body mass index 
CBC 
Complete blood count 
Ct 
Plasma drug concentration at a specified time t after the 
administration of a given dose 
CI 
Confidence interval 
Cmax 
Maximum concentration 
CMP 
Comprehensive metabolic panels 
CoV 
Coronavirus 
COVID-19 
Coronavirus Disease – 2019 
CRF 
Case report form 
DAIDS 
Division of acquired immune deficiency syndrome 
DB 
Double-blind 
EAS 
Evaluable analysis set 
ECG 
Electrocardiogram 
eCRF 
Electronic case report forms 
Hgb 
Hemoglobin 
ICU 
Intensive care unit 
IL-6 
Interleukin 6  
ITT 
Intention-to-treat 
LOD 
Limit of detection 
MAR 
Missing at random 
MCAR 
Missing completely at random 
MedDRA 
Medical dictionary for regulatory activities 
MMRM 
Mixed model for repeated measures 
NHC 
N4-Hydroxycytidine 
NHC-TP 
5′-triphosphate metabolite of NHC 
NP 
Nasopharyngeal 
PBMC 
Peripheral blood mononuclear cells 
PCR 
Polymerase chain reaction 
PK 
Pharmacokinetic 
PPS 
Per-protocol set 
PT 
Preferred term 
qPCR 
Quantitative polymerase chain reaction 
QTc 
Corrected QT 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 


Statistical Analysis Plan 
Sponsor Name: Ridgeback Biotherapeutics LP 
Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
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Document Date:24-Mar-21 
 
 
 
SD 
Standard deviation 
SI 
International system of units 
SOC 
System organ class 
SNP 
Single-nucleotide polymorphism 
SRC 
Safety review committee 
TFLs 
Tables, figures and listings 
ULN 
Upper limit of normal 
WHO 
World health organization 
 
 


Statistical Analysis Plan 
Sponsor Name: Ridgeback Biotherapeutics LP 
Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
Page 7 of 44 
Document Date:24-Mar-21 
 
 
 
STATISTICAL ANALYSIS PLAN AMENDMENT 1 
The statistical analysis plan has been updated to reflect the changes in the protocol 
from v3.2 to v5.0. These include: 
 
An increase in the total sample size from 60 up to 80 
 
3 additional dose groups at dose levels of 400mg, 800mg and an optional third 
group in part 4, at a dose level to be determined 
 
The 200mg dose level will be discontinued 
 
Clarification of the sequence of enrollment for each study part 
 
The secondary virological endpoint for measurement of the decline in viral RNA 
was revised to include endpoints corresponding to each of the planned 
sampling timepoints 
 
Secondary clinical endpoint #1 was modified to remove convalescent plasma 
 
Exploratory viral endpoints related to nasal swabs, saliva, and stool samples 
have been removed 
 
Removal of stratification by intention to use remdesivir in the randomization 
 
Removal of prolonged QTc to ≥500 msec was deleted, as this parameter is not 
being collected 
STATISTICAL ANALYSIS PLAN AMENDMENT 2 
Minor amendment from SAP v2.0 to SAP v2.1 to clarify details which include: 
 
Categorization of age and BMI 
 
Definition of baseline 
 
Definition for how the onset of COVID-19 symptoms is to be determined 
 
Removal of screen failure table, since this is not collected 
 
Definition of antiviral medication 
 
Addition of imputation rules for concomitant medication dates 
 
 


Statistical Analysis Plan 
Sponsor Name: Ridgeback Biotherapeutics LP 
Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
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Document Date:24-Mar-21 
 
 
 
STATISTICAL ANALYSIS PLAN AMENDMENT 3 
Amendments from SAP v2.1 to SAP v3.0 to clarify details which include: 
 
Update to versioning of TFLs to be consistent with the SAP 
 
Visit window updates in Section 5.1 
 
Imputation of infectivity assay added to Section 5.2 
 
Additional covariates added to Section 6.5.2.2 and 6.5.2.3 
 
Baseline summary added to Section 6.5.4.1 
 
COVID-19 Risk group updated in Section 6.5.3 with the addition of a new table 
 
New table added for undetectable infections vital RNA in Section 6.5.4.1 
 
 


Statistical Analysis Plan 
Sponsor Name: Ridgeback Biotherapeutics LP 
Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
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Document Date:24-Mar-21 
 
 
 
1. Source Documents 
The Statistical Analysis Plan (SAP) was written based on the following documentation: 
Document 
Date 
Version 
Protocol 
11 March 2021 
6.0 
eCRF 
27-Aug-2020 
1.0 
2. Protocol Details 
2.1 Study Objectives 
 
Primary: 
1. To test whether orally administered EIDD-2801 results in a greater 
proportion of clearance from nasopharyngeal (NP) swabs compared to 
placebo in hospitalized adults by achieving undetectable (below the limit 
of detection [LOD] of the assay) viral RNA by day 5 after initiation of 
study drug. 
2. To evaluate the safety of treatment with EIDD-2801 in participants 
diagnosed with COVID-19. 
 
Secondary: 
1. To evaluate the efficacy of EIDD-2801 on clearance of SARS-CoV-2 RNA. 
2. To evaluate the effect of EIDD-2801 on improvement of clinical 
symptoms and signs of COVID-19. 
3. To evaluate EIDD-1931 pharmacokinetics in plasma in a subset of 
participants. 
 
Exploratory: 
1. To evaluate the efficacy of EIDD-2801 to clear SARS-CoV-2 RNA and 
infectious virus. 
2. To ascertain the role of EIDD-2801 in improvement of clinical symptoms 
and signs of COVID-19. 
3. To characterize the pharmacokinetics of EIDD-2061 (NHC-TP) in 
peripheral blood mononuclear cells (PBMC) in a subset of participants. 
2.2 Overall Study Design 
This study is a phase 2a randomized, placebo-controlled, double-blinded clinical trial 
of EIDD-2801 in adult men and women who have tested positive for severe acute 
respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection by polymerase chain 
reaction (PCR) test within 6 days (144 hours) prior to randomization and are 
hospitalized with a diagnosis of COVID-19. Rapid enrollment and treatment will be 
initiated such that the first dose of EIDD-2801 or placebo will be administered as 
soon as possible and within 8 days of onset of symptoms. 


Statistical Analysis Plan 
Sponsor Name: Ridgeback Biotherapeutics LP 
Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
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Document Date:24-Mar-21 
 
 
 
Participants will be enrolled in up to 4 sequential study parts. During Part 1, 
participants will be randomized in a 1:1:1 ratio to:200 mg EIDD-2801:400 mg 
EIDD-2801: placebo. In Part 2 of the study, 21 participants will be randomized in a 
2:1 ratio to receive EIDD-2801 400 mg or placebo and in Part 3 of the study, 21 
participants will be randomized in a 2:1 ratio to receive EIDD-2801 800 mg or 
placebo. An optional Part 4 may be added during which 21 participants will be 
randomized in a 2:1 to EIDD-2801: placebo and the dose of EIDD-2801 may be the 
same or lower than doses studied in previous Part(s), but not to exceed 800mg bis 
in die (BID, twice a day). In v2.0 of the protocol, participants were randomized in a 
1:1:1 ratio to 200 mg EIDD-2801:300 mg EIDD-2801: placebo. The EIDD-2801 300 
mg arm was replaced with EIDD-2801 400 mg in v3.0 of the protocol. 
The study parts will be conducted in sequence as follows: Enrollment into Part 1 of 
the study may be terminated upon approval and implementation of Protocol 
Amendment 3, and enrollment into Part 2 will be initiated immediately thereafter. 
Enrollment into Part 3 will be initiated once Part 2 has been fully enrolled. If initiated, 
Part 4 may begin enrolling participants as soon as Part 3 has been fully enrolled. 
Study parts 2 and 3 may be terminated prematurely based on emerging data from 
this and other ongoing studies of EIDD-2801. 
EIDD2801 (100- and 200-mg capsules) and matching placebo will be supplied as dry 
filled capsules for oral administration. Doses of EIDD-2801 or matching placebo will 
be administered as combinations of 100- and 200-mg capsules in such a way as to 
preserve the study blind and as appropriate for the dose level. Participants will be 
administered study drug BID for 5 days (10 doses). In the event of missed doses, if 
the total number of missed doses is 4 or fewer, the number of days of study drug 
can be extended by no more than one day (through day 6) with the equivalent of 
missed doses up to 2 doses. If the participant misses more than 4 consecutive doses, 
or more than 5 total doses, then the participant will be discontinued from any further 
study drug administration and followed for safety for the remainder of the study. 
The study is comprised of 3 periods: screening period, treatment period, and follow-
up period. The screening period may last up to 2 days. The treatment period is 5 
days of dosing with study drug. The follow-up period is 23 days and continues to at 
least day 28. For inpatients, clinical assessments will occur on days 3, 5, 8, 11, 15, 
19, and 28. PK assessments will initiate on day 3 for participants who are still 
inpatients and be collected up to 24 hours’ post-day 3 on day 4 where possible. For 
patients who are discharged (outpatients), clinical assessments will occur on days 3, 
5, 8, 11, and 28 with a telephone assessment on day 15 (±1). 
Interim analyses will be conducted after 25% and 50% of randomized participants 
reach day 14 after the initiation of study drug. No formal stopping rule is specified. 
Blinded data will be reviewed by the principal investigators and the sponsor, further 
details are provided in section 6.7. 
2.3 Sample Size and Power 
Because of the multiple arm design (placebo versus multiple doses of EIDD-2801), 
the power calculations are based on an individual dose arm versus placebo 
comparison, using a Fisher’s exact test. Participants receiving the same doses across 


Statistical Analysis Plan 
Sponsor Name: Ridgeback Biotherapeutics LP 
Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
Page 11 of 44 
Document Date:24-Mar-21 
 
 
 
study parts will be pooled together in the final analysis. It is expected that 14 or more 
participants will receive EIDD-2801 in the higher dose groups, and at least 14 
participants will receive placebo across the study parts. Based on previous data 
(Wolfel, Nature, 2020), it is conservatively assumed that 20% of placebo recipients 
(n=20) will have clearance, i.e., undetectable SARS-CoV-2 RNA at day 5, compared 
to 80% clearance in an EIDD-2801 arm (n=20). This will provide83% power to detect 
a difference with α=0.05. 
2.4 Randomization 
To allow non-Johns Hopkins University sites to enroll, the randomization list is further 
stratified by site. To prevent incomplete blocks per site and unequal randomization, 
each site must completely enroll all assigned blocks of 6. Upon the overall recruitment 
target being met the overall number and allocation of study drug arms will be 
reviewed to determine if a significant random imbalance in the allocation of study 
drugs has occurred which would impact the power of the study. Depending upon the 
balance of screening failures by study drug arm, it is anticipated that randomization 
will continue to allow for up to 80 participants in the efficacy analysis set (EAS). 
3. Efficacy and Safety Variables 
3.1 Primary Efficacy Endpoint 
 
Achievement of undetectable (below the limit of detection of the assay) SARS-
CoV-2 RNA by day 5 in NP swabs by quantitative Polymerase Chain Reaction 
(qPCR). 
3.2 Secondary Efficacy Endpoints 
 
Time to clearance of viral RNA in NP swabs by qPCR. 
 
