Clinical trial NCT04705597
Conditions: Covid19
Keywords: COVID-19 BGE-175 BioAge Respiratory failure
Sponsor: BioAge Labs, Inc.
Start date: 2021-03-18; Completion date: 2022-05-19
Enrollment: 194 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of BGE-175 in participants ≥ 50 years of age hospitalized with documented COVID-19.

Detailed description:
This is a randomized, placebo-controlled, parallel-group, multicenter, double-blind study of BGE-175 administered PO or NG in participants ≥ 50 years of age and hospitalized with documented COVID-19 who are not yet in respiratory failure.

After signing informed consent, participants will be screened upon presentation at the hospital. Screening will include full physical examination, vital signs, safety laboratory evaluation, oxygen saturation, pre-diagnostics to measure prostaglandin D2 (PGD2) status, and baseline assessment of World Health Organization (WHO) Ordinal Scale for COVID-19. If confirmed that the participant qualifies for this protocol according to listed inclusion and exclusion criteria, participants will receive the first dose of study medication, PO. The participant will then receive study medication PO or NG (if intubated or unable to swallow medication) once daily, at approximately the same time each day for up to 13 additional days. Study medication will be administered in addition to standard of care deemed appropriate by the treating physician(s). Participants will be randomized to receive BGE-175 or placebo. Participants will be monitored daily for all relevant efficacy outcomes, oxygen saturation, and adverse events. Blood will be drawn periodically for safety laboratory measurements, plasma kinetics, lymphocyte subsets, C-reactive protein, and cytokines. Nasopharyngeal swabs will be collected to measure viral load. Participants will be monitored for 14 days after administration of the last dose (Day 28) and followed through Day 57.

Arms: arm 1: BGE-175 tablet to be taken by mouth once a day for 14 days arm 2: Placebo tablet to be taken by mouth once a day for 14 days
Interventions: intervention 1: BGE-175 intervention 2: Placebo
Intervention descriptions: intervention 1: Drug intervention 2: Placebo

Protocol documents:
Prot_000.pdf: 
Official Title of Study: 
 
Phase 2, Multicenter, Randomized, Double-blind, Placebo-
controlled, Phase 2 Study to Investigate the Efficacy and Safety of 
Asapiprant in Hospitalized Adults With COVID-19 
 
 
 
Protocol Number: 
BGE-175-201 
 
ClinicalTrials.gov Identifier: 
NCT04705597 
 
Document Version [Date]: Protocol Version 5.0, Amendment 04 [07 Sep 2021] 








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SUMMARY OF MAJOR PROTOCOL CHANGES 
Protocol 
Version 
Summary of change 
Rationale for change 
5.0, A0.4 
Updated estimated number of sites from 20 to 35  
Update to reflect better estimate of 
actual site number 
5.0, A0.4 
Increased sample size from 132 to 312 subjects, and 
updated statistical rationale for the sample size 
calculation 
Recently published data indicate 
that progression in the control arm 
to meet the primary endpoint in 
similar studies occurs at a lower 
rate than the original estimate used 
for this study’s sample size 
calculation. The sample size 
adjustment reflects these external 
data. An interim analysis will use 
conditional power calculations by 
the independent DMC for the final 
sample size determination. 
5.0, A0.4 
The timing of the interim analysis was changed from 
66 subjects to 208 subjects 
A larger sample size at interim 
analysis will provide a more 
accurate assessment of a potential 
treatment effect 
5.0, A0.4 
Added new secondary endpoint to assess the 
proportion of subjects who survive without 
progression to RF at Day 14, Day 28, and Day 57 
Provides an assessment of whether 
study drug not only improves 
survival but reduces the severity of 
disease  
5.0, A0.4 
Added time windows for laboratory sample 
collections at home visits, including not requiring the 
repeat of study procedures at Day 5 if they were 
completed at Day 4 prior to discharge 
Reduces the burden on study 
patients and provides time for 
managing logistics of sample 
collection and shipping for 
outpatients, especially on 
weekends 
5.0, A0.4 
Updated Exclusion #4 to reflect requirement of 
positive test for influenza A or influenza B within 1 
week prior to screening 
Clarification 
4.0, A0.3 
Updated interim analysis to collect data from subjects 
through Day 28 
Matches interim analysis timing 
and primary endpoint timing per 
FDA request   
4.0, A0.3 
Randomization stratification factors added to the 
model as covariates in the primary analyses 
Protocol now lists all covariates 
that are described in the statistical 
analysis plan per FDA request 


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4.0, A0.3 
Updated wording in IP Discontinuation or Study 
Withdrawal section to clarify that the only reason for 
withdrawal from study assessments is withdrawal of 
patient consent 
Reinforces instructions that all 
patients should be followed even if 
IP is discontinued per FDA request  
4.0, A0.3 
Updated footer (h) on Table 1 by removing reference 
to viral titers being measured on the Day after 
treatment ends 
The footer now agrees with the 
body of the table 
4.0, A0.3 
Updated Statistical Analysis Process section to 
specify that the primary analysis including covariates 
will use the log-odds model for superiority described 
in Ge et al., 2011. All covariates are now listed. Also 
clarifies how insufficient data will be handled. 
FDA request 
4.0, A0.3 
Updated Planned Interim Analysis, Adaptive Design, 
and Data Monitoring Committee section. Specifies 
how randomized patients will be assessed who reach 
Day 28 (or would have reached Day 28 had they not 
died, withdrawn, or been lost to follow-up)  
FDA request 
3.0, A02 
Lowered patient eligibility age from 60 years to 50 
years 
Responds to changing COVID-19 
patient demographics and Increases 
number of eligible patients without 
increasing safety risks or affecting 
anticipated efficacy 
2.0, A01 
Clarified that optional nasal swabs collected for local 
qualitative testing; quantitative testing 
nasopharyngeal swabs can be stopped with negative 
local qualitative results 
Reduces patient burden, risk of 
staff exposure  
2.0, A01 
Updated inclusion criterion #7 to specify not 
allowing “critical COVID illness” rather than 
“respiratory failure” 
Internal consistency with endpoint 
and FDA guidance for patient 
population 
2.0, A01 
Updated inclusion criterion #8 to define female 
subjects of childbearing potential 
Clarification 
2.0, A01 
Deleted Exclusion #4 
Repeated from inclusion criterion 
#7 
2.0, A01 
Updated Exclusion #5 and #6  to indicate “history” of 
HIV, Hepatitis B and hepatitis C to clarify that test 
results are not required at screening 
Clarification 
2.0, A01 
Added new exclusion #8 for Hepatic function 
impairment defined as a Child-Pugh score of 7 or 
greater  
FDA request 


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2.0, A01 
Updated exclusion #9 to reflect that stage 4 or worse 
renal failure is excluded 
FDA request and clarification 
2.0, A01 
Clarified analysis populations and statistical 
methodology 
FDA request 
2.0, A01 
Primary endpoint updated to be consistent with entry 
criterion definition of respiratory failure 
FDA request and clarification 
2.0, A01 
New secondary endpoint to assess incidence of 
critical COVID disease 
Internal consistency  
2.0, A01 
Updated secondary endpoint of time to extubation to 
“incidence and duration of intubation” 
FDA Request 
2.0, A01 
Updated interim analysis to be performed by the 
independent data monitoring committee 
FDA request 
2.0, A01 
Clarified that subjects are only discontinued from the 
study if they withdraw consent and will complete all 
visit assessments if treatment is stopped early 
FDA Request 
2.0, A01 
Changed dosing regimen to 100 mg daily for all 
subjects 
FDA Request, reduce risk for 
dosing errors 
2.0, A01 
Administrative changes/corrections throughout 
Clarifications/corrections 
 


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TABLE OF CONTENTS 
PROTOCOL BGE-175-201 .............................................................................................................1 
PROTOCOL SIGNATURE PAGE .................................................................................................2 
EMERGENCY CONTACT INFORMATION ................................................................................3 
SUMMARY OF MAJOR PROTOCOL CHANGES ......................................................................4 
LIST OF TABLES .........................................................................................................................10 
LIST OF FIGURES .......................................................................................................................10 
ABBREVIATIONS .......................................................................................................................11 
STUDY SYNOPSIS ......................................................................................................................15 
 
BACKGROUND INFORMATION .......................................................................................26 
 
Indication and Current Treatment Options ...............................................................26 
 
Investigational Product Asapiprant ..........................................................................26 
 Product Background...............................................................................................26 
 Immunomodulation in the Prostaglandin D2(PGD2)-D Prostanoid (DP)1 
Signaling Pathway .................................................................................................27 
 Preclinical Information ..........................................................................................27 
 Clinical Information ...............................................................................................27 
 
Risk/Benefit and Ethical Assessment .......................................................................27 
 
Compliance Statement ..............................................................................................27 
 
STUDY RATIONALE, OBJECTIVES AND ENDPOINTS .................................................28 
 
Rationale for the Study .............................................................................................28 
 
Study Objectives ......................................................................................................29 
 Secondary Objectives .............................................................................................29 
 Other Objectives ....................................................................................................30 
 
Endpoints ..................................................................................................................30 
 Primary Endpoint ...................................................................................................30 
 Secondary Endpoints .............................................................................................30 
 Exploratory Endpoints ...........................................................................................31 
 
STUDY DESIGN ...................................................................................................................32 
 
Study Design and Flow Chart ..................................................................................32 
 
Duration and Study Completion Definition .............................................................33 
 
Sites and Regions .....................................................................................................33 
 
STUDY POPULATION .........................................................................................................34 
 
Sample Size ..............................................................................................................34 
 
Inclusion Criteria ......................................................................................................34 
 
Exclusion Criteria .....................................................................................................35 
 
Restrictions ...............................................................................................................36 
 
Stopping Criteria ......................................................................................................36 


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Discontinuation of Subjects .....................................................................................36 
 Reasons for IP Discontinuation .............................................................................36 
 Subjects ‘Lost to Follow-up’ Prior to Last Scheduled Visit ..................................37 
 
PRIOR AND CONCOMITANT TREATMENT ...................................................................38 
 
Prior and Concomitant Treatment ............................................................................38 
5.1.1 Permitted Treatment..................................................................................................38 
 
INVESTIGATIONAL PRODUCT ........................................................................................39 
 
Identity of Investigational Product ...........................................................................39 
 Blinding the Treatment Assignment ......................................................................39 
 
Administration of Investigational Product(s) ...........................................................39 
 Allocation of Subjects to Treatment ......................................................................39 
 Dosing ....................................................................................................................39 
6.2.2.1 
Treatment Period ....................................................................................40 
 Unblinding the Treatment Assignment ..................................................................40 
 
Labeling, Packaging, Storage, and Handling ...........................................................40 
 Labeling .................................................................................................................40 
 Packaging ...............................................................................................................41 
 Storage ...................................................................................................................41 
 
Drug Accountability .................................................................................................41 
 
Subject Compliance ..................................................................................................42 
 
Retention of Bioavailability and Bioequivalence Testing Samples .........................42 
 
STUDY PROCEDURES ........................................................................................................43 
 
Study Schedule .........................................................................................................43 
 Screening Period ....................................................................................................43 
7.1.1.1 
Screening Failure ....................................................................................43 
7.1.1.2 
Rescreening of Subjects .........................................................................44 
 Treatment Period ....................................................................................................44 
7.1.2.1 
Visits Summary ......................................................................................44 
7.1.2.2 
End of Treatment, Follow-up and End of Study Period .........................44 
 Additional Care of Subjects After the Study .........................................................45 
 
Study Evaluations and Procedures ...........................................................................45 
7.2.1.1 
Adverse Event Collection .......................................................................45 
7.2.1.2 
Independent Data Monitoring Committee ..............................................46 
 Medical History / Demographic Information ........................................................46 
 Physical Examination (Including Height at Screening Visit Only and 
Weight) ..................................................................................................................47 
7.2.3.1 
Abbreviated Physical Examination ........................................................47 
 Vital Signs ..............................................................................................................47 


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 Safety Laboratory Tests .........................................................................................48 
 O2 Saturation/FiO2 .................................................................................................50 
 Pre-dose Serological Markers - PGD2 ...................................................................51 
 Nasopharyngeal Viral Titers ..................................................................................51 
 Blood for Inflammation Markers ...........................................................................51 
 Proteomic, Metabolomic and Transcriptomic Sample Collection .........................51 
 Twelve-lead Electrocardiogram (ECG) .................................................................51 
 Pharmacokinetic Procedures ..................................................................................52 
7.2.12.1 
Blood Sample Collection and Handling Procedures ..............................52 
7.2.12.2 
Shipment of Plasma Pharmacokinetic Samples .....................................53 
7.2.12.3 
Plasma Drug Assay Methodology ..........................................................53 
 Pharmacodynamic Assessments ............................................................................53 
7.2.13.1 
Blood Sample Collection and Handling Procedures ..............................53 
7.2.13.2 
Shipment of Plasma Pharmacokinetic and Pharmacodynamic 
Samples ..................................................................................................54 
 Volume of Blood to be Drawn from Each Subject ................................................54 
 
DATA MANAGEMENT AND STATISTICAL METHODS ...............................................56 
 
Data Collection .........................................................................................................56 
 
Clinical Data Management .......................................................................................56 
 
Data Handling ..........................................................................................................56 
 
Statistical Analysis Process ......................................................................................56 
 
Planned Interim Analysis, Adaptive Design, and Data Monitoring Committee ......58 
 
Sample Size Calculation and Power Considerations ................................................58 
 
Study Population ......................................................................................................58 
 Pharmacokinetic Analysis ......................................................................................59 
8.7.1.1 
Statistical Analysis of Pharmacokinetic Parameters ..............................60 
 Pharmacodynamic Analysis ...................................................................................60 
8.7.2.1 
Statistical Analysis of Pharmacodynamic Parameters ...........................60 
 
Safety Analyses ........................................................................................................60 
 
Other Analyses .........................................................................................................61 
 
REFERENCES .......................................................................................................................62 
 APPENDICES ........................................................................................................................63 
APPENDIX 1 .................................................................................................................................64 
PROTOCOL HISTORY ................................................................................................................65 
APPENDIX 2 .................................................................................................................................66 
 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ..............67 
Regulatory and Ethical Considerations ..............................................................................68 
 
SPONSOR’S RESPONSIBILITIES .......................................................................................69 


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INVESTIGATOR’S RESPONSIBILITIES ...........................................................................70 
 
DOCUMENTATION AND RETENTION OF RECORDS ...................................................71 
 
AUDIT/INSPECTION ...........................................................................................................72 
 
FINANCIAL DISCLOSURE .................................................................................................73 
 
ETHICAL CONSIDERATIONS ............................................................................................74 
 
STUDY RESULTS / PUBLICATION POLICY ...................................................................76 
APPENDIX 3 .................................................................................................................................77 
Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-Up, 
and Reporting ...........................................................................................................78 
 
Adverse Event Definitions .......................................................................................79 
 
Collection of Adverse Events ...................................................................................81 
 
Assessment of Adverse Events ................................................................................82 
 
Safety Reporting .......................................................................................................85 
Serious Adverse Event Collection Time Frame .................................................................86 
Serious Adverse Event Onset and Resolution Dates .........................................................87 
Fatal Outcome ....................................................................................................................88 
 
Pregnancy .................................................................................................................89 
 
Abuse, Misuse, Overdose, and Medication Error ....................................................90 
 
Urgent Safety Measures ...........................................................................................91 
 
Regulatory Agency, Institutional Review Board, Ethics Committee, and Site 
Reporting................................................................................................................92 
APPENDIX 4 .................................................................................................................................93 
Child-Pugh System1 .................................................................................................................94 
 
LIST OF TABLES 
Table 1: 
Schedule of Assessments ...............................................................................23 
Table 2: 
World Health Organization Ordinal Scale for COVID-19 ............................30 
Table 3: 
Estimated Volume of Blood to be Drawn from Each Subject .......................54 
Table 4: 
Pharmacokinetic Endpoint Summary ............................................................59 
 
LIST OF FIGURES 
Figure 1:  
Mortality and Body Weight Change in SARS-CoV Infected Mice ..............28 
Figure 2: 
Investigational Product Asapiprant Inhibits PGD2 Signaling via the 
DP1 Receptor1 to Potentially Treat COVID-19 ............................................29 
Figure 3: 
Overall Study Design Flow Schematic ..........................................................32 
 


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ABBREVIATIONS 
AE 
Adverse event 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
aPTT 
Activated partial thromboplastin time 
ARDS 
Acute respiratory distress syndrome 
AST 
Aspartate aminotransferase 
AUClast 
Area under the curve from the time of dosing to the last measurable 
concentration 
β-HCG 
Beta-human chorionic gonadotropin 
°C 
Degree(s) Celsius 
CCR7 
C-C motif chemokine receptor 7 
CD 
Cluster of differentiation 
CL/F 
Total body clearance for extravascular administration divided by the 
fraction of dose absorbed 
Cmax 
Maximum concentration occurring at tmax 
COVID-19 
Coronavirus disease of 2019 
CP 
Conditional power 
CRA 
Clinical research associate 
CRF 
Case report form 
CRO 
Contract research organization 
CRP 
C-reactive protein 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV% 
Coefficient of variation 
DC 
Dendritic cell 
DP 
D prostanoid 
DP1 
Prostaglandin D2 receptor 1 
DMC 
Data Monitoring Committee 
DVT 
Deep vein thrombosis 
EC 
Ethics committee 
ECG 
Electrocardiogram 
ECMO 
Extracorporeal membrane oxygenation 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 


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EOT 
End of treatment 
EU 
European Union 
FDA 
Food and Drug Administration 
FiO2 
Fractional inspired oxygen 
λz 
First-order rate constant associated with the terminal (log-linear) portion of the 
curve 
GCP 
Good Clinical Practice 
GGT 
Gamma glutamyl transferase 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
IA 
Interim Analysis 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
ICMJE 
International Committee of Medical Journal Editors 
IFN-α 
Interferon alpha 
IFN-γ 
Interferon gamma 
IL 
Interleukin 
INR 
International normalized ratio 
IP 
Investigational product 
IP-10 
Interferon gamma-induced protein 10 
IRB 
Institutional review board 
IRB/EC 
Institutional Review Board / Independent Ethics Committee 
IRT 
Interactive response technology 
ITT/FAS 
Intention to Treat / Full Analysis Set 
K2EDTA  
Dipotassium ethylenediaminetetraacetic acid  
LDH  
Lactate dehydrogenase  
MAP 
Mean arterial pressure 
MCP-1 
Monocyte chemoattractant protein-1 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 


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mITT 
Modified Intent-to-Treat population 
NA 
Not applicable 
NG 
Nasogastric tube 
NIPPV 
Noninvasive positive pressure ventilation 
NK cell 
Natural killer cell 
NPO 
Nothing by mouth (withhold food and fluids) 
NYHA 
New York Heart Association 
O2 
Oxygen 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic(s) 
PGD2 
Prostaglandin D2 synthase 
PGD2-DP1 
the therapeutic target of the investigational drug BGE-175 to treat 
COVID-19 
PK 
Pharmacokinetic(s) 
PO 
Oral administration 
PT 
Prothrombin time 
QTcF 
QT interval corrected for heart rate by Fridericia’s formula  
RDW 
Red blood cell distribution width 
RECIST 
Response Evaluation Criteria in Solid Tumours 
RF 
Respiratory failure 
RTI 
Respiratory tract infection 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SD 
Standard deviation 
SOC 
Standard of care 
SpO2 
Oxygen saturation 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t1/2 
Terminal half-life 
TEAE 
Treatment-emergent adverse event 
TNF-α 
Tumor necrosis factor alfa 
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of normal 
US CFR 
United States Code of Federal Regulations 


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Vz /F 
Volume of distribution associated with the terminal slope following 
extravascular administration divided by the fraction of dose absorbed 
WHO 
World Health Organization 
WHO-UMC 
World Health Organization-Uppsala Monitoring Center (system 
for standardized case causality assessment) 


