Conditions: COVID-19 Pneumonia Acute Lung Injury ARDS
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 88
Healthy volunteers: no

Brief summary:
The study is a prospective, randomized, placebo-controlled, double-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT (Lymphotoxin-like, exhibits Inducible expression, and competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a receptor expressed by T lymphocytes), for the treatment of patients with 2019 novel coronavirus disease (COVID-19) pneumonia who have mild to moderate Acute Respiratory Distress Syndrome (ARDS).

LIGHT is a cytokine in the tumor necrosis factor super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS.

The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: CERC-002 intervention 2: Placebo
Intervention descriptions: intervention 1: Administered once subcutaneously at 16 mg/kg dose up to a maximum dose of 1200 mg. intervention 2: Administered once subcutaneously

Protocol document:
Prot_000.pdf: 
PROTOCOL TITLE: 
A Randomized, Double-blind, Placebo-controlled, Multicenter, 
Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of 
CERC-002 in Adults with COVID-19 Pneumonia and Acute 
Lung Injury 
PROTOCOL NUMBER: 
CERC-002-CVID-201 
NCT NUMBER: 
NCT04412057 
PROTOCOL DATE: 
12 August 2020  
 
 
 




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1 
APPROVAL SIGNATURES 
 
PROTOCOL NUMBER: 
CERC-002-CVID-201 
 
PROTOCOL TITLE: 
A Randomized, Double-blind, Placebo-controlled, Multicenter, 
Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CERC-
002 in Adults with COVID-19 Pneumonia and Acute Lung Injury 
 
FINAL PROTOCOL: 
 
12 August 2020 
I, the undersigned, have read this protocol and confirm that to the best of my knowledge it 
accurately describes the planned conduct of the study. 
 
 
Date  




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3 
REASON FOR AMENDMENT AND SUMMARY OF CHANGES 
The protocol was amended to clarify study procedures and conduct detail. Substantive changes 
include the following: 
• Revised the reference to the pharmacokinetic (PK), pharmacodynamics (PD), and 
immunogenicity of CERC-002 being compared with placebo in addition to standard of care  
• Revised the endpoint of change in partial pressure of arterial oxygen/percentage of inspired 
oxygen (PaO2/FiO2) ratio at defined study milestones to remove the “change in” text as 
the observed PaO2/FiO2 will be used as an endpoint. In addition, the endpoint has been 
revised to remove the “at defined study milestones” text as the ratio will be calculated 
whenever the values are collected as part of standard of care.  
• Removed the endpoint of oxygen saturation index trajectory. 
• Revised endpoint of partial pressure of oxygen (PO2) from baseline to end of study to 
remove from baseline to end of study as all timepoints will be utilized. 
• Clarified that a subject’s oxygen saturation at rest in ambient air is <93% if the data is 
available.  
• Revised endpoint of time to invasive ventilation at defined study milestones to remove at 
defined study milestones.  
• Revised the PK exploratory endpoint to plasma concentrations of CERC-002 over time. 
• Clarified that the intervals at which the Data Monitoring Committee (DMC) will review 
study data is defined in the DMC charter.  
• Clarified that the use of corticosteroids as part of standard of care measures in severe 
COVID-19 patients is permitted when clinically indicated and discussed with the Medical 
Monitor.  
• Clarified that CERC-002 will be administered by SC injection in the abdomen in a zone of 
4 to 10 cm from the umbilicus with the injection site rotated based on the number of 
syringes used. 
• Removed electrocardiogram results from the list of continuous safety variables for which 
descriptive statistics will be generated for all reported values as only the categorical 
electrocardiogram interpretation is recorded. 
• Clarified that if the site is unable to do a quantitative test in order to obtain viral load, the 
viral load sample at Days 1 and 5 are not required to be collected. 
• Moved C-reactive protein from Table 1 (Schedule of Assessments) to Table 2 (Standard of 
Care Procedures).  
• Clarified that the PK sample collected on Day 2 is to be collected 24 hours (± 2 hours) post 
Day 1 dosing. 
• Removed the reference to the Day 8 pharmacokinetic sample being collected prior to 
dosing. 


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• Clarified that An ADA sample will be collected at Days 8, 14, 28/ET in addition to when 
an immunologically related adverse event is reported. 
• Clarified that if a subject is discontinued from the study or is discharged from the hospital 
prior to Day 28, the Day 28/ET visit procedures should be performed and that no further 
visits would be required to be performed with the exception of the Day 28 and Day 60 
follow-up calls. 
• Clarified that Day 28 is to be conducted as a follow-up call for subjects who are 
discontinued from the study and for subjects who are discharged prior to the Day 28 visit.  
• Clarified that a safety follow-up call is to be conducted approximately 59 days (±7 days) 
after administration of investigational product. 
• Revised the pregnancy testing requirement to apply to women of childbearing potential. 
• Defined that a subject is not considered to be of childbearing potential if they are 
post-menopausal (12 consecutive months of spontaneous amenorrhea and age ≥ 51 years, 
and/or surgically sterile (having undergone one of the following surgical acts:  
hysterectomy, bilateral tubal ligation, bilateral oophorectomy or bilateral salpingectomy) 
and at least 6 weeks post-sterilization. 
• Clarified that placebo will be sourced locally. 
• Added height to the list of assessments included as part of vital signs.  
• Revised the clinical severity assessment of an adverse event to use the definitions outlined 
in Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. 
• Removed exposure and compliance summaries for days on treatment and cumulative 
exposure as study is a single dose.  
• Revised the reference to Glasgow Coma Score to Glasgow Coma Scale. 
 
 


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4 
SYNOPSIS 
PRODUCT NAME 
CERC-002 (formerly AEVI-002, MDGN-002) 
PROTOCOL NUMBER 
CERC-002-CVID-201 
DEVELOPMENT 
PHASE 
Phase 2 
PROTOCOL TITLE 
A Randomized, Double-Blind, Placebo-controlled, Multicenter, Phase 2 Clinical Trial 
to Evaluate the Efficacy and Safety of CERC-002 in Adults with COVID-19 
Pneumonia and Acute Lung Injury 
OBJECTIVES 
Primary Objective 
• 
To evaluate the effect of CERC-002 compared with placebo in addition to standard 
of care, on prevention of acute respiratory distress syndrome (ARDS) in adults with 
2019 novel coronavirus disease (COVID-19) pneumonia and acute lung injury. 
Secondary Objectives 
• 
To evaluate the safety and tolerability of CERC-002 compared with placebo in 
addition to standard of care, in adults with COVID-19 pneumonia and acute lung 
injury. 
• 
To evaluate the effect of CERC-002 compared with placebo in addition to standard 
of care, on mortality in adults with COVID-19 pneumonia and acute lung injury. 
Exploratory Objectives 
• 
To evaluate the effect of CERC-002 compared with placebo in addition to standard 
of care, on viral load in adults with COVID-19 pneumonia and acute lung injury. 
• 
To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and 
immunogenicity of CERC-002, in adults with COVID-19 pneumonia and acute 
lung injury.  
ENDPOINTS 
Primary endpoints 
• 
The proportion of patients treated with CERC-002 compared with placebo in 
addition to standard of care, alive and free of respiratory failure over 28 days. 
Respiratory failure defined based on resource utilization requiring at least one of 
the following: 
o 
Endotracheal intubation and mechanical ventilation 
o 
Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen 
delivered via reinforced nasal cannula at flow rates >20L/min with fraction of 
delivered oxygen ≥0.5) 
o 
Noninvasive positive pressure ventilation, 
o 
Extracorporeal membrane oxygenation 
Secondary endpoints 
• 
1-month mortality defined as the proportion of subjects who are alive at Day 
28/early termination (ET) 
• 
Partial pressure of arterial oxygen/percentage of inspired oxygen (PaO2/FiO2) 
ratio  
• 
Time to invasive ventilation 
• 
Duration of ventilation support 
• 
Intensive care unit (ICU) length of study 
• 
Hospital length of stay 
• 
Time to return to room air with resting pulse oximeter >93% 
• 
Peak PaO2/FiO2 ratio 
• 
Partial pressure of oxygen (PO2)  
• 
Change in Sequential Organ Failure Assessment (SOFA) score 


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• 
Change in body temperature 
• 
Adverse event (AE) monitoring and safety laboratory determination  
Exploratory endpoints 
• 
Viral load in nasopharyngeal aspirates 
• 
LIGHT (Lymphotoxin-like, exhibits Inducible expression, and competes with 
Herpes Virus Glycoprotein D for Herpes virus Entry Mediator, a receptor 
expressed by T lymphocytes) levels, and inflammatory biomarker patterns 
(InflammationMAP) 
• 
Plasma concentrations of CERC-002 over time 
• 
Measurement of anti-drug antibody (ADA) 
STUDY DESIGN 
This is a multicenter, double-blind, Phase 2 clinical trial in adults with documented 
COVID-19 pneumonia and acute lung injury. Subjects will be randomized to one of 
two treatment groups (CERC-002 or placebo) in a 1:1 ratio. CERC-002 (16 mg/kg 
[maximum 1200 mg] or placebo will be administered subcutaneously (SC) at baseline 
(Day 1) addition to standard of care. Standard of care is to be maintained throughout 
the study and may include off-label use of other drugs, devices, or interventions used 
to treat COVID-19. All subjects will be followed until the end of study (Day 60) for 
safety monitoring. The primary efficacy endpoint will be assessed within 4 weeks after 
the first dose of CERC-002 or placebo is administered. The duration of the study period 
will be 60 days. 
A safety review committee will be analyzing data from individual subjects and across 
all subjects treated in a daily fashion to assess any safety signals with dosing.  This will 
allow close monitoring of safety changes in real time.   
An external, independent Data Monitoring Committee (DMC) will review the study 
data for the duration of the study at intervals defined in the DMC charter.  
Safety monitoring will be performed continuously throughout the study in accordance 
with this protocol. 
All subjects will undergo efficacy, PK, ADA, and PD assessments. Subjects will also 
be monitored for AEs and will undergo safety laboratory tests.  
PLANNED NUMBER 
OF SUBJECTS 
Approximately 82 subjects are planned to be included in this study.  
PLANNED NUMBER 
OF STUDY SITES 
Approximately 10 sites from the United States will participate in this study.  
STUDY ENTRY 
CRITERIA 
Inclusion Criteria 
1. Subject/legally authorized representative (LAR) is able to understand and provide 
written informed consent, and assent (as applicable) to participate in this study. 
2. Subject is ≥18 years of age at the time of informed consent and assent 
(as applicable). 
3. Subject is male or non-pregnant, non-lactating female, who if of childbearing 
potential agrees to comply with any applicable contraceptive requirements if 
discharged from the hospital prior to completing the study.  
4. Subject has a diagnosis of COVID-19 infection through an approved testing 
method. 
5. Subject has been hospitalized due to clinical diagnosis of pneumonia with acute 
lung injury defined as diffuse bilateral radiographic infiltrates with PaO2/FiO2 
>100 and <300. 
6. If available, subject’s oxygen saturation at rest in ambient air <93%.  
Exclusion Criteria 
1. 
Subject is intubated. 


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2. 
Subject is currently taking immunomodulators or anti-rejection drugs. . The use 
of corticosteroids as part of standard of care measures in severe COVID-19 
patients is permitted when clinically indicated and discussed with the Medical 
Monitor. 
3. 
Subject has been administered an immunomodulating biologic drug within 60 
days of baseline.  
4. 
Subject is in septic shock defined as persistent hypotension requiring vasopressors 
to maintain mean arterial pressure (MAP) of 65 mm Hg or higher and a serum 
lactate level greater than 2 mmol/L (18 mg/dL) despite adequate volume 
resuscitation. 
5. 
Subject has alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) 
>5× upper limit of normal (ULN) or creatinine >2.5 mg/dl 
6. 
Subject has neutrophils <500/ml3 
7. 
Subject has platelets <50,000/ml3 
8. 
Subject has known hypersensitivity to any of the components of CERC-002 or 
placebo. 
9. 
Subject has received any live attenuated vaccine, such as varicella-zoster, oral 
polio, or rubella, within 3 months prior to the baseline visit.  
CONCOMITANT 
TREATMENT 
During the study, new initiation of investigational compounds, and the current use of 
immunomodulatory or anti-rejection drugs is prohibited. The use of corticosteroids as 
part of standard of care measures in severe COVID-19 patients is permitted when 
clinically indicated and discussed with the Medical Monitor. 
INVESTIGATIONAL 
PRODUCT, DOSE 
AND MODE OF 
ADMINISTRATION 
CERC-002 will be supplied in vials containing 360 mg CERC-002 (concentrated 
150 mg/mL). CERC-002 will be administered by SC injection in the abdomen in a zone 
of 4 to 10 cm from the umbilicus with the injection site rotated based on the number of 
syringes used. 
Placebo will be sourced locally and provided as volume matched normal saline for 
injection and will be administered by SC injection in the abdomen in a zone of 4 to 10 
cm from the umbilicus with the injection site rotated based on the number of syringes 
used. 
TREATMENT 
REGIMEN AND 
DURATION 
CERC-002 or placebo will be administered at baseline (Day 1). CERC-002 will be 
administered at 16 mg/kg dose (maximum dose of 1200 mg). The investigational 
product will be administered in addition to standard of care. Standard of care is to be 
maintained and may include off-label use of other drugs, devices, or interventions. 
COORDINATING 
PRINCIPAL 
INVESTIGATOR / 
PRINCIPAL 
INVESTIGATOR  
 
 
 
 
 


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CRITERIA FOR 
EVALUATION 
Efficacy 
The efficacy of CERC-002 will be determined by measuring survival status, the need 
for invasive ventilation, PaO2/FiO2, SOFA score, body temperature, and viral load in 
nasopharyngeal aspirates. Apart from these tests, time to invasive ventilation, duration 
of ventilation support, duration of time in the ICU, duration of the time in the hospital, 
and duration of time requiring O2 by nasal canula will also be determined. 
Safety 
The safety of CERC-002 will be determined by the reporting of AEs, according to 
Common Terminology Criteria for Adverse Events (CTCAE) criteria (v 5.0), findings 
on physical exam, and the results of ECGs and safety laboratory determinations.  
Pharmacokinetics 
The PK of CERC-002 will be determined by obtaining plasma levels of CERC-002 at 
various time points after administration. 
Pharmacodynamics 
The PD will be determined by measuring the levels of LIGHT and InflammationMAP 
biomarker patterns.  
Immunogenicity 
The immunogenicity of CERC-002 will be determined by measuring ADA levels.  
STATISTICAL 
METHODS 
All efficacy and safety variables will be summarized using descriptive statistics.  
Descriptive statistics for continuous data will include number of subjects (n), mean, 
standard deviation, median, minimum, and maximum. Summaries of change from 
baseline variables will include only subjects who have both a baseline value and 
corresponding value at the timepoint of interest. Descriptive statistics for categorical 
data will include frequency and percentage.  
The proportion of subjects alive and free of respiratory failure with 90% confidence 
interval will be presented by treatment group. In addition, the proportion of subjects 
alive and free of respiratory failure in the CERC-002 group will be compared to that in 
the placebo group using a Chi-square test or similar method.  
AE data will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). The overall incidence of subjects having at least one AE will be 
summarized. The incidence of treatment-emergent adverse events (TEAEs) will be 
summarized by treatment group, system organ class (SOC), and preferred term (PT). 
Each subject will be counted only once per SOC and PT. For all continuous safety 
variables (eg, laboratory and vital sign measures), descriptive statistics for all reported 
values and change from baseline values will be summarized by treatment group and 
time point. 
SAMPLE SIZE 
DETERMINATION 
A total of 82 subjects are planned to either with CERC-002 or placebo. This sample 
size will provide greater than 80% power to detect a difference of 0.25 in the proportion 
of subjects alive and free of respiratory failure using a Chi-square test at a one-sided 
significance level of 0.05. This calculation assumes that the proportion alive and free 
of respiratory failure will be 0.60 in the placebo group  and 0.85 in the CERC-002 
group.   
STUDY AND 
TREATMENT 
DURATION 
CERC-002 and placebo treatment will be administered on Day 1 in addition to standard 
of care. A safety follow-up contact will be performed at Day 60 making the overall 
duration of the study period 60 days. 
 