The decline in viral RNA copies/mL by days 3, 5, 8, 11, 15, and 19after 
initiation of study drug in NP swabs by qPCR. 
 
The rate of decline in viral RNA (change in log10 viral RNA copies/mL per day) 
in NP swabs by qPCR. 
3.3 Exploratory Efficacy Endpoints 
 
Achievement of undetectable (below the LOD of the assay) viral titers by day 
5 in NP swabs by infectivity assay. 
 
Time to clearance of infectious virus in NP swabs by infectivity assay. 
 
Clearance of infectious virus by day 3 and day 5 in NP swabs by infectivity 
assay. 
 
The number of acquired single-nucleotide polymorphisms (SNPs) in SARS-
CoV-2 genomes by day 5 or day 11 in NP swabs by viral sequencing. 
3.4 Primary Safety Endpoints 
1. Adverse events (AEs) 


Statistical Analysis Plan 
Sponsor Name: Ridgeback Biotherapeutics LP 
Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
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2. Serious adverse events (SAEs) 
3. Physical examination including vital signs 
4. Safety laboratory assessments: 
a. complete blood counts (CBC) with differentials 
i. decrease in hemoglobin (Hgb) by >1 g/dL, or to <9 g/dL 
ii. decrease in platelet count by 50,000/µL, or to <75,000/µL 
b. comprehensive metabolic panels (CMP) including liver function tests 
i. increase in aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), amylase, or lipase to ≥3xthe upper 
limit of normal (ULN) 
c. urinalysis 
5. Electrocardiograms (ECGs) 
3.5 Secondary Clinical Endpoints 
1. Peak stage on the World Health Organization (WHO) Ordinal Scale for Clinical 
Improvement OR clinical requirement for addition of other therapeutics 
including but not limited to: 
- PEGylated interferon alpha 
- Inhaled interferon beta1 
- Ribavirin (any formulation) 
- Any interleukin (IL)-6 inhibitor 
2. Number of days of supplemental oxygen  
3. Number of days of mechanical ventilation 
4. Number of days in the Intensive Care Unit (ICU) 
5. Death 
3.6 Exploratory Clinical Endpoints 
1. Days of hospitalization 
2. Time to resolution of COVID-19 symptoms defined as: 
- Fevers OR  
- At least one of the following symptoms: cough, shortness of breath, 
respiratory rate ≥20, radiographic evidence of pneumonia OR 
- other clinical symptoms or signs of pneumonia that are not otherwise 
explained by comorbidities or co-diagnoses 
3. Number of days until a 2-point decrease in stage according to the WHO 
Ordinal Scale for Clinical Improvement. 
4. Radiologic improvement by grading chest diagnostics (when radiography is 
available) 


Statistical Analysis Plan 
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Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
CONFIDENTIAL 
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5. Change in IL-6 levels by day 5 
3.7 Pharmacokinetic Endpoints 
In Plasma: 
1. Maximum EIDD-1931 concentration (Cmax) 
2. 1.5-hour EIDD-1931 concentration (C1.5) 
3. 3-hour EIDD-1931 concentration (C3) 
4. Area under the concentration: time curve of EIDD-1931 (AUC0-8) 
5. Elimination half-life (t1/2) of EIDD-1931 
(EIDD-1931 is the primary circulating form of EIDD-2801 in plasma) 
4. Analysis populations 
4.1 Screened 
All participants who consent to participate and who undergo screening will be 
included in the screened population. 
4.2 Randomized 
All participants who consent to participate and who are randomized will be included 
in the randomized population.  
4.3 Safety 
All participants treated with at least one dose of study drug will be included in the 
Safety population. Safety participants are analyzed according to their actual 
treatment received. Participants who received EIDD-2801 300mg will be analyzed in 
the 200mg study group in all analyses using the safety population. 
4.4 Intent-to-treat Set 
The Intent-to-treat set (ITT) will consist of all randomized participants consistent with 
v5.0 of the protocol. ITT participants are analyzed according to their randomized 
treatment. Participants originally allocated to EIDD-2801 300mg will be analyzed in 
the 200mg study group in all analyses using the ITT population. 
4.5 Efficacy Analysis Set 
The Efficacy Analysis Set (EAS) will consist of all participants treated with at least 
one dose of study drug and with at least 1 post baseline assessment of SARS-CoV-2 
RNA in NP swabs by qPCR. Efficacy analysis set participants are analyzed according 
to their actual treatment received. Participants who received EIDD-2801 300mg will 
be analyzed in the 200mg study group in all analyses using the EAS population. 
4.6 Per Protocol Set 
The Per-Protocol Set (PPS) will consist of all participants in the ITT population who 
do not have any important protocol deviations leading to exclusion from the PPS. 


Statistical Analysis Plan 
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Sponsor Protocol ID: EIDD-2801-2004 
 
 
 
 
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Protocol deviations are defined as any change, divergence, or departure from the 
study design or procedures defined in the study protocol. Important protocol 
deviations are a subset of protocol deviations that may significantly impact the 
correctness, accuracy, and/or reliability of the study data or that may significantly 
affect a subject’s rights, safety, or well-being. Section 4.6.1 details important 
protocol deviations. 
4.6.1 Important Protocol Deviations Potentially Leading to Exclusion 
from the PPS Analysis 
Only those important protocol deviations considered to have a major effect on 
efficacy will lead to exclusion of the participants from the PPS. For the purposes of 
this study, the following criteria have been identified as potentially important protocol 
deviations, as it is considered that the occurrences of any of these criteria might have 
an important influence on the primary efficacy endpoint. Participants will be assessed 
purely by comparison of their electronic case report form (eCRF) data with the criteria 
below; protocol waivers will not be taken into consideration. 
Type 
Important Protocol 
Deviation  
Method of Identification 
Inclusion/Exclusion 
Criteria Violation 
Any violation of 
inclusion/exclusion criteria as 
specified in section 3.1 and 3.2 
of the protocol . 
Violations will be identified through 
site monitoring and entered into 
the deviation log. 
Prohibited 
Medication 
Prohibited medications 
identified in section 4.7 of the 
protocol include any other 
nucleos(t)ide analog drugs 
Identified using the concomitant 
medications eCRF. 
Minimum exposure 
to study treatment 
Any participant who misses 
more than 4 consecutive doses, 
or more than 5 total doses. 
Identified using the study drug 
administration eCRF. 
Visit compliance 
Any participant where the day 
5 visit occurs more than 24 
hours from the scheduled visit 
date. 
Identified using the virologic 
sampling eCRF. 
Unblinding 
Any participant whose 
treatment allocation is 
accidentally unblinded or 
unblinded as part of an 
emergency because of safety 
concerns. 
Identified through reports of 
protocol deviation or records of 
emergency unblinding. 
All-important protocol deviations, potentially leading to exclusion from the PPS, will 
be reviewed and approved by Ridgeback Biotherapeutics LP prior to database lock 
and unblinding. Should additional important protocol deviations leading to exclusion 
from the PPS not anticipated at the time of preparing this SAP be identified during 


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the study and prior to unblinding, they will be documented in a SAP amendment and 
included in all relevant protocol deviation reviews and approvals. 
4.7 Pharmacokinetic 
All participants treated with at least one dose of study drug with at least one 
reportable 
concentration 
of 
EIDD-1931 
will 
be 
included 
in 
the 
plasma 
pharmacokinetic (PK) population and their data included in the plasma population PK 
dataset. Participants will be considered evaluable for the formal PK endpoints if 
specimens were collected for protocol-specified time points necessary to define those 
endpoints. 
5. DataHandling 
5.1 Time points and Visit Windows 
Day 1 is defined as the day of first dose of study drug. Relative days after day 1 are 
calculated as (assessment date – day 1 date) + 1. Relative days prior to day 1 are 
calculated as (assessment date – day 1 date). The day prior to day 1 is day -1.  
For all populations, all other assessments will be assigned to visits as follows: 
 
Assessments with missing data and assessments marked “Not Done” will be 
considered as providing a missing response and are not permitted to be 
assigned to a visit window. 
 