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STUDY SYNOPSIS 
Title of Study: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study 
to Investigate the Efficacy and Safety of Asapiprant in Hospitalized Adults With COVID-19 
Name of Sponsor/Company: BioAge Labs 
Name of Finished Product: Not applicable (NA) 
Name of Active Ingredient: Asapiprant 
Objectives:  
Primary 
To evaluate the efficacy of asapiprant given by oral (PO) or nasogastric tube (NG) 
administration versus placebo on the clinical signs and symptoms of COVID-19 infection in 
hospitalized subjects ≥ 50 years of age 
Secondary 
• To evaluate the ability of asapiprant given by PO or NG administration to accelerate 
the clearance of the COVID-19 virus in subjects with symptomatic disease requiring 
hospitalization 
• To determine the efficacy of asapiprant by demonstrating improvement in COVID-19 
illness and prevention of progression to respiratory failure (RF) using various 
endpoints 
• To evaluate the safety profile of asapiprant given by PO or NG administration in 
subjects ≥ 50 years of age hospitalized with COVID-19 infection 
Other Objectives 
• To investigate the effect of asapiprant on inflammation markers of COVID-19 
infection, including but not limited to interleukin (IL)-6, C-reactive protein (CRP), 
IL-10, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interferon 
alpha (IFN-α), IFN-γ-induced protein 10 (IP-10), monocyte chemoattractant protein-1 
(MCP-1), cluster of differentiation (CD)4+ and CD8+ T cells, and absolute lymphocyte 
count 
• Determine peak and trough concentrations of study drug after first dose and at steady 
state and, if possible, develop a population pharmacokinetic (PK) model 
Study Design: This is a randomized, placebo-controlled, parallel-group, multicenter, double-
blind study of asapiprant administered PO or NG in subjects ≥ 50 years of age and hospitalized 
with documented COVID-19 infection who are not yet in RF. 
After signing informed consent, subjects will be screened upon presentation at the hospital. 
Screening will include full physical examination, vital signs, safety laboratory evaluation, 
oxygen (O2) saturation, pre-diagnostics to measure prostaglandin D2 (PGD2) status, and 
baseline assessment of World Health Organization (WHO) Ordinal Scale for COVID-19 that 
is derived from the subject oxygen supplementation requirements. If confirmed that they 
qualify for this protocol according to listed inclusion and exclusion criteria, subjects will 
receive their first dose of study medication, PO. They will then receive study medication PO 
once daily, at approximately the same time each day for up to 13 additional days. Subjects 


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who progress to RF and require intubation or subjects who are unable to swallow will receive 
study medication by NG tube administration. Study medication will be administered in 
addition to standard of care deemed appropriate by the treating physician(s). Subjects will be 
randomized to receive asapiprant or placebo. Subjects will be monitored daily for all relevant 
efficacy outcomes, O2 saturation and adverse events (AEs). Treatment will be discontinued in 
subjects who develop hepatic function impairment defined as a Child-Pugh score of 7 or 
greater. Blood will be drawn periodically for safety laboratory measurements, plasma kinetics, 
lymphocyte subsets, CRP, and cytokines (see Table 1). Nasopharyngeal swabs will be 
collected to measure viral load and separate nasal swabs may be collected for optional local 
qualitative testing. Subjects will be monitored at follow-up visits on Day 28 (approximately 14 
days after last dose) and Day 57 (approximately 43 days after last dose). 
Number of Study Centers: Approximately 35 sites will be selected based on likelihood of 
adequate patient population at the time of study implementation. Site selection will include an 
assessment of sites’ prior research and COVID-19 study experience, current and projected 
rates of infection, concurrent clinical trials that may limit patient population availability, and 
current standard of patient care. 
Duration of Participation: Each subject will participate in the study for approximately 
8 weeks from the time the subject signs the informed consent form (ICF) through the final 
contact. 
After screening, each subject will receive one daily dose of assigned treatment, Days 1 through 
14.  
WHO Ordinal Scale for COVID-19 will be derived daily while hospitalized, at Day 14, and at 
follow-up visits until the subject has completed the study. 
Duration of Study: The study will require approximately 4 months from the beginning to the 
end of the study (first subject signing the ICF to last contact with last subject). 
Key Inclusion/Exclusion Criteria: Subjects with a diagnosis of COVID-19 requiring 
hospitalization will be selected to participate in the study. 
Inclusion: 
1. Ability to voluntarily provide informed consent that is documented per local 
requirements 
2. An understanding, ability, and willingness to fully comply with study procedures and 
restrictions 
3. Hospitalized subjects with a confirmed severe acute respiratory syndrome coronavirus 
2 (SARS-CoV-2) infection 
4. Laboratory (polymerase chain reaction [PCR]) confirmed infection with SARS-CoV-2  
5. Age > 50 years 
6. COVID-19 illness of any duration, and O2 saturation measurements ≤ 94% over 
5 minutes on room air (Note: low flow O2 is permitted, but room air O2 saturation must 
be ≤ 94%) 
7. Not with evidence of critical COVID-19 illness as defined by at least one of the 
following: 
a. RF defined by requiring at least one of the following: 
• Endotracheal intubation and mechanical ventilation 


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• O2 delivered by high-flow nasal cannula at flow rates > 20 L/min with fraction 
of delivered O2 ≥ 0.5 
• Noninvasive positive pressure ventilation (NIPPV) 
• Extracorporeal membrane oxygenation (ECMO) 
• Clinical diagnosis of RF (i.e., clinical need for one of the preceding therapies, 
but preceding therapies are not able to be administered in setting of resource 
limitation) 
b. Hemodynamic compromise (defined by systolic blood pressure < 90 mm Hg, or 
diastolic blood pressure < 60 mm Hg) or requiring vasopressors 
c. Multi-organ dysfunction/failure 
8. Female subjects of childbearing potential must have a negative pregnancy test at 
screening or pre-treatment on Day 1 
Note: Female subjects of childbearing potential are defined as pre-menopausal, < 12 
months of amenorrhea post-menopause, or no history of surgical sterilization 
(hysterectomy or oophorectomy) or tubal ligation. 
9. Male and female subjects of childbearing potential must agree to use methods of 
contraception that are consistent with local regulations for those participating in 
clinical studies 
 
Exclusion: 
1. Participation in any other randomized, controlled clinical trial of an experimental 
treatment for COVID-19 (uncontrolled, compassionate use trials are allowed) 
2. In the opinion of the Investigator, progression to death is imminent and inevitable 
within the next 24 hours, irrespective of the provision of treatments 
3. Currently participating in a vaccination trial for SARS-CoV-2 
4. Known positive test for influenza A or influenza B at the time of screening 
5. History of human immunodeficiency virus (HIV) infection that is not controlled with 
current treatment 
6. History of Hepatitis B surface antigen, or Hepatitis C positive prior to screening. 
Subjects who are positive for Hepatitis C but have Hepatitis C virus (HCV) RNA 
below the limit of quantitation may be enrolled. Subjects with Hepatitis B, but with 
undetectable viral load, may be enrolled. 
7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × the upper 
limit of normal (ULN) 
8. Hepatic function impairment defined as a Child-Pugh score of 7 or greater. 
9. Stage 4 or higher severe chronic kidney disease (i.e., estimated glomerular filtration 
rate [eGFR] < 30 mL/min) or acute renal failure resulting in eGFR < 30 mL/min 
10. Serious co-morbidity, including: 
a. Myocardial infarction (within the last month) 
b. Moderate or severe heart failure (New York Heart Association [NYHA] class III or 
IV) 
c. Acute stroke (within the last month) 
d. Uncontrolled malignancy. Uncontrolled malignancy would include cancers that are 
not considered in remission, or solid tumor or haematological malignancies with 
evidence of disease progression in the past 3 months (i.e., there is evidence of 


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disease progression by Response Evaluation Criteria in Solid Tumours [RECIST] 
or equivalent relevant criterion for the type of malignancy), and are not considered 
effectively managed with ongoing treatment as determined by the Investigator  
e. Recent severe thromboembolic disease or evidence of severe thromboembolic 
disease defined as a current large vessel thromboembolic event or a 
thromboembolic event within the past 3 months (e.g., deep vein thrombosis 
[DVT], pulmonary embolism, ischemic stroke, transient ischemic attack) requiring 
interventional treatment. This exclusion does not prohibit prophylaxis for 
thromboembolic events, including those considered possible with concurrent 
SARS-CoV-2 infection.  
11. History of severe allergic or anaphylactic reactions or hypersensitivity to the study 
drug 
12. Consideration by the Investigator, for any reason, that the subject is an unsuitable 
candidate to receive study treatment 
Investigational Product, Dose, Route of Administration, and Regimen: 
Test product: Asapiprant, a DP1 antagonist, will be provided as a 50 mg tablet for oral use  
Placebo: Matching tablet without active drug 
Two 50 mg tablets of asapiprant (100 mg) or matching placebo will be taken immediately after 
screening evaluation, confirmation of eligibility, and randomization on Day 1, and within 30 
minutes of eating. Time of dosing in relation to meal will be documented. Subjects will 
continue dosing for 14 days, including if they are discharged or if the subject progresses to RF. 
Subjects taking nothing by mouth (NPO) or not being fed through an NG tube will take study 
medication at approximately the same time they received prior daily doses.  
Statistical Methods: 
Analysis Populations: 
Enrolled Analysis Set: all patients who provided informed consent. 
Intent-to-Treat (ITT): all patients who have been randomized. The ITT will be used for 
efficacy endpoints. Patients will be analyzed according to the treatment group to which they 
were randomized. The ITT will be used for the primary efficacy analysis. 
Modified Intent-to-Treat population (mITT): all ITT patients with exclusion of randomized 
untreated patients and randomized ineligible patients.  
Per-protocol Set: all mITT patients with further exclusion of patients with major protocol 
deviations related to data integrity or eligibility as judged by clinical/biostatistical study 
personnel prior to database lock. This population will be formed only if > 5% of patients 
would be excluded. 
Safety Analysis Set: all patients who have received at least 1 dose of either asapiprant or 
placebo. The Safety Analysis Set will be used for safety analysis. Patients will be analyzed 
under actual treatment being received. 
Pharmacokinetic (PK) Set: all patients who have received at least 1 dose of asapiprant and 
have at least 1 evaluable post-dose PK concentration value. 
Pharmacodynamic (PD) Set: all patients who have received at least 1 dose of asapiprant and 
have at least 1 evaluable post-dose PD value. 


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Sample Size: The sample size estimate of 312 total subjects is based on 31% progressing to 
respiratory failure by Day 28 in the placebo group and 15% progressing to RF in the 
asapiprant group using data from recently published COVID-19 studies (Guimaraes et al 2021, 
Temesgen et al, 2021). Using a Fishers Exact test with two-sided 5% Type 1 error and 90% 
power, the sample size to detect a 16% absolute improvement in the primary endpoint is 312 
subjects (1:1 randomization). Randomization will be stratified based on the subject’s 
enrollment region (North America vs. South America) and age (50 to < 75 vs. ≥ 75 years of 
age). 
Interim Analysis (IA): An IA for safety and efficacy will be conducted when 208 subjects 
complete assessments through the 28-day follow up (Day 28) approximately 14 days after the 
final dose of study drug. No α spend is incorporated into the sample size to account for this 
look, as there is no potential for early stopping for superiority. If the conditional power (CP) at 
IA is less than 34%, then by the IA rules, the study will continue to completion. If the CP is at 
least 90% the study can continue as planned. If the CP is between 34% and 90%, the study will 
be considered in the promising zone and the study sample size may be adjusted up to a 
maximum of 624 total subjects. 


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Efficacy Analysis: 
Primary endpoint – proportion of subjects who have died or progressed to RF as defined by 
progressing to the need for high-flow nasal cannula O2 delivery, noninvasive positive pressure 
ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation 
(ECMO) therapy at Day 28. 
Secondary Endpoints 
1. Safety as assessed by AEs as measured by the Common Terminology Criteria for 
Adverse Events (CTCAE) v 5.0 
2. Proportion of subjects surviving [Time Frame: at Day 14, at Day 28, at Day 57] 
3. Proportion of subjects who survive without progression to RF [Time Frame: at Day 14, 
at Day 28, at Day 57] 
4. Time to two successive negative viral titers in nasopharyngeal swab 
5. Time to clinical worsening from baseline value (defined by time to ≥ 1-point 
worsening on WHO Ordinal Scale for COVID-19): 
 
World Health Organization Ordinal Scale for COVID-19 
Subject State 
Description 
Score 
Uninfected 
No clinical or virological evidence of infection 
0 
Ambulatory 
No limitation of activities 
1 
Limitation of activities 
2 
Hospitalized, Mild 
Disease 
Hospitalized, no oxygen therapy 
3 
Oxygen by mask or nasal prongs 
4 
Hospitalized, 
Severe Disease 
Noninvasive ventilation or high-flow oxygen 
5 
Intubation and mechanical ventilation 
6 
Ventilation + additional organ support – pressors, RRT, ECMO 
7 
Dead 
Death 
8 
Abbreviations: ECMO = extracorporeal membrane oxygenation; RRT = renal replacement therapy 
6. Proportion of patients who develop critical COVID-19 illness as defined by at least one 
of the following: 
A. RF defined by requiring at least one of the following: Endotracheal intubation 
and mechanical ventilation, oxygen delivered by high-flow nasal cannula 
(heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates 
> 20 L/min with fraction of delivered oxygen ≥ 0.5), NIPPV, ECMO, clinical 
diagnosis RF (i.e., clinical need for one of the preceding therapies, but preceding 
therapies not able to be administered in setting of resource limitation) 
B. Hemodynamic compromise (defined by systolic blood pressure < 90 mm Hg, or 
diastolic blood pressure < 60 mm Hg or requiring vasopressors)  
C. Multi-organ dysfunction/failure 
7. Time to clinical improvement from baseline value (defined by time to ≥ 1-point 


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improvement on WHO Ordinal Scale for COVID-19 score – must be maintained 
through Day 28) 
8. Mean change from baseline in WHO Ordinal Scale for COVID-19 score at Day 14/End 
of Treatment, Day 28, Day 57 
9. Incidence and duration of intubation 
10. Length of intensive care unit stay 
11. Incidence and duration of supplemental O2 administration 
12. Incidence and duration of noninvasive ventilation or high-flow nasal cannula O2 
administration 
13. Incidence and duration of mechanical ventilation 
14. Incidence and duration of mechanical ventilation plus additional organ support using 
vasopressors, and/or renal replacement therapy and/or ECMO 
15. Daily ratio of oxygen saturation (SpO2) to fractional inspired O2 (SpO2/FiO2)  
16. Length of hospital stay 
17. Incidence of re-hospitalization through Day 57 
18. Proportion of subjects requiring intensive care unit admission post randomization 
Exploratory Endpoints 
1. Inflammation markers including: IL-6, CRP, IL-10, TNF-α, IFN-γ, IFN-α, IP-10, 
MCP-1, CD4+ and CD8+ T cells, and absolute lymphocyte count 
2. Assess peak and trough concentrations of asapiprant at steady state 
3. Assess PGD2 pre-diagnostic to assess correlation with response to treatment for 
COVID-19 based on change in the WHO Ordinal Scale for COVID-19 score 
Safety Analysis: 
Safety endpoints: 
1. Incidence and severity of treatment-emergent AEs  
2. Safety outcome measure: 
a. Occurrence of AEs 
b. Laboratory safety parameters such as complete blood count, blood glucose, 
electrolyte, hepatic and renal functions taken before the first dose and on Days 2, 
5, 14, 28 and the time of discharge to find any changes or any systemic effect after 
treatment 
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 23.1. The incidence of all AEs reported during the study will be summarized by 
treatment group and system organ class and preferred term. Safety will be evaluated by 
comparing the nature, severity, and frequency of AEs between/among the treatment groups.  
 
Safety Monitoring: Study Investigators will monitor subject safety on an ongoing basis while 
hospitalized, including a review of vital signs, local safety laboratory measurements, and 
observations of subject status. If discharged prior to the end of treatment, subjects will be 
discharged to home, and home health resources will be utilized to manage daily subject dosing 
and status, including the collection of protocol-specified laboratory tests and assessments. The 
home assessments will be monitored by the study Investigator. 
BioAge Labs will have a blinded Medical Lead assigned for safety oversight and will work 
closely with a contract research organization (CRO) partner to provide ongoing reviews of 


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subject safety data, including findings associated with laboratory tests, electrocardiograms 
(ECGs), vital signs, physical examinations, and AE. Routine Medical Monitor review will be 
conducted on an ongoing basis during study conduct. The CRO will provide a drug safety 
team to manage serious adverse event reporting.  
An IA for efficacy will be planned when 208 subjects complete study assessments through the 
28-day follow up (Day 28) approximately 14 days after the final dose of study drug. 
An independent Data Monitoring Committee (DMC) will be utilized during the study to 
monitor subject safety throughout study conduct. A DMC charter will be developed before 
study initiation and will define DMC processes and meetings. The DMC will meet at regular 
planned intervals during study conduct and also meet ad hoc as required for any identified 
urgent safety findings. Independent of the Sponsor, the DMC will be responsible for 
performing the IA and evaluating the interim results.  
To aid the DMC in their recommendation to BioAge regarding conduct of the trial beyond the 
IA, a table of multiple possible true effects and potential stopping rules will be developed by 
BioAge and presented in the DMC charter.  The operating characteristics of potential decision 
rules will be shared and understood by the DMC. 
Interim Analysis: An IA is planned when approximately 208 subjects complete study 
assessments through the 28-day follow up (Day 28) approximately 14 days after the final dose 
of study drug. 
 
 


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Table 1: 
Schedule of Assessments 
 
Screening Baseline 
Treatment 
Time of 
Dischargea 
28-Day 
Follow-up 
End of Study 
Follow-up 
Study Day (Window) 
Day 
-3 to -1 
Day 1 
2 
3 
4 
5 
+ 
2 
6  7 
8 
9 
10 
11 
12 
13 
14/ 
EOT 
+ 2 
 
Day 28 
(±2 days) 
 
Day 57 
(±4 days) 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria review 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history/ 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examinationb  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviated physical 
examinationb 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
 
Vital signsb 
X 
X 
X X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
 
Prior medication review 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety laboratory tests 
X i 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
X 
 
O2 Saturation/ FiO2  
X 
X 
X X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
 
WHO Ordinal Scale for 
COVID-19c 
X 
X 
X X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG 
 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
Xe 
Xe 
 
 
Concomitant medication 
review 
X 
X 
X X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment for AEs 
 
X 
X X X X X X X X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dosing 
 
X 
X X X X X X X X 
X 
X 
X 
X 
X 
 
 
 
PK peakg 
 
X 
 
 
 
X 
 
 
 
 
 
 
 
 
Xe 
Xf 
 
 


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Screening Baseline 
Treatment 
Time of 
Dischargea 
28-Day 
Follow-up 
End of Study 
Follow-up 
Study Day (Window) 
Day 
-3 to -1 
Day 1 
2 
3 
4 
5 
+ 
2 
6  7 
8 
9 
10 
11 
12 
13 
14/ 
EOT 
+ 2 
 
Day 28 
(±2 days) 
 
Day 57 
(±4 days) 
 
X (Collect PK sample following first NG dosing, if 
applicable) 
 
 
 
PK troughd, e, f 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Xe 
Xf 
 
 
PGD2 pre-diagnostic 
sample collection 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral titers 
nasopharyngealh 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
Blood for inflammation 
markers 
X 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
X 
 
 
Proteomic, 
metabolomics, and 
transcriptomic sample 
collection 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Abbreviations: AE = adverse event; FiO2 = fractional inspired oxygen; ECG = electrocardiogram; EOT = end of treatment; NG = nasogastric tube; O2 = oxygen; 
PGD2 = prostaglandin D2; PK = pharmacokinetic(s) 
a Visit procedures at time of discharge will occur at the date of the dosing visit if visit occurs prior to Day 14, will occur at the Day 14 visit if occurs on Day 14, or 
will occur on the date of discharge after dosing if after Day 14. This visit is not required if discharge occurs within 2 days after Day 14. If discharge occurs on Day 
4, the Day 5 assessments of abbreviated physical exam, safety labs, trough and peak PK, and blood for inflammation markers will not be collected if they were 
completed as part of the discharge procedures on Day 4. 
b Same-day medical record examinations may be used for study purposes to reduce the possible exposure of site staff to COVID-19 risk.  Physical examinations 
may be conducted as standard of care examinations. Abbreviated physical examinations may be conducted by qualified home health care providers or 
remote/telemedicine visits. Abbreviated physical examinations that cannot be performed at day 5 may be performed up to Day 7. 
c WHO Ordinal Scale is derived from subject’s oxygen supplementation requirements, hypotension or need for vasopressors, need for renal dialysis, and activity 
limitations for outpatients. 
d Trough PK samples collected within 30 minutes prior to dose. 
e ECG and PK sampling to be performed on last day of study treatment if subject remains hospitalized through Day 14. ECG and PK samples are not required on 
Day 14/EOT if subject is discharged to home before Day 14.  
f ECG and PK sampling to be performed at the time of hospital discharge if subject is discharged prior to Day 14. ECG and PK sampling are not required at time 
of discharge if discharge occurs after the Day 14 visit. 