 


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Table 1: 
Schedule of Assessments  
Procedure 
Baseline 
(Day 1) 
Day 2 
Day 5 
Day 8 
Day 9 
Day 14 
Day 
28/ET1 
Safety 
Follow-up 
Phone Call 
Day 602 
Informed consent and 
assent (as applicable) 
X 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
Concomitant medications3 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events4 
X 
X 
X 
X 
X 
X 
X 
X 
Viral load in 
nasopharyngeal aspirates9  
X 
 
X 
 
 
 
 
 
ECG7 
X 
X 
X 
X 
X 
X 
X 
 
Pregnancy test10 
X 
 
 
 
 
 
 
 
PK  
 
X6 
 
X 
 
X 
X 
 
LIGHT and 
InflammationMAP 
X5 
X6 
X 
X 
X 
X 
X 
 
ADA8 
 
 
 
X 
 
X 
X 
 
Investigational product 
administration 
X 
 
 
 
 
 
 
 
Abbreviations: 
ADA 
= 
antidrug 
antibodies; 
ECG 
= 
electrocardiogram; 
ET 
= 
early 
termination; 
InflammationMAP = inflammatory biomarker patterns; LIGHT = Lymphotoxin-like, exhibits Inducible expression, and 
competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a receptor expressed by T lymphocytes; 
PK = pharmacokinetics. 
1. Day 28 is to be conducted as a follow-up call for subjects who are discontinued from the study and for subjects who are 
discharged prior to the Day 28 visit. Additionally, if a subject is discontinued from the study or is discharged from the hospital 
prior to Day 28, the Day 28/ET visit procedures should be performed. No further visits will be required to be performed with 
the exception of the Day 28 and Day 60 follow-up calls.  
2. A safety follow-up call to be conducted approximately 59 days (±7 days) after administration of investigational product. 
3. Concomitant medications to be collected throughout the study period.  
4. Adverse events to be collected throughout the study period.  
5. Sample to be collected prior to investigational product administration.  
6. Sample to be collected 24 hours (± 2 hours) post Day 1 dosing.  
7. An ECG will be collected daily when a subject is not being assessed by cardiac monitoring. 
8. An ADA sample will be collected at Days 8, 14, 28/ET. Additionally, a sample is to be collected when an immunologically 
related adverse event is reported (e.g., a skin reaction, lupus-like syndrome, unexplained thrombocytopenia). 
9. If the site is unable to do a quantitative test in order to obtain viral load, the viral load samples to be collected at Days 1 and 
5 are not required to be collected. 
10. For females of childbearing potential. A subject is not considered to be of childbearing potential if they are post-menopausal 
(12 consecutive months of spontaneous amenorrhea and ≥ age 51 years, and/or surgically sterile (having undergone one of the 
following surgical acts:  hysterectomy, bilateral tubal ligation, bilateral oophorectomy or bilateral salpingectomy) and at least 6 
weeks post-sterilization. 
 
 
 


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Table 2: 
Standard of Care Procedures  
Procedure 
ABG 
Chest CT / CXR 
Glasgow Coma Scale 
Laboratory procedures including CBC, chemistry and urinalysis 
CRP 
Physical examination 
Pulse Oximetry 
SOFA  
Temperature 
Vital signs 
Abbreviations: ABG = arterial blood gas; CBC = complete blood count; CRP = C-reactive protein; CT = computed 
tomography; CXR = chest x-ray; SOFA = Sequential Organ Failure Assessment. 
These procedures will be performed per the site’s practice unless defined otherwise.  


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5 
TABLE OF CONTENTS 
1 
APPROVAL SIGNATURES ............................................................................................... 2 
2 
EMERGENCY CONTACT INFORMATION .................................................................. 3 
3 
REASON FOR AMENDMENT AND SUMMARY OF CHANGES ............................... 4 
4 
SYNOPSIS ............................................................................................................................. 6 
5 
TABLE OF CONTENTS ................................................................................................... 12 
LIST OF TABLES ...................................................................................................................... 16 
LIST OF ABBREVIATIONS .................................................................................................... 17 
6 
INTRODUCTION .............................................................................................................. 20 
6.1 
Background and Rationale ............................................................................................ 20 
6.2 
Nonclinical Experience ................................................................................................. 21 
6.3 
Clinical Experience ....................................................................................................... 22 
6.4 
Summary of Potential Risks and Benefits .................................................................... 23 
7 
STUDY OBJECTIVES AND ENDPOINTS ..................................................................... 23 
7.1 
Study Objectives ........................................................................................................... 23 
7.1.1 Primary Objective ..................................................................................................... 23 
7.1.2 Secondary Objectives ................................................................................................ 23 
7.1.3 Exploratory Objectives ............................................................................................. 23 
7.2 
Study Endpoints ............................................................................................................ 23 
7.2.1 Primary Endpoints .................................................................................................... 23 
7.2.2 Secondary Endpoints ................................................................................................ 24 
7.2.3 Exploratory Endpoints .............................................................................................. 24 
8 
STUDY DESIGN ................................................................................................................. 24 
8.1 
Overall Study Design and Plan ..................................................................................... 24 
8.2 
Discussion of Study Design .......................................................................................... 25 
8.3 
Study Sites .................................................................................................................... 25 
8.4 
Selection of Study Population ....................................................................................... 25 
8.5 
Study Entry Criteria ...................................................................................................... 25 
8.5.1 Inclusion Criteria ...................................................................................................... 25 
8.5.2 Exclusion Criteria ..................................................................................................... 26 
8.6 
Screen Failures .............................................................................................................. 26 


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8.7 
Premature Subject Withdrawal ..................................................................................... 26 
8.8 
Subject Replacement Criteria ....................................................................................... 27 
9 
TREATMENTS .................................................................................................................. 27 
9.1 
Identification of Investigational Product(s), Dose and Mode of Administration ......... 27 
9.2 
Labeling and Packaging ................................................................................................ 27 
9.2.1 Labeling .................................................................................................................... 27 
9.2.2 Packaging .................................................................................................................. 27 
9.3 
Treatment Preparation ................................................................................................... 27 
9.4 
Treatments Administered .............................................................................................. 28 
9.5 
Dispensing and Storage ................................................................................................. 28 
9.6 
Blinding and Unblinding Treatment Assignment ......................................................... 28 
9.7 
Selection of Doses in the Study .................................................................................... 29 
9.8 
Dose Adjustment Criteria ............................................................................................. 29 
9.9 
Drug Accountability ...................................................................................................... 29 
9.10 
Handling and Disposal .................................................................................................. 29 
9.11 
Permitted and Prohibited Therapies .............................................................................. 30 
9.11.1 Prior Therapies .......................................................................................................... 30 
9.11.2 Concomitant Therapies ............................................................................................. 30 
9.11.3 Permitted Therapies .................................................................................................. 30 
9.11.4 Prohibited Therapies ................................................................................................. 30 
9.12 
Treatment after End of Study ........................................................................................ 30 
10 STUDY PROCEDURES .................................................................................................... 30 
10.1 
Study Duration .............................................................................................................. 31 
10.2 
Assessments .................................................................................................................. 31 
10.2.1 Efficacy ..................................................................................................................... 31 
10.2.2 Safety ........................................................................................................................ 32 
10.2.3 Pharmacokinetics and Immunogenicity Analyses .................................................... 34 
10.2.4 Pharmacodynamics ................................................................................................... 34 
10.3 
Definition of Adverse Events, Period of Observation, Recording of Adverse Events . 34 
10.3.1 Adverse Event Collection ......................................................................................... 34 
10.3.2 Severity of Adverse Events ....................................................................................... 35 
10.3.3 Relationship Categorization ...................................................................................... 35 


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10.3.4 Serious Adverse Events ............................................................................................ 36 
10.3.5 Fatal Outcome ........................................................................................................... 38 
10.4 
Special Considerations .................................................................................................. 38 
10.4.1 Adverse Events of Special Interest ........................................................................... 38 
10.4.2 Pregnancy .................................................................................................................. 38 
10.4.3 Anaphylaxis .............................................................................................................. 39 
10.4.4 Reporting to Regulatory Agency, Institutional Review Board/Ethics Committee 
(EC) and Site ......................................................................................................................... 40 
11 SAFETY REVIEW COMMITTEE .................................................................................. 40 
12 DATA MONITORING COMMITTEE ............................................................................ 40 
13 STATISTICS ....................................................................................................................... 40 
13.1 
Sample Size Determination ........................................................................................... 40 
13.2 
Analysis Populations ..................................................................................................... 41 
13.3 
Statistical Analyses ....................................................................................................... 41 
13.3.1 Study Subjects and Demographics ............................................................................ 41 
13.3.2 Prior and Concomitant Medications ......................................................................... 42 
13.3.3 Exposure and Compliance ........................................................................................ 42 
13.3.4 Safety and Tolerability Analyses .............................................................................. 42 
13.3.5 Efficacy Analyses ..................................................................................................... 42 
13.3.6 Pharmacokinetic Analyses ........................................................................................ 42 
13.3.7 Pharmacodynamic Analyses ..................................................................................... 43 
13.3.8 Immunogenicity Analyses ........................................................................................ 43 
13.3.9 Interim Analysis ........................................................................................................ 43 
14 STUDY CONDUCT ............................................................................................................ 43 
14.1 
Sponsor and Investigator Responsibilities .................................................................... 43 
14.1.1 Sponsor Responsibilities ........................................................................................... 43 
14.1.2 Investigator Responsibilities, Protocol Adherence and Investigator Agreement ..... 43 
14.2 
Study Documents .......................................................................................................... 44 
14.2.1 Case Report Forms .................................................................................................... 44 
14.2.2 Recording, and Retention of Source Data and Study Documents ............................ 44 
14.3 
Data Quality Control ..................................................................................................... 44 
14.3.1 Access to Study and Source Documents ................................................................... 44 
14.3.2 Data Management ..................................................................................................... 45 


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14.3.3 Quality Assurance Audit / Inspection ....................................................................... 45 
14.4 
Study Termination ........................................................................................................ 46 
14.5 
Study Site Closure ........................................................................................................ 46 
14.5.1 Record Retention ...................................................................................................... 46 
14.5.2 Sample Retention ...................................................................................................... 46 
14.6 
Changes to the Protocol ................................................................................................ 46 
14.7 
Use of Information and Publication .............................................................................. 47 
15 PUBLIC POSTING OF STUDY INFORMATION ........................................................ 47 
16 ETHICAL AND LEGAL CONSIDERATIONS .............................................................. 47 
16.1 
Declaration of Helsinki and Good Clinical Practice ..................................................... 47 
16.2 
Subject Information and Informed Consent .................................................................. 47 
16.3 
Institutional Review Board or Ethics Committees ........................................................ 48 
16.4 
Financial Disclosure ...................................................................................................... 48 
16.5 
Privacy and Confidentiality .......................................................................................... 48 
17 REFERENCES .................................................................................................................... 50 
Investigator’s Agreement ........................................................................................................... 51 
 
 


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LIST OF TABLES 
Table 1: 
Schedule of Assessments ...............................................................................10 
Table 2: 
Standard of Care Procedures ..........................................................................11 
Table 3: 
The Sequential Organ Failure Assessment (SOFA) score .............................31 
Table 4: 
Sampled Blood Volume per Subject ..............................................................32 
Table 5: 
Assessment of Relationship to Investigational Product .................................36 
Table 6: 
Clinical Criteria for Diagnosing Anaphylaxis ...............................................39 
 
 
 


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LIST OF ABBREVIATIONS 
ADA 
anti-drug antibody  
AE 
adverse event 
ABG 
arterial blood gas 
ALT 
alanine aminotransferase 
ARDS 
acute respiratory distress syndrome 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUC0-t 
area under the plasma concentration time curve from time zero to the 
last observed concentration  
AUC0-tau 
area under the curve from time zero to the time of the end of dosing 
interval 
BLQ 
below the level of quantification 
CL 
clearance 
COVID-19 
2019 novel coronavirus disease 
Cmax 
maximum observed concentration 
CRA 
clinical research associate 
CRF 
case report form 
CRO 
contract research organization  
CRP 
C-reactive protein  
CT 
Computed tomography 
CXR 
chest x-ray 
DcR3 
decoy receptor 3  
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
ECMO 
extracorporeal membrane oxygenation 
eCRF 
electronic case report form 
EC 
Ethics committee 
ELISA 
enzyme-linked immunosorbent assay 
ET 
early termination 
EU 
European Union 
FDA 
Food and Drug Administration 
FiO2 
percentage of inspired oxygen 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  


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HSV 
herpes simplex virus  
HVEM 
herpes virus entry mediator 
IB 
Investigator’s Brochure 
IC50 
50% inhibitory concentration 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IFN-γ 
interferon gamma  
IgG4 
immunoglobulin G subclass 4  
IL 
interleukin  
InflammationMAP 
inflammatory biomarker patterns 
IRB 
Institutional Review Board 
LAR 
legally authorized representative 
LIGHT 
Lymphotoxin-like, exhibits Inducible expression, and competes with 
Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a 
receptor expressed by T lymphocytes 
LTβR 
lymphotoxin β receptor  
MAb 
monoclonal antibody 
MAP 
mean arterial pressure 
MedDRA 
Medical Dictionary for Regulatory Affairs  
PaO2 
partial pressure of arterial oxygen 
PBMC 
peripheral blood mononuclear cells 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PO2 
partial pressure of oxygen 
PT 
preferred term  
RANTES 
Regulated upon Activation, Normal T cell Expressed and Secreted 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
SD 
standard deviation  
SOC 
system organ class 
SOFA 
Sequential Organ Failure Assessment 
SOP 
standard operating procedure  
TEAE 
treatment emergent adverse event 
TNF 
tumor necrosis factor 
t1/2 
terminal half-life 


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tmax 
time to maximum observed concentration 
ULN 
Upper limit of normal 
US 
United States 
Vd 
volume of distribution 
WHO 
World Health Organization  


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6 
INTRODUCTION 
6.1 
Background and Rationale 
COVID-19 (2019 novel coronavirus [2019-nCoV] disease) 
COVID-19 (2019 novel coronavirus disease) is an acute respiratory disease, caused by a novel 
coronavirus (SARS-CoV-2). On 30 January 2020, the World Health Organization (WHO) 
Emergency Committee declared COVID-19 a global health emergency based on increasing 
number of cases in China and other countries. Cases are still growing rapidly and almost all 
countries are affected. As of April 2020, United States (US) has the highest number of COVID-19 
cases and deaths due to COVID-19 (Coronavirus 2019‐nCoV, CSSE). 
The initial clinical sign of COVID‐19 that allowed the case detection was pneumonia 
(Chan et al, 2020). Complications of COVID-19 pneumonia include acute respiratory distress 
syndrome (ARDS), arrhythmia, shock, acute kidney injury, acute cardiac injury, liver dysfunction, 
and secondary infection (Huang et al, 2020; Wang et al, 2020). The main cause of mortality in 
COVID-19 appears to be dysregulated hyperimmune response causing cytokine storm, acute lung 
injury and ARDS. Fifteen to 20% of COVID-19 patients experience severe respiratory illness, 
requiring hospitalization and oxygen therapy (Huang et al, 2020). 
Currently, there are no treatments to prevent progression of COVID-19 pneumonia to ARDS in 
patients with COVID-19. 
Role of LIGHT, an immunoregulatory cytokine, in viral infection 
An important immunoregulatory cytokine, LIGHT (homologous to lymphotoxin, exhibits 
inducible expression and competes with herpes simplex virus [HSV] glycoprotein D for binding 
to herpes virus entry mediator [HVEM], a receptor expressed on T lymphocyte) is secreted in high 
levels during viral infection, which supports ARDS-related lung fibrosis and cytokine storm, but 
has not been studied in the patients with COVID-19 or other human coronavirus infections 
(Xu et al, 2019). Neutrophils and macrophages express high levels of LIGHT and tumor necrosis 
factor (TNF) and are a major source of these inflammatory cytokines (Kwon et al, 1997).  
LIGHT (also known as tumor necrosis factor superfamily member 14) belongs to the TNF 
superfamily and is expressed by activated T cells, monocytes, macrophages and additional types 
of antigen presenting cells. LIGHT has a key role in the communication system which controls 
immune response. LIGHT activates two key receptors, HVEM and lymphotoxin β receptor 
(LTβR), both expressed on lung epithelial cells. Early in infection, LIGHT released from 
neutrophils and macrophages bind cellular receptors, which causes inflammatory cell infiltration, 
releasing high level of TNF. LIGHT also has a co-stimulatory role in T cell activation driving 
proinflammatory and tissue damaging effects (Ware, 2008; Ware, 2009). An additional receptor 
for LIGHT is a decoy receptor 3 (DcR3), which binds LIGHT and interferes with its activity by 
competing with receptor binding (Steinberg et al, 2009; Wroblewski et al, 2003). In hyper 
inflammation and cytokine storm conditions, DcR3 is likely to be overwhelmed, generating high 
DcR3-free (active) LIGHT. 
Rationale for CERC-002, an anti-LIGHT antibody, in COVID-19 
While a primary focus of treatment of COVID‐19 is the development of appropriate antiviral and 
vaccination approaches, currently no established therapy exists. Agents targeting cytokine storm 
include cytokine‐directed therapies, including interleukin (IL)‐1 and IL‐6 antagonists; however, 