If multiple measurements are available within a visit window then the closest 
measurement taken to the scheduled day of visit will be used. If two 
measurements are equidistant to the scheduled day of visit then the latest 
measurement will be used (e.g. if measurements are available for day 4 and 6 
then day 6 will be used for day 5 analysis measurement) 
For virologic endpoints (NP swabs, BAL and/or sputum), clinical endpoints (WHO 
ordinal scale and clinical assessments) and safety endpoints of AE/SAE reporting, 
vital signs, pulse oximetry, full physical examination and chest radiography the 
following visit windows will be applied: 
Visit 
Scheduled Day of Visit 
Visit Window 
Screening 
Nominal visit 
NA 
Day 1 
1 
1 
Day 3 
3 
2 to 3 
Day 5 
5 
4 to 6 
Day 8 
8 
7 to 9 
Day 11 
11 
10 to 13 
Day 15 
15 
14 to 17 
Day 19 
19 
18 to 24 
Day 28 
29 
≥25 
Early Discontinuation 
Nominal visit 
NA 
 


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For laboratory assessments the following visit windows will be applied: 
Visit 
Scheduled Day of Visit 
Visit Window 
Screening 
Nominal visit 
NA 
Day 1 
1 
1 
Day 3 
3 
2 to 3 
Day 5 
5 
4 to 6 
Day 8 
8 
7 to 11 
Day 15 
15 
12 to 17 
Day 19 
19 
≥18 
Early Discontinuation 
Nominal visit 
NA 
 
For targeted physical examination the following visit windows will be applied: 
Visit 
Scheduled Day of Visit 
Visit Window 
Screening 
Nominal visit 
NA 
Day 1 
1 
1 
Day 3 
3 
2 to 3 
Day 5 
5 
4 to 6 
Day 8 
8 
7 to 9 
Day 11 
11 
10 to 13 
Day 15 
15 
14 to 17 
Day 19 
19 
≥18 
Early Discontinuation 
Nominal visit 
NA 
12-lead ECG measurements will not be assigned a visit and are analyzed as baseline 
or post-baseline only. 
5.2 Handling of Dropouts, Missing Data, and Outliers 
Participants who prematurely discontinue from the study without receiving a single 
dose of study drug or placebo will be replaced. Participants who prematurely 
discontinue should undergo an end of study visit at day 28 to evaluate clinical 
assessments, AEs and SAEs. 
For the analysis of the primary efficacy endpoint, if a participant’s NP swab at day 5 
is not available for analysis then a participant’s response will be imputed to have a 
detectable level of SARS-CoV-2 RNA by qPCR (non-response). For participants 
enrolled prior to protocol v5.0, both NP swabs need to be unavailable for a 
participant’s response to be imputed as a detectable level of SARS-CoV-2 RNA by 
qPCR (non-response). Longitudinal analyses of secondary endpoints, such as the rate 
of decline of log10 viral RNA copies/mL in NP swabs, will use mixed effect models 
(described in Section 6.5.2) which are robust for missing data when this is missing 
completely at random (MCAR) or missing at random (MAR). Time to event analyses 
of secondary endpoints, such as the time to clearance of viral RNA in NP swabs, will 
use Kaplan-Meier analyses which will censor participants who are lost to follow-up 
with no measurements available at their last available assessment. 


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For the analysis of the exploratory efficacy endpoints, analyzing infectivity assay 
data, subjects with missing infectivity data will be imputed based on the rules 
provided in the following table. 
Visit Before 
Visit After 
Imputed Infectivity Result 
Negative 
Negative 
Negative 
Positive 
Positive 
Positive 
Negative or missing 
Positive 
Positive* 
Missing 
Negative 
Missing 
Any Value 
Missing 
Missing 
* Subjects with missing baseline and reported the first post baseline value of positive, 
the baseline will be imputed as positive. 
Missing safety data will generally not be imputed. However, safety assessment values 
of the form of “<x” (i.e. below the lower limit of quantification) or “>x” (i.e. above 
the upper limit of quantification) will be imputed as “x” in the calculation of summary 
statistics but displayed as “<x” or “>x” in the listings. Additionally, AEs that have 
missing causality (after data querying) will be assumed to be related to study drug. 
For missing start AE and concomitant medication dates, the following will be applied: 
 
Missing day – impute the 1st of the month unless month is same as month of 
first dose of study drug then impute first dose date. 
 
Missing day and month – impute 1st January unless year is the same as first 
dose date then impute first dose date. 
 
Completely missing – impute first dose date unless the end date suggests it 
could have started prior to this in which case impute the 1st January of the 
same year as the end date. 
Note: When imputing a start date, ensure that the new imputed date is sensible i.e. 
is prior to the end date of the AE or treatment. 
For missing end AE and concomitant medication dates, the following will be applied: 
 
Missing day – impute the last day of the month unless month is the same as 
month of scheduled end of study visit (day 28) then impute scheduled end of 
study visit (day 28). 
Missing day and month – impute 31st December unless year is the same as scheduled 
end of study visit (day 28) then impute scheduled end of study visit (day 28). No 
imputation of AE grade will occur for AEs missing DAIDS grade. 
No rules for outlier detection are planned. 


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6. Statistical Methods 
6.1 General Principles 
All data processing, summarization and analyses will be performed using 
 
 statistical software package. 
Unless specified, participants receiving or assigned the same treatment across parts 
of the study will be pooled in all analyses e.g., presentations of the placebo study 
group will include participants from parts 1-4. Safety endpoints will be presented for 
all study groups. 
Listings of virological endpoints will include all sample collection methods. 
For SARS-CoV-2 RNA values reported as below the lower limit of quantification 
(<1018), the lower value (1017) will be used in the analyses. 
Baseline is defined as the last scheduled assessment collected prior to the first dose 
of the study drug except where otherwise indicated. For assessments on the same 
date as the first dose of study drug, but where assessment time is missing, the 
assessment will be presumed to take place prior to the first dose of study drug and 
used as a baseline assessment. 
The following principles will be applied to all tables, figures and listings (TFLs) unless 
otherwise stated: 
Principle 
Value 
Significant tests 
Two-sided and use a 5% significance level for main effects and 
5% significance level for interaction terms. 
Treatment group labels 
and order presented 
Placebo 
200mg EIDD-2801 
EIDD-2801 (listings only) 
400mg EIDD-2801 
800mg EIDD-2801 
<Part 4 TBD> EIDD-2801 
For baseline and demographic tables: All Participants 
For efficacy tables: All EIDD-2801 
Tables 
Data in summary tables will be presented by study group, 
assessment and visit (where applicable). 
Listings 
All data collected presented by study group, participant, 
assessment and visit (where applicable), unless otherwise 
specified. 
Descriptive summary 
statistics for continuous 
variables 
Number of participants/observations (N), mean, standard 
deviation (SD), median and range. 
Descriptive summary 
statistics for categorical 
variables 
Frequency counts and percentages [n (%)] 
Denominator for 
percentages 
Number of participants in the analysis population, unless 
stated otherwise in table shell(s). 
Include “Missing” as 
category 
Yes, when the number missing is greater than zero for at least 
one study group. 
Display for 0 percentages 
Blank 


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Principle 
Value 
Display to one more 
decimal place than 
collected value 
Mean 
Standard Error 
Mean Difference 
Median 
Display to two more 
decimal places than 
collected value 
Standard Deviation 
Confidence Interval 
Limit of precision for 
displays 
3 significant figures 
If minimum is ≥100% display to 0 decimal places 
If reported as x.xxx, display to 3 decimal places 
Date Format 
DDMMMYYYY 
Source footnotes 
Each table will have a footnote that lists the source data 
listing(s). Each figure will have a footnote that list the source 
table(s). 
Dictionary names and 
versions 
The dictionary names and versions will be included in a 
footnote in all AE and prior or concomitant medication TFLs 
that present coded terms from the dictionaries. 
6.2 Subject Disposition and Data Sets Analyzed 
Participant disposition will be listed and summarized by study group and overall. 
Furthermore, a summary for each study part and overall will be presented. Patient 
disposition will include the number and percentage of participants: 
 
screened; 
 
randomized; 
 
randomized and not treated; 
 
treated; 
 
included in each study population (Safety, ITT, EAS, PPS, PK). 
In addition, the number and percentage of participants who complete treatment 
(defined as ≥10 doses) and who discontinue early (missed more than 4 consecutive 
doses or more than 5 total doses.) will be presented. Furthermore, for subjects who 
do not complete the study, the primary reason for not completing the study will be 
presented. 
A summary of participant enrollment by site will also be provided by study group and 
overall for the safety population. 
6.3 Protocol Deviations 
All protocol deviations will be listed and summarized by study group for the ITT 
population. 
All-important protocol deviations leading to exclusion from the PPS population (see 
Section 4.6.1 will be listed and summarized by study group for the ITT population. 
The deviations will be identified before data are unblinded. 


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6.4 Demographics and Other Baseline Characteristics 
Demographic and important baseline characteristics will be listed and summarized by 
study group and overall for the Safety and ITT Populations. Furthermore, a summary 
for each study part and overall will be presented for the safety and ITT populations. 
Standard descriptive statistics will be presented for the continuous variables of: 
 
age (years); 
 
weight (kg); 
 
height (cm); 
 
body mass index (BMI) (kg/m2) (categories: <25, ≥25 to <30, and ≥30) 
 
baseline viral RNA (log10 copies/mL) 
 
baseline Peripheral Capillary Oxygen Saturation (SpO2) 
 
baseline Systolic blood pressure (mmHg) 
 
baseline Diastolic blood pressure (mmHg) 
 
baseline pulse rate (beats/min) 
 
baseline body temperature (ºC) 
 
baseline respiratory rate (breaths/min) 
 
days from onset of symptoms to first dose (defined as the date of first dose 
– date of symptom onset + 1, where date of symptom onset is the earliest 
date collected in medical history where “COVID-related” is recorded) 
The total counts and percentages of participants will be presented for the categorical 
variables of: 
 
age group (years) (grouped as <40, ≥40 to <65 and 65); 
 
use of remdesivir as a concomitant medication 
 
sex; 
 
race; 
 
ethnicity; 
 
baseline WHO ordinal scale for clinical improvement 
No formal tests of statistical significance will be performed on the demographic and 
baseline data (if no inferential tests are planned).   
Other baseline measurements, such as laboratory measurements, will be 
summarized by study group with the post-baseline measurements. 
6.4.1 Medical History 
Medical history will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) Version 23.1 (or a later version if updated during the study). All medical 
history will be listed, and the number and percentage of participants with any medical 


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history will be summarized for the Safety Population by system organ class (SOC) 
and preferred term (PT) for each study group and overall. 
6.4.2 Previous and Concomitant Medications 
Medications received prior to or concomitantly with study drug will be coded by 
 using the WHODrug Dictionary Version March 2019 Global Dictionary 
Version B3 (or a later version if updated during the study), Anatomical Therapeutic 
Chemical (ATC) Classification codes. Additional antivirals including, but not limited 
to, PEGylated interferon alpha, inhaled interferon beta1, ribavirin (any formulation) 
and any interleukin (IL)-6 inhibitor will be flagged. 
Prior medications and concomitant medications are defined as follows: 
 
Prior medications are those taken prior to study drug with a stop date prior to 
the first dose of study drug. 
 