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g Peak PK samples collected 3-6 hours after dose. 
h Done every other day until 2 qualitative test done at local laboratory is negative. After qualitative test is negative, do viral titer nasopharyngeal testing only on 
Day 28. For outpatients, scheduled viral titer tests may be skipped on Saturday or Sunday and/or may be skipped if dry ice shipments are not available. In the 
Saturday or Sunday situation Day 13 tests should be done on the following Monday. 
i Safety labs collected within 48 hours prior to consent as part of standard of care can be used to confirm eligibility.  


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BACKGROUND INFORMATION 
For clarification purposes, the investigational product (IP) “BGE-175”, as identified in the 
Investigator’s Brochure (IB), is referred to as asapiprant hereafter in this document, unless 
otherwise noted. BGE-175-201 refers specifically to the protocol number (identifier) for this 
study. 
Always refer to the latest version of the asapiprant IB for the overall benefit/risk assessment and 
the most accurate and current information regarding drug metabolism, pharmacokinetics (PK), 
efficacy, and safety of asapiprant.  
 
Indication and Current Treatment Options  
The effective treatment of COVID-19 remains an unmet medical need. Despite evolving 
treatments and intervention, mortality and morbidity associated with COVID-19 remains 
substantial, particularly in older patients, and there remains a clear need for novel treatments. To 
the best of our knowledge, there are no available treatments that address the clear deficits in the 
aging immune system that lead to accentuated morbidity and mortality. 
Aging of the immune system increases COVID-19 severity, as seen in the exponential increase 
with age in hospitalizations and mortality in infected individuals. Compared to a 20-year-old 
with COVID-19, a 65-year-old is 5 times more likely to be hospitalized and 90 times more likely 
to die. An 85-year-old has even worse chances, with a 13 times higher risk of hospitalization and 
630 times higher risk of death (Centers for Disease Control and Prevention, 2020). Age-related 
deficits in immune function that are already well understood in other infections like influenza, 
including reduced ability to mount an effective adaptive immune response, as well as an over-
active innate immune response (macrophages and neutrophils), cause lung damage and lead to 
acute respiratory distress syndrome (ARDS) and mortality (Chen et al., 2020; Cunha et al., 2020; 
Wu et al., 2020). A therapy that specifically addresses the mechanisms underlying the age-
dependence of COVID-19 severity is more likely to be effective in the most patients, and for 
those at highest risk of poor outcomes. 
Building upon the existing safety database, this study will evaluate the efficacy of a novel oral 
small-molecule drug candidate in the highly vulnerable older patient population with COVID-19 
infection that is inadequately served by the existing standard of care, resulting in high morbidity, 
disability, poor patient quality of life, and high costs to the healthcare system. 
 
Investigational Product Asapiprant 
 Product Background 
Asapiprant, a small molecule in the D prostanoid (DP) receptor antagonist drug class, is a novel 
inhibitor of the prostaglandin D2 (PGD2) DP1 signaling pathway. This mechanism of action is 
immune modulating with the potential to treat respiratory infections and reduce further 
complication of respiratory distress. Asapiprant is being developed to treat COVID-19 based on 
observations in animal models of severe acute respiratory syndrome coronavirus (SARS-CoV) 
infection, previous human experience (different indication), and established manufacturing 
processes (tablet formulation). 


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 Immunomodulation in the Prostaglandin D2(PGD2)-D Prostanoid (DP)1 
Signaling Pathway 
PGD2-DP1 signaling inhibits an effective antiviral immune response via suppression of dendritic 
cell migration to draining lymph nodes as well as natural killer (NK) cell activation and 
interferon gamma (IFN-γ) production. The extent of this suppression strongly correlates with 
worse disease outcomes. This pathway is simultaneously dysregulated by immune aging and in 
COVID-19 patients. Older patients with COVID-19, as well as other patients at high risk for 
severe disease, have a less effective antiviral and adaptive immune response (via decreased 
dendritic cell and NK cell function), plus an exaggerated neutrophil response that results in 
increased tissue damage. 
Furthermore, the mortality and morbidity of SARS-CoV-2 infection is largely mediated by 
damage to pulmonary tissue, which is infiltrated by excessive and ultimately damaging numbers 
of neutrophils. Although neutrophil activation is a normal component of the immune response to 
infection, COVID-19 patients exhibit neutrophil overactivation, exaggerated pulmonary 
inflammation, and cytokine storms leading to acute lung injury and death. Aging of the immune 
system is characterized by increased numbers of neutrophils and by nonspecific damage caused 
by overactive neutrophils that likely underlies much of the age-associated increase in mortality 
due to respiratory infections (Kulkarni et al., 2019; Li et al., 2014). 
Modulation of PGD2-DP1 signaling has the potential to simultaneously boost the antiviral 
immune response against SARS-CoV-2 infection (mediated by dendritic cell and NK cells) while 
also reducing the nonspecific tissue damage caused by infiltration of neutrophils into the lungs of 
infected patients (Figure 2) (Jandl et al., 2016). Therefore, inhibition of PGD2-DP1 by asapiprant 
can potentially counteract age-related dysregulation of both the adaptive and innate immune 
systems and is expected to therapeutically benefit all COVID-19 patients, but most specifically 
older patients, who have the highest morbidity and mortality in this disease. 
 Preclinical Information 
Refer to the asapiprant IB for a detailed preclinical (nonclinical) information and safety profile. 
 Clinical Information 
Refer to the asapiprant IB for detailed Clinical Information. 
 
Risk/Benefit and Ethical Assessment 
Refer to the asapiprant IB for information on the Risk/Benefit and Ethical Assessment. 
 
Compliance Statement 
This study will be conducted in accordance with this protocol, the International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for 
Good Clinical Practice E6 (ICH GCP, 1996; E6 R2, 2017), Title 21 of the United States Code of 
Federal Regulations (US CFR), the European Union (EU) Directives (2001/20/EC; 2005/28/EC), 
and applicable national and local regulatory requirements. The responsibilities of BioAge Labs 
and Investigator(s) are described fully in Appendices 2.2 and 2.3, respectively. 


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STUDY RATIONALE, OBJECTIVES AND ENDPOINTS 
 
Rationale for the Study 
The effect of asapiprant treatment on SARS-CoV infection was evaluated in female 8-month old 
C57BL/6 mice that had been infected intranasally with mouse-adapted SARS-CoV. Mice were 
monitored daily for weight loss (morbidity) and mortality for up to 14 days. Asapiprant 
(30 mg/kg) was administered by oral gavage (PO) to fed mice once daily starting in the morning 
of Day 2 post infection and ending on the morning of Day 5 post infection (4 administrations). 
Two independent treatment studies were performed. Treatment with asapiprant was associated 
with a significantly reduced body weight loss as compared to control groups. As shown in 
Figure 1, untreated mice rapidly lost body weight after infection. Six of the 7 mice in the study 
shown were euthanized in the vehicle group for reaching the humane endpoint of ≥ 25% body 
weight loss. In contrast, when treatment with asapiprant started on Day 2, body weight loss 
stopped and reversed, and all 7 treated mice survived the infection. Therefore, once daily 
treatment with 30 mg/kg asapiprant for 4 days starting 2 days after infection effectively stopped 
weight loss (morbidity) and completely prevented mortality in a lethal mouse model of 
SARS-CoV. In a satellite group of 3 animals each, asapiprant-treatment was associated with an 
84% reduction of lung virus titers at Day 5 after infection as compared to the vehicle control 
group. 
Figure 1:  Mortality and Body Weight Change in SARS-CoV Infected Mice 
 
Once daily oral treatment with 30 mg/kg asapiprant for 4 days starting 2 days after infection. Mortality: log-rank (Mantel-Cox) 
Test; vehicle (n=7) vs asapiprant (n=7); p value = 0.0012. Source: Report BRR175001IVVP20 
This clinical study will evaluate the PGD2-DP1 axis as a therapeutic target for severe COVID-
19. This target is simultaneously dysregulated by immune aging and in COVID-19 patients. 
Therefore, inhibition of the PGD2-DP1 axis is expected to therapeutically benefit all COVID-19 
patients, but most specifically older patients, who have the highest morbidity and mortality in 
this disease, and hence the highest unmet medical need. Modulation of this target can 
simultaneously boost the antiviral immune response against SARS--CoV-2 infection (mediated 


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by dendritic and NK cells) while also reducing the nonspecific tissue damage caused by 
infiltration of neutrophils into the lungs of infected patients (Figure 2) (Jandl et al., 2016). 
Figure 2: Investigational Product Asapiprant Inhibits PGD2 Signaling via the DP1 
Receptor1 to Potentially Treat COVID-19 
 
Abbreviations: CCR7 = C-C motif chemokine receptor 7; COVID-19 = coronavirus disease 2019; DC = dendritic cell; 
DP1 = prostaglandin D2 receptor 1; IFN-𝛾𝛾 = interferon gamma; NK cell = natural killer cell; PGD2-DP1 signaling = the 
therapeutic target of the investigational drug BGE‑175 to treat COVID-19; RTIs = respiratory tract infections 
1 Consequences of DP1 inhibition include improved dendritic cell migration and NK-cell function (and thus a boost in the 
adaptive immune response), plus reduced neutrophil infiltration, thus reducing immune-mediated tissue damage. “Cohorts” refers 
to BioAge Labs longitudinal human cohort data where molecular profiling of blood samples have linked specific mechanisms to 
the aging process, future longevity, and healthspan in aging individuals. 
 
Study Objectives 
To evaluate the efficacy of asapiprant given by PO or nasogastric tube (NG) administration 
versus placebo on the clinical signs and symptoms of COVID-19 infection in hospitalized 
subjects ≥ 50 years of age. 
 Secondary Objectives 
• To evaluate the ability of asapiprant given by PO or NG administration to accelerate the 
clearance of the COVID-19 virus in subjects with symptomatic disease requiring 
hospitalization 
• To determine the efficacy of asapiprant by demonstrating improvement in COVID-19 
illness and prevention of progression to respiratory failure (RF) using various endpoints 
• To evaluate the safety profile of asapiprant given by PO or NG administration in subjects 
≥ 50 years of age hospitalized with COVID-19 infection 


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 Other Objectives 
• To investigate the effect of asapiprant on inflammation markers of COVID-19 infection, 
including but not limited to interleukin (IL)-6, C-reactive protein (CRP), IL-10, tumor 
necrosis factor alpha (TNF-α), IFN-γ, interferon alpha (IFN-α), IFN-γ-induced protein 10 
(IP-10), monocyte chemoattractant protein-1 (MCP-1), cluster of differentiation (CD)4+ 
and CD8+ T cells, and absolute lymphocyte count 
• Determine peak and trough concentrations of study drug after first dose and at steady 
state and, if possible, develop a population PK model 
 
Endpoints 
 Primary Endpoint 
Proportion of subjects who have died or progressed to RF as defined by progressing to the need 
for high-flow nasal cannula O2 delivery, noninvasive positive pressure ventilation, invasive 
mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) therapy at Day 28. 
 Secondary Endpoints 
1. Safety as assessed by adverse events (AEs) as measured by the Common Terminology 
Criteria for Adverse Events (CTCAE) v 5.0 
2. Proportion of subjects surviving [Time Frame: at Day 14, at Day 28, at Day 57] 
3. Proportion of subjects who survive without progression to RF [Time Frame: at Day 14, at 
Day 28, at Day 57] 
4. Time to two successive negative viral titers in nasopharyngeal swab 
5. Time to clinical worsening from baseline value (defined by time to ≥ 1-point worsening on 
the World Health Organization (WHO) Ordinal Scale for COVID-19 [Table 2]): 
Table 2: 
World Health Organization Ordinal Scale for COVID-19 
Patient State 
Description 
Score 
Uninfected 
No clinical or virological evidence of infection 
0 
Ambulatory 
No limitation of activities 
1 
Limitation of activities 
2 
Hospitalized, Mild 
Disease 
Hospitalized, no oxygen therapy 
3 
Oxygen by mask or nasal prongs 
4 
Hospitalized, Severe 
Disease 
Noninvasive ventilation or high-flow oxygen 
5 
Intubation and mechanical ventilation 
6 
Ventilation + additional organ support – pressors, RRT, ECMO 
7 
Dead 
Death 
8 
Abbreviations: ECMO = extracorporeal membrane oxygenation; RRT = renal replacement therapy 


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6. Proportion of patients who develop critical COVID-19 illness as defined by at least one of 
the following: 
A. RF defined based on resource utilization requiring at least one of the following: 
Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow 
nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at 
flow rates > 20 L/min with fraction of delivered oxygen ≥ 0.5), noninvasive positive 
pressure ventilation, ECMO, clinical diagnosis respiratory failure (i.e., clinical need 
for one of the preceding therapies, but preceding therapies not able to be administered 
in setting of resource limitation) 
B. Hemodynamic compromise (defined by systolic blood pressure < 90 mm Hg, or 
diastolic blood pressure < 60 mm Hg or requiring vasopressors)  
C. Multi-organ dysfunction/failure 
7. Time to clinical improvement from baseline value (defined by time to ≥ 1-point improvement 
on the WHO Ordinal Scale for COVID-19 score – must be maintained through Day 28) 
8. Mean change from baseline in WHO Ordinal Scale for COVID-19 score at Day 14/EOT, 
Day 28, Day 57 
9. Incidence and duration of intubation  
10. Length of intensive care unit stay 
11. Incidence and duration of supplemental O2 administration 
12. Incidence and duration of noninvasive ventilation or high-flow nasal cannula O2 
administration 
13. Incidence and duration of mechanical ventilation 
14. Incidence and duration of mechanical ventilation plus additional organ support using 
vasopressors, and/or renal replacement therapy and/or ECMO 
15. Daily ratio of oxygen saturation (SpO2) to fractional inspired O2 (SpO2/FiO2)  
16.  Length of hospital stay 
17. Incidence of re-hospitalization through Day 57 
18. Proportion of subjects requiring intensive care unit admission post randomization 
 Exploratory Endpoints 
1. Inflammation markers including: IL-6, CRP, IL-10, TNF-α, IFN-γ, IFN-α, IP-10, MCP-1, 
CD4+ and CD8+ T cells, and absolute lymphocyte count 
2. Assess peak and trough concentrations of asapiprant at steady state 
3. Assess PGD2 pre-diagnostic to assess correlation with response to treatment for COVID-19 
based on change in WHO Ordinal Scale for COVID-19 score 


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STUDY DESIGN 
 
Study Design and Flow Chart 
This is a randomized, placebo-controlled, parallel-group, multicenter, double-blind study of 
asapiprant administered PO or NG in subjects ≥ 50 years of age and hospitalized with 
documented COVID-19 infection who are not yet in RF. 
After signing informed consent, subjects will be screened upon presentation at the hospital. 
Screening will include full physical examination, vital signs, safety laboratory evaluation, O2 
saturation, pre-diagnostics to measure PGD2 status, and baseline assessment of WHO Ordinal 
Scale for COVID-19 (Table 2) that is derived from oxygen supplementation requirements.  
Certain standard of care assessments completed within 1 day of consent (e.g. physical 
examination, safety laboratory evaluations) may be used for screening purposes. If confirmed 
that they qualify for this protocol according to listed inclusion and exclusion criteria, subjects 
will receive their first dose of study medication PO. They will then receive study medication PO 
once daily, at approximately the same time each day for 13 additional days. Subjects who 
progress to RF and require intubation or subjects who are unable to swallow will receive study 
medication by NG tube administration. Study medication will be administered and subjects will 
receive standard of care treatments deemed appropriate by the treating physician(s). Subjects will 
be randomized to receive asapiprant or placebo. Subjects will be monitored daily for all relevant 
efficacy outcomes, O2 saturation and AEs. Treatment will be discontinued in subjects who 
develop hepatic function impairment defined as a Child-Pugh score (Appendix 4) of 7 or greater. 
Blood will be drawn periodically for safety laboratory measurements, plasma kinetics, 
lymphocyte subsets, CRP, and cytokines (see Table 1). Nasopharyngeal swabs will be collected 
to measure viral load and nasal swabs may be collected for optional local qualitative testing. 
Subjects will be monitored at follow-up visits on Day 28 (approximately 14 days after last dose) 
and Day 57 (approximately 43 days after last dose) to measure viral load. Subjects will be 
monitored for 14 days after administration of the last dose and followed through Day 57. 
Figure 3: Overall Study Design Flow Schematic 
 


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Duration and Study Completion Definition 
The subject’s maximum duration of participation is expected to be approximately 57 days. 
The Study Completion Date is defined as the date on which the last subject in the study 
completes the final protocol-defined assessment(s). Please note that this includes the follow-up 
visit or contact, whichever is later (refer to Section Error! Reference source not found. for the 
defined follow-up period for this protocol). 
 
Sites and Regions 
This study will be performed at multiple study sites within the United States, Brazil and 
Argentina. 


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STUDY POPULATION 
Each subject must and provide informed consent that is documented by a signed and dated 
consent form or documented by the local standard process before any procedures specified in the 
protocol are performed. 
 
Sample Size 
The planned size for this study is 312 subjects, randomized 1:1 Active + standard of care (SOC) 
vs. Placebo + SOC. Randomization will be stratified based on the subject’s enrollment region 
(North America vs. South America) and age (50 to < 75 vs. ≥ 75 years of age). Subjects will 
receive IP per the randomization code. The blind for the treatment assignment must not be 
broken during the study except in emergencies where the identification of the IP is required for 
further treatment of the subject(s) or to assess any safety and tolerability questions. 
 
Inclusion Criteria 
The subject will be considered eligible for the study after meeting all of the criteria below. 
1. Ability to voluntarily provide informed consent that is documented per local requirements 
2. An understanding, ability, and willingness to fully comply with study procedures and 
restrictions 
3. Hospitalized subjects with a confirmed SARS-CoV-2 infection 
4. Laboratory (polymerase chain reaction [PCR]) confirmed infection with SARS-CoV-2  
5. Age > 50 years 
6. COVID-19 illness of any duration, and O2 saturation measurements ≤ 94% over 5 minutes on 
room air (Note: low flow O2 is permitted, but room air O2 saturation must be ≤ 94%) 
7. Not with evidence of critical COVID-19 illness as defined by at least one of the following: 
a. RF defined by requiring at least one of the following: 
• Endotracheal intubation and mechanical ventilation 
• O2 delivered by high-flow nasal cannula at flow rates > 20 L/min with fraction of 
delivered O2 ≥ 0.5) 
• Noninvasive positive pressure ventilation (NIPPV) 
• Extracorporeal membrane oxygenation (ECMO) 
• Clinical diagnosis of RF (i.e., clinical need for one of the preceding therapies, but 
preceding therapies are not able to be administered in setting of resource limitation) 
b. Hemodynamic compromise (defined by systolic blood pressure < 90 mm Hg, or diastolic 
blood pressure < 60 mm Hg) or requiring vasopressors 
c. Multi-organ dysfunction/failure 
8. Female subjects of childbearing potential must have a negative pregnancy test at screening or 
pre-treatment on Day 1 


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Note: Female subjects of childbearing potential are defined as pre-menopausal, < 12 months 
of amenorrhea post-menopause, or no history of surgical sterilization (hysterectomy or 
oophorectomy) or tubal ligation. 
9. Male and female subjects of childbearing potential must agree to use methods of 
contraception that are consistent with local regulations for those participating in clinical 
studies 
 
Exclusion Criteria 
The subject will be excluded from the study if any of the following exclusion criteria are met. 
1. Participation in any other randomized, controlled clinical trial of an experimental treatment 
for COVID-19 (uncontrolled, compassionate use trials are allowed) 
2. In the opinion of the Investigator, progression to death is imminent and inevitable within the 
next 24 hours, irrespective of the provision of treatments 
3. Currently participating in a vaccination trial for SARS-CoV-2  
4. Known positive test for influenza A or influenza B within 1 week prior to screening. 
5. History of human immunodeficiency virus (HIV) infection that is not controlled with current 
treatment 
6. History of Hepatitis B surface antigen, or Hepatitis C positive prior to screening. Subjects 
who are positive for Hepatitis C but have Hepatitis C virus (HCV) RNA below the limit of 
quantitation may be enrolled. Subjects with Hepatitis B, but with undetectable viral load, 
may be enrolled. 
7. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 × the upper limit of 
normal (ULN) 
8. Hepatic function impairment defined as a Child-Pugh score of 7 or greater. See Appendix 4 
for description of the Child-Pugh system. 
9. Stage 4 or higher severe chronic kidney disease (i.e., estimated glomerular filtration rate 
[eGFR] < 30 mL/min) or acute renal failure resulting in eGFR < 30 mL/min 
10. Serious co-morbidity, including: 
a. Myocardial infarction (within the last month) 
b. Moderate or severe heart failure (New York Heart Association [NYHA] class III or IV) 
c. Acute stroke (within the last month) 
d. Uncontrolled malignancy. Uncontrolled malignancy would include cancers that are not 
considered in remission, or solid tumor or hematological malignancies with evidence of 
disease progression in the past 3 months (i.e., there is evidence of disease progression by 
Response Evaluation Criteria in Solid Tumours [RECIST] or equivalent relevant criterion 
for the type of malignancy), and are not considered effectively managed with ongoing 
treatment as determined by the Investigator  
e. Recent severe thromboembolic disease or evidence of severe thromboembolic disease 
defined as a current large vessel thromboembolic event or a thromboembolic event within 


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the past 3 months (e.g., deep vein thrombosis [DVT], pulmonary embolism, ischemic 
stroke, transient ischemic attack) requiring interventional treatment. This exclusion does 
not prohibit prophylaxis for thromboembolic events, including those considered possible 
with concurrent SARS-CoV-2 infection. 
11. History of severe allergic or anaphylactic reactions or hypersensitivity to the study drug 
12. Consideration by the Investigator, for any reason, that the subject is an unsuitable 
candidate to receive study treatment  
 
Restrictions 
Concurrent use of other investigational therapies are generally prohibited in this study; however, 
therapies being used under Emergency Use Authorization will be permitted. 
 