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there is no established single therapy for the treatment and/or prevention of acute lung injury 
associated with cytokine storm. The development of a safe and effective therapy for 
COVID-19-associated acute lung injury and ARDS could significantly reduce the mortality and 
post-infectious morbidity of this global pandemic and alleviate the severe strain placed on 
healthcare systems. 
LIGHT protein has been reported to be elevated in peripheral blood mononuclear cells (PBMCs) 
of patients presenting severe pneumonia caused by viral infection. LIGHT levels correlate with 
disease severity; as disease progresses from minor to severe, LIGHT levels are elevated 
(Xu et al, 2019). In humans, LIGHT is functionally neutralized by DcR3, which tightly binds 
LIGHT and inhibits its interactions with HVEM and LTβR.   
CERC-002 (formerly AEVI-002, MDGN-002) is an anti-LIGHT, fully human, monoclonal 
antibody (MAb), which binds to LIGHT at the DcR3 binding site. It is anticipated that neutralizing 
LIGHT using CERC-002 may be beneficial in COVID-19 infected patients with impending 
respiratory failure. The present study will evaluate the effect of CERC-002 on prevention of ARDS 
in patients with COVID-19 pneumonia and acute lung injury. 
6.2 
Nonclinical Experience 
CERC-002 is a fully human immunoglobulin G subclass 4 (IgG4) MAb specific to human LIGHT. 
CERC-002 binds human and cynomolgus monkey LIGHT with high affinity; there was no 
apparent binding of CERC-002 to LIGHT from any other species tested. In vitro, LIGHT-mediated 
chemokine release is comparably inhibited by CERC-002 in a human or cynomolgus cell line. 
Based on these data, the monkey is considered to be the only relevant species for toxicological 
evaluation of CERC-002, and all toxicology studies are performed in cynomolgus monkeys. 
CERC-002 does not demonstrate any potential for off-target binding, cytokine release syndrome, 
or cytotoxicity. In a 2-month toxicity study in cynomolgus monkeys using doses of 6, 30, and 
60 mg/kg subcutaneous (SC) administered every 2 weeks, CERC-002 was well tolerated at all 
doses. Ventricular premature complexes were observed in 3 animals during electrocardiogram 
(ECG) evaluation; however, attribution to treatment is considered unlikely. The only test 
article-related microscopic finding was a minimal increase in incidence and severity of multifocal 
lymphocytic infiltration around small hypodermal vessels at the sites of SC administration and 
adjacent inguinal areas at 60 mg/kg per dose. As this finding is considered non-adverse, the no 
observed adverse effect level was the high dose of 60 mg/kg per dose. 
Toxicokinetic results showed that all dosed cynomolgus monkeys were exposed to CERC-002. 
CERC-002 was slowly absorbed with a time to maximum observed concentration (tmax) of 
approximately 24 to 144 hours. CERC-002 exposures increased in a less than dose-proportional 
manner, and CERC-002 exposure increased slightly during treatment. At the 60 mg/kg dose the 
maximum observed concentration (Cmax) was 1,730 and 1,620 μg/mL, and the area under the curve 
(AUC) was 343,000 and 388,000 μg•h/mL for male and female cynomolgus monkeys, 
respectively. No significant gender effect was observed. 
Anti-CERC-002 antibodies were observed in drug-treated animals on Day 15 (6 of 10 at 6 mg/kg 
per dose; 3 of 10 at 30 mg/kg per dose; and 1 of 10 at 60 mg/kg per dose); and at Day 57 (3 of 4 
at 6 mg/kg per dose, 1 of 4 at 30 mg/kg per dose, and 0 of 4 at 60 mg/kg per dose). There was no 
clear impact of antidrug antibodies on CERC-002 toxicokinetics and exposure. 


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In vitro functional assays were conducted to examine the effect of CERC-002 on secretion of 
Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) from cynomolgus 
monkey skin fibroblast cells stimulated with soluble recombinant cynomolgus LIGHT protein. 
CERC-002 inhibited cynomolgus LIGHT-induced secretion of RANTES from cynomolgus skin 
fibroblasts in a concentration-dependent manner with a 50% inhibitory concentration (IC50) of 
5.67 nM.  
In the toxicokinetic study in cynomolgus monkeys, results indicated that a CERC-002:LIGHT 
molar ratio of 1:2 was sufficient to inhibit LIGHT activity. All animals in the toxicology study had 
serum LIGHT concentrations below the limit of detection (62.5 pg/mL) prior to the start and at the 
end of the dosing period. The lowest serum CERC-002 concentration recorded in the 6 mg/kg per 
dose group on Day 15 (prior to administration of the second CERC-002 dose) was 26 μg/mL, 
indicating that at least a 6.9×104:1 molar ratio of CERC-002:soluble LIGHT in blood was 
maintained throughout the study. The concentration of CERC-002 in tissue is expected to be 10% 
to 50% of that observed in blood (4); therefore, the molar ratio of CERC 002:soluble LIGHT in 
tissue is anticipated to be at least 6.9×103:1. Given the low basal expression of membrane-bound 
LIGHT, the considerable molar excess of CERC-002 would also be anticipated to saturate 
membrane-bound LIGHT.  
In secondary pharmacology studies, CERC-002 did not induce antibody dependent cell-mediated 
cytotoxicity, did not promote complement dependent cytotoxicity and did not significantly induce 
IL-1β, IL-2, IL-6, interferon gamma (IFN-γ), IL-4, or TNFα relative to unstimulated PBMCs or 
whole blood. Air-dried CERC-002 did induce IL-8 in PBMCs, but not in whole blood, and to a 
lesser extent than did IgG4 or anti CD3 or phorbol myristate acetate plus ionomycin positive 
controls. Wet bound CERC-002 did not induce significant levels of IL-8. Plate-bound CERC-002 
did not significantly alter PBMC viability nor induce proliferation relative to unstimulated PBMCs 
at any of the concentrations tested. 
6.3 
Clinical Experience 
One study (SAR252067-TDU11937) of CERC-002 in humans has been conducted. 
SAR252067-TDU11937 was a single-center, randomized, double-blind, placebo-controlled study 
of the tolerability and pharmacokinetics (PK) of ascending, single, SC doses of CERC-002 in 
healthy subjects. Subjects were healthy adult males and females 18 to 65 years of age, inclusive, 
who received a single SC doses of 40, 120, 300, 600, 900, or 1200 mg CERC-002 on Day 0 as 
determined by the dose escalation schedule. A total of 48 subjects, 8 subjects per dose group (6 
active and 2 placebo), were enrolled.  
Treatment-emergent adverse events (TEAEs), abnormal vital signs, ECG parameters and 
laboratory values were relatively infrequent in all dose groups and there were no apparent 
dose-dependent differences among the dose groups. There were no clinically important local 
tolerability issues in any dose group. There were no clinically significant immunogenicity findings. 
CERC-002 was absorbed with the median tmax ranging from 5.0 to 8.5 days and eliminated with 
the mean terminal half-life (t1/2) ranging from 18.0 days to 27.0 days. 
CERC-002 exposure increased in a close-to-dose-proportional manner, with a 30-fold increase 
over the entire dose range of 40 to 1200 mg resulting in 25.7-, 28.2-, and 29.1-fold increases in 
geometric mean Cmax, area under the plasma concentration versus time curve from time zero to the 
last observed concentration (AUC0-tau), and AUC, respectively. 


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A Phase 1b, dose escalating, open-label, signal-finding study to evaluate the safety, tolerability, 
and short-term efficacy of CERC-002 in adults with moderate to severe active Crohn's disease who 
previously failed treatment with an anti-TNFα agent, with and without loss of function mutations 
in DcR3 is currently ongoing.  
6.4 
Summary of Potential Risks and Benefits 
The potential benefit of study participation is that subjects with COVID-19 pneumonia and acute 
lung injury may not progress to ARDS after receiving treatment with CERC-002. Subjects will 
also understand that they are contributing to the scientific knowledge that may lead to expansion 
of the treatment options for patients with COVID-19 pneumonia and acute lung injury. No other 
benefits of participation are anticipated. 
The potential risks of study participation include those associated with exposure to CERC-002 and 
the risks of medical evaluation, including subcutaneous administration of study treatment. 
A summary of the pharmaceutical properties and known potential risks of CERC-002 is provided 
in the current version of the Investigator’s Brochure (IB). The investigator must become familiar 
with all sections of the CERC-002 IB before the start of the study. 
7 
STUDY OBJECTIVES AND ENDPOINTS 
7.1 
Study Objectives  
7.1.1 Primary Objective 
• To evaluate the effect of CERC-002 compared with placebo in addition to standard of care on 
prevention of ARDS in adults with COVID-19 pneumonia and acute lung injury. 
7.1.2 Secondary Objectives 
• To evaluate the safety and tolerability of CERC-002 compared with placebo in addition to 
standard of care, in adults with COVID-19 pneumonia and acute lung injury. 
• To evaluate the effect of CERC-002 compared with placebo in addition to standard of care, on 
mortality in adults with COVID-19 pneumonia and acute lung injury. 
7.1.3 Exploratory Objectives 
• To evaluate the effect of CERC-002 compared with placebo in addition to standard of care, on 
viral load in adults with COVID-19 pneumonia and acute lung injury. 
• To evaluate the PK, pharmacodynamics (PD), and immunogenicity of CERC-002 in adults 
with COVID-19 pneumonia and acute lung injury. 
7.2 
Study Endpoints 
7.2.1 Primary Endpoints 
• The proportion of subjects alive and free of respiratory failure. Respiratory failure is defined 
based on resource utilization including one of the following: 
o Endotracheal intubation and mechanical ventilation 
o Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via 
reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) 
o Noninvasive positive pressure ventilation 


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o Extracorporeal membrane oxygenation (ECMO) 
7.2.2 Secondary Endpoints 
• 1-month mortality defined as the proportion of subjects who are alive at the Day 28/early 
termination (ET)  
• Partial pressure of arterial oxygen/percentage of inspired oxygen (PaO2/FiO2) ratio  
• Time to invasive ventilation  
• Duration of ventilation support 
• Intensive care unit (ICU) length of study 
• Hospital length of stay 
• Time to return to room air with resting pulse oximeter >93% 
• Peak PaO2/FiO2 ratio 
• Partial pressure of oxygen (PO2)  
• Change in Sequential Organ Failure Assessment (SOFA) score 
• Change in body temperature 
• Adverse event (AE) monitoring and safety laboratory determination  
7.2.3 Exploratory Endpoints 
• Viral load in nasopharyngeal aspirates 
• LIGHT levels and inflammatory biomarker patterns (InflammationMAP).  
• Plasma concentrations of CERC-002 over time 
• Measurement of anti-drug antibody (ADA) 
8 
STUDY DESIGN 
8.1 
Overall Study Design and Plan 
This is a multicenter, randomized, double-blind, Phase 2 clinical trial in adults with documented 
COVID-19 pneumonia and acute lung injury. Subjects will receive either CERC-002 at a dose of 
16 mg/kg (maximum 1200 mg) SC or placebo at baseline (Day 1) in addition to standard of care.  
The standard of care is to be maintained throughout the study and may include off-label use of 
other drugs, devices, or interventions used to treat COVID-19. All subjects will be followed until 
the end of study (Day 60) for safety monitoring. The primary efficacy endpoint will be assessed 
within 4 weeks after the dose is administered. CERC-002 or placebo treatment will be administered 
on Day 1 and the duration of the study period will be 60 days. 
Approximately 82 subjects are planned to be included and dosed with either CERC-002 or placebo 
in addition to their standard of care in this study.  
Subjects must have a diagnosis of COVID-19 infection through an approved testing method and 
have been hospitalized due to a clinical diagnosis of pneumonia with acute lung injury defined as 
diffuse bilateral radiographic infiltrates with PaO2/FiO2 >100 and <300 and if available, have 
oxygen saturation at rest in ambient air <93%. 
Subject will not be eligible if they are intubated, are currently taking immunomodulating or 
anti-rejection drugs, has been administered an immunomodulating drug with 60 days of baseline, 
are in septic shock despite adequate volume resuscitation, have alanine aminotransferase 
(ALT)/aspartate aminotransferase (AST) >5× upper limit of normal (ULN),  creatinine >2.5 mg/dl, 


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neutrophils <500/ml3, or platelets <50,000/ml3. The use of corticosteroids as part of standard of 
care measures in severe COVID-19 patients is permitted when clinically indicated and discussed 
with the Medical Monitor. 
An external, independent Data Monitoring Committee (DMC) will review the study data at 
intervals defined in the DMC charter and will monitor the trial for safety signals.  
All subjects will undergo efficacy, PK, PD, and immunogenicity assessments. All subjects will be 
monitored for AEs and will undergo physical exams, ECG, and routine safety laboratory tests. The 
PK of CERC-002 will be based on plasma levels obtained at various time points after 
administration, and the PD will be based on LIGHT levels and InflammationMAP.  
8.2 
Discussion of Study Design 
This study will determine the efficacy and safety of CERC-002 compared with placebo in addition 
to standard of care, administered SC in subjects with COVID-19 pneumonia and acute lung injury. 
The primary objective of this study is to evaluate the effect of CERC-002 on prevention of ARDS 
in adults with COVID-19 pneumonia and acute lung injury. The efficacy of CERC-002 will be 
determined by measuring PaO2/FiO2; alive, respiratory failure days; alive ventilator-free days; 
ICU and hospital length of stay; return to room air or baseline oxygen requirement; SOFA score; 
body temperature; viral load in nasopharyngeal aspirates; time to invasive ventilation; and duration 
of ventilation support. These are routinely used and accepted methods to assess respiratory 
functions. The study will also assess 1-month mortality rate, apart from other parameters.  
8.3 
Study Sites 
The study will take place at approximately 10 study sites in the US. 
8.4 
Selection of Study Population 
Approximately 82 adults diagnosed with COVID-19 pneumonia and acute lung injury will be 
enrolled in the study.  
Justification of the sample size is presented in Section 13.1. 
A screening log of study candidates will be maintained at each study site. 
8.5 
Study Entry Criteria 
8.5.1 Inclusion Criteria 
Subjects must fulfill the following requirements to be randomized into the study: 
1. Subject/legally authorized representative (LAR) is able to understand and provide written 
informed consent and assent (as applicable) to participate in this study. 
2. Subject is ≥18 years of age at the time of informed consent and assent (as applicable). 
3. Subject is male or non-pregnant, non-lactating female, who if of childbearing potential agrees 
to comply with any applicable contraceptive requirements if discharged from the hospital 
prior to completing the study.  
4. Subject has a diagnosis of COVID-19 infection through an approved testing method. 
5. Subject has been hospitalized due to clinical diagnosis of pneumonia with acute lung injury 
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It is important for investigators to gather as much data in this study as possible, even from subjects 
who discontinue because of withdrawal of consent or lack of effect.  The investigators is asked to 
encourage subjects who discontinue therapy to remain in the study and to continue follow-up for 
key outcomes through the Day 28 and Day 60 follow-up calls. It is especially important to record 
vital status for all subjects who have participated in the trial where possible at the specified 
endpoints even if they have withdrawn from the study. 
8.8 
Subject Replacement Criteria 
Subjects who withdraw or are discontinued from the study may be replaced. 
9 
TREATMENTS 
9.1 
Identification of Investigational Product(s), Dose and Mode of Administration 
The following investigational product will be used in this study in addition to standard of care: 
• CERC-002 (150 mg/mL) will be supplied in vials.  
• Placebo will be sourced locally and provided as volume-matched normal saline for 
injection  
• CERC-002 or placebo will be administered by SC injection in the abdomen in a zone of 4 
to 10 cm from the umbilicus with the injection site rotated based on the number of syringes 
used. 
• CERC-002 or placebo will be administered at baseline (Day 1). CERC-002 will be 
administered at 16 mg/kg dose (maximum dose of 1200 mg). 
9.2 
Labeling and Packaging 
All packaging and labeling operations will be performed by the sponsor or designee per Good 
Manufacturing Practice and Good Clinical Practice (GCP) rules. The investigational product will 
be sent to the study site by the sponsor or designee. Labeling will be in local language and 
dependent upon local regulations. 
9.2.1 Labeling 
The vials will have affixed a label that meets the applicable regulatory requirements and may 
include the following: name of compound, dosage strength, medication identifier, protocol 
number, caution statement (“New Drug – Limited by Federal (or United States) Law to 
Investigational Use”), storage conditions, and sponsor identification. 
The investigator will be asked to save all used or unused vials for final disposition by the sponsor.  
Syringes used for dosing must be treated as biologic waste and disposed of properly. 
9.2.2 Packaging 
CERC-002 (150 mg/mL) will be supplied by the sponsor in 2.4 mL vials and will be packaged 
separately into bulk, open-labeled cartons.  Placebo will be sourced locally and supplied as volume 
matched normal saline for injection.  
9.3 
Treatment Preparation 
Preparation of syringes will be described in the pharmacy manual.  