Concomitant medications are those with a start date on or after the first dose 
date of study drug, or those with a start date before the first dose date of study 
drug and a stop date on or after the first dose date of study drug or ongoing 
end of study. 
If a medication cannot be classified as “prior” or “concomitant” after applying 
imputation rules for missing/incomplete dates, it will be classified as concomitant. 
Prior medications and concomitant medications will be listed together and 
summarized separately for the Safety population. Antiviral prior and concomitant 
medications will be identified in the listings using ATC-level 2 code J05. 
The number and percentage of participants using each medication will be displayed 
together with the number and percentage of participants using at least one 
medication within each therapeutic class (ATC-Level 2), chemical subgroup (ATC-
Level 4), and generic term. 
6.5 Efficacy 
6.5.1 Primary Efficacy Analysis 
The response rate per study group will be calculated by the number of subjects below 
the LOD for SARS-CoV-2 RNA as measured using qPCR divided by the number of 
subjects randomized to that study group in the ITT population and will be presented 
along with 95% exact binomial confidence intervals for each study group. Each active 
dose group and the pooled EIDD-2801 group will be compared to the placebo group 
separately using the Fisher’s Exact Test with a two-sided alpha level of 0.05. For 
subjects randomized prior to protocol v5.0, the response rate per study drug will be 
calculated using the number of subjects where both NP swabs at day 5 are below the 
limit of quantification for SARS-CoV-2 RNA as measured using qPCR for the 
numerator. If only one swab measurement is available, then this measurement will 
be used and if neither swab measurement is available participants will be imputed to 
have a value above the limit of quantification (non-response). If both measurements 
are available but the results are inconsistent then the participant will be considered 
to be above the limit of detectability. 


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6.5.2 Secondary Efficacy Analyses 
6.5.2.1 
Time to clearance of viral RNA in NP swabs 
The time to clearance of viral RNA in NP swabs will not be formally assessed. The 
number and percentage of participants with detectable SARS-CoV-2 RNA in NP swabs 
as measured using qPCR will be presented for each visit in the schedule of 
assessments where NP swabs are collected. Furthermore, the change in viral RNA 
from baseline (log10 copies/mL) will be calculated as log10 viral RNA at visit – 
baseline viral RNA. For participants randomized prior to v5.0 where measurements 
of viral RNA are available from both baseline NP swabs, the average will be used. The 
number and percentage of subjects with a 1 log10 copies/mL, 2 log10 copies/mL and 
3 log10 copies/mL decrease from baseline will be presented at each visit. Each active 
dose group and the pooled EIDD-2801 group will be compared to the placebo group 
separately using the Fisher’s Exact Test with a two-sided alpha level of 0.05. 
6.5.2.2 
Rate of decline in viral RNA in NP swabs 
The individual rate of SARS-CoV-2 RNA decline will be derived as Average Area 
Under the Curve Minus Baseline (AAUCMB) for the 0-3 days, 0-5 days, 0-8 days, 
and 0-11 days using the following formulas: 


AUC 










t
t
x
x
i
i
i
i
i
n
1
1
1
1
2
, 






1
1
1
1
1
1
AUC
2
AAUC
t
t
t
t
x
x
t
t
n
n
n
i
i
i
i
i














, and 
AAUCMB=AAUC – Baseline (x at time i=1) 
where, xi is the data value at the ith time point and ti is the time value at the ith time 
point. 
The AAUCMB will be analyzed using an Analysis of Covariance (ANCOVA) model with 
terms for study group, days from onset of symptoms to first dose and baseline SARS-
CoV-2 RNA by the time interval.  The estimated treatment difference for “Active – 
Placebo” for each time interval will be displayed in the summary of statistical analysis 
together with the 95% confidence interval and the associated p-value. Least Squares 
Means will also be presented with the standard error. 
6.5.2.3 
Decline in viral RNA in NP swabs 
The decline in log10 viral RNA copies/mL in NP swabs by qPCR will be calculated using 
a mixed effect model for repeated measures in the EAS population. The dependent 
variable will be log10 viral RNA copies/mL in NP swabs by qPCR, both swab 
measurements from a visit for a participant will be included if available. The 
independent fixed effect variables will include study drug (reference group will be 
placebo), days from first dose of study drug (day of NP swab-first dose of study drug 


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+1), baseline log10 viral RNA copies in NP swabs by qPCR, days from onset of 
symptoms to first dose, an interaction of days from onset of symptoms to first dose 
and visit, an interaction of baseline RNA and visit, and an interaction term between 
study drug and days from first dose of study drug (formal significance for the 
interaction term will be determined by p<0.05). A random intercept will be included 
per participant and an unstructured covariance matrix will be used, estimated using 
restricted maximum likelihood. 
The statistical model estimated will be used to calculate the least squares mean 
(LSmean), treatment estimates, treatment differences (each active EIDD-2801 dose 
– placebo) and 95% CI at days 3, 5, 8, 11, 15(in patient only), 19 (in patient only) 
and 28 (outpatient only). 
6.5.3 Subgroup Analysis 
Exploratory analyses of the primary and secondary efficacy endpoints discussed in 
sections 6.5.1 and 6.5.2, as well as all safety endpoints for adverse events and 
laboratory assessments discussed in sections 6.6.2 and 6.6.3, will be performed for 
the following subgroups: 
 
Use of remdesivir as a concomitant medication (No use, use) 
 
COVID-19 risk group (0, 1, ≥2) 
Note that for purposes of analyses the COVID-19 risk groups may be collapsed to 0 
and ≥1, if the data warrants it. 
A participant’s COVID-19 risk group is defined based on the number of the below 
criteria applicable at baseline assessment: 
 
Cancer   
 
Chronic kidney disease  
 
COPD (chronic obstructive pulmonary disease)   
 
Down Syndrome   
 
Heart conditions, such as heart failure, coronary artery disease, or 
cardiomyopathies   
 
Immunocompromised state (weakened immune system) from solid organ 
transplant   
 
Currently receiving immunosuppressive treatment   
 
Obesity (body mass index [BMI] of 30 kg/m2 or higher but < 40 kg/m2)   
 
Body mass index of 35 or higher     
 
Are 65 years or older  
 
Are 55 years or older and have hypertension) 
 
Sickle cell disease   
 
Smoking (Current or former) 
 
Type 2 diabetes mellitus 
Note that subjects assigned to the obesity (BMI of 30<- to <40) and the BMI of 35 
or higher risk groups will be counted as 1 risk factor.  Note, for the subgroup 
analysis by use of remdesivir the fixed terms for the use of remdesivir will be 


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removed from the models. The use of remdesivir as a concomitant medication will 
be determined using the rules defined in section 6.4.2. 
6.5.4 Exploratory Efficacy Analysis 
6.5.4.1 
Undetectable infectious viral RNA by day 3 and day 5 in NP 
swabs 
Infectious viral RNA in NP swabs will be determined using an infectivity assay and 
will provide a binary indication if infectious viral RNA is present. The presence of 
infectious viral RNA at days 1, 3, 5, 8, 11, 15 (in patient only), 19 (in patient only) 
and 28 (outpatient only) will be analyzed using the same method as specified in 
section 6.5.1 for the primary efficacy endpoint in the EAS population. The analysis 
will be repeated for subjects with a positive infectious viral RNA at baseline. 
Participants without a result for viral RNA in NP swabs by infectivity assay will be 
presented as missing for a visit and no imputation will be applied. 
 
6.5.5 Secondary Clinical Analyses 
6.5.5.1 
Peak Stage of WHO Ordinal Scale for Clinical Improvement 
The number and percentage of participants per peak stage on the WHO Ordinal Scale 
for Clinical Improvement will be presented by study drug group in the safety 
population. Peak stage will refer to the highest (worst) measured scale per participant 
recorded after baseline. For WHO Ordinal Scale, the baseline measurement will allow 
for measurements to be taken up to 4 hours after the first dose of study treatment. 
6.5.5.2 
Requirement for additional antivirals 
The number and proportion of participants receiving additional antivirals (including, 
but not limited to, PEGylated interferon alpha, inhaled interferon beta1, ribavirin (any 
formulation) and any interleukin (IL)-6 inhibitor) after baseline will be presented per 
study drug group in the safety population along with the two-sided 95% CI using the 
Clopper-Pearson method (exact CI for a binomial proportion). 
6.5.5.3 
Number of days of supplemental oxygen 
The number of total days of supplemental oxygen is calculated per participant. This 
will be summarized continuously by study group. Participants who remain on 
supplemental oxygen at the end of study visit will have their value imputed as number 
of days of supplemental oxygen+1. Participants who require no supplemental oxygen 
will be analyzed with a value of 0. The peak amount of oxygen used will be 
summarized descriptively where available. These analyses will use the safety 
population. 
6.5.5.4 
Number of days of mechanical ventilation 
The number of total days of mechanical ventilation is calculated per participant. This 
will be summarized continuously by study group. Participants who remain on 
mechanical ventilation at the end of study visit will have their value imputed as 
number of days of mechanical ventilation+1. Participants who require no mechanical 