Stopping Criteria 
Given the lack of toxicity observed to date, this study has no specific stopping criteria associated 
with asapiprant use. Nonetheless, asapiprant is an investigational drug and is being evaluated for 
a new indication in this study. Investigators should monitor for any new serious, unexpected AEs 
and assess for possible causality. Any serious adverse event (SAE) thought to be related to study 
drug will be reviewed by the Data Monitoring Committee (DMC), and the DMC will provide 
guidance for ongoing study conduct. Treatment will be discontinued in subjects who develop 
hepatic function impairment defined as a Child-Pugh score (Appendix 4) of 7 or greater. 
 
Discontinuation of Subjects 
A subject may withdraw consent to participate in the study at any time for any reason without 
prejudice to his/her future medical care.  
If IP is discontinued, regardless of the reason, the end of treatment evaluations listed in Table 1 
are to be performed as completely as possible. Whenever possible, all subjects with IP 
administration discontinued should undergo follow-up evaluations. Comments (spontaneous or 
elicited) or complaints made by the subject must be recorded in the source documents. The 
reason for IP discontinuation, date of IP discontinuation, and the total amount of IP administered 
must be recorded in the source documents.  If a subject has been discharged, then the dosing 
diary and IP supplies must be collected. 
 Reasons for IP Discontinuation 
The reason for IP discontinuation must be determined by the Investigator and recorded in the 
subject’s source document. If a subject’s IP administration is discontinued for more than 
one reason, each reason should be documented in the source document, and the most clinically 
relevant reason should be indicated. Subjects should continue to be followed with study 
assessments after discontinuing IP administration unless they withdraw consent. 


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 Subjects ‘Lost to Follow-up’ Prior to Last Scheduled Visit 
A minimum of 3 documented attempts must be made to contact any subject lost to follow-up at 
any time point prior to the last scheduled contact (office visit or telephone contact). At least 1 of 
these documented attempts must include a written communication sent to the subject’s last 
known address via courier or mail (with an acknowledgement of receipt request) asking that they 
return to the site for final safety evaluations and return any unused IP. 


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PRIOR AND CONCOMITANT TREATMENT 
 
Prior and Concomitant Treatment 
Prior treatment includes all treatment (including but not limited to herbal treatments, vitamins, 
non-pharmacological treatment such as psychotherapy as appropriate) received within 30 days 
(or PK equivalent of 5 half-lives, whichever is longer) of the date of first dose of IP. 
Concomitant treatment refers to all treatment taken between the dates of the first dose of IP and 
the end of the follow-up period, inclusive. Prior and concomitant treatment information must be 
recorded on the appropriate CRF page. 
5.1.1 Permitted Treatment 
Any medication which is considered necessary for the subject’s safety and wellbeing may be 
given at the discretion of the Investigator. The administration of all medications (including IP) 
must be listed on the appropriate CRF page. As noted previously in Section 4.4 concurrent use of 
other investigational therapies are generally prohibited in this study; however, therapies being 
used under Emergency Use Authorization will be permitted. 
 


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INVESTIGATIONAL PRODUCT 
 
Identity of Investigational Product 
The test product, asapiprant will be provided as 50 mg tablets for oral use. Additional 
information is provided in the current asapiprant IB. The reference/comparator product is 
placebo, which will be provided as a tablet to match the active IP asapiprant. The placebo tablet 
will be identical to the active tablet except for the active ingredient. 
All IP will be provided in 30-count bottles. All IP will be shipped to the site as blinded supply. 
 Blinding the Treatment Assignment 
This is a double-blind, placebo-controlled study. The blind will be maintained for the entirety of 
the 57-day study conduct for every subject, until unblinding for the final Day 28 topline results 
for all subjects or unless unblinding is required for subject safety reasons. The actual treatment 
given to individual subjects is determined by a randomization schedule. The associated treatment 
assignments giving details of individual subject treatment are available from the interactive 
response technology (IRT). The IRT will assign bottle numbers in a blinded manner and will be 
dispensed by appropriately delegated study staff. 
Each bottle of IP will be assigned a unique 5-character alphanumeric packaging identification 
number. When a bottle of IP is assigned to a subject, the packaging identification number will be 
recorded in the drug accountability records. 
 
Administration of Investigational Product(s) 
 Allocation of Subjects to Treatment 
This is a double-blind, placebo-controlled study. 
Subject (screening) numbers are assigned to all subjects by the EDC as they consent to take part 
in the study. Within the site (numbered uniquely within a protocol), the subject number is 
assigned to subjects according to the sequence of presentation for study participation. 
The actual treatment given to individual subjects is determined by a randomization schedule. 
The randomization number represents a unique number corresponding to IP allocated to the 
subject and will be allocated prior to dosing after eligibility has been determined. 
A 5-digit alpha and/or numeric -Identifier, will be allocated immediately prior to dosing after 
eligibility has been determined. If a randomization number is allocated incorrectly, the study 
monitor must be notified as soon as the error is discovered. Once a randomization number has 
been assigned, that number must not be used again if, for example, a subject is withdrawn from 
the study. For randomized subjects, the randomization number will be the identifying number 
used throughout CRF. 
 Dosing 
Subjects will be dosed concurrently with their meal (± 30 minutes) at 100 mg. Subjects will take 
two 50 mg tablets of asapiprant or matching placebo immediately after the screening evaluation, 


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confirmation of eligibility, and randomization on Day 1. Dosing will continue daily at 
approximately the same time of day for the next 13 days. Subjects who are not eating will take 
the same 100 mg (two 50 mg tablets) total daily dose. The fed status and prescribed 100 mg dose 
will be entered into the electronic data capture (EDC)/IRT 
 daily. 
Subjects will continue dosing for 14 days, including if they are discharged or if they progress to 
RF. Subjects taking nothing by mouth (NPO) or not being fed through an NG tube will take 
study medication at approximately the same time they received prior daily doses. 
6.2.2.1 
Treatment Period 
Each subject will participate in the study for approximately 8 weeks from the time the subject 
signs the informed consent form (ICF) through the final contact. After screening, each subject 
will receive, daily, 1 dose of assigned treatment between Day 1 and Day 14. The WHO Ordinal 
Scale for COVID-19 (Table 2) will be derived daily while hospitalized, at Day 14, and at follow-
up visits until the subject has completed the study (Day 57 or at time of early withdrawal). 
 Unblinding the Treatment Assignment 
The treatment assignment must not be unblinded during the study except in emergency situations 
where the identification of the IP is required for further treatment of the subject. 
In the event that the treatment assignment is unblinded, the date, the person who unblinded the 
code, and the reason for unblinding the code will be recorded. Upon unblinding, IP 
administration will be discontinued, and the subject should be followed with study assessments. 
Any unblinding that occurs must be reported to the contract research organization (CRO) or 
Sponsor, as appropriate. Unblinding information will be available using the study IRT. 
 
Labeling, Packaging, Storage, and Handling 
 Labeling 
Labels containing study information and pack identification are applied to the IP container. 
All IP containers are labeled with a minimum of the protocol number, medication identification 
number (if applicable), dosage form (including product name and quantity in pack), directions 
for use, storage conditions, expiry date (if applicable), lot number and/or packaging reference, 
the statements ‘For clinical trial use only’, and/or ‘CAUTION: New Drug - Limited by Federal 
(or United States) Law to investigational use’, ‘Keep Out of Sight and Reach of Children’, and 
the Sponsor name, address and phone number. Additional labelling will be completed to comply 
with local regulations. 
Additional labels (e.g., those used when dispensing product) may, on a case-by-case basis, be 
applied to the IP in order to satisfy local or institutional requirements, but must not: 
• Contradict the clinical study label 
• Obscure the clinical study label 
• Identify the study subject by name 
Additional labels may not be added without the Sponsor’s prior full agreement. 


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 Packaging 
Investigational product will be packaged in labeled containers as 30-count, white, round bottles 
with an induction seal. 
Changes to BioAge Labs-supplied packaging prior to dosing may not occur without BioAge 
Labs’ prior full agreement.  
 Storage 
The Investigator has overall responsibility for ensuring that IP is stored in a secure, limited-
access location. Limited responsibility may be delegated to the pharmacy or member of the study 
team, but this delegation must be documented. Investigational products are distributed by the 
pharmacy or nominated member of the study team. The pharmacist/nominated team member will 
enter the unique subject identifier on the IP bottle/carton labels as they are dispensed. 
Investigational product must be stored in accordance with labeled storage conditions. 
Temperature monitoring is required at the storage location to ensure that the IP is maintained 
within an established temperature range. The Investigator is responsible for ensuring that the 
temperature is monitored throughout the duration of the study and that records are maintained; 
the temperature should be monitored continuously by using either an in-house system, a 
mechanical recording device such as a calibrated chart recorder, or by manual means, such that 
both minimum and maximum thermometric values over a specific time period can be recorded 
and retrieved as required. Such a device (i.e., certified min/max thermometer) would require 
manual resetting upon each recording. The Sponsor must be notified immediately upon 
discovery of any excursion from the established range. Temperature excursions will require site 
investigation as to cause and remediation. The Sponsor or its representative(s) will determine the 
ultimate impact of excursions on the IP and will provide supportive documentation as necessary. 
Under no circumstances should the product be dispensed to subjects until the impact has been 
determined and the product is deemed appropriate for use by the Sponsor (or a nominated 
designee). 
The Sponsor (or a nominated designee) should be notified immediately if there are any changes 
to the storage area of the IP that could affect the integrity of the product(s), e.g., fumigation of a 
storage room. 
 
Drug Accountability 
The Investigator will be provided with sufficient amounts of the IP to carry out this protocol for 
the agreed number of subjects. The Investigator or designee will acknowledge receipt of the IP, 
documenting shipment content and condition. Accurate records of all IP dispensed, used, 
returned, and/or destroyed must be maintained as detailed further in this section. 
The Investigator has overall responsibility for administering/dispensing IP. Where permissible, 
tasks may be delegated to a qualified designee (e.g., a pharmacist) who is adequately trained in 
the protocol and who works under the direct supervision of the Investigator. This delegation 
must be documented in the applicable study delegation of authority form. 


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The Investigator or his/her designee (as documented by the Investigator in the applicable study 
delegation of authority form) will administer the IP only to subjects included in this study 
following the procedures set out in the study protocol. 
Each subject will be given only the IP carrying his/her treatment assignment. All 
administered/dispensed medication will be documented in the subject's source and/or other IP 
record. 
No IP stock or returned inventory from a BioAge Labs-Sponsored study may be removed from 
the site where originally shipped without prior knowledge and consent by the Sponsor. If such 
transfer is authorized by the Sponsor (or a nominated designee), all applicable local, state, and 
national laws must be adhered to for the transfer. 
The Sponsor (or a nominated designee) must be permitted access to review the supplies storage 
and distribution procedures and records provided that the blind of the study is not compromised. 
With the written agreement of the Sponsor (or a nominated designee) at the end of the study, all 
unused stock and empty/used IP packaging may be destroyed at the site or a local facility. In this 
case, destruction records identifying what was destroyed, when and how, must be obtained with 
copies provided to the Sponsor (or a nominated designee). Destruction of IP must be in 
accordance with local, state, and national laws. 
Based on entries in the site drug accountability forms, it must be possible to reconcile IPs 
delivered with those used and returned. All IPs must be accounted for and all discrepancies 
investigated and documented to the Sponsor (or designee) satisfaction. 
 
Subject Compliance 
Subject compliance will be ensured with a combination of the following methods: 
• Inpatient: Compliance must be assessed by observation of dosing by the Investigator or 
designee. The Investigator/designated person will record details on the drug accountability 
log(s) and/or source documents. In addition, details of the dosing time (time, date, dose level) 
will be captured in the appropriate CRF. 
• Outpatient: subjects will be instructed how to dose daily, and home health visits or other 
subjects contact (e.g., virtual teleconferences with the subject and Investigator or a designee 
may be held) to verify subject compliance and comprehension of dose assignment. Subjects 
will be instructed to return all used and unused study medication and bottles to complete drug 
accountability. 
 
Retention of Bioavailability and Bioequivalence Testing Samples 
Not Applicable. 


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STUDY PROCEDURES 
 
Study Schedule 
The following “priority order” will be in effect when more than 1 procedure or assessment is 
required at a particular time point. 
• Spontaneous or solicited AE reporting 
• Electrocardiogram (ECG) 
• Vital signs  
• PK blood sampling 
• Pharmacodynamic (PD) blood sampling 
• O2 saturation  
• Clinical laboratory tests 
• Physical examination 
• Viral titers nasopharyngeal 
• WHO Ordinal Scale for COVID-19 (Table 2) derived from oxygen supplementation 
requirement, hypotension or need for vasopressors, need for renal dialysis, and activity level in 
outpatients 
• Documentation of administered supplemental oxygen (e.g. flow rates, equipment) 
NOTE: Blood sampling for PK and PD evaluation must be performed at the precise protocol-
scheduled time. Actual sampling time(s) must be accurately recorded in the source document and 
appropriate CRF. Pharmacokinetic samples should always be collected prior to PD samples, 
when scheduled at the same timepoint. 
 Screening Period 
The screening procedures must be completed within 3 days prior to the administration of the 
dose or first dose of IP. All screening assessments and procedures are to be performed by the 
Principal Investigator or a qualified designee. 
Signed and dated informed consent from the subject prior to the performance of any study 
related procedures must be obtained by the Investigator or designee. A copy of the signed 
informed consent form must be given to the subject for their records. 
See Table 1 for a complete list of screening procedures to be performed. 
7.1.1.1 
Screening Failure 
A screen failure is a subject who has given informed consent and failed to meet the inclusion 
and/or met at least 1 of the exclusion criteria and has not been enrolled/randomized or 
administered IP. 


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For purposes of data collection, all subjects who give consent to the study, but are not enrolled 
and/or randomized, will be considered as screen failures even if they were otherwise fully 
eligible for the study, for example alternates/reserve subjects. 
7.1.1.2 
Rescreening of Subjects 
Subjects who fail to meet all inclusion/exclusion criteria will not be permitted to be rescreened 
for the study at any point. However, subjects may be re-screened if screen failure occurred due to 
administrative reasons. 
Eligible subjects who meet all inclusion/exclusion criteria but are unable to participate in the 
study due to scheduling conflicts/timing may be rescreened based on Investigator discretion and 
Sponsor (or a nominated designee) approval should their availability to participate fall outside 
the screening window. In these cases, a new screening number must be assigned for each subject 
who is re-screened, and new informed consent must be documented. The sponsor will provide 
guidance regarding screening procedures that must be repeated if a subject is rescreened so that 
unnecessary site staff exposure is minimized. 
 Treatment Period 
7.1.2.1 
Visits Summary  
Subjects who meet all the eligibility criteria before will be allowed to enter the Treatment period 
(Day 1). They will then be randomized to an IP (asapiprant or placebo). Subjects will take study 
drug for 14 days according to the randomization schedule. 
If screening and Day 1 occur on the same day, screening procedures do not need to be repeated if 
also required on Day 1.  Standard of care labs can be used to confirm eligibility and baseline 
safety assessments if completed within 48 hours prior to screening. 
This is a double-blind, placebo-controlled study. The Investigator, study site staff, and the 
subject are blinded to study treatment, but not to the dose (number of tablets) or dosing 
frequency. The Sponsor and designees, except the personnel analyzing the PK samples, are 
blinded to study treatment, dose, and dosing frequency. Sponsor study team members 
responsible for IRT system are blinded to study treatment and can, in exceptional cases, be 
unblinded to dose and dosing frequency. 
Asapiprant and matching placebo tablets will be identical in appearance, packaging, and labeling 
to maintain the blind. Treatment assignments will be unblinded after database lock. 
Any intentional or unintentional unblinding should be reported and documented. Unblinding (for 
a single subject) should be considered only when knowledge of the treatment assignment is 
deemed essential by the Investigator for the subject’s care. Unplanned unblinding will result in 
the discontinuation of subject participation from the study treatment but the subject should 
participate in protocol-defined follow-up procedures. 
7.1.2.2 
End of Treatment, Follow-up and End of Study Period 
The end of treatment visit is the date when the subject has completed the final study treatment as 
outlined in the schedule of assessments. 


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There is a follow-up visit to occur at Day 28 (approximately 14 days after the final dose of study 
drug). 
The end of study visit is to occur on Day 57 (approximately 43 days after the final dose of study 
drug). This visit will be a telephone call initiated by the site staff to query for SAEs, AEs, and 
concomitant treatments. All AEs and SAEs that are not resolved through 30 days after the last 
dose of study drug will be followed to closure (see Appendix 3.2). 
 Additional Care of Subjects After the Study 
No after care is planned for this study. 
 
Study Evaluations and Procedures 
The name and address of each third-party vendor (e.g., clinical laboratory) used in this study will 
be maintained in the Investigator’s and Sponsor (or designee) files. The Sponsor expects that the 
Investigator will ensure that every reasonable effort is made to perform all assessments at the 
protocol-scheduled time. 
Study Investigators will monitor subject safety on an ongoing basis while hospitalized, including 
a review of vital signs, local safety laboratory measurements, and observations of subject status. 
If discharged prior to the end of treatment, subjects will be discharged to home, and home health 
resources will be utilized to manage subject daily dosing and status, including the collection of 
protocol-specified laboratory tests and assessments. The home assessments will be monitored by 
the study Investigator. 
BioAge Labs will have a blinded Medical Lead assigned for safety oversight and will work 
closely with a CRO partner to provide ongoing reviews of subject safety data, including findings 
associated with laboratory tests, ECGs, vital signs, physical examinations, and AEs. Routine 
Medical Monitor review will be conducted on an ongoing basis during study conduct. The CRO 
will provide a drug safety team to manage SAE reporting. 
An independent DMC will be utilized throughout the study to monitor subject safety. A DMC 
charter will be developed preceding study initiation, which will define DMC processes and 
meetings. The DMC will meet at regular planned intervals during study conduct and also meet ad 
hoc as required for any identified urgent safety findings. 
An interim analysis (IA) will be planned when 208 subjects complete study assessments though 
the end of treatment and 14-day follow-up (Day 28). The IA will include an assessment of safety 
and efficacy and will include stopping rules. Independent of the Sponsor, the DMC will be 
responsible for performing the IA and evaluating the interim results. 
7.2.1.1 
Adverse Event Collection 
Adverse events will be assessed and monitored from when the subject signs the informed consent 
form to completion of the study (including screen failure or drop/out discontinuation, if 
applicable). During the study, subject safety will be closely monitored by vital sign 
measurements, ECG measurements, clinical safety laboratory measurements, and physician 
oversight. 