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9.4 
Treatments Administered 
Eligible subjects will receive CERC-002 or placebo on Day 1 in addition to standard of care. The 
standard of care is to be maintained throughout the study and may include off-label use of other 
drugs, devices, or interventions used to treat COVID-19.  
9.5 
Dispensing and Storage 
CERC-002 supplied by Aevi Genomic Medicine, LLC is to be used exclusively in this clinical 
study per the instructions of this protocol. Placebo will be sourced locally and provided as volume 
matched injection of normal saline. The investigator is responsible for dispensing the 
investigational product per the dosage scheme and for ensuring proper storage of the 
investigational product. 
The unblinded pharmacist must confirm the receipt of the investigational product with his/her 
signature. A copy of this receipt must be kept by the unblinded pharmacist, and another copy will 
be stored at Aevi Genomic Medicine, LLC and/or designee. Until the investigational product is 
dispensed to the subjects, it must be stored at 2°C to 8°C (35.6 °F to 46.4 °F) and protected from 
light. Investigators or other authorized persons (e.g., pharmacists) are responsible for storing the 
investigational product provided by the sponsor in a secure and safe place in accordance with local 
regulations, labeling specifications, institutional policies and procedures.  
Control of storage conditions for the investigational product provided by the sponsor, especially 
control of temperature (e.g., refrigerated storage) and daily temperature monitoring, and 
information on in-use stability and instructions for handling the investigational product must be 
managed according to the rules provided by the sponsor in the Pharmacy Manual. 
9.6 
Blinding and Unblinding Treatment Assignment 
This is a double-blind study.  All subjects, investigators, and study personnel involved in the 
conduct of the study, including data management, will be blinded to treatment assignment except 
for the following individuals: 
• Specified unblinded statistician from the Contract Research Organization (CRO) who will 
have access to the randomization code. 
• Specified unblinded pharmacist(s) from the hospital who will have access to the 
randomization code in order to prepare the investigational product.   
The unblinded pharmacist(s) and unblinded statistician will not otherwise participate in the study 
or data analysis prior to unblinding of the study. 
Treatment unblinding is discouraged if knowledge of the treatment assignment will not materially 
change the planned management of a medical emergency.  Unblinding is permitted in a medical 
emergency that requires immediate knowledge of the subject’s treatment assignment. Whenever 
possible unblinding should be discussed with the Sponsor Medical Monitor.  For emergency 
unblinding the Investigator will contact the unblinded pharmacist(s). If the Investigator is not able 
to discuss treatment unblinding in advance, then they should notify the Sponsor Medical Monitor 
as soon as possible about the unblinding incident without revealing the subject’s treatment 
assignment.  The Investigator or designee must record the date and reason for study discontinuation 
on the appropriate eCRF for that subject.  In all cases that are not emergencies, the Investigator 
should discuss the event with the Sponsor Medical Monitor prior to unblinding the subject’s 
treatment assignment.  


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If the treatment assignment is unblinded for an individual subject, the Investigator will be notified 
of that subject’s treatment assignment without unblinding the treatment assignments for the 
remaining subjects in the study.  The Investigator will make this decision after consultation with 
the Sponsor Medical Monitor.   
9.7 
Selection of Doses in the Study 
The dose of 16 mg/kg (maximum dose of 1200 mg) was selected in an effort to maximize the 
ability to achieve the blockade of LIGHT while ensuring patient safety.  In a robust toxicology 
program CERC-002 was dosed as high as 100 mg/kg in monkeys and was well tolerated while the 
NOAEL was determined to be 60 mg/kg.  In dosing in humans, CERC-002 was safe and well 
tolerated in single ascending doses up to 1200 mg in healthy volunteers.  There were no clinically 
meaningful treatment-emergent adverse events or changes in ECG parameters or laboratory 
values.  A safety review committee will be analyzing data from individual subjects and across all 
subjects treated in a daily fashion to assess any safety signals with dosing.   
9.8 
Dose Adjustment Criteria 
No dose adjustments are allowed.  
9.9 
Drug Accountability 
The investigator must ensure that adequate records showing the receipt, dispensing, or other 
disposition of the investigational product including the date, lot identifier, dosage, volume 
administered to each subject, and identification of subjects (subject number and initials) who 
received the investigational product are maintained by an unblinded pharmacist. The investigator 
will not supply the investigational product to any person except those named as subinvestigators 
on the US Food and Drug Administration (FDA) Form FDA 1572 and designated study personnel, 
and subjects in this study. The investigator will not dispense the investigational product from any 
study locations other than those listed on Form FDA 1572. If any of the investigational product is 
not dispensed, is lost, stolen, spilled, unusable, or received in a damaged container, this 
information must be documented and reported to Aevi Genomic Medicine, LLC and appropriate 
regulatory agencies, as required. 
Upon completion of the study, unused investigational product must be left in the original 
packaging for final disposition by the sponsor or per the site’s standard practice. Any partially used 
investigational product and all empty packaging (e.g., vials) must also be saved for final 
disposition by the sponsor, returned to the sponsor’s designee for destruction, or per the site’s 
standard practice. 
9.10 Handling and Disposal 
Investigational product reconciliation must be performed at the site by the unblinded pharmacist(s) 
using treatment log forms and documented on the site’s investigational product inventory. 
After reconciliation authorization by the sponsor, all used, partially used, and unused vials and all 
original packaging will be disposed of by the sponsor or per the site’s standard practice. This 
process will be provided to the site by the sponsor’s designee.       


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9.11 Permitted and Prohibited Therapies 
All non-study therapies including but not limited to over-the-counter and non-pharmacological 
treatments received within 7 days prior to baseline and through the end of study must be recorded 
on the appropriate electronic case report form (eCRF) page. 
9.11.1 Prior Therapies 
Prior treatment includes all treatment received within 7 days of the date of first dose of 
investigational product. Prior treatment information must be recorded on the appropriate eCRF 
page. 
9.11.2 Concomitant Therapies 
Concomitant therapies refer to all therapies taken between the dates of the first dose of 
investigational product and the end of the follow-up period, inclusive. Concomitant treatment 
information must be recorded on the appropriate CRF page. 
9.11.3 Permitted Therapies 
Medications considered necessary for the subject’s welfare, may be administered at the discretion 
of the investigator.  The Sponsor Medical Monitor should be contacted in the event the site in a 
situation where further clarity is needed. 
Acceptable methods of birth control are implants, injectables, combined oral contraceptives, 
intrauterine device, sexual abstinence or vasectomized partner. 
9.11.4 Prohibited Therapies 
Subjects may not have been administered an immunomodulating biologic drug within 60 days 
prior to the baseline visit, or have received any live attenuated vaccine, such as varicella-zoster, 
oral polio, or rubella, within 3 months prior to the baseline visit.  During the study, new initiation 
of investigational compounds is prohibited, with the exception of corticosteroids administered as 
part of standard of care measures in severe COVID-19 patients are permitted when clinically 
indicated and discussed with the Medical Monitor. The current use of immunomodulatory or anti-
rejection drugs is prohibited. The Sponsor Medical Monitor should be contacted in the event the 
site in a situation where further clarity is needed.  
9.12 Treatment after End of Study  
Subjects will be treated per standard clinical practice throughout the study. 
10 STUDY PROCEDURES 
Subjects/LAR will provide written informed consent and assent (as applicable) before any 
study-related procedures are initiated. 
For the timing of assessments and procedures throughout the study, refer to the schedule of 
events (Table 1 and Table 2). The procedures listed in Table 2 are considered standard of care 
and will be performed per the site’s practice unless defined otherwise. Throughout the 
study, every reasonable effort should be made by study personnel to follow the timing of 
assessments and procedures in the schedule of events for each subject.  




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Reference: Vincent et al, 1996. 
10.2.2 Safety 
Safety and tolerability assessments will include the frequency and severity of AEs as well as the 
evaluation of changes in clinical laboratory values, vital signs, ECG recordings, and physical 
examination findings. 
10.2.2.1 Clinical Laboratory Safety Assessments 
10.2.2.1.1 Clinical Laboratory Tests to be Performed 
A sample for C-reactive protein will be collected at the time points specified in the Schedule of 
Assessments (Table 2). With the exception of PK, LIGHT and InflammationMAP samples, all 
other laboratory samples are considered standard of care and will be performed per the 
site’s practice.  
Laboratory specimens will be analyzed at the hospital laboratory per their collection and 
processing requirements.  
10.2.2.1.2 Sampled Blood Volume  
The sampled blood volume for this study is shown in Table 4. 
Table 4: 
Sampled Blood Volume per Subject 
Assessment 
Sample Volume 
(mL) 
Number of Samples 
Total Volume 
(mL) 
CERC-002 concentration 
and PK analysis 
2.0 
4 
8.0 
Anti-drug Antibodies 
2.0 
3 
6.0 
LIGHT / 
InflammationMAP 
2.5 
7 
17.5 
Total mL 
-- 
-- 
27.5 
InflammationMAP = inflammatory biomarker patterns; LIGHT = Lymphotoxin-like, exhibits Inducible expression, and 
competes with Herpes Virus Glycoprotein D for Herpesvirus Entry Mediator, a receptor expressed by T lymphocytes 
10.2.2.2 CERC-002 Concentration, Pharmacokinetic and Anti-drug Antibody Assessments 
The name and address of the bioanalytical laboratories for this study is defined in the Investigator 
study file. 
Pharmacokinetics and ADA assessments will be calculated from the plasma concentrations of 
CERC-002. 
10.2.2.2.1 Specimen Handling Requirements 
The transmission of infectious agents may occur through contact with contaminated needles and 
blood or blood products. Consequently, appropriate blood and body fluid precautions should be 
employed by all study personnel involved in the collection of blood and handling of specimens in 
both the clinic and laboratory settings. Refer to current recommendations of the appropriate 
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In addition to appropriate handling of subject samples, specific regulations exist regarding the 
shipment of biologic/etiologic samples. Procedures and regulations for the packaging and shipping 
of infectious samples are outlined in the site and/or study laboratory manual. The investigator is 
responsible for ensuring that all study samples that are to be transported to another location are 
appropriately packed and shipped per the applicable regulations. 
10.2.2.2.2 Evaluation of Laboratory Values 
The normal ranges of values for the laboratory assessments in this study will be provided by the 
local laboratory of each hospital. They will be regarded as the reference ranges on which decisions 
will be made for the specific site. 
If a laboratory value is out of the reference range, it is not necessarily clinically relevant. The 
investigator must evaluate the out-of-range values and record his/her assessment of the clinical 
relevance in the subject’s source documentation. 
All laboratory values which, in the investigator’s opinion, show clinically relevant or pathological 
changes during or after termination of the treatment are to be discussed with the medical monitor, 
as necessary, and reported as AEs and followed, as described in Section 10.3.1. 
All measurements described in this section are recognized standard methods. 
10.2.2.3 Clinical Examinations 
10.2.2.3.1 Blood Pressure, Pulse Rate, Respiratory Rate, Temperature, Height, and Body 
Weight 
Blood pressure, pulse rate, respiratory rate, temperature, height, and body weight are considered 
standard of care and will be performed per the site’s practice. Additional blood pressure and pulse 
rate measurements may be performed, as determined by the investigator, to ensure appropriate 
monitoring of subject safety and accurate recording of vital sign measurements. Any changes from 
baseline which are deemed clinically significant by the investigator are to be recorded as an AE.  
10.2.2.3.2 Electrocardiogram 
A standard 12-lead ECG is considered standard of care and will be performed daily for those who 
are not being assessed by cardiac monitor. They will be performed per the site’s practice unless 
defined otherwise in Table 2. All ECG recordings will be identified with the subject 
number, subject initials, date, and time of the recording and a copy will be included with the 
subject’s source documentation. All ECGs will be performed using the equipment 
supplied by the investigational site.  
Electronic ECG tracings will be analyzed per the site’s practice. In addition, the investigator’s 
assessment of the ECG tracing as normal or abnormal must be documented, and if abnormal, 
his/her determination of whether the abnormality is clinically significant or not will be documented 
on the tracing.  All ECGs collected are to be entered into the eCRF.  
All ECG values which, in the investigator’s opinion, show clinically relevant or pathological 
changes during or after termination of the treatment are to be discussed with the Sponsor Medical 
Monitor and reported as AEs and followed, as described in Section 10.3.1. 