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ventilation will be analyzed with a value of 0. This analysis will use the safety 
population. 
6.5.5.5 
Number of days in the ICU 
The number of total days in the intensive care unit (ICU) is calculated per participant. 
This will be summarized continuously by study group. Participants who remain in the 
ICU at the end of study visit will have their value imputed as number of days in the 
ICU+1. Participants who no require ICU will be analyzed with a value of 0. This 
analysis will use the safety population. 
6.5.5.6 
Death 
The number and proportion of participants who died will be presented by study group 
along with the two-sided 95% CI using the Clopper-Pearson method (exact CI for a 
binomial proportion) for the safety population. 
6.5.6 Exploratory Clinical Analyses 
6.5.6.1 
Number of days of hospitalization 
The number of days of hospitalization is calculated as last day of the 
hospitalization/end of study – first day in ICU +1). Participants will be 
administratively censored at the end of study visit date if participants still require 
hospitalization. The median (95% CI) number of days of hospitalization will be 
presented by study drug using the Kaplan-Meier method for the safety population. 
This will be summarized continuously by study group. Participants who remain in 
hospital at the end of study visit will have their value imputed as number of days of 
hospitalization+1. This analysis will use the safety population. 
6.5.6.2 
Time until on room air without requirement for supplemental 
oxygen 
The time until on room air without requirement for supplemental oxygen is defined 
as the time from first use of supplemental oxygento the first date where supplemental 
oxygen is no longer required (date supplemental oxygen discontinued – date of first 
use of supplemental oxygen + 1).The median (95% CI) time until on room air without 
the requirement for supplemental oxygen will be presented by study group using the 
Kaplan-Meier method for the safety population excluding participants who do not 
require supplemental oxygen. 
6.5.6.3 
Time to resolution of COVID-19 symptoms 
The time to resolution of COVID-19 symptoms is defined as the time from first dose 
of study drug to the first date where COVID-19 symptoms have been completely 
resolved (date COVID-19 symptom free– date of randomization +1). Resolution of 
COVID-19 symptoms is defined as the complete resolution of symptoms including: 
fever, cough, shortness of breath, respiratory rate ≥ 20 breaths per minute and other 
clinical symptoms or signs that are not otherwise explained by comorbidities or co-
diagnoses. COVID-19 symptoms will be collected on the medical history eCRF at 
baseline and adverse event form during the study with a check box indicating if the 
sign or symptom is COVID-19 related. All adverse events and medical history related 
to COVID-19 must be resolved for a participant to be declared COVID-19 symptom 


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free. The median (95% CI) time to resolution of COVID-19 symptoms will be 
presented by study drug using the Kaplan-Meier method for the safety population. 
6.5.6.4 
Number of days until a 2-point decrease in WHO Clinical 
improvement scale 
The time to a 2-point decrease in the WHO clinical improvement scale is defined as 
the time from first dose of study drug to the first date where a 2-point decrease is 
detected (date 2-point decrease – date of randomization +1). The median (95% CI) 
time to a 2-point decrease will be presented by study drug using the Kaplan-Meier 
method for the safety population. 
6.5.6.5 
Radiological improvement 
Radiological impression from available radiographic reports will be listed by study 
drug, participant and visit. 
6.5.6.6 
Change in interleukin (IL)-6 levels 
The change from baseline in IL-6 levels will be summarized by study drug group at 
day 5, 19 (inpatient only) and 28 (outpatient only) after randomization in the EAS 
population. An ANCOVA analysis will be conducted with dependent variables of IL-6 
at day 5 and independent variables of baseline IL-6 and study drug. The LSmean, 
treatment estimates, treatment differences (each active EIDD-2801 dose – placebo) 
and 95% CI will be presented. Other cytokine/inflammatory biomarkers analyzed as 
part of this clinical endpoint will be analyzed as described above. All IL-6 and other 
cytokine/inflammatory biomarkers will be listed. 
6.5.7 Pharmacokinetic Analyses 
6.5.7.1 
Pharmacokinetic Analysis 
PK parameters will be determined using non-compartmental methods in validated 
software program, Phoenix WinNonlin (Certara, Version 8.1 or higher). 
The pharmacokinetic analysis and presentation for PBMC samples will be analyzed 
separately with analyses pre-specified in a separate analysis plan. 
The following parameters will be calculated where possible from the plasma 
concentrations of EIDD-2801 and EIDD-1931: 
Parameter 
Unitsa 
Definition 
AUC0-8 
h*ng/mL 
area under the plasma concentration-time curve during 
a dosing intervalb 
Cmax 
ng/mL 
maximum observed concentration 
C1.5 
ng/mL 
concentration at 1.5 hours postdose 
C3 
ng/mL 
concentration at 3 hours postdose 
tmax 
h 
time of the maximum observed concentration 
tlast 
h 
time of the last quantifiable concentration 


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t1/2 
h 
apparent terminal elimination half-life 
a Units are based on concentration units (provided by bioanalytical lab) and dose units used in the 
study. 
b AUC will be calculated using the linear trapezoidal rule for increasing concentrations and the 
logarithmic rule for decreasing concentrations (linear up/log down rule). 
 
Additional pharmacokinetic parameters may be calculated where appropriate. 
Pharmacokinetic analysis will, where possible, be carried out using actual blood 
sampling times postdose. If an actual time is missing, the sample concentration 
result will be treated as missing unless there is scientific justification to include the 
result using the nominal time.  
Pharmacokinetic parameters will be derived where possible for all subjects. Data 
from subjects with incomplete profiles (missed blood draws, lost samples, samples 
unable to be quantified) may be used if PK parameters can be estimated using the 
remaining data points.  
The following molecular weights (MW) will be used in calculations where required 
EIDD-1931  
259.22 g/mol 
EIDD-2061  
TBC g/mol 
Cmax, tlast and tmax will be obtained directly from the concentration-time profiles. If 
Cmax occurs at more than 1 timepoint, tmax will be assigned to the first occurrence of 
Cmax.  
PBMC EIDD-2061 : plasma EIDD-1931 ratios will be calculated, adjusting for the 
difference in molecular weight as follows: 
 
(ConcentrationEIDD-1931/MWEIDD-1931)/(ConcentrationEIDD-2061/MWEIDD-2061) 
 
Ratios will not be calculated where the time difference between the plasma and 
PBMC sample actual times differs by more than 10%. 
6.5.7.2 
Criteria for the Calculation of Apparent Terminal Elimination 
Rate Constant and Half-Life 
The start of the terminal elimination phase for each subject will be defined by visual 
inspection and generally will be the first point at which there is no systematic 
deviation from the log-linear decline in concentrations.  
The apparent terminal elimination rate constant (λz) will only be calculated when a 
reliable estimate can be obtained using at least 3 data points, preferably not including 
Cmax, and the adjusted coefficient for determination of exponential fit (R2-adj) of the 
regression line is ≥0.7. Parameters requiring λz in their calculation (e.g., AUC0-12, t1/2) 
will only be calculated if the R2-adj value of the regression line is ≥0.7.  


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The following regression-related diagnostic PK parameters will be determined:  
Parameter 
Units 
Definition 
λz 
1/h 
apparent terminal elimination rate constant 
λz Upper 
h 
end of exponential fit 
λz Lower 
h 
start of exponential fit 
λz N 
Not applicable 
number of data points included in the log-linear 
regression 
λz Span Ratio 
Not applicable 
time period over which λz was determined as a ratio of 
t1/2 
R2-adj 
Not applicable 
adjusted coefficient for determination of 
exponential fit 
Where possible, the span of time used in the determination of λz (i.e. the difference 
between λz Upper and λz Lower) should be ≥2 half-lives. If the λz Span Ratio is <2, 
the robustness of the t1/2 values will be discussed in the CSR. 
6.5.7.3 
Criteria for Calculation and Reporting of Area Under the 
Concentration-time Curve 
The minimum requirement for the calculation of AUC will be the inclusion of at least 
3 consecutive concentrations above the lower limit of quantification. If there are only 
3 consecutive concentrations, at least 1 should follow Cmax.  
6.5.7.4 
Criteria for Handling Below the Limit of Quantification or 
Missing Concentrations for Pharmacokinetic Analysis 
Plasma concentration values that are below the limit of quantification (BLQ) will be 
set to a value of zero, with the following defined exceptions which will be set to 
missing: 
● Any embedded BLQ value (between 2 quantifiable concentrations). 
● BLQ values following the last quantifiable concentration in a profile. 
● If an entire concentration-time profile is BLQ, it will be excluded from PK 
analysis. 
Where 2 or more consecutive concentrations are BLQ at the end of a profile, the 
profile will be deemed to have terminated and any further quantifiable 
concentrations will be set to missing for the calculation of the PK parameters unless 
they are considered to be a true characteristic of the profile of the drug. 
If a predose plasma concentration is missing, it may be set to zero by default. 