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All AEs spontaneously reported by the subject or reported in response to the open question at 
scheduled time points (i.e., “Have you had any health problems since you were last asked {or 
since the last visit})?” will be collected from the time informed consent is signed. 
AEs include worsening of a preexisting medical condition as well as clinically significant 
changes from baseline laboratory values/conditions. Worsening of the preexisting medical 
condition (e.g., diabetes, hypertension) means that it has increased in severity, frequency, and/or 
duration, and/or has an association with a significantly worse outcome. A preexisting condition 
that has not worsened during the study is not considered an AE. 
7.2.1.2 Independent Data Monitoring Committee 
An independent DMC, whose members who are not affiliated with the Sponsor or CRO, will be 
utilized during the study to monitor subject safety throughout study conduct. The DMC will have 
access to unblinded data to perform comparative analyses during study conduct. A DMC charter 
will be developed preceding study initiation, which will define DMC processes and meetings. 
The DMC will meet at regular planned intervals during study conduct and also meet ad hoc for 
any identified urgent safety findings. Additionally, the DMC charter will define when a pause in 
enrollment is required pending a DMC safety review. The following criteria will trigger a pause 
in enrollment pending a DMC safety review: 
• Death in any subject in which the cause of death is judged to be related to the study drug by 
the Investigator. 
• One occurrence of an AE of special interest, which will be defined as an SAE considered 
related to the study drug and consistent with the toxicity profile defined in the IB. For 
asapiprant, there are no known AEs of special interest. 
 Medical History / Demographic Information 
Concomitant medications, including over-the-counter medications and supplements used during 
the study, will be recorded in the CRF. Drug names and start/stop dates, including dose, route of 
administration, and dosing frequency, will be recorded for concomitant medications (e.g., iron, 
anti-hypertensive medications). 
A complete medical and medication history, as well as demographic information, will be 
collected at the screening visit/time points as described in Table 1 by a qualified licensed 
physician, physician’s assistant, or nurse practitioner. The medical history will be reviewed, and 
clinically relevant history (per the Investigator) is to be recorded in the source records and on the 
appropriate history CRF page(s), including: 
• Date of birth 
• Sex 
• Race and ethnicity 
• 
 Use of medication within 30 days before entering the screening period 
• History of respiratory, cardiovascular, renal, gastrointestinal, hepatic, endocrine, 
hematological, neurological, psychiatric, and other diseases 
• SARS-CoV-2 (COVID-19) history 


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 Physical Examination (Including Height at Screening Visit Only and Weight) 
A complete physical examination will be performed at the time points described in Table 1 by a 
qualified licensed physician, physician’s assistant, or nurse practitioner. 
The physical examination will include a review of the following body systems: 
• General appearance 
• Skin 
• Head, eyes, ears, nose, and throat 
• Spine/neck/thyroid 
• Musculoskeletal 
• Respiratory 
• Cardiovascular 
• Neurological 
• Abdomen (including liver and kidneys) 
Clinically significant abnormalities identified at the screening visit will be documented in the 
subject’s source documents and on the Medical History CRF. Clinically relevant changes after 
the initial screening period visit will be captured on the AE CRF page, as deemed by the 
Investigator. 
Weight should be collected at screening but will not be required for any other visits throughout 
the study. 
7.2.3.1 Abbreviated Physical Examination 
An abbreviated examination will be performed at the time points described in Table 1 by a 
qualified licensed physician, physician’s assistant, nurse practitioner, or registered nurse. The 
abbreviated physical examination will consist of a review of the following body systems plus a 
targeted review for those areas where a subject may raise concern through AE questioning. 
• Cardiovascular 
• Respiratory 
• Abdomen (including liver and kidneys) 
• A targeted physical review for areas/systems of medical relevance 
Clinically relevant changes will be captured as AEs on the AE CRF page, as deemed by the 
Investigator. 
 Vital Signs 
Vital signs consisting of blood pressure, temperature, respiratory rate, and pulse rate will be 
taken at the time points described in Table 1 by appropriately delegated personnel. One reading 
of blood pressure and pulse rate will be taken and recorded in the source document and the CRF. 
Blood pressure 
One reading of supine systolic blood pressure/diastolic blood is to be collected at the described 
time points. 
The same method for obtaining blood pressure measurement (auscultatory or oscillometric) 
should be used throughout the study for all subjects (and documented). The cuff should have a 
bladder length that is 80% and a width that is at least 40% of arm circumference (a length-to-
width ratio of 2:1). 
The subject should remove all clothing that covers the location of cuff placement. The subject 
should not have exercised or consumed caffeine, alcohol, or nicotine within 30 minutes of 
collection. The subject should be instructed to relax as much as possible for at least 5 minutes 
prior to collection. The subject should remain quiet during this time and through the 
measurement. 


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The subject should be lying comfortably, with the legs uncrossed. The arm should be supported 
with a pillow, such that the middle of the cuff on the upper arm is at the level of the right atrium 
(approximately halfway between the bed and the level of the sternum). 
The area in which the vital signs are measured should be controlled and as consistent as possible 
during the study to minimize the external variability of the readings. It should be collected at a 
comfortable room temperature with little to no background noise, using the appropriately sized 
cuff placed at the same location of the same arm during the study. The bladder should be deflated 
(calibrated for oscillometric method or manually by the auscultatory method) at a rate of 
2-3 mmHg/second. The first and last audible sounds recorded are the systolic and diastolic 
pressure, respectively. 
At the Screening Visit, blood pressure should be compared between both arms. When there is a 
consistent inter-arm difference confirmed over 3 consecutive measurements (> 10 mmHg), the 
arm with the higher blood pressure should be used for inclusion at screening and the last 
measurement recorded in the CRF. The same (right or left) arm with the higher blood pressure 
will be used throughout the study. 
Pulse rate 
One reading of the supine pulse rate should be collected at the described time points. The subject 
should be instructed to relax as much as possible for at least 5 minutes prior to collection. The 
subject should remain quiet during this time and through the measurement. 
The use of automated devices for measuring pulse rate is acceptable, although, when done 
manually, the pulse rate will be measured in the brachial/radial artery for at least 30 seconds. 
When the timing of these measurements coincides with a blood collection, blood pressure and 
pulse rate should be obtained before the nominal time of the blood collection. The same 
measurement technique for obtaining pulse should be used throughout the study for all subjects 
(and documented). 
Body Temperature 
Temperature should be taken as per hospital protocol. 
 Safety Laboratory Tests 
Blood for safety laboratory tests will be taken at the time points described in Table 1 by an 
appropriately delegated employee. 
All safety laboratory tests will be performed according to the laboratory’s standard procedures. 
The laboratory will supply reference ranges. The Investigator should determine out-of-range 
safety laboratory values for clinical significance, indicating if the value(s) is/are not clinically 
significant or clinically significant. Out-of-range values and changes within the “normal range” 
during the study may be associated with, or constitute, an AE. Abnormal safety laboratory 
values, which are unexpected or not explained by the subject’s clinical condition, may, at the 
discretion of the Investigator or BioAge Labs, be repeated as soon as possible until confirmed, 
explained, or resolved. 
The safety laboratory assessments described in the following sections will be performed. 


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7.2.5.1.1 Biochemistry 
Blood samples (8.5 mL) for serum biochemistry will be collected into a red top gel separator 
tube at the time points described in Table 1. The following parameters will be assessed: 
Sodium 
Phosphate 
Potassium 
Protein 
Glucose  
Carbon dioxide 
Urea nitrogen 
Albumin 
Creatinine 
Aspartate aminotransferase (AST) 
Calcium 
Alanine aminotransferase (ALT) 
Chloride 
Gamma glutamyl transferase (GGT) 
Thyroid stimulating hormone (TSH)a 
Alkaline phosphatase (ALP) 
 Lactate dehydrogenase (LDH) 
 
Total bilirubin  
Indirect bilirubin 
 
Uric acid 
a See Table 1 
 
 
7.2.5.1.2 Hematology 
Blood samples (3 mL) for hematology will be collected into a K2EDTA tube at the time points 
described in Table 1. The following parameters will be assessed: 
Hemoglobin 
Total neutrophils (absolute and percent)* 
Hematocrit 
Eosinophils (absolute and percent)* 
Red blood cells 
Monocytes (absolute and percent)* 
Platelet count 
Basophils (absolute and percent)* 
White blood cell count; total and differential 
Mean corpuscular volume (MCV) 
Mean corpuscular hemoglobin (MCH) 
MCH concentration (MCHC) 
Red blood cell distribution width (RDW) 
Lymphocytes (absolute and percent)* 
Reticulocyte count 
 
*absolute and percent preferred, but it will 
be acceptable to only collect one based on 
local lab reporting 
 


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7.2.5.1.3 Coagulation 
Blood samples (2.7 mL) for coagulation will be collected into a sodium citrate tube at the time 
points outlined in Table 1. The following parameters will be assessed: 
Prothrombin time (PT) 
Activated partial thromboplastic 
time (aPTT) 
International normalized 
ratio (INR) 
 
7.2.5.1.4 Urinalysis 
A urine sample for urinalysis will be collected at the time points described in Table 1. The 
following parameters will be assessed: 
pH 
Blood 
Nitrites 
Glucose 
Ketones 
Leukocyte esterase 
Protein 
Bilirubin 
Specific gravity 
Microscopic examination will be conducted if protein and/or blood is/are detected during 
urinalysis. At a minimum the microscopic examination will consist of red blood cells, white 
blood cells, casts, and bacteria.  
7.2.5.1.5 Serology Screen  
At the Screening Visit, a blood sample of approximately 8.5 mL will be drawn into a serum 
separator tube to test for the presence of HIV, Hepatitis B surface antigen (HBsAg), and HCV 
antibody among other parameters. 
The test results from the Screening Visit need not be confirmed negative prior to enrollment in 
the study. Patients with a previous history of HIV that is not controlled with current therapy will 
be excluded. Patients with previous positive serology for Hepatitis B or Hepatitis C will be 
excluded unless viral RNA blood levels are below the level of detection (see exclusion criteria 
for details).  Results of the serology screen will be reviewed and verified by the study monitor 
and will be collected in the CRF database. 
 O2 Saturation/FiO2 
The O2 saturation/FiO2 ratio will be collected on the study days as specified in Table 1. 
Oxygen saturation will be documented as a representative value at approximately the same time 
daily and will use a finger pulse oximeter to approximate O2 saturation. 
FiO2 values will be obtained at the corresponding time to the O2 saturation values daily. If a 
subject is receiving supplemental O2 using a device that reports FiO2 values, then the FiO2 value 
will be reported from the device and recorded in the CRF. However, if there is no FiO2 readout 
available (e.g., subject is receiving supplemental O2 by nasal prongs), the site will record the 
method of O2 delivery and the flow rate in liters of O2 per minute (L/min) in the CRF. If the 
subject is breathing room air, this will be captured in the CRF rather than the O2 delivery flow 
rate. Note: High Flow Oxygen will only be documented when using a high flow oxygen delivery 
device that warms and humidifies the oxygen. 


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The Sponsor will derive the O2 saturation/FiO2 ratio, using accepted standards for converting O2 
delivery rates to FiO2 values. 
 
 Pre-dose Serological Markers - PGD2 
A single predose blood sample for circulating PGD2/PGD2 metabolites will be  
obtained at the time specified in Table 1. Sample collection, handling, storage and shipment 
instructions will be provided in the study laboratory manual. 
 Nasopharyngeal Viral Titers  
Nasopharyngeal swabs for quantitative viral titer assessments will be collected at the times 
specified in Table 1 by appropriately delegated study staff. These nasopharyngeal swabs will be 
completed every other day until two confirmed negative qualitative tests are obtained. 
Qualitative COVID-19 tests are not required and may be elected by the subject and Investigator. 
Qualitative tests are performed at the site’s local laboratory. When a qualitative negative result is 
confirmed (two consecutive tests are negative), the site will verify that a final quantitative 
nasopharyngeal swab has been collected for at least one visit following the first qualitative 
negative result. The study laboratory manual will outline proper sample handling for quantitative 
viral titer assessments.  Qualitative testing will be performed per the site’s local laboratory 
standard testing procedures. 
 Blood for Inflammation Markers 
Blood samples will be collected at the times specified in Table 1 for measurement of IL-6, CRP, 
IL-10, TNF-α, IFN-γ, IFN-α, IP-10, MCP-1, CD4+ and CD8+ T cells, and absolute lymphocyte 
count. Sample collection, handling, storage and shipment instructions will be provided in the 
study laboratory manual. 
 Proteomic, Metabolomic and Transcriptomic Sample Collection 
Blood collection samples (4 mL) will be taken at the time points described in Table 1. The name 
and address of the laboratory(ies) performing these assessments for this study will be maintained 
in the Investigator’s files at each site and in the Trial Master File at the Sponsor. A full 
description of the blood collection, handling, storage, and shipping can be found in the 
laboratory manual. 
Following completion of the study, blood collection samples from one or more time points may 
undergo untargeted transcriptomic, metabolomic, or proteomic analysis. For untargeted 
transcriptomic analysis, the appropriate amount of collected blood will be sent to 
 for 
RNA-seq analysis. For untargeted proteomics, the appropriate amount of collected blood will be 
sent to 
 for analysis using the 
. 
Actual blood sample collection times must be captured, and these data will be collected. The 
Sponsor expects the Investigator to ensure that a reasonable effort is made to collect all blood 
samples at time points in described in Table 1. 
 Twelve-lead Electrocardiogram (ECG) 
Twelve-lead ECGs will be performed at the times specified in Table 1 by appropriately delegated 
study staff. The following parameters will be recorded on the appropriate CRF page: heart rate, 


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rhythm, PR, RR, QRS, and QT intervals, and any wave form abnormalities. The QT interval 
corrected for heart rate by Fridericia’s formula (QTcF) will be from the Investigator’s read. The 
Investigator’s assessment of the ECG tracing as normal or abnormal must be documented. If the 
Investigator feels that the ECG is abnormal, he/she needs to determine if the abnormality is 
significant or not. Overall, ECG significance is to be documented on the tracing and recorded in 
the CRF. 
The subject will be asked to remove all clothing that covers the location of lead placement. The 
subject should not have exercised or consumed caffeine, alcohol, or nicotine within 30 minutes 
of collection. The subject must be resting in the supine position for at least 5 minutes before 
collecting the ECG. 
In some cases, it may be appropriate to repeat abnormal ECGs to rule out improper lead 
placement as contributing to the ECG abnormality. It is important that leads are placed in the 
same positions each time to achieve precise ECG recordings. 
A single ECG recording, including a 10-second rhythm strip, will be obtained for all 
assessments. ECG results will be recorded in the CRF. The ECG recording should be 
immediately assessed to verify that it is a valid recording and if not valid, it should be repeated to 
obtain a valid recording. Invalid recordings will not be entered in the CRF. 
To ensure the safety of the subjects, a qualified individual at the Investigator site will make 
comparisons to baseline measurements. 
If a machine-read QTcF value is prolonged, repeat measurements may not be necessary if a 
qualified physician’s interpretation determines that the QTcF values are in the acceptable range. 
 Pharmacokinetic Procedures 
The name and address of the bioanalytical laboratory performing the PK assessment for this 
study will be maintained in the Investigator’s files at the/each site and in the Trial Master File at 
BioAge Labs. 
Actual PK blood sample collection times versus time of dosing will be monitored. The time of 
meal will also be captured, as dosing should occur within 30 minutes of eating. The BioAge Labs 
expectation is that the Investigator will ensure that every effort is made to collect all PK blood 
samples at the precise protocol scheduled time. Pre-dose (trough) pharmacokinetic blood 
collection should be collected within 30 minutes prior to the dose. If subjects are being dosed at 
home, the subject should be instructed to not dose until the home health visit is conducted. Post-
dose (peak) PK blood samples should be collected between 3 and 6 hours after the daily dose. 
Samples drawn outside these parameters will be considered a protocol deviation. 
7.2.12.1 
Blood Sample Collection and Handling Procedures 
Pharmacokinetic blood samples will be collected at the times specified in Table 1 to measure 
plasma concentrations of asapiprant and metabolites thereof. A full description of PK blood 
collection, handling, storage and shipping can be found in the provided laboratory manual. 
Plasma sample tubes for bioanalysis must be freezer-safe and identified with freezer-safe labels 
provided by the CPU. The labels will contain the following information: 


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• 
Study number (BGE-175-201) 
• 
Subject identifier (This number consists of a 5-digit number. The first digit will identify the 
Study Part the subject is assigned to; the second and third digit will identify the cohort 
number that the subject is assigned to within the study part; and the fourth and fifth digits 
will identify the subject number within a cohort). 
• 
Nominal day (e.g., Day 1) 
• 
Nominal time (e.g., predose) 
• 
Matrix identifier (plasma) 
• 
Split (primary or back-up). 
7.2.12.2 
Shipment of Plasma Pharmacokinetic Samples 
Instructions for shipment of PK samples (along with the corresponding documentation) can be 
found in the laboratory manual, provided separately. 
Pharmacokinetic samples will be stored nominally at -70°C or below prior to and after analysis 
at the CRO until further directions are authorized by the Sponsor (or a nominated designee). 
7.2.12.3 
Plasma Drug Assay Methodology 
Plasma sample analysis will be performed according to relevant Sponsor (or a nominated 
designee) Standard Operating Procedures. 
Plasma concentrations will be measured using the most current validated bioanalytical method. 
In addition, selected plasma samples may be used to investigate incurred sample reproducibility 
(full details will be described in the bioanalytical study plan). Raw data will be stored in the 
archive of the designated bioanalytical contract laboratory. 
 Pharmacodynamic Assessments 
The name and address of the bioanalytical laboratory performing the PD assessment for this 
study will be maintained in the Investigator’s files at the/each site and in the Trial Master File at 
the Sponsor. 
Actual PD blood sample collection times versus time of dosing will be monitored. The Sponsor’s 
expectation is that the Investigator will ensure that every reasonable effort is made to collect all 
PD blood samples at time points in Table 1. 
A blood sample to assess proteomics, metabolomics, and transcriptomics will be collected at Day 
1 and at the End of Treatment visit as described in Table 1. 
7.2.13.1 
Blood Sample Collection and Handling Procedures 
Pharmacodynamic blood samples will be collected at the times specified in the laboratory 
manual to measure plasma concentrations. A full description of PD blood collection, handling, 
storage and shipping can be found in the provided laboratory manual. 


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Plasma sample tubes for bioanalysis must be freezer-safe and identified with freezer-safe labels 
provided by the central lab. The labels will contain the following information: 
• Study number (BGE-175-201) 
• Subject identifier  
• Nominal day (e.g., Day 1) 
• Nominal time (e.g., predose) 
• Matrix identifier (e.g., plasma) 
• Split (primary or back-up). 
7.2.13.2 
Shipment of Plasma Pharmacokinetic and Pharmacodynamic Samples 
Instructions for shipment of PK and PD samples (along with the corresponding documentation) 
can be found in the laboratory manual, provided separately. 
Pharmacodynamic samples will be stored nominally at -70°C or below prior to and after analysis 
at the CRO until further directions are authorized by the Sponsor (or a nominated designee). 
 Volume of Blood to be Drawn from Each Subject 
During this study, it is expected the total volume of blood taken will not exceed 500 mL for any 
subject in any part of the study, regardless of sex. 
The amount of blood to be drawn for each assessment is an estimate. The amount of blood to be 
drawn may vary according to the instructions provided by the manufacturer or laboratory for an 
individual assessment. When more than 1 blood assessment is to be done at the same time 
point/period, if they require the same type of tube, the assessments may be combined. 
Table 3 provides the estimated volume of blood to be drawn for each subject. 
Table 3: 
Estimated Volume of Blood to be Drawn from Each Subject 
Assessment 
Sample Volume (mL) 
Number of Samples 
Total Volume (mL) 
Pharmacokinetic samples a 
4 
7 
 28 
Pre-dose Serological markers - PGD2 
4 
1 
4 
Blood for Inflammation markers b 
4 
10 
40 
Proteomic, metabolomic, and 
transcriptomic samples 
4 
2 
8 
Safety 
Biochemistry c 
8.5 
6  
51 
Coagulation  
(PT, aPTT, INR) 
3 
6  
18 
Hematology 
3 
6  
18 
Total 
 
 
167 mL 
 HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; TSH = thyroid 
stimulating hormone 
a If a catheter is used for any blood draw or series of blood draws, then the first 1 mL is to be discarded. The 1-mL discard has 
been taken into account in the table above and the total blood volume required for this study. 