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10.2.2.3.3 Physical Examination 
A complete physical examination is considered standard of care and will be performed per the 
site’s practice unless defined otherwise in Table 2. Any clinically significant physical 
examination findings are to be and reported as AEs and followed, as described in Section 10.3.1. 
10.2.2.4 Adverse Events 
The definitions and management of and special considerations for AEs are provided in 
Section 10.4.1. 
The investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE described previously. Any clinically relevant observations made 
during the period of hospitalization will also be considered AEs. 
10.2.3 Pharmacokinetics and Immunogenicity Analyses 
Blood samples for PK analysis will be collected on Day 2 at 24 hours (±2 hours) post dose and at 
any time on Days 8, 14 and 28. Blood samples for ADA analysis will be collected at any time on 
Days 8, 14 and 28. Additionally, a sample will be collected when an immunologically related 
adverse event is reported.  Samples will be processed to plasma (see the Laboratory Manual). Time 
of PK samples will be recorded in the eCRF. A total of 1.0 mL plasma per PK and ADA sample 
will be collected from each subject to measure plasma concentrations of CERC-002 and ADAs. 
Pharmacokinetic and ADA samples will be processed according to the methods and directions set 
forward in the Laboratory Manual(s) and guidance(s). Pharmacokinetic and ADA plasma sample 
analysis will be performed by laboratory defined in the Laboratory Manual(s) and guidance(s), 
according to their standard operating procedures (SOPs) using a validated enzyme-linked 
immunosorbent assay (ELISA). Assay and analysis details will be described in the method 
validation and bioanalytical information. 
10.2.4 Pharmacodynamics 
Blood samples will be collected for exploratory analyses. Exploratory analyses may include but 
are not limited to LIGHT levels and InflammationMAP as specified in T a b l e  1 . 
Exploratory biomarker analyses will be performed at the laboratories specified in the 
Laboratory Manual(s) and guidance(s). 
10.3 Definition of Adverse Events, Period of Observation, Recording of Adverse Events 
10.3.1 Adverse Event Collection 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
the product. An AE can therefore be any unfavorable and unintended sign (including a new, 
clinically important abnormal laboratory finding), symptom, or disease, temporally associated 
with the product, whether related to the product. An AE will be considered treatment-emergent if 
it occurs after the first dose of investigational product and within 30 days of a subject’s last dose 
of investigational product.  
All AEs are collected from the time of the informed consent is signed until the end of study 
(Day 60). This includes events occurring regardless of whether investigational product is 
administered. Where possible, a diagnosis rather than a list of symptoms should be recorded. If a 
diagnosis has not been made, then each symptom should be listed individually. All AEs should be 


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captured on the appropriate AE pages in the eCRF and in source documents. In addition, to 
untoward AEs, unexpected benefits outside the investigational product indication should also be 
captured in the source documents and AE eCRF.  
All AEs must be followed to closure (the subject’s health has returned to his/her baseline status or 
all variable have returned to normal), 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. 
When appropriate, medical tests and examinations are performed so that resolution of an event(s) 
can be documented.  
10.3.2 Severity of Adverse Events 
The severity of AEs must be recorded during the course of the event including the start and stop 
dates for each change in severity. An event that changes in severity should be captured as a new 
event. Worsening of a pre-treatment events, after initiation of investigational product must be 
recorded as new AEs. For example, if the subject experiences mild, intermittent headaches prior 
to dosing with investigational product; however, the headache intensity increases to moderate after 
the first dose of investigational product, a new AE of moderate intermittent headaches is to be 
recorded in the source documents and eCRF.   
The medical assessment of clinical severity of an AE will be determined using the definitions 
outlined in Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 (Published 
November 27, 2017 by the US Department of Health and Human Services, National Institutes of 
Health, National Cancer Institute): 
Grade 1 
Mild; asymptomatic or mild symptoms; or clinical or diagnostic observations only; 
or intervention not indicated  
Grade 2 
Moderate; or minimal, local or non-invasive intervention indicated; or limiting age-
appropriate instrumental activities of daily living (ADL) 
Grade 3 
Severe or medically significant but not immediately life-threatening; or 
hospitalization or prolongation of hospitalization indicated; or disabling; or limiting 
self-care ADL  
Grade 4 
Life-threatening consequences; or urgent intervention indicated 
Grade 5 
Death related to AE 
Please refer to the above-referenced CTCAE document for full description of CTCAE terms and 
instrumental and self-care ADLs. It is important to distinguish between severe AEs and SAEs. 
Severity is a classification of intensity whereas an SAE is an AE that meets serious criteria, as 
described in Section 10.3.4.3. 
10.3.3 Relationship Categorization 
A physician investigator must make the assessment of relationship to investigational product for 
each AE. The investigator should decide whether, in his or her medical judgment, there is a 
reasonable possibility that the event may have been caused by the investigational product. If there 
is no valid reason for suggesting a relationship, then the AE should be classified as “not related”. 


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Otherwise, the AE should be categorized per the guidelines below. The causality assessment must 
be documented in the source document and the eCRF (Table 5).  
Table 5: 
Assessment of Relationship to Investigational Product 
Relationship 
Description 
Not Related 
Exposure to investigational product has not occurred. 
OR 
The administration of investigational product and the occurrence of the AE are not 
reasonably related in time 
OR  
The AE is considered likely to be related to an etiology other than the use of the 
investigational product, that is, there are no facts/evidence or arguments to suggest a causal 
relationship to the investigational product.  
Possibly Related 
The administration of the investigational product and the occurrence of the AE are 
reasonably related in time.  
AND 
The AE could not be explained equally well by factors or causes other than exposure to 
investigational product 
Probably Related 
The administration of investigational product and the occurrence of the AE are reasonably 
related in time.  
AND 
The AE is more likely explained by exposure to investigational product than by other factors 
or causes. 
AE = adverse event. 
10.3.3.1 Outcome at the Time of Last Observation 
The outcome at the time of last observation will be classified as: 
•
Recovered/resolved
•
Recovered/resolved with sequelae
•
Recovering/resolving
•
Not recovered/not resolved
•
Fatal*
•
Unknown
*See Section 10.3.5.
10.3.4 Serious Adverse Events
10.3.4.1 Investigational Product Safety Information
The IB is the reference document for safety information pertaining to this study. The IB is provided 
separately. 
10.3.4.2 Reporting of Serious Adverse Events 
Initial and follow-up SAE reports must be completed by the investigator or designee and sent to 
the CRO within 24 hours of the first awareness of an SAE. The investigator or designee must 
complete, sign and date the appropriate SAE form and verify the accuracy of the information 
against corresponding source documents. This information is to be sent to the CRO 
Pharmacovigilance Department by e-mail or fax at one of the methods noted below. For questions 




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10.3.4.5 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 symptoms resolve, or the event 
is considered chronic. In the case of hospitalization, the hospital admission and discharge dates are 
considered respectively, the onset and resolution date of the SAE.  
Any signs or symptoms experienced by the subject after signing the informed consent form and 
assent form (if applicable), or leading up to the onset date of the SAE or following the resolution 
date of the SAE must be recorded as an AE.  
10.3.5 Fatal Outcome 
Fatal should only be selected as an outcome when the AE results in death. If more than 1 AE is 
possibly related to the subject’s death, the outcome of death should be indicated for each such AE.  
Any AE that results in the subject’s death must have fatal checked as an outcome with the date of 
death recorded as the resolution date. AEs resulting in death must be reported within 24 hours as 
a SAE, if not already reported as such. In the event of a subject’s death, data should be collected 
on whether the death occurred after the withdrawal of care and, if so, the reason for the withdrawal 
of care.  
For other AEs, 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.  
10.4 Special Considerations 
10.4.1 Adverse Events of Special Interest 
There are no events from research to date which qualify as AEs of special interest. Adverse drug 
reactions observed in a CERC-002 pre-clinical study as well as reactions with other biologic agents 
include:   
CERC-002 pre-clinical observation: 
• Injection site reactions 
Observations for other biologic agents:  
• Potential for increased infection (including opportunistic infections such as tuberculosis) 
• Hypersensitivity reactions (including anaphylaxis) 
• Immunogenicity 
• Malignancy 
• Impaired immunization 
Any new infection that occurs on study, regardless of the infecting agent (i.e. viral or non-viral), 
should be captured. Additionally, the site of infection and source of culture (bronchoalveolar 
lavage, tracheal aspirate, sputum, blood, urine etc.) should be captured.  
Please refer to the IB for further details on possible risks and adverse drug reactions.  
10.4.2 Pregnancy 
All females of childbearing potential who participate in the study should be counseled on the need 
to practice adequate birth control and on the importance of avoiding pregnancy during study 


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participation. Females should be instructed to contact the investigator or study staff immediately 
if pregnancy occurs or is suspected. 
Pregnancy testing will be conducted on females of childbearing potential at baseline. A female 
who is found to be pregnant at baseline will be excluded from the study and considered to be a 
screening failure. A female who is found to be pregnant after the dosing is required to be 
discontinued from the study and the end of study visit assessments performed as soon as possible 
after learning of the pregnancy.   
The investigator must report the pregnancy of any female (study participant or female partner of 
male study participant) who becomes pregnant during investigational product treatment or within 
60 days of being randomized and receiving the investigational product. The pregnancy must be 
reported within 24 hours of learning of the pregnancy to the CRO using the Pregnancy Data 
Collection Form via the same fax and email address as for SAE reporting. The investigator should 
contact the designated individual(s) who receive SAE notification and record information related 
to the pregnancy on an Exposure in Utero form/other designated form provided by the sponsor or 
its designee. 
The investigator is also responsible for following the pregnancy until delivery or termination. 
These findings must be reported on the Pregnancy Data Collection Form and forwarded to the 
designated individual(s). The event meets the SAE criterion only if it results in a spontaneous 
abortion or a congenital anomaly. 
10.4.3 Anaphylaxis 
Any AE that represents an anaphylactic reaction should be classified using the definitions provide 
in Sampson et al, 2006 and shown in Table 6. 
Table 6: 
Clinical Criteria for Diagnosing Anaphylaxis 
Anaphylaxis is highly likely when any one of the following 3 criteria are fulfilled: 
1.
Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (eg,
generalized hives, pruritus or flushing, swollen lips-tongue-uvula)
AND AT LEAST ONE OF THE FOLLOWING
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
b. Reduced BP or associated symptoms of end-organ dysfunction (eg, hypotonia [collapse], syncope,
incontinence) 
2.
Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to
several hours):
a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen lips-tongue-uvula)
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)
c. Reduced BP or associated symptoms (eg, hypotonia [collapse], syncope, incontinence)
3.
Reduced BP after exposure to known allergen for that patient (minutes to several hours):
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP*
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline
Abbreviations: Peak expiratory flow; BP = blood pressure 
*Low systolic blood pressure for children is defined as less than 70 mm Hg from 1 month to 1 year, less than
(70  mm  Hg  +  [2 x  age]) from 1 to 10 years, and less than 90 mm Hg from 11 to 17 years.
Reference: Sampson et al, 2006


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10.4.4 Reporting to Regulatory Agency, Institutional Review Board/Ethics Committee 
(EC) and Site 
The sponsor or its designee is responsible for notifying the relevant regulatory authorities and if 
applicable, US central institutional review board (IRB) of related, unexpected SAEs. 
In addition, the sponsor and the CRO are responsible for notifying active sites of all related, 
unexpected SAEs occurring during all interventional studies across the development program.  
The investigator is responsible for notifying the local IRB, local ethics committee (EC), or the 
relevant local regulatory authority of all SAEs that occur at his/her site, as required.  
11 SAFETY REVIEW COMMITTEE 
A safety review committee will be analyzing data from individual subjects and across all subjects 
treated in a daily fashion to assess any safety signals with dosing.  This will allow close monitoring 
of safety changes in real time. 
12 DATA MONITORING COMMITTEE 
An external, independent DMC comprising physicians, scientists and a biostatistician will review 
the study data at intervals defined in the DMC charter and will monitor the trial for safety signals.  
Safety monitoring will be performed continuously throughout the study in accordance with this 
protocol. The DMC’s role is to protect the interests of the subjects in the study and those still to 
be entered in the study by reviewing cumulative data. The DMC’s meeting schedule may be 
adjusted based on recommendations made by the DMC, the amount of incremental safety data, 
and other practical considerations. The data provided to the DMC may not be monitored and will 
not be considered “clean” until the database is locked at the completion of the study. 
Data Monitoring Committee recommendation will be documented in meeting minutes which will 
include, at a minimum: 
• List of meeting participants 
• Summary of data considered during the meeting 
• Summary of the DMC recommendation(s)  
The sponsor is responsible for the decision to continue, modify or terminate the study. A copy of 
the DMC meeting recommendation and sponsor decision will be sent to the study sites. 
13 STATISTICS 
13.1 Sample Size Determination 
A total of 82 subjects are planned to be randomized to one of two treatment groups (CERC-002 or 
placebo in addition to standard of care) in a 1:1 ratio. This sample size will provide greater than 
80% power to detect a difference of 0.25 in the proportion of subjects alive and free of respiratory 
failure using a Chi-square exact test at a one-sided significance level of 0.05. This calculation 
assumes that the proportion alive and free of respiratory failure will be 0.60 in the placebo group 
and 0.85 in the CERC-002 group. 


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13.2 Analysis Populations 
This study will have the following populations of interest: 
• The Randomized Analysis Set will include all subjects who are randomized in the study.  
Subjects will be categorized according to their randomized treatment group. The 
Randomized Analysis Set will be used for all disposition, protocol deviations, and 
demographic and other baseline characteristics analyses.   
• The Safety Analysis Set will include all subjects who are randomized in the study and 
receive at least one dose of investigational product. Subjects will be categorized according 
to their actual treatment group. The Safety Analysis Set will be used for all exposure and 
safety analyses. 
• The Full Analysis Set will include all subjects who receive at least one dose of 
investigational product and have a baseline and at least one post-baseline efficacy 
assessment. Subjects will be categorized according to their randomized treatment group. 
The Full Analysis Set will be used for all efficacy and pharmacodynamic analyses. 
• The PK Analysis Set will include all subjects who receive at least one dose of 
investigational product and have at least one post dose measurable plasma sample.  
Subjects will be categorized according to their actual treatment group. The PK Analysis 
Set will be used for all PK analyses.   
13.3 Statistical Analyses 
This section presents a summary of the planned statistical analyses. Additional details regarding 
data handling, analytical methods, and presentation of results will be described in the Statistical 
Analysis Plan (SAP) for this study. The SAP will be finalized prior to database lock.  
All efficacy and safety variables will be summarized using descriptive statistics. Descriptive 
statistics for continuous data will include number of subjects (n), mean, standard deviation (SD), 
median, minimum, and maximum. Summaries of change from baseline variables will include only 
subjects who have both a baseline value and corresponding value at the timepoint of interest. 
Descriptive statistics for categorical data will include frequency and percentage.  
Listings will be provided for all collected study data. 
13.3.1 Study Subjects and Demographics 
13.3.1.1 Disposition and Withdrawals 
The disposition of all subjects randomized in this study will be summarized by treatment group 
and completion/discontinuation status. Subjects who discontinue the study prematurely will be 
summarized by treatment group and reason for discontinuation. The number of subjects in each 
analysis set will also be summarized by treatment group. 
13.3.1.2 Protocol Deviations 
All subject data will be reviewed for the occurrence of protocol deviations. Prior to database lock, 
all protocol deviations will be reviewed and classified with respect to the potential to influence 
experimental outcomes. Protocol deviations will be summarized by treatment group. 