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6.5.7.5 
Treatment of Outliers in Pharmacokinetic Analysis 
If a value is considered to be anomalous due to being inconsistent with the expected 
PK profile, it may be appropriate to exclude this point from the PK analysis. However, 
the exclusion of data must have strong justification and will be documented in the 
CSR.   
Quantifiable pre-dose concentration values prior to the first dose will be considered 
anomalous and set to missing for the PK analysis.  
6.5.7.6 
Presentation of Pharmacokinetic Data 
If the actual time of sample collection deviates by greater than ±10% from the 
protocol scheduled time the concentration will be flagged for exclusion from summary 
tables and corresponding figures.  
Individual concentrations that are deemed to be anomalous will be flagged in the 
listings and excluded from the summary statistics.  Summary tables, arithmetic 
mean figures, overlaying individual figures, and individual figures by treatment and 
time post-dose will be provided for plasma PK concentrations. All figures will be 
produced on both linear and semi-logarithmic scales. Individual (separate and 
overlaying) figures will be plotted using actual sample times and will be based upon 
the safety analysis set.  Arithmetic mean figures will be based upon the PK 
population. 
Summary tables by study group will be provided for all plasma PK parameters, with 
the exception of diagnostic regression-related PK parameters, which will be listed 
but not summarized. 
A listing of PK blood sample collection times as well as derived time deviations and 
all reportable concentrations will be presented for EIDD-1931 for all participants for 
the safety population. 
Plasma concentrations will be summarized for the PK population for each time point 
using protocol scheduled times and appropriate descriptive statistics (i.e., n, n below 
LLOQ, geometric mean [gmean], geometric standard deviation [gSD], , geometric 
coefficient of variance expressed as a percentage [gCV%], arithmetic mean [mean], 
arithmetic SD [SD], coefficient of variance expressed as a percentage [CV%], 
median, minimum and maximum). 
The gmean is calculated as exponential (µ), where µ is the arithmetic mean calculated 
using log transformed data. 
The gCV% is calculated as 100 x sqrt[exp(s2)-1], where s is the SD of the log-
transformed data. 
The gmean±gSD (gmean-gSD and gmean+gSD) are calculated as exp(µ±s). 
Individual concentrations below the LLOQ of the bioanalytical assay will be reported 
as BLQ in the listings with the LLOQ defined in the footnotes of the relevant tables, 
figures and listings. 


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Individual plasma concentrations that are Not Reportable will be reported as NR and 
those that are missing willbe reported as NS (No Sample) in the listings. 
Plasma concentrations that are BLQ, NR or NS will be handled as follows for the 
provision of the descriptive statistics. 
 
Any values reported as NR or NS will be excluded from the summary tables 
and corresponding figures. 
 
At a timepoint where less than or equal to 50% of the concentration values 
are BLQ, all BLQ values will be set to 0, and all descriptive statistics will be 
calculated accordingly. 
 
At a timepoint where more than half of the values are BLQ, the gmean, 
gmean+gSD, gmean-gSD, gCV%, mean, SD and CV% will be set to NC. The 
maximum value will be reported from the individual data, and the minimum 
and median will be set to BLQ. 
 
If all values are BLQ at a time point, no descriptive statistics will be 
calculated for that time point. The gmean, mean, minimum, median and 
maximum will be reported as BLQ and gmean±gSD, gCV%, SD and CV% as 
NC. 
The number of values below LLOQ (n <LLOQ) will be reported for each time point 
together with the total number of collected values (n). 
Three observations >LLOQ are required as a minimum for a plasma concentration 
to be summarized. Two values >LLOQ are presented as a minimum and maximum 
with the other summary statistics as NC. 
Plasma concentrations that are BLQ will be handled as follows for display in figures: 
 
Arithmetic mean plots will use the same BLQ handling rules as for the 
summary statistics 
 
For individual plots and combined individual plots: BLQ values prior to the 
first quantifiable concentration in that profile will be set to zero (linear plots 
only); after the first quantifiable concentration of the profile any BLQ values 
will be set to missing. 
All reportable PK parameters will be listed for EIDD-1931 for participants in the PK 
population.  
Plasma PK parameters for EIDD-1931 will be summarized for the PK analysis set by 
drug group using the following descriptive statistics: 
 
Cmax C1.5, C3,AUC(0-8), tmax and t1/2will present n, gmean, gSD, gmean 95% CI, 
gCV (%), mean, SD, CV%, median, min and max. 
For the calculation of summary statistics of PK parameters, all not reportable (NR) 
and not calculated (NC) values will be set to missing. Three reportable values are 
required as a minimum for a PK parameter to be summarized. Two values are 
presented as a minimum and maximum with the other summary statistics as NC. If 


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one or more values for a given parameter is zero (or imputed with zero), then no 
geometric statistics will be calculated for that parameter and the results for 
geometric statistics will be set to “NA”, not applicable. 
6.5.7.7 
Precision and Rounding Rules 
PK concentration data will be presented in the listings to the same number of 
significant digits as the data received from the bioanalytical laboratory (usually to 3 
significant figures) and against the same units as received.  
PK concentration descriptive statistics will all be presented to 4 significant figures 
with the exception of the minimum and maximum which will be presented to 3 
significant figures and n and n<LLOQ which will be presented as integers.  
For plasma PK parameters, the listings will be presented according to the following 
rules: 
 
Cmax, C1.5, C3– will be presented to the same number of significant figures as 
received from the bioanalytical laboratory 
 
tmax, tlastwill be presented as received in the data, usually to 2 decimal places 
 
AUC(0-12)and t1/2 - will be presented to 3 significant figures 
For PK parameter data the descriptive statistics will be presented according to the 
following rules: 
 
Css, Cmax, C1.5, C3, AUC(0-8) and t1/2- all descriptive statistics will be presented 
to 4 significant figures with the exception of the minimum and maximum 
which will be presented to 3 significant figures and n which will be presented 
as integers 
6.5.7.8 
Dose Proportionality 
Dose proportionality will not be formally analyzed but will be summarized 
descriptively using dose normalized PK parameters Cmax and AUC(0-8). 
6.5.7.9 
(Relationship between exposure parameters and virologic 
endpoints 
The response-response relationship between Plasma PK parameters (AUC0-8, Cmax 
and trough concentration, pre-dose at day 3) and efficacy endpoint of change from 
baseline in SARS-CoV-2 RNA at day 5 will be analyzed using a simple linear model. 
The paired concentration and efficacy endpoint(s) will be plotted with a fitted 
regression line superimposed. Additional statistical models will be explored if data 
warrant. 


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6.6 Safety 
6.6.1 Extent of Exposure 
Exposure will be defined in terms of numbers of doses taken. The percentage of 
expected exposure received will be calculated as the number of doses taken/10 
expected doses and will be presented descriptively by study drug. 
Where timing of dose is unavailable for a day but dosing is recorded the participant 
will be imputed to have received both doses of study drug. 
6.6.2 Adverse Events 
All adverse events (AEs) recorded on the eCRF will be coded using the MedDRA 
dictionary Version 23.1 (or a later version if updated during the study)]. 
All AE data will be listed by study group. Furthermore, all EIDD-2801 study groups 
will be pooled and presented as All EIDD-2801. In addition, corresponding listings of 
SAEs, AEs leading to discontinuation of study drug and AEs resulting in death will be 
produced. 
The number and percentage of participants reporting each AE will be summarized for 
each study group and overall, by System Organ Class (SOC) (sorted alphabetically) 
and Preferred Term (PT) (sorted by descending overall total) for the Safety 
population. 
The relationship between an AE and study drug is assessed as related or not 
related. A study drug-related AE is an AE considered by the investigator as related 
to study drug or with unknown/missing relationship to study drug. 
An overview table will summarize the number and percentage of participants with 
at least one of the following AEs, where participants with more than one AE in a 
particular category are counted only once in that category: 
 
any AE;  
 
any AE by maximum grading (mild, moderate, severe, potentially life-threatening, 
death); 
 
study drug-related AE;  
 
SAE;  
 
AE leading to study drug discontinuation;  
 
Study drug-related SAE;  
 
SAE leading to death; 
 
Any grade 3/4 AE 
 
Any deaths 
The overview table will also summarize the number of the following AEs: 


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 
any AE;  
 
any AE by maximum grading (mild, moderate, severe, potentially life-threatening, 
death); 
 
study drug-related AE;  
 
SAE;  
 
AE leading to study drug discontinuation;  
 
Study drug-related SAE;  
 
SAE leading to death; 
 
Any grade 3/4 AE 
 
Any deaths 
The number and percentage of participants reporting each AE will be summarized by 
System Organ Class (SOC) and Preferred Term (PT) for the Safety population.  Tables 
will be sorted alphabetically by SOC.  PTs will be sorted by descending overall total.  
The following summaries will be produced: 
 
AEs, by SOC and PT; 
 
AEs by PT; 
 
AEs related to study drug, by SOC and PT; 
 
AEs by maximum grade, by SOC and PT; 
 
AEs leading to study drug discontinuation, by SOC and PT; 
 
AEs related to study drug causing discontinuation from study drug, by SOC and 
PT; 
 
SAEs, by SOC and PT; 
 
SAEs related to study drug, by SOC and PT; 
 
Grade 3 or 4 AEs, by SOC and PT; 
 
AEs leading to death, by SOC and PT 
In the above summaries, participants with more than one AE within a particular SOC 
are counted only once for that SOC.  Similarly, participants with more than one AE 
within a particular PT are counted only once for that PT.  For summaries by maximum 
grade, participants with multiple AEs within a particular SOC or PT will be counted 
under the category of their most severe AE within that SOC or PT. AEs with missing 
intensity/severity will be included (as severe) in the overall count of participants with 
AEs, but will not be included in the counts of participants with AEs within a SOC or 
PT. 
The following listings will be produced: 
 
All deaths 
 
All SAEs 


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 
All AEs leading to discontinuation of study drug 
No statistical comparisons of AEs between study groups will be performed. 
6.6.3 Laboratory Evaluations 
Data for the following hematology, blood chemistry, and urinalysis analytes recorded 
in the eCRF will be listed and summarized by study group and visit. If data for any 
additional analytes are also recorded, then these will be listed only. 
 