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b Two 2.7-mL samples are to be drawn for each pharmacodynamics blood sampling time point. 
c Serology panel (HBsAg, HIV, HCV), and thyroid panel (TSH) will be included in the biochemistry panel and collected at 
screening only. 


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DATA MANAGEMENT AND STATISTICAL METHODS 
 
Data Collection 
A validated EDC System will be used during study conduct. The Investigators’ authorized site 
personnel must enter the information required by the study CRF Completion Guidelines or 
similar for all data requiring transcription of the source. This study will be monitored according 
to ICH GCP Guidelines. 
A study monitor will visit each site in accordance with the monitoring plan and review the CRF 
data against the source data for completeness and accuracy. Discrepancies between source data 
and data entered on the CRF will be addressed by qualified site personnel. When a data 
discrepancy warrants correction, the correction will be made by authorized site personnel (in an 
auditable manner). Data collection procedures will be discussed with the site at the site initiation 
visit and/or at the Investigator’s meeting. Once a subject is randomized, it is expected that site 
personnel will complete the CRF entry within approximately 3 business days of the study visit 
date. 
 
Clinical Data Management 
Data are to be entered into a clinical database as specified in the Data Management Plan and 
according to the study CRF Completion Guidelines. Quality control and data validation 
procedures are applied to ensure the validity and accuracy of the clinical database. 
Data are to be reviewed and checked for omissions, errors, and values requiring further 
clarification using computerized and manual procedures. Data queries requiring clarification are 
to be communicated to the site for resolution. Only authorized personnel will make corrections to 
the clinical database, and all corrections are documented in an auditable manner. 
 
Data Handling 
Data that may potentially unblind the treatment assignment (e.g., IP serum concentrations, 
treatment allocation, and IP preparation/accountability data) will be handled with special care 
during the data cleaning and review process. Unless otherwise specified, these data will be 
handled in such a way that, prior to unblinding, any data that may unblind study team personnel 
will be presented as blinded information or otherwise will not be made available. If applicable, 
unblinded data may be made available to quality assurance representatives for the purposes of 
conducting independent drug audits. 
All analyses/summaries will be based on observed data, with no imputation for missing data, 
unless otherwise specified in the statistical analysis plan (SAP). 
 
Statistical Analysis Process 
The study will be analyzed by the Sponsor (or a nominated designee). 
The primary endpoint (proportion who have died or progressed to RF at Day 28) will be 
analyzed using a logistic regression with treatment group and covariates, age group (50 to <75 
years, and > 75 years), baseline WHO ordinal clinical scale (3 or 4), and region.  Other 
covariates including previous COVID-19 therapy may be explored.  Estimation of the covariate-


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adjusted difference in proportion responding will be reported using Cochran-Mantel-Haenszel 
(CMH) weighting and estimates from the logistic regression (LR) as described by Ge and 
colleagues (Ge et al., 2011, Appendix C). This analysis will be repeated without the covariate. 
Deaths prior to Day 28 will be included in the endpoint (RF, death). WHO Ordinal Scale for 
COVID-19 scores (Table 2) will be analyzed by carrying forward any early deaths through Day 
28; other categorical and continuous outcomes will be described. The primary analysis will be 
based on the Intent-to-Treat population (ITT), analyzed as randomized. The denominator for the 
proportions alive and RF-free at Day 28 will include all randomized subjects. Subjects lacking 
sufficient data to confirm RF-free and alive at Day 28 will be included in the primary analysis as 
treatment failures.  If more than 5% of subjects have insufficient data to confirm RF-free and 
alive at Day 28, BioAge will employ a MI strategy (SAS MI, MIANALYZE) based on the 
patients last known status. For example, the last known WHO Score for a patient lost to follow-
up can be used to impute missing primary outcome from patients with known primary outcome 
and similar WHO Scores.  For the primary comparison, analysis by treatment group will be, “as 
randomized”.  Secondary analyses of the primary endpoint may be repeated for the mITT and the 
per protocol populations, analyzed as treated. Time-to-RF will be analyzed using methods of 
Kaplan-Meier (KM), with time zero at randomization. Hazard ratios (Cox PHREG) with 95% 
confidence intervals will describe the treatment effect. 
 
A sensitivity analysis may be completed to assess concurrent treatments and prior SARS-CoV-2 
vaccinations in relation to the primary endpoint.  
 
Secondary endpoints that are proportions will be analyzed like the primary endpoint, using 
logistic regression with and without the designated covariates and by FET. 95% confidence 
intervals and p-values (without correction) will be presented for these descriptive analyses. 
Time-to-event analyses will use the methods of Kaplan-Meier with censoring rules for the 
different endpoints provided in the SAP. Descriptive statistics for TTE will be median times to 
event with 95 confidence intervals and log-rank statistics to test for treatment differences; Cox 
proportional hazards with 95% CI will be presented.   
“Incidence and duration” secondary endpoints will be analyzed by counting days per subject and 
then forming 95% confidence intervals and Wilcoxon tests and t-tests to compare treatments. 
Incidence will also be compared using FET. 
 
These analyses of secondary endpoints will be done using the ITT population and may be 
repeated for the mITT and PP populations. 
 
No secondary endpoints are designated as, “key” for any labeling purposes.  
Results of secondary endpoint analyses will not be corrected for multiplicity.  
The Sponsor does not intend formal statistical analyses for safety data. However, odds ratios 
(95% CI) for common adverse events will be displayed. 
The SAP will further describe the statistical methods and definitions for the analysis of the 
efficacy endpoints, PK, PD, and safety data, as well as describe the approaches to be taken for 
summarizing other study information, such as subject disposition, demographics and baseline 
characteristics, IP exposure, and prior and concomitant medications. The SAP will also include 
further description of how missing and spurious data will be addressed. 


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To preserve the integrity of the statistical analysis and study conclusions, the SAP will be 
finalized prior to the IA. Analysis rules and methods for the IA are planned to be the same as the 
rules and methods for the final analysis. 
Unless noted otherwise, all statistical analyses will be performed using SAS Version 9.3 or later 
(SAS Institute, Cary, NC 27513). 
 
Planned Interim Analysis, Adaptive Design, and Data Monitoring Committee 
An IA for safety and efficacy will be conducted after 208 subjects complete assessments through 
the end of treatment (Day 28). Unblinded IA results will be reviewed by the independent DMC 
for safety evaluation. The interim efficacy analysis will be performed by an unblinded 
independent statistician. 
Analysis at the interim look will be a logistic regression as described for the final analysis.  The 
IA will be restricted to patients who reach Day 28 (or would have reached Day 28 had they not 
died, withdrawn, or been lost to follow-up). Patients included in the IA will have been 
randomized at least 28 days prior to IA. It is BioAge’s intent that the final and interim analysis 
do not differ in any important way. 
An α spend is not incorporated into the sample size to account for this look. 
Efficacy analyses at IA may yield Conditional Power (CP) results in the Mehta and Pocock 
promising zone (0.34, 0.90) (Mehta and Pocock, 2011).  If so, to maintain the statistical power of 
the study and to avoid any type 1 error penalty, the Sponsor will consider the option of 
increasing the sample size (according to the rules provided by Mehta and Pocock), not to exceed 
N=624 (twice the planned sample size).  For this planned IA, Z-score evidence at the IA of 
between Z=1.41 and 2.21 would define the promising zone and opportunity for BioAge to 
expand the study.  For example, if at IA, Z=1.8 (CP=0.66), then to maintain the power at 0.90 the 
study could be expanded from 312 subjects to 431.  For results in the Mehta and Pocock 
unfavorable zone, or in the favorable zone, the study will continue to conclusion at N=312 
subjects.  
The decision to stop the study at IA will be based on a full safety and an early review of efficacy 
by the Data Monitoring Committee (DMC).  To aid the DMC in their recommendation to 
BioAge regarding conduct of the trial beyond the IA, a table of multiple possible true effects and 
potential stopping rules will be developed by BioAge and presented in the DMC charter.  The 
operating characteristics of potential decision rules will be shared and understood by the DMC. 
 
Sample Size Calculation and Power Considerations 
Assuming a 31% RF rate in the placebo group and a 15% RF rate in the asapiprant group, for a 
Fishers Exact test with two-sided 5% Type 1 error and 90% power, the sample size to detect a 
16% absolute improvement in the primary endpoint is 312 subjects (1:1 randomization). 
Randomization will be stratified based on the region within which a subject is enrolled (North 
America vs. South America) and age (50 to < 75 vs. ≥ 75 years of age). 
 
Study Population 
Enrolled Analysis Set: all patients who provided informed consent. 


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Intent-to-Treat (ITT): all patients who have been randomized. The ITT will be used for 
efficacy endpoints. Patients will be analyzed according to the treatment group to which they 
were randomized. The ITT will be used for the primary efficacy analysis. 
Modified Intent-to-Treat population (mITT): all ITT patients with exclusion of randomized 
untreated patients and randomized ineligible patients.  
Per-protocol Set: all mITT patients with further exclusion of patients with major protocol 
deviations related to data integrity or eligibility as judged by clinical/biostatistical study 
personnel prior to database lock. This population will be formed only if > 5% of patients would 
be excluded. 
Safety Analysis Set: all patients who have received at least 1 dose of either asapiprant or 
placebo. The Safety Analysis Set will be used for safety analysis. Patients will be analyzed under 
actual treatment being received. 
Pharmacokinetic (PK) Set: all patients who have received at least 1 dose of asapiprant and have 
at least 1 evaluable post-dose PK concentration value. 
Pharmacodynamic (PD) Set: all patients who have received at least 1 dose of asapiprant and 
have at least 1 evaluable post-dose PD value. 
 Pharmacokinetic Analysis 
PK parameters will be calculated from plasma asapiprant concentration-time data using 
noncompartmental methods, and all calculations will be based on actual sampling times. PK 
parameters will include, but not be limited to, the following: 
Table 4: 
Pharmacokinetic Endpoint Summary 
Pharmacokinetic Parameter Definition 
Cmax  
Maximum concentration occurring at tmax 
tmax  
Time of maximum observed concentration sampled post-dose 
AUClast  
Area under the curve from the time of dosing to the last measurable 
concentration 
t1/2  
Terminal half-life 
λz  
First-order rate constant associated with the terminal (log-linear) 
portion of the curve 
CL/F 
Total body clearance for extravascular administration divided by the 
fraction of dose absorbed 
Vz /F  
Volume of distribution associated with the terminal slope following 
extravascular administration divided by the fraction of dose absorbed 
 


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8.7.1.1 
Statistical Analysis of Pharmacokinetic Parameters 
Single samples for PK analysis will be drawn at the time described in Table 1. The times of 
dosing and sample collection are to be captured. Attempts will be made to develop a PK 
Population model based on the data. The results of the Population PK analysis will be published 
in a separate report. 
Listing of individual PK concentrations and individual PK parameters of asapiprant will be based 
on the PK Analysis Sets. Individual concentrations and PK parameters of asapiprant will be 
listed and summarized by treatment with descriptive statistics (number, arithmetic mean, 
standard deviation [SD], coefficient of variation [CV%], median, minimum, maximum, 
geometric mean, and CV% of geometric mean). Figures of individual and mean (± SD) 
concentration-time profiles of asapiprant by treatments and study parts will be generated based 
on nominal time points. 
 Pharmacodynamic Analysis 
Exploratory inflammation markers are planned for this study. Pharmacodynamic samples may be 
maintained for up to 5 years after the clinical study report has been finalized. 
Remaining aliquots of blood or tissue samples from any of the scheduled time points may also be 
analyzed for additional exploratory inflammation markers or PK-related activities (i.e., 
validation of a new bioanalytical method). This exploratory research is intended to aid the further 
understanding of asapiprant provided it does not add to the blood volume presented in Table 3. 
Any results from this additional exploratory research will be reported separately from the main 
clinical study report. The results may be used internally to help support the design of further 
clinical studies, form part of scientific publication, or be made known to the regulatory 
authorities as part of a new drug application. The Sponsor has no obligation to perform this 
additional exploratory research. 
8.7.2.1 
Statistical Analysis of Pharmacodynamic Parameters 
 
Safety Analyses 
Safety endpoint: 
1. 
Incidence and severity of treatment-emergent AEs (TEAEs) 
2. 
Safety outcome measure: 
a) Occurrence of AEs 
b) Laboratory safety parameters such as complete blood count, blood glucose, electrolyte, 
hepatic and renal functions taken before the first dose and on Days 2, 5, 14, 28 and at the 
time of discharge to find any changes or any systemic effect after treatment 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 23.1. The number of events, incidence, and percentage of TEAEs will be calculated 
overall, by system organ class, by preferred term, and by treatment group for each cohort and 
treatment group. The number and percentage of subjects with TEAEs will be further summarized 


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by severity and relationship to IP. Adverse events related to IP, AEs leading to withdrawal, 
SAEs, and deaths will be similarly summarized/listed. 
Clinical laboratory tests, vital signs, and ECG findings will be summarized by treatment group 
and visit for the study. Descriptive statistics will be calculated for quantitative safety data as well 
as for the difference from baseline, if applicable. Frequency counts will be compiled for 
classification of qualitative safety data. Baseline for safety data will be defined as the last value 
prior to dose. Potentially clinically important findings will also be summarized or listed. 
 
Other Analyses 
No other analyses are planned in this study. 
 


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REFERENCES 
Centers for Disease Control and Prevention (2020). COVID-19 hospitalization and death by age. 
https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-
death-by-age.html <Accessed 23 November 2020>. 
Chen, J., Kelley, W.J., and Goldstein, D.R. (2020). Role of aging and the immune response to 
respiratory viral infections: potential implications for COVID-19. J Immunol 205, 313–320. 
Cunha, L.L., Perazzio, S.F., Azzi, J., Cravedi, P., and Riella, L.V. (2020). Remodeling of the 
immune response with aging: immunosenescence and its potential impact on COVID-19 immune 
response. Front Immunol 11. 
Ge M, Durham LK, and Meyer DR. (2011) Covariate-adjusted difference in proportions from 
clinical trials using logistic regression and weighted risk differences. Drug Information Journal 
45:481-493 
Guimaraes PO, Quirk D, Furtado RH, et al. Tofacitinib in Patients Hospitalized with Covid-19 
Pneumonia. N Engl J Med 2021;385(5):406-415. DOI: 10.1056/NEJMoa2101643. 
Jandl, K., Stacher, E., Bálint, Z., Sturm, E.M., Maric, J., Peinhaupt, M., Luschnig, P., Aringer, I., 
Fauland, A., Konya, V., et al. (2016). Activated prostaglandin D2 receptors on macrophages 
enhance neutrophil recruitment into the lung. J Allergy Clin Immunol 137, 833–843. 
Kulkarni, U., Zemans, R.L., Smith, C.A., Wood, S.C., Deng, J.C., and Goldstein, D.R. (2019). 
Excessive neutrophil levels in the lung underlie the age-associated increase in influenza 
mortality. Mucosal Immunol 12, 545–554. 
Li, J., Chen, Q., Luo, X., Hong, J., Pan, K., Lin, X., Liu, X., Zhou, L., Wang, H., Xu, Y., et al. 
(2014). Neutrophil‐to‐lymphocyte ratio positively correlates to age in healthy population. J Clin 
Lab Anal 29, 437–443. 
Mehta, C.R., and Pocock, S.J. (2011) Adaptive increase in sample size when interim results are 
promising: a practical guide with examples. Stat Med 40, 3267–3284. 
Temesgen Z, Burger CD, Baker J, et al. Lenzilumab Efficacy and Safety in Newly Hospitalized 
Covid-19 Subjects: Results from the Live-Air Phase 3 Randomized Double-Blind Placebo-
Controlled Trial. medRxiv 2021. DOI: 10.1101/2021.05.01.21256470. 
Wu, S., Du, Z., Shen, S., Zhang, B., Yang, H., Li, X., Cui, W., Chen, F., and Huang, J. (2020). 
Identification and validation of a novel clinical signature to predict the prognosis in confirmed 
COVID-19 patients. Clin Infect Dis:ciaa793 [Epub ahead of print].  
 
 


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APPENDICES 


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APPENDIX 1 




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 APPENDIX 2 


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REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 


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REGULATORY AND ETHICAL CONSIDERATIONS 
This study is conducted in accordance with current applicable regulations including ICH E6(R2), 
EU Directive 2001/20/EC, and all updates, as well as local ethical and legal requirements. 
Compliance with these regulations and guidelines also constitutes compliance with the ethical 
principles described in the Declaration of Helsinki. 
The name and address of each third-party vendor (e.g., CRO) used in this study will be 
maintained in the Investigator’s and Sponsor’s files, as appropriate. 


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SPONSOR’S RESPONSIBILITIES 
Good Clinical Practice Compliance 
The study Sponsor and any third party to whom aspects of the study management or monitoring 
have been delegated will undertake their assigned roles for this study in compliance with all 
applicable industry regulations, current ICH GCP guideline E6 (1996 [R2, 2016]), EU Directive 
2001/20/EC Guidelines, as well as all applicable national and local laws and regulations. 
Visits to sites are conducted by representatives of the study Sponsor and/or the company 
organizing/managing the research on behalf of the Sponsor to inspect study data, subjects’ 
medical records, and CRFs in accordance with current GCP and the respective local and 
(inter)national government regulations and guidelines. Records and data may additionally be 
reviewed by auditors or by regulatory authorities. 
The Sponsor (or a nominated designee) ensures that local regulatory authority requirements are 
met before the start of the study. The Sponsor (or a nominated designee) is responsible for the 
preparation, submission, and confirmation of receipt of any regulatory authority approvals 
required prior to release of investigational product for shipment to the site. 
Indemnity/Liability and Insurance 
The Sponsor (or a nominated designee) ensures that suitable clinical study insurance coverage is 
in place prior to the start of the study. An insurance certificate is supplied to the Investigator as 
necessary. 
Public Posting of Study Information 
The Sponsor (or a nominated designee) is responsible for posting appropriate study information 
on applicable websites. Information included in clinical study registries may include 
participating Investigators’ names and contact information. 
The timing for study registration and results summary posting must be in accordance with 
applicable local and national requirements. 
Submission of Summary of Clinical Study Report to Competent Authorities of Member 
States Concerned and Ethics Committees 
The Sponsor (or a nominated designee) will provide a summary of the clinical study report to the 
competent authority of the member state(s) concerned as required by regulatory requirement(s) 
and to comply with the Community guideline on GCP. This requirement will be fulfilled within 
6 months of study completion date for pediatric studies and within 1 year for non-pediatric 
studies as per guidance. 
Study Suspension, Termination, and Completion 
The Sponsor (or a nominated designee) may suspend or terminate the study, or part of the study, 
at any time for any reason. If the study is suspended or terminated, the Sponsor (or a nominated 
designee) will ensure that applicable sites, regulatory agencies, and IRBs/ECs are notified as 
appropriate. Additionally, the discontinuation of a registered clinical study which has been 
posted to a designated public website will be updated accordingly. 