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13.3.1.3 Demographics and Other Baseline Characteristics 
Demographic and other baseline characteristics will be summarized by treatment group using 
descriptive statistics. 
13.3.2 Prior and Concomitant Medications  
All prior and concomitant medications will be coded using the WHO Drug Dictionary. Prior and 
concomitant medications will be summarized by treatment group using descriptive statistics. 
13.3.3 Exposure and Compliance 
Exposure to investigational product will be summarized by treatment group using descriptive 
statistics.  
13.3.4 Safety and Tolerability Analyses 
Safety analyses will be conducted using data from the Safety Analysis Set (as defined in 
Section 13.2). Safety variables will include TEAEs, clinical laboratory values, vital signs, and 
ECG results. No formal inferential analyses will be conducted for any safety variables, unless 
otherwise noted.  
13.3.4.1 Adverse Events 
Adverse event verbatim terms will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). The overall incidence of subjects having at least one AE will be 
summarized by treatment group. The incidence of TEAEs will be summarized by treatment group, 
system organ class (SOC) and preferred term (PT). Each subject will be counted only once per 
SOC and preferred term. An AE will be considered treatment-emergent if it occurs after the first 
dose of investigational product and within 30 days after a subject’s last dose of investigational 
product.  
13.3.4.2 Clinical Laboratory Evaluations 
For all continuous laboratory test variables, descriptive statistics for all reported values and change 
from baseline values will be summarized by treatment group and time point.    
13.3.4.3 Vital Signs and Electrocardiograms 
For all continuous vital sign and ECG variables, descriptive statistics for all reported values and 
change from baseline values will be summarized by treatment group and time point. In addition, 
the frequency and percentage of subjects with abnormal ECG findings will be summarized.   
13.3.5 Efficacy Analyses  
The proportion of subjects alive and free of respiratory failure with 90% confidence interval will 
be presented. In addition, the proportion of subjects alive and free of respiratory failure in the 
CERC-002 group will be compared to that in the placebo group using a Chi-square test or similar 
methods. Other dichotomous efficacy variables will be analyzed similarly.  
All efficacy variables will also be summarized using descriptive statistics.  
13.3.6 Pharmacokinetic Analyses 
For all PK variables, descriptive statistics will be presented by collection timepoint (where 
applicable) using the PK Analysis Set. Descriptive statistics for plasma concentrations will include 
n, number of subjects with concentrations below the level of quantification (BLQ), mean, SD, 


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coefficient of variation, median, minimum, and maximum. For descriptive summaries, plasma 
concentrations reported as BLQ will be set to zero. 
13.3.7 Pharmacodynamic Analyses 
For all PD variables, descriptive statistics will be presented by treatment group and time point.   
13.3.8 Immunogenicity Analyses 
For all immunogenicity variables, descriptive statistics will be presented by treatment group and 
time point.  
13.3.9 Interim Analysis 
No formal interim analysis is planned for this study.  
14 STUDY CONDUCT 
Steps to ensure the accuracy and reliability of data include the selection of qualified investigators 
and appropriate study sites, review of protocol procedures with the investigator and associated 
personnel prior to the study, periodic monitoring visits, and meticulous data management. 
14.1 Sponsor and Investigator Responsibilities 
14.1.1 Sponsor Responsibilities 
The sponsor is obligated to conduct the study in accordance with strict ethical principles 
(Section 16). The sponsor reserves the right to withdraw a subject from the study (Section 8.7), to 
terminate participation of a study site at any time (Section 14.5), and/or to discontinue the study 
(Section 14.4). 
Aevi Genomic Medicine, LLC agrees to provide the investigator with sufficient material and 
support to permit the investigator to conduct the study per the study protocol. 
14.1.2 Investigator Responsibilities, Protocol Adherence and Investigator Agreement 
By signing the Investigator’s Agreement, the investigator indicates that she/he has carefully read 
the protocol, fully understands the requirements, and agrees to adhere to the protocol as detailed 
in this document. 
The investigator also agrees to conduct this study in accordance with all laws, regulations, and 
guidelines of the pertinent regulatory authorities, including and in accordance with the April 1996 
International Council for Harmonisation (ICH) Guidance for Industry E6 GCP and in agreement 
with the 1996 Version of the Declaration of Helsinki. While delegation of certain aspects of the 
study to subinvestigators and study coordinators is appropriate, the investigator will remain 
personally accountable for closely overseeing the study and for ensuring compliance with the 
protocol and all applicable regulations and guidelines. The investigator is responsible for 
maintaining a list of all persons that have been delegated study-related responsibilities 
(e.g., subinvestigators and study coordinators) and their specific study-related duties. 
Investigators should ensure that all persons who have been delegated study-related responsibilities 
are adequately qualified and informed about the protocol, investigational products, and their 
specific duties within the context of the study. Investigators are responsible for providing Aevi 
Genomic Medicine, LLC with documentation of the qualifications, GCP training, and research 


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experience for themselves and their staff as required by the sponsor and the relevant governing 
authorities. 
To ensure compliance with the guidelines, the study may be audited by an independent person. 
The investigator agrees, by written consent to this protocol, to cooperate fully with compliance 
checks by allowing access to all study documentation by authorized individuals. 
Per local laws and regulations, the investigator, sponsor or sponsor designee will communicate 
with the IRB/EC to ensure accurate and timely information is provided throughout the study.  
14.2 Study Documents 
All documentation and material provided by Aevi Genomic Medicine, LLC for this study are to 
be retained in a secure location and treated as confidential material. 
14.2.1 Case Report Forms 
By signing the Investigator’s Agreement, the investigator agrees to complete the eCRFs and 
maintain source documentation as part of the case histories for all subjects/LAR who sign an 
informed consent form (ICF) and assent (as applicable). 
Case report forms are considered confidential documents and should be handled and stored 
accordingly. The sponsor or its designee will provide the necessary training on the use of the 
specific eCRFs used during the study to ensure that the study information is captured accurately 
and appropriately. 
To ensure data accuracy, eCRF data for individual subject visits should be completed as soon as 
possible after the visit. All requested information must be entered in the eCRF per the completion 
guidelines provided by the sponsor or its designee. All data will have separate source 
documentation; no data will be recorded directly into the eCRF.  
The eCRFs will be signed by the investigator or a subinvestigator to whom this authority has been 
delegated. These signatures serve to attest that the information contained in the eCRF is accurate 
and true. 
14.2.2 Recording, and Retention of Source Data and Study Documents 
All study information must be recorded in the subject’s medical records and no data will be 
recorded directly onto the eCRF. Data recorded in the eCRF must be supported by corresponding 
source documentation. Examples of acceptable source documentation include, but are not limited 
to, hospital records, clinic and office charts, laboratory reports and notes, and recorded data from 
automated instruments, memoranda, and pharmacy dispensing records.  
14.3 Data Quality Control 
Aevi Genomic Medicine, LLC and its designees will perform quality control checks on this clinical 
study. 
14.3.1 Access to Study and Source Documents  
Aevi Genomic Medicine, LLC and/or designee will conduct site visits to monitor the study and 
ensure compliance with the protocol, GCP, and applicable regulations and guidelines. The consent 
form includes a statement by which the subject agrees to the monitor/auditor from the sponsor or 
its representatives, national or local authorities, or the IRB/EC, having access to the source data 


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(for example, subject’s medical records, appointment books, original laboratory reports, 
radiographic exams and reports, etc.) 
The assigned clinical research associate(s) (CRA[s]) will visit the investigator and study site at 
periodic intervals and maintain periodic communication. The investigator agrees to allow the 
CRA(s) and other authorized Aevi Genomic Medicine, LLC personnel access. The CRA(s) will 
maintain current personal knowledge of the study through observation, review of study records 
and source documentation, and discussion of the conduct of the study with the investigator and 
staff. While on site, the CRA(s) will review: 
• 
Regulatory documents, directly comparing entries in the eCRF with the source documents. 
• 
Consenting procedures. 
• 
Adverse event procedures. 
• 
Storage and accountability of investigational product and study materials. 
The CRA will ask for clarification and/or correction of any noted inconsistencies. Procedures for 
correcting eCRFs will be described for the study personnel as part of training. As representatives 
of the sponsor, CRAs are responsible for notifying project management of any noted protocol 
deviations. 
By signing the Investigator’s Agreement, the investigator agrees to meet with the CRA(s) during 
study site visits; to ensure that study staff is available to the CRA(s) as needed, to provide the 
CRA(s) access to all study documentation, to the clinical supplies dispensing and storage area, and 
to assist the monitors in their activities, if requested. Further, the investigator agrees to allow Aevi 
Genomic Medicine, LLC or designee auditors or inspectors from IRBs/ECs or regulatory agencies 
to review records and to assist the inspectors in their duties, if requested. 
14.3.2 Data Management 
Aevi Genomic Medicine, LLC or designee will be responsible for activities associated with the 
data management of this study. The standard procedures for handling and processing records will 
be followed per GCP and the designee’s SOPs. Data are to be reviewed and checked for omissions, 
errors, and values requiring further clarification using computerized and manual procedures. A 
comprehensive data management plan will be developed including a data management overview, 
database contents, annotated eCRF, self-evident correction conventions, and consistency checks. 
Study site personnel will be responsible for providing resolutions to all data queries. The 
investigator will be required to document electronic data review to ensure the accuracy of the 
corrected and/or clarified data. Procedures for soliciting and documenting resolution to data 
queries will be described.  
14.3.3 Quality Assurance Audit / Inspection 
This study may be subject to audit by Aevi Genomic Medicine, LLC or designee. The audits 
undertaken will check compliance with GCP guidelines. Aevi Genomic Medicine, LLC or 
designee may conduct additional audits on a selection of study sites, requiring access to subject 
notes, study documentation, and facilities or laboratories used for the study. 
The study site, facilities, all data (including source data), and documentation will be made available 
for audit by quality assurance auditors and for IRB or regulatory authorities per GCP guidelines. 


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The investigator agrees to cooperate with the auditor during the visit and will be available to supply 
the auditor with eCRFs or other files necessary to conduct that audit.   
If a regulatory authority informs the investigator that it intends to conduct an inspection, the 
investigator will/must notify Aevi Genomic Medicine, LLC immediately. 
14.4 Study Termination 
The study may be terminated at Aevi Genomic Medicine, LLC discretion at any time and for any 
reason. 
If the investigator suspends or terminates the study at their site, the investigator will promptly 
inform the sponsor and the IRB/EC and provide them with a detailed written explanation. The 
investigator will return all investigational product, containers, and other study materials to the 
sponsor.  
14.5 Study Site Closure 
At the end of the study, all study sites will be closed. Aevi Genomic Medicine, LLC may terminate 
participation of a study site at any time. Examples of conditions that may require premature 
termination of a study site include, but are not limited to, the following: 
• 
Noncompliance with the protocol and/or applicable regulations and guidelines. 
• 
Inadequate subject enrollment. 
14.5.1 Record Retention 
It is the investigator’s responsibility for maintaining adequate and accurate study and medical 
records. The investigator shall retain and preserve 1 copy of all data generated during the study, 
specifically including, but not limited to, those defined by ICH GCP as essential until 
• 
At least 2 years after the last marketing authorization for the investigational product has been 
approved or the sponsor has discontinued its research with the investigational product, or 
• 
At least 2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product. 
These documents should be retained for a longer period, however, if required by the applicable 
regulatory requirement(s) or if needed by the sponsor. 
At the end of such period, the investigator must notify the sponsor in writing of her/his intent to 
move and/or destroy any study material. Approval from the sponsor must be granted prior to any 
action being taken.  
14.5.2 Sample Retention 
All samples will be retained according to applicable SOPs and regulations. Blood samples may be 
stored and used for further analysis related to this research.  
14.6 Changes to the Protocol 
This protocol cannot be altered or changed except through a formal protocol amendment, which 
requires the written approval of Aevi Genomic Medicine, LLC. The protocol amendment must be 
signed by the investigator and approved by the IRB before it may be implemented. Protocol 


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amendments will be filed with the appropriate regulatory agency(ies) having jurisdiction over the 
conduct of the study. 
14.7 Use of Information and Publication 
All information concerning CERC-002, Aevi Genomic Medicine, LLC operations, patent 
applications, formulas, manufacturing processes, basic scientific data, and formulation 
information supplied by Aevi Genomic Medicine, LLC or designee to the investigator and not 
previously published, is considered confidential and remains the sole property of Aevi Genomic 
Medicine, LLC. Case report forms also remain the property of Aevi Genomic Medicine, LLC. The 
investigator agrees to use this information for purposes of study execution through finalization. 
The information developed in this study will be used by Aevi Genomic Medicine, LLC in 
connection with the continued development of CERC-002 and thus may be disclosed as required 
to other clinical investigators or government regulatory agencies. 
The information generated by this study is the property of Aevi Genomic Medicine, LLC. 
Publication or other public presentation of CERC-002 data resulting from this study requires prior 
review and written approval of Aevi Genomic Medicine, LLC. Abstracts, manuscripts, and 
presentation materials should be provided to Aevi Genomic Medicine, LLC for review at least 
30 days prior to the relevant submission deadline. 
It is agreed that the results of the study will not be submitted for presentation, abstract, poster 
exhibition or publication by the investigator until Aevi Genomic Medicine, LLC has reviewed and 
commented on such a presentation or manuscript for publication. 
15 PUBLIC POSTING OF STUDY INFORMATION 
The Sponsor is responsible for posting appropriate study information on applicable websites. 
Information included in clinical study registries may include participating investigator information 
(e.g. site name, investigator name, site location, site contact information). 
16 ETHICAL AND LEGAL CONSIDERATIONS 
16.1 Declaration of Helsinki and Good Clinical Practice 
This study will be conducted in compliance with the protocol, the April 1996 ICH Guidance for 
Industry E6 GCP (including archiving of essential study documents), the 1996 Version of the 
Declaration of Helsinki, and the applicable regulations of the country(ies) in which the study is 
conducted. 
16.2 Subject Information and Informed Consent 
It is the responsibility of the investigator to ensure that written informed consent and assent 
(as applicable) is obtained from the subjects/LARs before any activity or procedure is undertaken 
that is not part of routine care including baseline assessments. All consent documentation must be 
in accordance with applicable regulations and GCP. Each subject or the subject’s LAR, as 
applicable, is requested to sign and date the subject informed consent and assent form (as 
applicable) or a certified translation, if applicable, after the subject/LAR has received and read (or 
been read) the written subject information and received an explanation of what the study involves, 
included but not limited to: the objectives, potential benefits and risks, inconveniences, and the 


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subject’s rights and responsibilities. A copy of the informed consent and assent documentation 
(if applicable [such as a complete set of subject information sheets and fully executed signature 
pages]) must be given to the subject. This document may require translation into local language. 
Signed consent/assent forms must remain in each subject’s study file and must be available for 
verification at any time.  
The principal investigator provides the sponsor with a copy of the consent and assent (as 
applicable) form which was reviewed by the IRB/EC and which received favorable 
opinion/approval. A copy of the IRB/EC’s written favorable opinion/approval of these documents 
must be provided to the sponsor, prior to the start of the study unless it is agreed to and documented 
(abiding by regulatory guidelines and national requirements) prior to the study start that another 
party (such as the sponsor or coordinating principal investigator) is responsible for this action. If 
the IRB/EC requires modification of the sample subject information and consent document 
provided by the sponsor, the documentation supporting this requirement must be provided to the 
sponsor.  
16.3 Institutional Review Board or Ethics Committees 
A properly constituted, valid IRB/EC according to local laws and regulations must review and 
approve the protocol, the investigator’s informed consent and assent (as applicable) document, and 
related subject information and any other study materials requiring review (such as recruitment 
information) before the start of the study. 
Until written approval by the IRB has been received by the investigator, no subject may undergo 
any study procedure solely for determining eligibility for this study. Investigational product will 
not be released until the sponsor or its designee has received written IRB/EC approval. 
Prior to implementing changes in the study, the sponsor and the IRB/EC must approve and provide 
documentation of favorable opinion/approval of any revisions to informed consent documents and 
amendments to the protocol unless there is a subject safety issue.  
Depending on location (outside European Union [EU] or inside EU) the IRB/EC will be apprised 
of the progress of the study and of any changes made to the protocol at least yearly. This may be 
done by the investigator (outside EU and in some cases, inside EU) or the sponsor (in some cases 
inside EU). These updates include information on any serious or significant AEs.  
Upon study completion, the investigator will provide the IRB/EC with final report/summary as 
required.  
16.4 Financial Disclosure 
The investigator is required to disclose any financial arrangement during the study and for 1 year 
after where 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. The following 
information is collected: any significant payments from sponsor or subsidiaries such as grant to 
fund ongoing research, compensation in the form of equipment, retainer for ongoing consulting or 
honoraria; any proprietary interest in investigational product; any significant equity interest in the 
sponsor or subsidiaries as defined in 21 CFR 54 (b) (1998). 
16.5 Privacy and Confidentiality 
All US-based sites and laboratories or entities providing support for this study, must, where 
applicable, comply with Health Insurance Portability and Accountability Act (HIPAA) of 1996. A 


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site that is not a covered entity as defined by HIPAA must provide documentation of this fact to 
the sponsor/CRO.  
The confidentiality of records that may be able to identify subjects will be protected in accordance 
with applicable laws, regulations and guidelines.  
After subjects/LAR have consented and assented (as applicable) to participate in a study, the 
sponsor and/or its representatives reviews their medical records and data collected as part of the 
study. These records and data may be reviewed by others including the monitor/auditor from the 
sponsor or its representatives, national or local authorities, or the IRB/EC which gave the approval 
for the study, third parties with whom the sponsor may develop, register or market the 
investigational product. The sponsor and its representatives 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, the initials and date of birth may also 
be collected and used to assist the sponsor to verify the accuracy of data.  
The results of the studies, containing the subjects’ unique identifying number, relevant medical 
records and possibly initials and dates of birth, will be recorded. They may be transferred to and 
used in other countries which may not afford the same level of protection that applies within the 
countries where the study is conducted. The purpose of such transfer would include supporting 
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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17 REFERENCES 
Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel 
coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 
2020;395(10223):514–523.  
Coronavirus 2019‐nCoV, CSSE. Coronavirus 2019‐nCoV Global Cases by Johns Hopkins 
CSSE. (Available from: 
https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467
b48e9ecf6 
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus 
in Wuhan, China [published correction appears in Lancet. 2020 Jan 30;:]. Lancet. 
2020;395(10223):497–506.  
Kwon BS, Tan KB, Ni J, et al. A newly identified member of the tumor necrosis factor receptor 
superfamily with a wide tissue distribution and involvement in lymphocyte activation. J Biol 
Chem. 1997;272(22):14272–14276.  
National Cancer Institute, National Institutes of Health, US Department of Health and Human 
Services. Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Published 
November 27, 2017; 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference 8.5x11.pdf. Accessed July 1, 2020. 
Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and 
management of anaphylaxis: Summary Report-Second National Institute of Allergy and Infectious 
Disease/Food Allergy and Anaphylaxis Network Symposium. J Allergy Clin Immunol 
2006;117(2):391-97). 
Steinberg MW, Shui JW, Ware CF, Kronenberg M. Regulating the mucosal immune system: the 
contrasting roles of LIGHT, HVEM, and their various partners. Semin Immunopathol. 
2009;31(2):207–221.  
Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score 
to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related 
Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 
1996;22(7):707–710.  
Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel 
Coronavirus–Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–1069. 
Ware CF. Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways. 
Immunol Rev. 2008;223:186–201. 
Ware CF. Targeting the LIGHT-HVEM pathway. Adv Exp Med Biol. 2009;647:146–155. 
Wroblewski VJ, Witcher DR, Becker GW, et al. Decoy receptor 3 (DcR3) is proteolytically 
processed to a metabolic fragment having differential activities against Fas ligand and LIGHT. 
Biochem Pharmacol. 2003;65(4):657–667.  
Xu W, Xu Z, Huang L, et al. Transcriptome Sequencing Identifies Novel Immune Response Genes 
Highly Related to the Severity of Human Adenovirus Type 55 Infection. Front Microbiol. 
2019;10:130.  