Complete Blood 
Counts (CBC) 
Comprehensive Metabolic Panels 
(CMP) 
Urinalysis 
Red Blood Cell Count  
Hematocrit 
Hemoglobin 
White Blood Cell Count 
Eosinophils 
Basophils 
Lymphocytes 
Neutrophils 
Monocytes 
Immature granulocytes 
Platelets 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST) 
Total Bilirubin  
Alkaline phosphatase  
Albumin 
Total protein  
Glucose  
Calcium  
Creatinine  
Estimated GFR 
Blood Urea Nitrogen  
Potassium 
Sodium  
Chloride 
Carbon Dioxide 
Anion Gap 
BUN/Creatinine ratio 
AST/ALT ratio 
Amylase 
Lipase 
Red blood Cell Count  
Glucose 
White Blood Cell Count 
Proteins 
Nitrites 
pH 
Ketones 
Bilirubin 
Blood 
Leukocyte 
Urobilinogen 
Hyaline casts 
Granular casts 
Epithelial cells 
Bacteria 
Crystals 
 
 
All laboratory data will be reported in International System of Units (SI)/Conventional 
units. Out-of-reference-range values will be flagged as high (H) or low (L) in the 
listings. 
For analysis purposes, values preceded by a “<” or a “>”sign (i.e. those below or 
above the limits of quantification) will be considered equal to the lower or upper limit 
of quantification, respectively. 
Laboratory data will be summarized by visit using standard descriptive statistics for 
the Safety population. Changes from baseline will also be summarized. 
The number and percentage of participants with treatment emergent laboratory 
toxicities (an increase of at least one grade from baseline, or any toxicity where 
baseline grade is 0) with a lab toxicity grade of 3 or 4 will be tabulated by study 
group. 


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The following changes in laboratory parameters will be dichotomized and the number 
and percentage of participants who achieve each threshold will be tabulated by study 
group and visit: 
 
A decrease in hemoglobin from baseline by >1 g/dL or to <9 g/dL 
 
A decrease in platelet count from baseline by >50,000/µL or to <75,000/µL 
 
Aspartate aminotransferase (AST) ≥ 3x the upper limit of normal 
 
Alanine aminotransferase (ALT) ≥ 3x the upper limit of normal 
 
Amylase ≥ 3x the upper limit of normal 
 
Lipase ≥ 3x the upper limit of normal 
For each laboratory analyte, the baseline value will be defined as last scheduled value 
collected prior to the first dose of study drug. Assessments carried out on the day of 
first study drug administration are considered to have taken place before the study 
drug administration, if the corresponding times have not been recorded. For post-
baseline, only data from scheduled visits will be included in the summary tables. All 
measurements will be included in listings and will be presented including the toxicity 
grade. 
6.6.4 Vital Signs 
The following vital signs will be listed and summarized by study group and visit. 
 
systolic and diastolic blood pressure (mmHg); 
 
heart rate (bpm); 
 
respiration rate (breaths/min); 
 
body temperature (°C) 
 
mean arterial pressure (mmHg) 
 
oxygen saturation, SpO2 (%) 
Vital signs data and changes from baseline in vital signs will be summarized by visit 
using standard descriptive statistics for the Safety population. The baseline value will 
be defined as last scheduled value collected prior to the first dose of study drug.  
Assessments carried out on day of first study drug administration are considered to 
have taken place before the study drug administration, if the corresponding times 
have not been recorded. For post-baseline, only data from scheduled visits will be 
included in the summary tables. If multiple vital sign measurements are available for 
a participant for the same visit the average will be calculated and used in the 
summary tables. 
6.6.5 Electrocardiograms 
An overall Investigator assessment of ECGs will be collected during the study 
(categories “normal”, “abnormal, not clinically significant” and “abnormal, clinically 
significant”). ECG assessments will be presented in listings. 


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6.6.6 Physical Examination 
Abnormalities identified from physical examinations are recorded in the eCRF as 
Medical History or Adverse Events as appropriate and will be listed and summarized 
as such [See Sections 6.4.1 (Medical History) and 6.6.2 (Adverse Events)]. 
6.6.7 Other Safety Variables – Not Applicable 
6.7 Interim Analysis 
Interim analyses are planned after 25% (n=15) and 50% (n=30) of planned 
participants reach day 14 after the initiation of study drug. Blinded data will be 
reviewed by the principal investigators and the sponsor. No formal interim analysis 
of the planned virological efficacy or clinical endpoints are planned so no 
adjustment is required to control for the type I error. Data to be reviewed will 
include blinded summaries of the primary efficacy endpoint (achievement of 
undetectable viral RNA by day 5 in NP swabs) and the primary safety endpoints. 
The interim analyses will be used to inform sponsor decisions about whether to 
continue, amend, or stop the study. 
A safety review committee (SRC), composed of the principal investigator for each 
study site and the medical monitor, will be established. The Committee will review 
blinded safety data at regular intervals.  SRC will determine if the study enrollment 
or study dosing should be interrupted or if study enrollment and study dosing may 
continue according to the protocol. Full details of the composition, responsibilities 
and procedures of the SRC are described in the SRC Charter. 
7. Changes in Planned Analysis 
The protocol v5.0 specifies that the time to clearance of viral RNA in NP swabs by 
qPCR should be analyzed as a secondary virologic endpoint. This SAP presents the 
number and proportion with detectable virus at each timepoint but does not 
formally estimate time to clearance of viral RNA in NP swabs. 
The protocol v5.0 specifies that the number of acquired single-nucleotide 
polymorphisms in SARS-CoV-2 genomes by days 5 and 11 in NP swabs by viral 
sequencing should be analyzed. The analysis plan for this endpoint will be described 
elsewhere and will not be included in this SAP or the associated TFL shells. 
The protocol v5.0 states that the cumulative incidence, risk difference and 95% CI 
will be calculated for the primary safety endpoints for each study arm at interim 
analyses. The assessment of safety specified for these endpoints will be as 
described in section 6.6.2.  


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8. Data Issues 
This section is not required at this time, but will be populated in a future approved 
version of this document. 
9. References 
1 
ICH. Statistical Principles for Clinical Trials, Guideline E9, 1998. Available at 
http://www.emea.eu.int/pdfs/human/ich/036396en.pdf 
2 
CPMP. Points to Consider on Missing Data. EMEA: London, 2001. Available 
at http://www.emea.eu.int/pdfs/human/ewp/177699EN.pdf 
3 
Phillips A and Haudiquet V. ICH E9 guideline “Statistical principles for 
clinical trials”: a case study. Statistics in Medicine 2003; 22:1-11 
4 
Brown D J. ICH E9 guideline “Statistical principles for clinical trials”: a case 
study. Response to A. Phillips and V. Haudiquet. Statistics in Medicine 
2003; 22:13-17 
5 
ICH. ICH E3 Guideline: Structure and Content of Clinical Study Reports 
Questions & Answers, 2012. Available at 
http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Eff
icacy/E3/E3_QAs_R1_Step4.pdf 
6 
Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, 
Niemeyer D, Jones TC, Vollmar P, Rothe C, Hoelscher M, Bleicker T, Brünink 
S, Schneider J, Ehmann R, Zwirglmaier K, Drosten C, Wendtner C. 
Virological Assessment of Hospitalized Patients With COVID-2019. Nature. 
2020 Apr 1. doi: 10.1038/s41586-020-2196-x. 32235945 
 
 


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10. Appendices 
Appendix 1: 
Document History 
Document Version, Status, Date 
Summary/Reason for Changes 
Version 2.0, Final, 22-Dec-2020 
Final version of 1.4 update 
Version 1.4, Draft, 22-Dec-2020 
Minor amendment for Ridgeback comments 
Version 1.3, Draft, 21-Dec-2020 
Incorporating review comments from 
Ridgeback 
Version 1.2, Draft, 09-Dec-2020 
Changes to reflect protocol v5.0 update 
Version 1.1, Draft, 09-Oct-2020 
Changes to reflect protocol v4.0 update 
Version 1, Final, 03-Sep-2020 
Not applicable; the first version 
Appendix 2: 
Table of Contents for SAP Shells - Tables 
TFL Number 
Title 
Analysis 
Population 
SRC 
14.1.1.1 
Participant Disposition 
Screened 
Y 
14.1.1.2 
Participant Disposition (Study 
Part) 
Screened 
Y 
14.1.2 
Participant Enrollment by Site 
Randomized 
N 
14.1.3.1 
All Protocol Deviations 
ITT 
Y 
14.1.3.2 
Important Protocol Deviations  
ITT 
N 
14.1.4.1 
Demographic and Important 
Baseline Characteristics 
Safety 
Y 
14.1.4.2 
Demographic and Important 
Baseline Characteristics 
ITT 
N 
14.1.4.3 
Demographic and Important 
Baseline Characteristics (Study 
Part) 
Safety 
N 
14.1.4.4 
Demographic and Important 
Baseline Characteristics (Study 
Part) 
ITT 
N 
14.1.5 
Medical History 
Safety 
N 
14.1.6.1 
Prior Medications 
Safety 
N 
14.1.6.2 
Concomitant Medications 
Safety 
N 
14.2.1.1 
Undetectable SARS-CoV-2 RNA 
by Day 5 by qPCR in NP Swabs 
ITT 
N 


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14.2.1.2 
Undetectable SARS-CoV-2 RNA 
by Day 5 by qPCR in NP Swabs 
by Use of Remdesivir 
ITT 
N 
14.2.1.3 
Undetectable SARS-CoV-2 RNA 
by Day 5 by qPCR in NP Swabs 
by COVID-19 Risk Group 
ITT 
N 
14.2.1.4 
Change in SARS-CoV-2 RNA by 
qPCR in NP Swabs 
EAS 
N 
14.2.1.5 
Change in SARS-CoV-2 RNA by 
qPCR in NP Swabs by Use of 
Remdesivir 
EAS 
N 
14.2.1.6 
Change in SARS-CoV-2 RNA by 
qPCR in NP Swabs by COVID-19 
Risk Group 
EAS 
N 
14.2.1.7 
Longitudinal Analysis of SARS-
CoV-2 RNA by qPCR in NP 
Swabs 
EAS 
N 
14.2.1.8 
Longitudinal Analysis of SARS-
CoV-2 RNA by qPCR in NP 
Swabs by Use of Remdesivir 
EAS 
N 
14.2.1.9 
Longitudinal Analysis of SARS-
CoV-2 RNA by qPCR in NP 
Swabs by COVID-19 Risk Group 
EAS 
N 
14.2.1.10 
Change from Baseline in SARS-
CoV-2 RNA by qPCR in NP 
swabs 
EAS 
N 
14.2.1.11 
Change from baseline in SARS-
CoV-2 RNA by qPCR in NP 
swabs by Use of Remdesivir 
EAS 
N 
14.2.1.12 
Change from baseline in SARS-
CoV-2 RNA by qPCR in NP 
swabs by COVID-19 Risk Group 
EAS 
N 
14.2.1.13 
Individual Rate of SARS-CoV-2 
RNA Decline 
EAS 
N 
14.2.1.14 
Individual Rate of SARS-CoV-2 
RNA Decline by Use of 
Remdesivir 
EAS 
N 
14.2.1.15 
Individual Rate of SARS-CoV-2 
RNA Decline by COVID-19 Risk 
Group 
EAS 
N 
14.2.1.16 
Summary of Risk Factors for 
Severe COVID-19 
Safety 
N 
14.2.2.1 
Undetectable Viral Titers by 
Infectivity Assay in NP Swabs 
EAS 
N 
14.2.2.2 
Undetectable Viral RNA by 
Infectivity Assay in NP Swabs in 
EAS 
N 