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INVESTIGATOR’S RESPONSIBILITIES  
Good Clinical Practice Compliance 
The Investigator must undertake to perform the study in accordance with ICH GCP Guideline E6 
(1996) and E6 R2 (2017), EU Directive 2001/20/EC, and applicable regulatory requirements and 
guidelines. 
It is the Investigator’s responsibility to ensure that adequate time and appropriately trained 
resources are available at the site prior to commitment to participate in this study. The 
Investigator should also be able to estimate or demonstrate a potential for recruiting the required 
number of suitable subjects within the agreed recruitment period. 
The Investigator will maintain a list of appropriately qualified persons to whom the Investigator 
has delegated significant study-related tasks, and shall, upon request of the Sponsor (or a 
nominated designee), provide documented evidence of any licenses and certifications necessary 
to demonstrate such qualification. Curriculum vitae for Investigators and sub-Investigators are 
provided to the study Sponsor (or a nominated designee) before starting the study. 
If a potential research subject has a primary care physician, the Investigator should, with the 
subject’s consent, inform them of the subject’s participation in the study. 
Agreement with the final clinical study report is documented by the signed and dated signature 
of the principal Investigator, in compliance with Directive 2001/83/EC as amended by Directive 
2003/63/EC and ICH Guidance E3 (1995). 
Protocol Adherence and Investigator Agreement 
The Investigator and any sub-Investigators must adhere to the protocol as detailed in this 
document. The Investigator is responsible for enrolling only those subjects who have met 
protocol eligibility criteria. Investigators are required to sign an Investigator agreement to 
confirm acceptance and willingness to comply with the study protocol. 
If the Investigator suspends or terminates the study at their site, the Investigator will promptly 
inform the Sponsor (or a nominated designee) and the IRB/EC and provide them with a detailed 
written explanation. The Investigator will also return all investigational product, containers, and 
other study materials to the Sponsor (or a nominated designee). Upon study completion, the 
Investigator will provide the Sponsor (or a nominated designee), IRB/EC, and regulatory agency 
with final reports and summaries as required by (inter)national regulations. 
Communication with local IRBs/ECs, to ensure accurate and timely information is provided at 
all phases during the study, may be done by the Sponsor (or a nominated designee), applicable 
CRO, Investigator, or for multicenter studies, the coordinating principal Investigator according to 
national provisions and will be documented in the Investigator agreement. 


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DOCUMENTATION AND RETENTION OF RECORDS 
Case Report Forms 
The Investigator is responsible for maintaining adequate and accurate medical records from 
which accurate information is recorded onto CRFs, which have been designed to record all 
observations and other data pertinent to the clinical investigation. Case report forms must be 
completed by the Investigator or designee as stated in the site delegation log. 
All data will have separate source documentation; no data will be recorded directly onto the 
CRF. 
All data sent to the Sponsor (or a nominated designee) must be endorsed by the Investigator. 
The CRA/study monitor will verify the contents against the source data per the monitoring plan. 
If the data are unclear or contradictory, queries are sent for corrections or verification of data. 
Recording, Access, and Retention of Source Data and Study Documents 
Original source data to be reviewed during this study will include, but are not limited to subject’s 
medical file, and original clinical laboratory reports. All key data must be recorded in the 
subject’s source documents. 
The Investigator must permit authorized representatives of the Sponsor (or a nominated 
designee), the respective national, local, or foreign regulatory authorities, the IRB/EC, and 
auditors to inspect facilities and to have direct access to original source records relevant to this 
study, regardless of media. 
The CRA/study monitor (and auditors, IRB/EC, or regulatory inspectors) may check the CRF 
entries against the source documents. The consent form includes a statement by which the 
subject agrees to the monitor/auditor from the Sponsor (or a nominated designee), national or 
local regulatory authorities, or the IRB/EC, having access to source data (e.g., subject’s medical 
file, appointment books, original laboratory reports, X-rays etc.). 
These records must be made available within reasonable times for inspection and duplication, if 
required, by a properly authorized representative of any regulatory agency (e.g., the US FDA, 
EMA, UK Medicines and Healthcare products Regulatory Agency) or an auditor. 
Essential documents must be maintained according to ICH GCP requirements and may not be 
destroyed without written permission from the Sponsor (or a nominated designee). 


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AUDIT/INSPECTION 
To ensure compliance with relevant regulations, data generated by this study must be available 
for inspection upon request by representatives of, for example, the US FDA (as well as other US 
national and local regulatory authorities), the EMA, the Medicines and Healthcare products 
Regulatory Agency, other regulatory authorities, the Sponsor (or a nominated designee) and the 
IRB/EC for each site. 


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FINANCIAL DISCLOSURE 
The Investigator is required to disclose any financial arrangement during the study and for 1 year 
after, whereby the outcome of the study could be influenced by the value of the compensation for 
conducting the study, or other payments the Investigator received from the Sponsor (or a 
nominated designee). The following information is collected: any significant payments from the 
Sponsor or subsidiaries such as a grant to fund ongoing research, compensation in the form of 
equipment, retainer for ongoing consultation or honoraria; any proprietary interest in 
investigational product; any significant equity interest in the Sponsor or subsidiaries as defined 
in 21 CFR 54 2(b) (1998). 


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ETHICAL CONSIDERATIONS 
Informed Consent 
It is the responsibility of the Investigator to obtain documented informed consent from all study 
subjects prior to any study-related procedures including screening assessments. All consent 
documentation must be in accordance with applicable regulations and GCP. Each subject or the 
subject’s legally-authorized representative, as applicable, is requested to sign and date the subject 
informed consent form or a certified translation if applicable, after the subject has received and 
read (or been read) the written subject information and received an explanation of what the study 
involves, including but not limited to: the objectives, potential benefits and risk, inconveniences, 
and the subject’s rights and responsibilities. Because of biosafety concerns with COVID-19 
infected patients’ investigational sites may have developed alternatives to written signature 
documentation. These alternative documentation methods are acceptable for this study. A copy 
of the informed consent documentation (i.e., a complete set of subject information sheets and 
fully executed signature pages) must be given to the subject or the subject’s legally authorized 
representative, as applicable. This document may require translation into the local language. 
Signed consent forms or alternative consent documentation forms must remain in each subject’s 
study file and must be available for verification at any time. 
The principal Investigator provides the Sponsor (or a nominated designee) with a copy of the 
consent form which was reviewed by the IRB/EC and which received their favorable 
opinion/approval. A copy of the IRB/EC’s written favorable opinion/approval of these 
documents must be provided to the Sponsor (or a nominated designee), prior to the start of the 
study unless it is agreed to and documented (abiding by regulatory guidelines and national 
provisions) prior to study start that another party (e.g., Sponsor [or a nominated designee]) or 
coordinating principal Investigator) is responsible for this action. Additionally, if the IRB/EC 
requires modification of the sample subject information and consent document provided by the 
Sponsor (or a nominated designee), the documentation supporting this requirement must be 
provided to the Sponsor (or a nominated designee). 
Institutional Review Board or Ethics Committee 
For sites outside the EU, it is the responsibility of the Investigator to submit this protocol, the 
informed consent document (approved by the Sponsor (or a nominated designee) or their 
designee), relevant supporting information and all types of subject recruitment information to the 
IRB/EC for review, and all must be approved prior to site initiation. 
The applicant for an EC opinion can be the Sponsor (or a nominated designee) or the Investigator 
for sites within the EU; for multicenter studies, the applicant can be the coordinating principal 
Investigator or Sponsor (or a nominated designee), according to national provisions. 
Responsibility for coordinating with IRBs/ECs is defined in the clinical trial agreement. 
Investigational product supplied will not be released until the Sponsor (or a nominated designee) 
has received written IRB/EC approval. 
Prior to implementing changes in the study, the Sponsor (or a nominated designee) and the 
IRB/EC must approve any revisions of all informed consent documents and amendments to the 


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protocol unless there is a subject safety issue. If required by local law, substantial amendments to 
the protocol must also be approved by the appropriate regulatory agency prior to implementation. 
For sites outside the EU, the Investigator is responsible for keeping the IRB/EC appraised of the 
progress of the study and of any changes made to the protocol, at least annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/EC. This can be the responsibility of the Sponsor (or a nominated designee) or Investigator 
for sites within the EU; or for multicenter studies, the coordinating principal Investigator, 
according to national provisions. The Investigator must also keep the local IRB/EC informed of 
any serious and significant AEs as required by IRB/EC procedures. 
 
Privacy and Confidentiality 
All US-based sites and laboratories or entities providing support for this study, must, where 
applicable, comply with the HIPAA of 1996. A site that is not a covered entity as defined by 
HIPAA must provide documentation of this fact to the Sponsor (or a nominated designee). 
The confidentiality of records that may be able to identify subjects will be protected in 
accordance with applicable laws, regulations, and guidelines. 
After subjects have consented to take part in the study, the Sponsor (or a nominated designee) 
reviews their medical records and data collected during the study. These records and data may, in 
addition, be reviewed by others including the following: independent auditors who validate the 
data on behalf of the Sponsor; third parties with whom the Sponsor may develop, register, or 
market BGE-175; national or local regulatory authorities; and the IRB/EC which gave approval 
for the study to proceed. The Sponsor and/or its representatives accessing the records and data 
will take all reasonable precautions in accordance with applicable laws, regulations, and 
guidelines to maintain the confidentiality of subjects’ identities. 
Subjects are assigned a unique identifying number; however, their initials and date of birth may 
also be collected, if permitted under local laws governing privacy. 
The results of studies containing subjects’ unique identifying number, relevant medical records, 
and possibly initials and dates of birth, where allowed per local law, may be transferred to, and 
used in, other countries which may not afford the same level of protection that applies within the 
countries where this study is conducted. The purpose of any such transfer would include: to 
support regulatory submissions, to conduct new data analyses to publish or present the study 
results, or to answer questions asked by regulatory or health authorities. 


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STUDY RESULTS / PUBLICATION POLICY 
The term “Publication” shall mean any paper, article, manuscript, report, poster, internet posting, 
presentation slides, abstract, outline, video, instructional material, presentation (in the form of a 
written summary), or other public disclosure of the study results, in printed, electronic, oral, or 
other form. The parties understand and agree that participation in the study may involve a 
commitment to publish the data from all sites participating in the study in a cooperative 
publication with other Investigators prior to publication or oral presentations of the study results 
on an individual basis. The site agrees not to publish or present the site’s study results until such 
time as either the aggregate multi-site study results are published in a cooperative publication or 
for a period of one (1) year after termination or completion of the study at all participating sites, 
whichever shall first occur. After that time, the site may publish the site’s study results in 
scientific journals or present the study results at symposia or other professional meetings in 
accordance with the following provisions: 
If the study is part of a multicenter study, the first publication of the study results shall be made 
by the Sponsor (or a nominated designee) in conjunction with the Sponsor (or a nominated 
designee) presentation of a joint, multicenter publication of the compiled and analyzed study 
results. If such a multicenter publication is not submitted to a journal for publication by the 
Sponsor (or a nominated designee) within an 18-month period after conclusion, abandonment, or 
termination of the study at all sites, or after the Sponsor (or a nominated designee) confirms there 
shall be no multicenter study publication of the study results, an Investigator may individually 
publish the study results from the specific site in accordance with this section. The Investigator 
must, however, acknowledge in the publication the limitations of the single site data being 
presented. 
At least sixty (60) days prior to submitting an abstract, manuscript, or other document for 
publication, a copy of the proposed publication will be provided to the Sponsor (or a nominated 
designee) by the site for review. Upon the Sponsor (or a nominated designee)’s request, the site 
agrees to remove any and all confidential information (expressly excluding study results) 
identified in the publication and to delay such submission or presentation for an additional sixty 
(60) day period in order to allow the Sponsor (or a nominated designee) time to file any patent 
application(s). All publications of the study results shall appropriately reference the multi-site 
study publication, if any, or the fact that the study results are a subset of data resulting from a 
larger multi-site study. 
BioAge Labs is committed to transparent dissemination of all scientific, technical, and medical 
manuscripts generated from BioAge Labs-supported research. Therefore, after January 1, 2018, 
BioAge Labs will require the submission of all BioAge Labs-supported research manuscripts to 
journals that offer public availability via Open Access (including publisher platforms/repositories 
and self-archiving). Open Access refers to the free at point of entry, online availability of 
published research output with, where available, rights of re-use according to an End User 
License. 
Unless otherwise required by the journal in which the publication appears, or the forum in which 
it is made, authorship will comply with the International Committee of Medical Journal Editors 
(ICMJE) Recommendation for the Conduct, Reporting, Editing and Publication of Scholarly 
Work in Medical journals. Participation as an Investigator does not confer any rights to 
authorship of publications. 


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APPENDIX 3 


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ADVERSE EVENTS: DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING 


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ADVERSE EVENT DEFINITIONS 
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
pharmaceutical product and that does not necessarily have a causal relationship with this 
investigational product or medicinal product. An AE can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product (ICH Guidance E2A 1995). 
Treatment-emergent Adverse Event 
A treatment-emergent adverse event (TEAE) is defined as any event emerging or manifesting at 
or after the initiation of treatment with an investigational product or medicinal product or any 
existing event that worsens in either intensity, frequency or relationship following exposure to 
the investigational product or medicinal product.  
Serious Adverse Event  
A serious adverse event (SAE) is any untoward medical occurrence (whether considered to be 
related to investigational product or not) that at any dose: 
• Results in death 
• Is life-threatening. 
Note: The term ‘life-threatening’ in the definition of “serious” refers to an event in which the 
subject 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 was more severe. 
• Requires inpatient hospitalization or prolongation of existing hospitalization. Note: 
Hospitalizations, that are the result of elective or previously scheduled investigations 
procedures or surgery for pre-existing conditions and have not worsened after initiation of 
treatment, should not be classified as SAEs. For example, an admission for a previously 
scheduled ventral hernia repair would not be classified as an SAE; however, complication(s) 
resulting from a hospitalization for an elective or previously scheduled surgery that meet(s) 
serious criteria must be reported as SAE(s). 
• Results in persistent or significant disability/incapacity 
• Results in a congenital abnormality/birth defect 
• Is an important medical event. 
Note: Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the subject and may require medical or surgical intervention to prevent 1 
of the outcomes listed in this definition. Examples of such medical events include 
bronchospasm associated with anaphylaxis requiring intensive treatment in an emergency 
room or at home; blood dyscrasias or convulsions that do not result in inpatient 
hospitalization; or the development of drug dependency or drug abuse. 
 


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Unexpected Adverse Event 
An unexpected AE is an AE whose nature, severity, specificity, or outcome is not consistent with 
the term, representation, or description used in the Reference Safety Information (RSI). 
“Unexpected” also refers to the AEs that are mentioned in the IB and/or prescribing information 
as occurring with a class of drugs or as anticipated from the pharmacological properties of the 
product, but are not specifically mentioned as occurring with the particular product under 
investigation. 
The expectedness of AEs will be determined by the Sponsor (or a nominated designee) and 
Investigator using the IB and/or prescribing information as the RSI. This determination will 
include considerations such as the number of AEs previously observed, but not based on what 
might be anticipated form the pharmacological properties of a product. 
Suspected Unexpected Serious Adverse Reaction  
A Suspected Unexpected Serious Adverse Reaction (SUSAR) is defined as any suspected 
adverse reaction to study treatment (e.g., including active comparators) that is both serious and 
unexpected.  
The event(s) must meet all the following: 
• Suspected adverse reaction 
• Serious 
• Unexpected 
• Assessed as related to study treatment 
Clinical Laboratory and Other Safety Assessment 
A change in the value of a clinical laboratory parameter, vital sign measure, or ECG assessment 
can represent an AE if the change is clinically relevant or if, during administration of 
investigational product, a shift of a parameter is observed from a value in the normative range to 
a value that is outside the normal range and considered clinically significant, or a further waning 
of an already clinically significant value. When evaluating such changes, the extent of deviation 
from the reference range, the duration until return to the reference range, either while continuing 
administration or after the end of administration with the investigational product, and the range 
of variation of the respective parameter within its reference range, should also be considered. 
If, at the end of the treatment phase, there are abnormal clinical laboratory (such as hematology 
panel or clinical chemistry panel), vital sign, or ECG values which were not present at the 
pretreatment evaluation observed closest to the start of study treatment, further investigations 
should be performed until the values return to within the reference range or until a plausible 
explanation (e.g., concomitant disease or expected disease evolution) is found for the abnormal 
values. 
The Investigator should assess, based on the above criteria and the clinical condition of the 
subject, whether a change in a clinical laboratory value, vital sign, or ECG parameter is clinically 
significant and represents an AE. 


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COLLECTION OF ADVERSE EVENTS 
All AEs/SAEs are collected from the time the informed consent is signed until the defined 
follow-up period stated in Section Error! Reference source not found.. This includes events 
occurring during the screening phase of the study, regardless of whether or not investigational 
product is administered. 
All AEs/SAEs must be followed to closure (the subject’s health has returned to his/her baseline 
status or all variables have returned to baseline), regardless of whether the subject is still 
participating in the study. Closure indicates that an outcome is reached, stabilization achieved 
(the Investigator does not expect any further improvement or worsening of the event), or the 
event is otherwise explained. 
Any subject who discontinues study treatment due to an AE will be followed through resolution 
and study completion and will be included in safety statistical analysis. Subjects who discontinue 
study drug early will be followed with follow-up visits per the protocol visit schedule and/or 
phone calls after the study visit schedule is completed. 




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Not Related 
The event can be readily explained by other factors such as the subject’s underlying 
medical condition, concomitant therapy, or accident and no plausible temporal or 
biologic relationship exists between the investigational product and the event. 
 
Another source of guidance is provided in the World Health Organization-Uppsala Monitoring 
Center (WHO-UMC) causality categories descriptions. When applying the WHO-UMC 
categories in this study any AE fitting the causality term of Possible or higher (Probable/Likely 
or Certain) should be consider related. Any AE fitting the causality term of Unlikely or lower 
(Conditional / Unclassified or Unassessable / Unclassifiable) should be considered not related. 
 
WHO-UMC Causality Categories 
Causality term  Assessment criteria* 
Certain 
• Event or laboratory test abnormality, with plausible time relationship to 
drug intake 
• Cannot be explained by disease or other drugs 
• Response to withdrawal plausible (pharmacologically, pathologically) 
• Event definitive pharmacologically or phenomenologically (i.e. an 
objective and specific medical disorder or a recognized pharmacological 
phenomenon) 
• 
Rechallenge satisfactory, if necessary 
Probable / 
Likely 
• Event or laboratory test abnormality, with reasonable time relationship to 
drug intake 
• Unlikely to be attributed to disease or other drugs 
• Response to withdrawal clinically reasonable 
• Rechallenge not required 
Possible 
• Event or laboratory test abnormality, with reasonable time relationship to 
drug intake 
• Could also be explained by disease or other drugs 
• Information on drug withdrawal may be lacking or unclear 
Unlikely 
• Event or laboratory test abnormality, with a time to drug intake that 
makes a relationship improbable (but not impossible) 
• Disease or other drugs provide plausible explanations 
Conditional / 
Unclassified 
• Event or laboratory test abnormality 
• More data for proper assessment needed, or 
• Additional data under examination 
Unassessable / 
Unclassifiable 
• Report suggesting an adverse reaction 
• Cannot be judged because information is insufficient or contradictory 
• Data cannot be supplemented or verified 
* All points should be reasonably complied with 
 
 
Outcome Categorization 
The outcome of AEs must be recorded in the Case Report Forms during the course of the study. 
Outcomes are as follows: 


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• Fatal 
• Not Recovered/Not Resolved 
• Recovered/Resolved 
• Recovered/Resolved with Sequelae 
• Recovering/Resolving 
• Unknown 


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SAFETY REPORTING 
Reference Safety Information 
The reference for safety information for this study is the Investigator Brochure which the 
Sponsor has provided under separate cover to all Investigators. 
Reporting Procedures 
SAEs that occur from the time of signing the ICF through 30 days after last dose of study 
drug require that a SAE report form be completed in the electronic data capture (EDC) system 
and submitted to the Sponsor or designee within 24 hours of the Investigator’s first knowledge of 
the event, even if the experience does not appear to be related to study drug. In the event that 
EDC is unavailable, the SAE paper report form must be filled out by the Investigator and sent via 
email within 24 hours of awareness of the event to the 
 
, and then the information entered into the EDC once available. 


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SERIOUS ADVERSE EVENT COLLECTION TIME FRAME 
All SAEs occurring in patients will be recorded in the eCRF from the time of signing the ICF 
through the Safety Follow-up visit or 30 days after the last dose of study drug. 
In addition, any SAE(s) considered “related” to the investigational product and discovered by the 
Investigator at any interval after the study has completed must be reported to the CRO using 
EDC data entry within 24 hours of the first becoming aware of the event. 


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SERIOUS ADVERSE EVENT ONSET AND RESOLUTION DATES 
The onset date of the SAE is defined as the date the event meets serious criteria. The resolution 
date is the date the event no longer meets serious criteria, the date the symptoms resolve, or the 
event is considered chronic. In the case of hospitalizations occurring after discharge from the 
original hospitalization at the time of study qualification, the hospital admission and discharge 
dates are considered the onset and resolution dates, respectively. 
In addition, any signs or symptoms reported by the subject after signing the informed consent 
form, or leading up to the onset date of the SAE, or following the resolution date of the SAE, 
must be recorded as an AE, if appropriate. 