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INVESTIGATOR’S AGREEMENT 
PROTOCOL NUMBER: 
CERC-002-CVID-201 
PROTOCOL TITLE: 
A Randomized, Double-blind, Placebo-controlled, Multicenter, 
Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of 
CERC-002 in Adults with COVID-19 Pneumonia and Acute Lung 
Injury 
FINAL PROTOCOL: 
12 August 2020 
I have read this protocol and agree to conduct this clinical trial as outlined herein. I will ensure 
that all subinvestigators and other study staff members have read and understand all aspects of this 
protocol. I agree to cooperate fully with Aevi Genomic Medicine, LLC and designee during the 
study. I will adhere to all FDA, ICH, and other applicable regulations and guidelines regarding 
clinical trials on an investigational product during and after study completion. 
Principal Investigator: 
Printed Name: 
Signature: 
Date: 

SAP_001.pdf: 
PROTOCOL TITLE: 
A Randomized, Double-blind, Placebo-controlled, Multicenter, 
Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of 
CERC-002 in Adults with COVID-19 Pneumonia and Acute 
Lung Injury 
PROTOCOL NUMBER: 
CERC-002-CVID-201 
NCT NUMBER: 
NCT04412057 
STATISTICAL ANALYSIS 
PLAN DATE: 
15 December 2020  
 
 
 


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Statistical Analysis Plan: CERC-002-CVID-201 
 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, Multicenter, 
Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of 
CERC-002 in Adults with COVID-19 Pneumonia and Acute 
Lung Injury 
Study Number: 
CERC-002-CVID-201 
Study Phase:  
2 
Sponsor: 
Aevi Genomic Medicine, LLC.  
435 Devon Park Drive, Suite 715 
Wayne, PA 19087 
Phone: 610-254-4201 
Fax: 
443-304-8001 
Version  
Version Final, 15 Dec 2020 
NCT Number: 
NCT04412057 
Date: 
15 Dec 2020 
 
Confidentiality Statement 
This document contains confidential and proprietary information, and is not to 
be distributed to any third party. 
 


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1 
TABLE OF CONTENTS 
1 
TABLE OF CONTENTS .........................................................................................................2 
2 
SIGNATURE PAGE ................................................................................................................5 
3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ...........................................6 
4 
INTRODUCTION ....................................................................................................................9 
5 
TRIAL OBJECTIVES ..............................................................................................................9 
5.1 
Primary Objectives ...............................................................................................................9 
5.2 
Secondary Objectives ...........................................................................................................9 
5.3 
Exploratory Objectives ........................................................................................................9 
6 
STUDY DESIGN CONSIDERATIONS ..................................................................................9 
6.1 
Study Design ........................................................................................................................9 
6.2 
Sample Size Determination ................................................................................................10 
6.3 
Efficacy Measures ..............................................................................................................10 
6.4 
Safety Measures .................................................................................................................11 
6.5 
Pharmacokinetic Measures ................................................................................................11 
6.6 
Immunogenicity Measures .................................................................................................12 
6.7 
Pharmacodynamic Measures .............................................................................................12 
7 
STUDY POPULATIONS .......................................................................................................12 
7.1 
Analysis Populations ..........................................................................................................12 
7.2 
Subgroups ..........................................................................................................................12 
8 
DEFINITION OF STUDY VARIABLES ..............................................................................13 
8.1 
Subject Disposition ............................................................................................................13 
8.2 
Protocol Deviations ............................................................................................................13 
8.3 
Demographic and Baseline Characteristics .......................................................................14 
8.4 
Prior and Concomitant Medications ..................................................................................14 
8.5 
Concomitant Procedures ....................................................................................................14 
8.6 
Medical History .................................................................................................................14 
8.7 
Treatment Exposure ...........................................................................................................15 
8.8 
Efficacy Endpoints .............................................................................................................15 
8.8.1 
Alive and Free of Respiratory Failure at Day 28 .........................................................15 
8.8.2  
Alive at Day 28 ............................................................................................................15 
8.8.3 
Changes in Arterial Blood Gas (ABG) Values ............................................................16 
8.8.4 
Resource Utilization/Hospitalization/ICU ...................................................................16 
8.8.5 
Pulse Oximetry .............................................................................................................17 
8.8.6 
Sequential Organ Failure Assessment (SOFA) Score .................................................17 
8.8.7 
Aspirate Viral Load ......................................................................................................18 
8.9 
Safety Endpoints ................................................................................................................19 
8.9.1 
Adverse Events ............................................................................................................19 
8.9.2 
Electrocardiograms ......................................................................................................21 
8.9.3 
Physical Examination/Chest CT/CXR .........................................................................21 


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8.9.4 
Laboratory Tests ..........................................................................................................21 
8.9.5 
Vital Signs ....................................................................................................................23 
8.10 
Pharmacokinetic (PK) Endpoints .......................................................................................24 
8.11 
Pharmacodynamic (PD) Endpoints ....................................................................................24 
8.11.1 
LIGHT and InflammationMAP ...................................................................................24 
8.11.2 
Anti-drug Antibody (ADA) .........................................................................................24 
8.12 
Visit Windows/Unscheduled Visits ...................................................................................24 
9 
OVERALL STATISTICAL CONSIDERATIONS ................................................................25 
9.1 
General Conventions ..........................................................................................................25 
9.2 
Handling of Missing Data ..................................................................................................26 
9.3 
Interim Analysis .................................................................................................................26 
10 STATISTICAL ANALYSIS METHODS ..............................................................................26 
10.1 
Subject Disposition ............................................................................................................27 
10.2 
Demographics and Baseline Characteristics ......................................................................27 
10.3 
Protocol Deviations ............................................................................................................27 
10.4 
Medical History .................................................................................................................27 
10.5 
Prior and Concomitant Medications ..................................................................................27 
10.6 
Concomitant Procedures ....................................................................................................28 
10.7 
Pharmacokinetics ...............................................................................................................28 
10.8 
Immunogenicity .................................................................................................................28 
10.9 
Pharmacodynamics ............................................................................................................28 
10.10 Treatment Compliance and Exposure ................................................................................28 
11 EFFICACY PARAMETERS ..................................................................................................28 
11.1 
Primary Analysis ................................................................................................................28 
11.2 
Secondary Analyses ...........................................................................................................28 
11.3 
Sensitivity Analyses ...........................................................................................................29 
11.4 
Exploratory Analyses .........................................................................................................29 
11.5 
Interim Analysis .................................................................................................................29 
11.6 
Subgroup Analyses ............................................................................................................29 
12 SAFETY AND TOLERABILITY ..........................................................................................30 
12.1 
Adverse Events ..................................................................................................................30 
12.2 
Electrocardiograms ............................................................................................................31 
12.2 
Laboratory Tests ................................................................................................................31 
12.3.1 
Laboratory Values and Changes Over Time ................................................................31 
12.3.2 
Shift from Baseline to Post-Baseline Laboratory Results ............................................31 
12.3.3 
Potentially Clinically Significant Laboratory Values ..................................................32 
12.4.1 
Vital Sign Values and Changes Over Time .................................................................32 
12.4.2 
Potentially Clinically Significant Vital Sign Values ...................................................32 
13 OTHER RELEVANT DATA ANALYSES/SUMMARIES ..................................................33 
14 DATA MONITORING COMMITTEE ..................................................................................33 
15 CHANGES TO PLANNED ANALYSES ..............................................................................33 


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15.1 
Changes to Analyses Specified in Protocol .......................................................................33 
15.2 
Changes to Approved Prior Versions of the SAP ..............................................................33 
16 REFERENCES .......................................................................................................................34 
17 APPENDICES ........................................................................................................................35 
 
LIST OF TABLES 
Table 1: 
The Sequential Organ Failure Assessment (SOFA) ..............................................18 
Table 2: 
Assessment of CTCAE Grade ...............................................................................20 
Table 3: 
Assessment of Relationship to Investigational Product .........................................20 
Table 4: 
Liver Function Potentially Clinically Important Criteria .......................................22 
Table 5: 
PCS Laboratory Criteria ........................................................................................23 
Table 6: 
Vital Signs PCS Criteria ........................................................................................24 
Table 7: 
Analysis Windows .................................................................................................25 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Assessments .......................................................................................36 
Appendix 2 
Summary of Efficacy Analyses .............................................................................38 
Appendix 3 
Imputation Rules for Missing or Partial Dates for AEs .........................................40 
Appendix 4 
Imputation Rules for Missing or Partial Dates for Prior and Concomitant 
Medications and Medical Procedures ....................................................................41 
Appendix 5 
Laboratory CTCAE Grade Version 5.0 Criteria ....................................................42 
Appendix 6 
Identification of Extreme Value at Visits ..............................................................44 
 


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2 
SIGNATURE PAGE 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, Multicenter, 
Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of 
CERC-002 in Adults with COVID-19 Pneumonia and Acute 
Lung Injury 
Study Number: 
CERC-002-CVID-201 
 
 
Prepared by:
 
Date: 
 
 
 
Reviewed by:
 
Date: 
 
 
 
Approved by
 
Date: 
 
 
 
Approved by
 
Date: 
 


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3 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ADA 
anti-drug antibody 
AE 
adverse event 
ABG 
arterial blood gas 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
Analysis of covariance analysis 
ARDS 
acute respiratory distress syndrome 
AST 
aspartate aminotransferase 
BLQ 
below the level of quantification 
BMI 
body mass index 
CI 
confidence interval 
COVID-19 
2019 novel coronavirus disease 
CRA 
clinical research associate 
CRF 
case report form 
CRO 
contract research organisation 
CT 
CTCAE 
Computed tomography 
Common terminology criteria for adverse events 
CXR 
chest x-ray 
DBP 
diastolic blood pressure 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
ECMO 
extracorporeal membrane oxygenation 
eCRF 
electronic case report form 
EC 
Ethics committee 
ELISA 
enzyme-linked immunosorbent assay 
ET 
early termination 
EU 
European Union 
FDA 
Food and Drug Administration 
FiO2 
percentage of inspired oxygen 
GCP 
Good Clinical Practice 
HCO3 
bicarbonate 
HIPAA 
Health Insurance Portability and Accountability Act 
HSV 
herpes simplex virus 


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HVEM 
herpes virus entry mediator 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
ICU 
intensive care unit 
IL 
interleukin 
InflammationMAP 
inflammatory biomarker patterns IRB 
LAR 
legally authorized representative 
IL 
interleukin 
LIGHT 
Lymphotoxin-like, exhibits Inducible expression, and competes 
with Herpes Virus Glycoprotein D for Herpesvirus Entry 
Mediator, a receptor expressed by T lymphocytes 
LLN 
lower limit of normal 
LTβR 
lymphotoxin β receptor 
MAb 
monoclonal antibody 
MAP 
mean arterial pressure 
MedDRA 
Medical Dictionary for Regulatory Affairs 
MMRM 
mixed model repeated measures 
O2CT 
oxygen content 
O2Sat 
oxygen saturation 
PaCO2 
partial pressure of carbon dioxide 
PaO2 
partial pressure of arterial oxygen 
PBMC 
PCI 
PCS 
peripheral blood mononuclear cells 
Potentially clinically important 
Potentially clinically significant 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PO2 
partial pressure of oxygen 
PT 
preferred term 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
systolic blood pressure 
SC 
subcutaneous 
SD 
standard deviation 


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SOC 
system organ class 
SOFA 
Sequential Organ Failure Assessment 
SOP 
standard operating procedure 
TBL 
total bilirubin 
TEAE 
treatment emergent adverse event 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
US 
United States 
WHO 
World Health Organization 


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4 
INTRODUCTION 
The purpose of this statistical analysis plan is to describe the framework for the reporting, 
summarization and statistical analysis methodology of the safety and efficacy parameters 
measured throughout the study. It is based on Protocol CERC-002-CVID-201 Version 4.0 dated 
12Aug 2020. 
5 
TRIAL OBJECTIVES 
5.1 Primary Objectives 
• To evaluate the effect of CERC-002 compared with placebo in addition to standard of care on 
prevention of acute respiratory distress syndrome (ARDS) in adults with 2019 novel 
coronavirus disease (COVID-19) pneumonia and acute lung injury. 
5.2 Secondary Objectives 
• To evaluate the safety and tolerability of CERC-002 compared with placebo in addition to 
standard of care, in adults with COVID-19 pneumonia and acute lung injury. 
• To evaluate the effect of CERC-002 compared with placebo in addition to standard of care, on 
mortality in adults with COVID-19 pneumonia and acute lung injury. 
5.3 Exploratory Objectives 
• To evaluate the effect of CERC-002 on viral load in adults with COVID-19 pneumonia and 
acute lung injury. 
• To evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of 
CERC-002 in adults with COVID-19 pneumonia and acute lung injury. 
6 
STUDY DESIGN CONSIDERATIONS 
6.1 Study Design 
This is a multicenter, randomized, double-blind, Phase 2 clinical trial in adults with 
documented COVID-19 pneumonia and acute lung injury. Subjects will receive either 
subcutaneous (SC) CERC-002 at a dose of 16 mg/kg (maximum 1200 mg) or placebo at 
baseline (Day 1) in addition to standard of care. The standard of care is to be maintained 
throughout the study and may include off-label use of other drugs, devices, or interventions 
used to treat COVID-19. All subjects will be followed until the end of study (Day 60) for 
safety monitoring. The primary efficacy endpoint will be assessed within 4 weeks after the 
dose is administered. CERC-002 or placebo treatment will be administered on Day 1 and the 
duration of the study period will be 60 days. 
Approximately 82 subjects are planned to be included and dosed with either CERC-002 or 
placebo in addition to their standard of care in this study. 
Subjects must have a diagnosis of COVID-19 infection through an approved testing method 
and have been hospitalized due to a clinical diagnosis of pneumonia with acute lung injury 
defined as diffuse bilateral radiographic infiltrates with PaO2/FiO2>100 and <300 and have 