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Patients With Positive Infectious 
RNA at Baseline 
14.2.3.1 
Summary of Peak WHO Ordinal 
Scale for Clinical Improvement 
Safety 
N 
14.2.3.2 
Summary of Requirement for 
Additional Antivirals 
Safety 
N 
14.2.3.3 
Summary of Requirement for 
Supplemental Oxygen During 
the First 28 Days 
Safety 
N 
14.2.3.4 
Summary of Requirement for 
Mechanical Ventilation 
Safety 
N 
14.2.3.5 
Summary of Requirement for 
Intensive Care Unit 
Safety 
N 
14.2.4.1 
Summary of Requirement for 
Hospitalization 
Safety 
N 
14.2.4.2 
Time Until On Room Air Without 
Requirement For Supplemental 
Oxygen 
Safety 
N 
14.2.4.3 
Time to Resolution of COVID-19 
Symptoms 
Safety 
N 
14.2.4.4 
Summary of 2-point Decrease 
in WHO Ordinal Scale for 
Clinical Improvement 
Safety 
N 
14.2.4.5 
Change from Baseline in 
Cytokine/Inflammatory 
Biomarkers 
Safety 
N 
14.2.5.1 
Summary of Plasma 
Concentrations of EIDD-2801 
(ng/mL) 
PK 
N 
14.2.5.2 
Summary of Plasma 
Concentrations of EIDD-1931 
(ng/mL) 
PK 
N 
14.2.5.3 
Summary of Pharmacokinetic 
Parameters of EIDD-1931 
PK 
N 
14.3.1.1 
Summary of Study Drug 
Exposure 
Safety 
Y 
14.3.2.1 
Summary of Adverse Events by 
Treatment Group 
Safety 
Y 
14.3.2.2 
Summary of Adverse Events by 
Treatment Group and Use of 
Remdesivir 
Safety 
N 
14.3.2.3 
Summary of Adverse Events by 
Treatment Group and COVID-
19 Risk Group 
Safety 
N 


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14.3.2.4 
Adverse Events by System 
Organ Class and Preferred 
Term 
Safety 
Y 
14.3.2.5 
Adverse Events by System 
Organ Class and Preferred 
Term and Use of Remdesivir 
Safety 
N 
14.3.2.6 
Adverse Events by System 
Organ Class and Preferred 
Term and COVID-19 Risk Group 
Safety 
N 
14.3.2.7 
Adverse Events by Preferred 
Term 
Safety 
N 
14.3.2.8 
Adverse Events by Preferred 
Term and Use of Remdesivir 
Safety 
N 
14.3.2.9 
Adverse Events by Preferred 
Term and COVID-19 Risk Group 
Safety 
N 
14.3.2.10 
Adverse Events by System 
Organ Class, Preferred Term 
and Relationship to Study Drug 
Safety 
Y 
14.3.2.11 
Adverse Events by System 
Organ Class, Preferred Term 
and Maximum DAIDS Grade 
Safety 
Y 
14.3.2.12 
Adverse events Leading to 
Discontinuation of Study Drug 
by System Organ Class and 
Preferred Term 
Safety 
Y 
14.3.2.13 
Serious Adverse Events by 
System Organ Class and 
Preferred Term 
Safety 
Y 
14.3.2.14 
Serious Adverse Events Related 
to Study Drug Treatment by 
System Organ Class and 
Preferred Term 
Safety 
Y 
14.3.2.15 
Grade 3 or 4 Adverse Events by 
System Organ Class and 
Preferred Term 
Safety 
Y 
14.3.2.16 
Grade 3 or 4 Adverse Events by 
System Organ Class and 
Preferred Term and Use of 
Remdesivir 
Safety 
N 
14.3.2.17 
Grade 3 or 4 Adverse Events by 
System Organ Class and 
Preferred Term and COVID-19 
Risk Group 
Safety 
N 
14.3.3.1 
Number of Participants with 
Adverse Events with Outcome 
of Death by System Organ 
Class and Preferred Term 
Safety 
Y 


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14.3.3.2 
Listing of Deaths 
Safety 
Y 
14.3.3.3 
Listing of SAEs 
Safety 
Y 
14.3.3.4 
Listing of AEs Leading To 
Discontinuation of Study 
Treatment 
Safety 
Y 
14.3.4.1.1 
Complete Blood Count and 
Comprehensive Metabolic Panel 
Laboratory Variables Over Time 
Safety 
Y 
14.3.4.1.2 
Treatment Emergent Chemistry 
Laboratory Abnormalities 
Safety 
N 
14.3.4.1.3 
Complete Blood Count and 
Comprehensive Metabolic Panel 
Laboratory Variables Changes 
Greater than Pre-specified 
Thresholds Over Time 
Safety 
Y 
14.3.4.1.4 
Complete Blood Count and 
Comprehensive Metabolic Panel 
Laboratory Variables Changes 
Greater than Pre-specified 
Thresholds Over Time by Use of 
Remdesivir 
Safety 
N 
14.3.4.1.5 
Complete Blood Count and 
Comprehensive Metabolic Panel 
Laboratory Variables Changes 
Greater than Pre-specified 
Thresholds Over Time by 
COVID-19 Risk Group 
Safety 
N 
14.3.4.1.6 
Grade 3 or 4 Treatment-
emergent Laboratory Toxicities 
Safety 
Y 
14.3.4.1.7 
Grade 3 or 4 Treatment-
emergent Laboratory Toxicities 
by Use of Remdesivir 
Safety 
N 
14.3.4.1.8 
Grade 3 or 4 Treatment-
emergent Laboratory Toxicities 
by COVID-19 Risk Group 
Safety 
N 
14.3.4.2.1 
Urinalysis Laboratory Variables 
Over Time 
Safety 
Y 
14.3.4.2.2 
Treatment Emergent Urinalysis 
Laboratory Abnormalities 
Safety 
Y 
14.3.4.2.3 
Treatment Emergent Urinalysis 
Laboratory Abnormalities by 
Use of Remdesivir 
Safety 
N 
14.3.4.2.4 
Treatment Emergent Urinalysis 
Laboratory Abnormalities by 
COVID-19 Risk Group 
Safety 
N 
14.3.4.3.1 
Summary of Vital Signs by 
Study Visit 
Safety 
Y 


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14.3.4.3.2 
Summary of Vital Signs by 
Study Visit by Use of 
Remdesivir 
Safety 
N 
14.3.4.3.3 
Summary of Vital Signs by 
Study Visit by COVID-19 Risk 
Group 
Safety 
N 
14.3.4.4.1 
Summary of Electrocardiogram 
Findings by Study Visit 
Safety 
Y 
14.3.4.4.2 
Summary of Electrocardiogram 
Findings by Study Visit by Use 
of Remdesivir 
Safety 
N 
14.3.4.4.2 
Summary of Electrocardiogram 
Findings by Study Visit by 
COVID-19 Risk Group 
Safety 
N 
Appendix 3: 
Table of Contents for SAP Shells - Figures 
TFL Number 
Title 
Analysis 
Population 
SRC 
14.2.5.4 
Arithmetic Mean 
Pharmacokinetic 
Concentration-time Profiles – 
EIDD-2801 
PK 
N 
Appendix 4: 
Table of Contents for SAP Shells - Listings 
TFL Number 
Title 
Analysis 
Population 
SRC 
16.2.1 
ParticipantDisposition 
Screened 
Y 
16.2.2 
Participants with Protocol 
Deviations 
Safety 
Y 
16.2.3 
Demographic and Baseline 
Characteristics 
Safety 
N 
16.2.4 
Medical History 
Safety 
N 
16.2.5 
Prior and Concomitant 
Medication 
Safety 
N 
16.2.6 
Administration of Study Drug 
Safety 
N 
16.2.7 
ParticipantWithdrawal 
Safety 
Y 
16.2.8 
Virologic Sampling and 
Results 
Safety 
N 
16.2.9 
Individual Pharmacokinetic 
Parameters 
Safety 
N 
16.2.10 
Individual Pharmacokinetic 
Concentration Data 
Safety 
N 
16.2.11 
Hospitalization 
Safety 
N 
16.2.12 
Chest Radiography 
Safety 
N 


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16.2.13 
Adverse Events 
Safety 
Y 
16.2.14 
Clinical Laboratory Data: 
Complete Blood Count 
Safety 
Y 
16.2.15 
Clinical Laboratory Data: 
Comprehensive Metabolic 
Panel 
Safety 
Y 
16.2.16 
Clinical Laboratory Data: 
Urinalysis 
Safety 
Y 
16.2.17 
Pregnancy Tests 
Safety 
N 
16.2.18 
Vital Signs 
Safety 
N 
16.2.19 
Electrocardiograms 
Safety 
N 
16.2.20 
Physical Examination 
Safety 
N 
16.2.21 
Serology Testing 
Safety 
N 
16.2.22 
WHO Ordinal Scale for Clinical 
Improvement 
Safety 
N