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FATAL OUTCOME 
Any SAE that results in the subject’s death (e.g., the SAE was noted as the primary cause of 
death) must have fatal checked as an outcome with the date of death recorded as the resolution 
date. For all other events ongoing at the time of death that did not contribute to the subject’s 
death, the outcome should be considered not resolved, without a resolution date recorded. 
For any SAE that results in the subject’s death or any ongoing events at the time of death, unless 
another investigational product action was previously taken (e.g., drug interrupted, reduced, 
withdrawn), the action taken with the investigational product should be recorded as “dose not 
changed” or “not applicable” (if the subject never received investigational product). The 
investigational product action of withdrawn should not be selected solely as a result of the 
subject’s death. 


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PREGNANCY 
All pregnancies are to be reported from the time informed consent is signed until the last 
follow-up visit. 
Any report of pregnancy for any female study participant or the partner of a male study 
participant must be reported within 24 hours to the CRO. The pregnant female study participant 
must be withdrawn from the study. 
Every effort should be made to gather information regarding the pregnancy outcome and 
condition of the infant. It is the responsibility of the Investigator to obtain this information within 
30 calendar days after the initial notification and approximately 30 calendar days post-partum. 
Pregnancy complications such as spontaneous abortion/miscarriage, elective abortion or 
congenital abnormality are considered SAEs and must be reported using the EDC. 
In addition to the above, if the Investigator determines that the pregnancy meets serious criteria, 
it must be reported as an SAE using the EDC. The test date of the first positive serum/urine β-
HCG test or ultrasound result will determine the pregnancy onset date. 


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ABUSE, MISUSE, OVERDOSE, AND MEDICATION ERROR 
Abuse, misuse, overdose, or medication error (as defined below) must be reported to the Sponsor 
(or a nominated designee) according to the SAE reporting procedure whether or not they result in 
an AE/SAE.  
Note: The 24-hour reporting requirement for SAEs does not apply to reports of abuse, misuse, 
overdose, or medication error s unless these result in an SAE.  
The categories below are not mutually exclusive; the event can meet more than 1 category. 
• Abuse – Persistent or sporadic intentional intake of investigational product when used for 
a non-medical purpose (e.g., to alter one’s state of consciousness or get high) in a manner 
that may be detrimental to the individual and/or society 
• Misuse – Intentional use of investigational product other than as directed or indicated at 
any dose (Note: this includes a situation where the investigational product is not used as 
directed at the dose prescribed by the protocol) 
• Overdose – Intentional or unintentional intake of a dose of investigational product higher 
than the protocol-prescribed dose 
• Medication Error – An error made in prescribing, dispensing, administration, and/or use 
of an investigational product. For studies, medication errors are reportable to the Sponsor 
only as defined below. 
Cases of subjects missing doses of the investigational product are not considered reportable as 
medication errors. 
Medication errors should be collected/reported for all products under investigation. 
The administration and/or use of the unassigned treatment is/are always reportable as a 
medication error. 
The administration and/or use of an expired investigational product should be considered as a 
reportable medication error. 


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URGENT SAFETY MEASURES 
An urgent safety measure is an immediate action taken, which is not defined by the protocol, in 
order to protect subjects participating in a clinical trial from immediate harm, these do not 
constitute de facto deviation from the protocol. Urgent safety measures may be taken by the 
Sponsor (or a nominated designee) or clinical Investigator, and may include any of the 
following: 
• Immediate change in study design or study procedures 
• Temporary or permanent halt of a given clinical trial or trials 
• Any other immediate action taken in order to protect clinical trial participants from 
immediate hazard to their health and safety 
The Investigator may implement urgent safety measures to protect study subjects from 
immediate hazard to their health or safety. The measures should implement immediately and 
does not require prior authorization from the Sponsor (or a nominated designee). In the event(s) 
of an apparent direct hazard to the subject, the Investigator will notify the Sponsor (or a 
nominated designee) immediately by phone and confirm notification to the Sponsor (or a 
nominated designee) in writing as soon as possible, and within 1 calendar day after the change is 
implemented. The Sponsor (or a nominated designee) will also ensure the responsible EC(s) and 
relevant competent authority(s) are notified of the urgent safety measures taken in such cases 
according to local regulations. 


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REGULATORY AGENCY, INSTITUTIONAL REVIEW BOARD, ETHICS 
COMMITTEE, AND SITE REPORTING 
The Sponsor (or a nominated designee) and CRO are responsible for notifying the relevant 
regulatory authorities/US local IRB of related, unexpected SAEs. 
In addition, the Sponsor (or a nominated designee) is responsible for notifying active sites of all 
related, unexpected SAEs occurring during all interventional studies across the asapiprant 
program. 
The Investigator is responsible for notifying the local IRB/EC of SAEs or significant safety 
findings, or the relevant local regulatory authority of all SAEs that occur at his or her site as 
required by IRB/EC procedures. 


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APPENDIX 4 


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CHILD-PUGH SYSTEM1 
 
Points Scored for Observed Findings 
 
1 
2 
3 
Encephalopathy grade2  
none 
1 or 2 
3 or 4 
Ascites  
absent 
slight 
moderate 
Serum bilirubin, mg/dL  
< 2 
2 to 3 
> 3 
Serum albumin, g/dL  
> 3.5 
2.8 to 3.5 
< 2.8 
Prothrombin time, sec prolonged  
< 4 
4 to 6 
> 6 
1 Assessment as good operative risk (A or mild) if 5 or 6 points; moderate risk (B or moderate) if 7 to 9 points; 
and poor operative risk (C or severe) if 10 to 15 points. (Developed for surgical evaluation of alcoholic 
cirrhotic.) 
2 Grade 0: normal consciousness, personality, neurological examination, electroencephalogram 
Grade 1: restless, sleep disturbed, irritable/agitated, tremor, impaired handwriting, 5 cps waves 
Grade 2: lethargic, time-disoriented, inappropriate, asterixis, ataxia, slow triphasic waves 
Grade 3: somnolent, stuporous, place-disoriented, hyperactive reflexes, rigidity, slower waves 
Grade 4: unrousable coma, no personality/behavior, decerebrate, slow 2-3 cps delta activity 
.  
 
 

SAP_001.pdf: 
Official Title of Study: 
 
Phase 2, Multicenter, Randomized, Double-blind, Placebo-
controlled, Phase 2 Study to Investigate the Efficacy and Safety of 
Asapiprant in Hospitalized Adults With COVID-19 
 
 
 
 
ClinicalTrials.gov Identifier: 
NCT04705597 
 
Document, Version [Date]: Statistical Analysis Plan, Version 5.0 [01 June 2022] 




 
Protocol No.: BGE-175-201 
CP Project ID: BGE20175   
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Version Date: 01JUN2022 
 
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SIGNATURE PAGE 
 
 
 
Sponsor 
 
 
 
Signature 
Date 
Biostatistician 
 
 
 
 
Signature 
Date 
 
 
 




 
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PaO2 
Arterial oxygen partial pressure 
PD 
Pharmacodynamic(s) 
PGD2 
Prostaglandin D2  
PK 
Pharmacokinetic(s) 
PO 
Oral administration 
PPS 
Per-protocol Set  
PT 
Prothrombin time 
QTcF 
QT interval corrected for heart rate by Fridericia’s formula  
RF 
Respiratory failure 
SAE 
Serious adverse event 
SAF 
Safety Analysis Set  
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SOC 
Standard of care 
SpO2 
Oxygen saturation 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TEAE 
Treatment-emergent adverse event 
TNF-α 
Tumor necrosis factor alfa 
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of normal 
WHO 
World Health Organization 




 
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10 Efficacy .................................................................................................................................... 18 
10.1 
Primary efficacy analysis ..................................................................................................... 18 
10.2 
Secondary efficacy analyses ................................................................................................ 20 
10.2.1 
Proportion of binary endpoints ................................................................................. 20 
10.2.2 
Time to event endpoints ........................................................................................... 21 
10.2.3 
Mean change in WHO Ordinal Scale for COVID-19 score at Day 14/End of Treatment, 
Day 28, Day 57 ......................................................................................................................... 21 
10.2.4 
Other continuous secondary efficacy endpoints ....................................................... 21 
11 Safety ...................................................................................................................................... 23 
11.1 
Adverse events ................................................................................................................... 23 
11.2 
Deaths ................................................................................................................................ 24 
11.3 
Vital signs ........................................................................................................................... 24 
11.4 
Clinical safety laboratory ..................................................................................................... 24 
11.5 
ECG ..................................................................................................................................... 25 
11.6 
Physical examination .......................................................................................................... 25 
12 Other Analyses – please specify ............................................................................................... 25 
13 Interim Analyses ...................................................................................................................... 25 
14 Statistical Analyses for Safety Monitoring ................................................................................ 26 
15 References ............................................................................................................................... 26 
16 Addendum ............................................................................................................................... 27 
 
 
 


 
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MODIFICATION HISTORY 
Unique Identifier for 
this Version 
Date of the Document 
Version 
Author 
Significant Changes 
from Previous 
Authorized Version 
1.0 
31Mar2021  
 
N/A – First Version 
2.0 
23Jun2021 
 
Updated per Protocol 
V4.0 (19May2021) 
3.0 
09SEP2021 
 
Updated per Protocol 
V5.0 (07SEP2021) 
4.0 
14MAR2022 
 
Updated per FDA 
comments dated 
November 24, 2021 
and BioAge response.  
5.0 
01JUN2022 
 
1. Update on 
primary endpoint 
analysis by 
removing baseline 
WHO ordinal 
scale/ Addendum 
is added for the 
justification.  
2. Other minor 
corrections 
 
 
 








 
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13. Incidence and duration of mechanical ventilation 
14. Incidence and duration of mechanical ventilation plus additional organ support using 
vasopressors, and/or renal replacement therapy and/or ECMO 
15. Daily ratio of oxygen saturation (SpO2) to fractional inspired O2 (SpO2/FiO2)  
16. Length of hospital stay 
17. Incidence of re-hospitalization through Day 57 
18. Proportion of patients requiring intensive care unit admission post randomization 
Exploratory Endpoints 
1. Inflammation markers including: IL-6, CRP, IL-10, TNF-α, IFN-γ, IFN-α, IP-10, MCP-1, and 
absolute lymphocyte count 
2. Assess peak and trough concentrations of asapiprant at steady state 
3. Assess PGD2 pre-diagnostic to assess correlation with response to treatment for COVID-19 
based on change in the WHO Ordinal Scale for COVID-19 score 
Safety endpoints 
1. Incidence and severity of treatment-emergent AEs (TEAEs) 
2. Safety outcome measure: 
a. Occurrence of AEs 
b. Laboratory safety parameters such as complete blood count, blood glucose, electrolyte, 
hepatic and renal functions taken before the first dose and on Days 2, 5, 14 and 28 and 
the time of discharge to find any changes or any systemic effect after treatment 
3 
Analysis Sets 
Enrolled Analysis Set: all patients who provided informed consent. 
Intent-to-Treat (ITT): all patients who have been randomized. The ITT will be used for efficacy 
endpoints. Patients will be analyzed according to the treatment group to which they were 
randomized. The ITT will be used for the primary efficacy analysis. 
Modified Intent-to-Treat population (mITT): all ITT patients with exclusion of randomized untreated 
patients and randomized ineligible patients.  
Per-protocol Set (PPS): all mITT patients with further exclusion of patients with major protocol 
deviations related to data integrity or eligibility as judged by clinical/biostatistical study personnel 
prior to database lock. This population will be formed only if > 5% of patients would be excluded. 
Safety Analysis Set (SAF): all patients who have received at least 1 dose of either asapiprant or 
placebo. The SAF will be used for safety analysis. Patients will be analyzed under actual treatment 
being received. 
Pharmacokinetic (PK) Set: all patients who have received at least 1 dose of asapiprant and have at 
least 1 evaluable post-dose PK concentration value. 
Pharmacodynamic (PD) Set: all patients who have received at least 1 dose of asapiprant and have at 
least 1 evaluable post-dose PD value. 










 
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• 
reason for discontinuation of study drug treatment 
• 
reason for withdrawing from the study as recorded in eCRF 
The denominators for percentages will be based on the number of patients in ITT by randomized 
treatment and overall, except for patients screened and patients randomized. 
Discontinued patients will be provided in a data listing by patient. 
5.3 
Protocol Deviations 
Major protocol deviations will be judged by clinical/biostatistical study personnel prior to database 
lock. 
Major protocol deviations may include but not limited to followings: 
• 
Deviations of inclusion and exclusion criteria 
• 
Receiving the wrong study intervention 
• 
Non-compliance with study intervention defined as the participant taking < 80% of the study 
intervention through their last day of dosing. 
• 
Taking a prohibited medication 
• 
Other 
The number and percentage of patients with major deviations will be summarized. The number of 
deviations by type of deviation will be summarized by treatment and overall. The denominators for 
percentages will be based on the number of patients in ITT population by randomized treatment and 
overall. 
All protocol deviations (both major and minor) will be provided in a data listing by patient. 
5.4 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria deviations will be provided in a data listing by patient. 
6 
Demographics and Disease Characteristics 
6.1 
Demographics and other baseline characteristics 
The following demographic characteristics will be summarized by treatment group and overall for 
patients in ITT population using descriptive statistics. No statistical hypothesis tests will be 
performed. 
• 
Sex (male, female) 
• 
Age (years) 
• 
Age group (50 to < 75, ≥ 75 years) 
• 
Race (American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or 
other Pacific Islander, White, Unknown, Other) 
• 
Ethnicity (Hispanic or Latino, not Hispanic or Latino, not reported, unknown) 
• 
Weight (kg) at baseline 
• 
Height (cm) at baseline 


 
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• 
BMI (kg/m2) at baseline 
• 
SARS-CoV-2 (COVID-19) history 
• 
PGD2 result at baseline 
• 
Virus serology result of presence of HIV, Hepatitis B surface antigen (HBsAg), and HCV 
antibody if collected in eCRF. 
Demographics and other baseline characteristics will be provided in a data listing by patient. 
6.2 
Medical History 
The medical conditions are coded according to Medical Dictionary for Regulatory Activities 
(MedDRA® version 23.1) and will be classified as follows: 
• 
Previous medical conditions, if medication is not “Ongoing at study entry” as indicated in CRF 
• 
Concomitant medical conditions, if medication is “Ongoing at study entry” as indicated in CRF 
The frequency and percentage of medical conditions recorded from medical history will be 
presented after classification into previous and concomitant conditions by system organ class (SOCs) 
and preferred terms (PT) by randomized treatment and overall. If patients have more than one 
disease within an SOC or PT, they will be counted only once for the respective SOC or PT. 
The denominators for percentages will be based on the number of SAF by treatment group and 
overall. 
7 
Exposure and Compliance 
7.1 
Extent of Exposure 
Duration of study drug exposure, defined as the number of days between the date of first dose 
following randomization and the date of the last dose, will be summarized by treatment group and 
over for the patients in SAF. 
Duration will be calculated as date of last dose – date of first dose + 1. 
If the date of first intake of IMP is missing, it will be assumed to be identical to the date of 
randomization. 
7.2 
Compliance 
Compliance will be calculated and summarized by treatment group and overall. Compliance will be 
calculated as 100 × (total number of tablets taken / total number of tablets expected to be taken). 
The number of tablets taken will be derived as the number of tablets dispensed minus the sum of 
the number of tablets returned and the number of tablets reported lost/missing based on the CRF 
reported doses taken in hospital and the dose log. The percent compliance will be summarized. 
Summaries will be presented for SAF. 
A listing of drug accountability will be presented for all medication distributed to each patient, 
including number of tablets dispensed, returned, lost/stolen, taken, and overall percent compliance. 
8 
Prior and Concomitant Medication 
Prior and concomitant medications are coded according to the World Health Organization drug 
dictionary (WHO-Drug version MAR, 01, 2019) and stored with ATC codes and generic names. 




 
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any missing primary outcomes as failures; 3) missing primary outcome imputed as success for drug 
and failure for controls; 4) missing primary outcome imputed as failure for drug and success for 
controls.  
If more than 5% of subjects have insufficient data to confirm RF-free and alive at Day 28, BioAge will 
employ a MI strategy (SAS MI, MIANALYZE) with missing at random (MAR) based protocol 
stratification factors (age and region), treatment, and the discharge status prior to or on Day 28. 
Following steps will be followed for multiple imputation. 
Step 1: which will be carried out to produce n (exp. 25) imputed datasets 
 
The SAS procedure PROC MI using the FCS (fully conditional specification method) statement with 
LOGISTIC imputation method to impute RF28 assuming no covariate will be missing.  
One must also specify a VAR statement with outcome variable being the last in the order. If any 
covariate is expected to have missing and need to be imputed as well 
“LOGISTIC(RF28SUB_MI=TRT01P REGION AGEGRN DISC28” also need to be added after the 
FCS statement. 
PROC MI DATA=RF28_DATA SEED=1305417 NIMPUTE=25 OUT=OUTLOG; 
 
CLASS RF28 TRT01P REGION AGEGRN DISC28; 
 
VAR TRT01P REGION AGEGRN DISC28 RF28; 
 
FCS LOGISTIC(RF28SUB_MI=TRT01P REGION AGEGRN DISC28) ; 
RUN; 
 
Where: 
RF28 is respiratory failure or death prior to or on Day 28 
TRT01P is randomized treatment (Placebo/Asapiprant) 
REGION: region of patient’s location (North America/South America) 
AGEGRPN: age group (50 - <75, >=75) 
DISC28: discharge status prior to or on Day 28 
Step 2: Each of 25 complete data set will be analyzed using standard logistic analyses as 
specified for primary efficacy analysis in SAP, i.e. PROC LOGISTIC will be used for RF28 with 
predefined covariates (region and age group) and treatment group.  
PROC LOGISTIC DATA=OUTLOG ; 
   CLASS RF28 TRT01P REGION AGEGRN ; 
   MODEL RF28=TRT01P REGION AGEGRN / COVB; 
   BY IMPUTATION ; 
   ODS OUTPUT PARAMETERESTIMATES=LGSPARMS; 
RUN; 
 
Step 3: The results logistic regression from the 25 complete data sets are combined for the 
parameter inference (i.e. coefficient estimate, 95% confidence interval, and p-value) using PROC 
MIANALYZE  
 
PROC MIANALYZE PARMS=LGSPARMS; 
   MODELEFFECTS INTERCEPT TRT01P REGION  AGEGRN; 
RUN; 








 
Protocol No.: BGE-175-201 
CP Project ID: BGE20175   
Version: v5.0 
Version Date: 01JUN2022 
 
 
QMS Document Name: Statistical Analysis Plan 
Page 23 of 27 
QMS No (include version ref): STF-015-GL.02 
Document date: 09JUL2019 
CONFIDENTIAL 
 
 
 
 
Face mask with reservoir 
(non-rebreather face mask) 
<6 
Follow nasal cannula 
 
6 
60 
 
7 
70 
 
8 
80 
 
9 
90 
 
10 
95 
 
>10 
100 
 
 
 
Venturi mask 
1 
22 
 
2 
24 
 
3 
26 
 
4 
28 
 
6 
31 
 
8 
40 
 
10 
50 
 
>10 
60 
In case of fractional value of flow rate (0.5, 1.5, 2.5, 3.5, 4.5), FiO2 = (Oxygen Flow Rate *4)+20 to 
avoid rounding. 
• 
Length of hospital stay, after start of study treatment, in days: which will be defined as duration 
from date of randomization to the date of first discharge. 
11 Safety 
All safety endpoints will be analyzed using the SAF under received treatment based on the data 
observed. No missing data will be imputed. 
11.1 
Adverse events 
Adverse events will be coded using MedDRA version 23.1 and will be graded according to the NCI-
CTCAE version 5.0. AE summaries will be presented by primary SOC and PT. 
Treatment-emergent Adverse events will be considered as any event or worsening of event with 
onset on or after receiving the first dose of study drug through Day 57. 
Summaries will be presented by actual treatment and overall using the SAF. Although a PT or SOC 
may be reported more than once for a patient, each patient will only be counted once. 
Number and frequencies of patients with TEAEs as well as number of events will be given by SOC and 
by PT within each SOC for the following: 
• 
All TEAEs by treatment group 
• 
Serious TEAEs by treatment group 
• 
All TEAEs considered related by treatment group 
• 
Serious TEAEs considered related by treatment group