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oxygen saturation at rest in ambient air <93%. 
Subjects will not be eligible if they are intubated, are currently taking immunomodulating or 
anti-rejection drugs, has been administered an immunomodulating drug with 60 days of 
baseline, are in septic shock despite adequate volume resuscitation, have alanine 
aminotransferase (ALT)/aspartate aminotransferase (AST) >5 × upper limit of normal (ULN), 
creatinine >2.5 mg/dL, neutrophils <500/mL3, or platelets <50,000/mL3. 
An external, independent Data Monitoring Committee (DMC) will review the study data at 
intervals defined in the DMC charter and will monitor the trial for safety signals. 
All subjects will undergo efficacy, PK, PD, and immunogenicity assessments. All subjects will 
be monitored for adverse events (AEs) and will undergo physical exams, ECG, and routine safety 
laboratory tests. The PK of CERC-002 will be based on plasma levels obtained at various time 
points after administration, and the PD will be based on LIGHT levels and InflammationMAP. 
6.2 Sample Size Determination 
A total of 82 subjects are planned to be randomized to one of two treatment groups (CERC-002 
or placebo in addition to standard of care) in a 1:1 ratio. This sample size will provide greater 
than 80% power to detect a difference of 0.25 in the proportion of subjects alive and free of 
respiratory failure using a Chi-square exact test at a one-sided significance level of 0.05. 
This calculation assumes that the proportion alive and free of respiratory failure will be 0.60 in 
the placebo group and 0.85 in the CERC-002 group. 
6.3 Efficacy Measures 
Primary Endpoint 
The primary efficacy endpoint is the proportion of subjects alive and free of respiratory failure 
up to Day 28/ET. Respiratory failure is defined based on resource utilization including 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 
• Extracorporeal membrane oxygenation (ECMO) 
Secondary Endpoints 
The secondary efficacy endpoints are: 
• Proportion of subjects with any use of invasive ventilation through Day 28/early termination 
(ET) 
• 1-month mortality defined as the proportion of subjects who are alive at the Day 28/ET 
visit 


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• Partial pressure of arterial oxygen/percentage of inspired oxygen (PaO2/FiO2) ratio (Arterial 
blood gas [ABG] test will be used to measure PaO2/FiO2 ratio) 
• Time to invasive ventilation (days) 
• Duration of invasive ventilation (days) 
• Duration of time in intensive care unit (ICU) (days) 
• Duration of time in hospital (days) 
• Duration of time requiring O2 nasal cannula (days) 
• Time to return to room air with resting pulse oximeter>93% (days) 
• Peak PaO2/FiO2 ratio 
• Partial pressure of oxygen (PO2)   
• Change in Sequential Organ Failure Assessment (SOFA) score   
• Change in body temperature (see Section 8.9.5) 
Efficacy responses will be assessed at the time points mentioned in the Schedule of Assessments 
(Appendix 1).  
Exploratory Endpoints 
The exploratory efficacy endpoints are: 
• Viral load in nasopharyngeal aspirates 
• LIGHT levels and inflammatory biomarker patterns (InflammationMAP) 
• Plasma concentrations of CERC-002 over time 
• Measurement of anti-drug antibody (ADA). 
6.4 Safety Measures 
Safety and tolerability assessments will include the frequency and severity of AEs as well as the 
evaluation of changes in clinical laboratory values, vital signs, ECG recordings, and physical 
examination findings. 
6.5 Pharmacokinetic Measures 
Blood samples for PK analysis will be collected on Day 2 at 24 hours post dose and at any time 
on Days 8, 14 and 28. A total of 1.0 mL plasma per sample will be collected from each subject 
to measure plasma concentrations of CERC-002. Pharmacokinetic samples will be processed 
according to the methods and directions set forward in the Laboratory Manual(s) and 
guidance(s). Pharmacokinetic plasma sample analysis will be performed by laboratory defined in 
the Laboratory Manual(s) and guidance(s), according to their standard operating procedures 
(SOPs) using a validated enzyme-linked immunosorbent assay (ELISA). Assay and analysis 
details will be described in the method validation and bioanalytical information. 


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6.6 Immunogenicity Measures 
Blood samples for ADA analysis will be collected at any time on Days 8, 14, and 28. 
Additionally, a sample will be collected when an immunologically related adverse event is 
reported. A total of 1.0 mL plasma per sample will be collected from each subject to measure 
plasma concentrations of ADAs. ADA samples will be processed according to the methods and 
directions set forward in the Laboratory Manual(s) and guidance(s). 
6.7 Pharmacodynamic Measures 
Blood samples will also be collected for exploratory analyses of pharmacodynamic endpoints. 
The analyses of pharmacodynamic endpoints will be described separately.  
7 
STUDY POPULATIONS 
7.1 Analysis Populations 
This study will have the following populations of interest: 
• The Randomized Analysis Set will include all subjects who are randomized in the study. 
Subjects will be categorized according to their randomized treatment group. The 
Randomized Analysis Set will be used for all disposition, protocol deviations, and 
demographic and other baseline characteristics analyses. 
• The Safety Analysis Set will include all subjects who are randomized in the study and 
receive at least one dose of investigational product. Subjects will be categorized according to 
treatment actually received. The Safety Analysis Set will be used for all exposure and 
safety analyses. 
• The Full Analysis Set will include all subjects who receive at least one dose of 
investigational product and have a baseline and at least one post-baseline efficacy 
assessment. Subjects will be categorized according to randomized treatment group. The 
Full Analysis Set will be used for all efficacy and pharmacodynamic analyses. 
• The PK Analysis Set will include all subjects who receive at least one dose of 
investigational product and have at least one post dose measurable plasma sample. Subjects 
will be categorized according to their actual treatment group. The PK Analysis Set will be 
used for all PK analyses. 
7.2 Subgroups 
The following subgroups will be explored in the analysis of key efficacy data. 
• Age group (<60 years, ≥60 years)  
• Concomitant corticosteroid use (yes, no) 
(see Section 10.5 for definition of concomitant use) 
Additional subgroup analyses may be conducted by LIGHT levels (categories to be determined) 
– if warranted.  


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8 
DEFINITION OF STUDY VARIABLES 
For each assessment, study day will be calculated as: (i) the date of assessment – the date of 
administration of study drug (for assessments prior to the day of study drug administration) or 
(ii) the date of assessment – the date study drug administration + 1 (for assessments on or after 
the day of study drug administration). As deviations are expected in the number of days from the 
date of dosing (i.e., study day 1) to the study day that planned assessments actually occur, visit 
windows will be used to derive visit numbers for use in efficacy analyses. Analysis windows and 
their associated derived visit numbers are defined in Table 7. 
For all efficacy and safety variables, baseline will be defined as the last assessment prior to the 
administration of study drug Change from baseline values will be calculated as the assessment 
value minus the baseline value. 
8.1 Subject Disposition 
The subject number, consent date, assent date (if applicable), and protocol version number 
enrolled under will be recorded in the electronic case report form (eCRF).  
In addition, study completion status, the completion/discontinuation timeframe, the date of study 
completion or discontinuation, occurrence of Day 28 phone call (Yes/No), date of the Day 28 
phone call, occurrence of Day 60 phone call (Yes/No), date of the Day 60 phone call, and reason 
for discontinuation (if applicable) will be recorded in the eCRF. The completion/discontinuation 
timeframe will be recorded as “Prior to Day 28” or “Day 28”. The reason for discontinuation will 
be recorded as “Subject Withdrew Consent”, “Lost to Follow-up”, “Adverse Event”, “Death”, 
“Study Terminated by Sponsor”, “Non-compliance with Study Procedure/Protocol”, 
“Investigator Decision”, or “Other”. 
8.2 Protocol Deviations 
The failure to meet any inclusion/exclusion criteria at Baseline and the specific criteria not met 
will be recorded in the eCRF. All subject data will be reviewed for the occurrence of protocol 
deviations; identified protocol deviations will be captured by the contract research organization 
(CRO) and identified as important or non-important, and categorized as follows: 
1. Inclusion Criteria 
2. Exclusion Criteria 
3. Study Drug 
4. Assessment – Safety 
5. Lab/ Endpoint Data 
6. Visit Window 
7. Informed Consent (ICF)  
8. Prohibited Co-Medication 
9. Overdose/Misuse 


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10. Other 
8.3 Demographic and Baseline Characteristics 
The date of consent, date of assent, protocol version enrolled under, subject initials, and date of 
birth, gender, race, and ethnicity will be recorded in the eCRF.  
Age at informed consent in years will be derived using SAS as: INTCK(“year”, date of birth, 
date of consent, “continuous”). In addition, the following age groups will be derived: 
• Age group 1: <60 years 
• Age group 2: ≥60 years  
Gender will be recorded as “Female” or “Male”. Race will be recorded as “American Indian or 
Alaska Native”, “Asian”, “Black or African American”, “Native Hawaiian or Other Pacific 
Islander”, “White”, “Multiple”, or “Other”. Ethnicity will be recorded in the eCRF as “Hispanic 
or Latino”, “Not Hispanic or Latino”, “Not reported”, or “Unknown”. 
Other baseline characteristics related to COVID history will be recorded in the eCRF. These 
characteristics include diagnosis date, diagnosis method, and presence (Yes/No) of the following 
symptoms: shortness of breath, cough, fever, chills, myalgia, sore throat, loss of taste, loss of 
smell, and nausea. For those symptoms present at Baseline, the start date and time will also be 
captured. 
8.4 Prior and Concomitant Medications 
For each prior or concomitant medication, the medication name, indication, start date, stop 
date (or ongoing indicator), dose, dose unit, route, and frequency will be recorded in the 
eCRF. Each medication will be coded using the World Health Organization Drug Dictionary 
(WHODrug) March 1, 2018 version or later.  
In addition, the following concomitant medication groups will be derived: 
• Concomitant medication group 1: concomitant corticosteroid use 
• Concomitant medication group 2: no concomitant corticosteroid use  
Concomitant corticosteroid use will include dexamethasone and other steroids used to treat 
COVID. The categorization of concomitant medications into corticosteroid use groups will be 
performed prior to database lock. 
8.5 Concomitant Procedures  
For each concomitant procedure, the procedure name, indication, start date, stop date, 
disease related procedure (Yes/No), and reason for procedure will be recorded in the eCRF. 
8.6 Medical History 
For each subject with significant medical history, the medical condition, start date, ongoing 


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indicator (Yes/No), end date (if applicable), and condition currently being treated indicator 
(Yes/No). The reported medical history condition will be coded using Medical Dictionary 
for Regulatory Affairs (MedDRA) version 21.0 or later. 
8.7 Treatment Exposure 
The date, time, and dose administered will be captured on the eCRF. 
8.8 Efficacy Endpoints 
8.8.1 Alive and Free of Respiratory Failure at Day 28 
For subjects having died during their participation in the study, the date of death, primary cause 
of death, occurrence of death after withdrawal of care (Yes/No), and reason for withdrawal of 
care (if applicable) will be recorded in the eCRF. For subjects experiencing respiratory failure 
during their study participation, the therapy type, start date, start time, stop date, and stop time 
will be recorded in the eCRF. 
The primary cause of death will be recorded as “COVID-19” or “Other”. Respiratory failure 
therapy type will be recorded as “Endotracheal Intubation and Mechanical Ventilation”, 
“Oxygen via High Flow Nasal Cannula”, “Noninvasive Positive Pressure Ventilation”, or 
“Extracorporeal Membrane Oxygenation (ECMO)”. 
The primary endpoint of alive and free of respiratory failure through 28 Days will be derived as: 
• IF the date of death is on or after the date of study drug administration and less than or 
equal to 28 days from the date of study drug administration OR the start date of 
respiratory failure is on or after the date of study drug administration and less than or 
equal to 28 days from the date of study drug administration (and no respiratory failure 
event started prior to study drug administration which is ongoing at study drug 
administration) OR the subject is alive at Day 28 and is receiving a respiratory failure 
therapy type of either “Oxygen via High Flow Nasal Cannula” or “Noninvasive Positive 
Pressure Ventilation” before and on the date of study drug administration and has a 
subsequent respiratory failure therapy record of either “Endotracheal Intubation and 
Mechanical Ventilation” or “Extracorporeal Membrane Oxygenation (ECMO)” after the 
date of study drug administration and less than 28 days from the date of study drug 
administration, THEN set the alive and free of respiratory failure indicator equal to 0. 
• IF the date of death or start date of respiratory failure is greater than 28 days from the 
date of study drug administration OR the completion/discontinuation timeframe = 
“Day 28” OR the completion/discontinuation timeframe = “Prior to Day 28” and the 
occurrence of either the Day 28 or Day 60 phone call = “Yes”, and in none of these cases 
there is a respiratory failure event started prior to study drug administration which is 
ongoing at study drug administration, THEN set the alive and free of respiratory failure 
indicator equal to 1. 
8.8.2  Alive at Day 28 
The alive through Day 28 endpoint will be derived as: 


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• IF the date of death is less than or equal to 28 days from the date of study drug 
administration, THEN set the alive at Day 28 indicator equal to 0. 
• IF the date of death is greater than 28 days after the date of study drug administration OR 
the completion/discontinuation timeframe = “Day 28” OR the completion/discontinuation 
timeframe = “Prior to Day 28” and the occurrence of the Day 28 phone call = “Yes” OR 
the completion/discontinuation timeframe = “Prior to Day 28” and the occurrence of the 
Day 60 phone call = “Yes”, THEN set the alive at Day 28 indicator equal to 1. 
8.8.3 Changes in Arterial Blood Gas (ABG) Values 
The date and time of arterial blood gas sample collection, partial pressure of oxygen (PaO2), 
partial pressure of carbon dioxide (PaCO2), pH, bicarbonate (HCO3), oxygen content (O2CT), 
oxygen saturation (O2Sat), and fraction of inspired oxygen (FiO2) will be collected on the eCRF. 
ABG change from baseline values will be calculated as the assessment value minus the baseline 
value. 
The PaO2/FiO2 ratio will be calculated as the PaO2 value divided by the FiO2 value at each ABG 
assessment. The peak PaO2/FiO2 ratio will be derived as the maximum value of the ratio over the 
ABG assessments at each visit. 
8.8.4 Resource Utilization/Hospitalization/ICU  
The hospital admission date, hospital discharge date, reason for hospital admission, admission to 
ICU (Yes/No), ICU admission date, ICU discharge date, and whether resource limitations 
affected the subject’s COVID-19 treatment (Yes/No) will be recorded in the eCRF. The reason 
for hospital admission will be recorded as “COVID-19” or “Other”. 
Any use of invasive ventilation through Day 28/ET will be derived as: 
• IF at least one respiratory failure therapy type recorded is equal to “Endotracheal 
Intubation and Mechanical Ventilation” or “Extracorporeal Membrane Oxygenation 
(ECMO)” AND the start date of this respiratory failure therapy type is on or after the date 
of study drug administration and less than or equal to 28 days from the date of study drug 
administration, and there is no respiratory failure therapy type recorded equal to 
“Endotracheal Intubation and Mechanical Ventilation” or “Extracorporeal Membrane 
Oxygenation (ECMO)” with a start date prior to date of study drug administration and 
end date on or after the date of study drug administration, THEN set the use of invasive 
ventilation indicator equal to 1. 
• IF there are no respiratory failure therapy type records of “Endotracheal Intubation and 
Mechanical Ventilation” or “Extracorporeal Membrane Oxygenation (ECMO)” where the 
start date of this respiratory failure therapy type is less than or equal to 28 days after the 
date of study drug administration, THEN set the use of invasive ventilation indicator 
equal to 0. 
For those subjects whose use of invasive ventilation indicator is set to 1, time to invasive 
ventilation will be calculated as the earliest date of invasive ventilation minus the date of study 
drug administration + 1. The stop date of invasive ventilation will be defined as the latest date 


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when either respiratory failure therapy type is stopped. The duration of invasive ventilation will 
be calculated as the sum of all the individual durations of invasive ventilation use between Days 
1 and 28. Subjects who did not receive invasive ventilation will have missing time to invasive 
ventilation and duration of invasive ventilation values. 
Duration of time requiring O2 nasal cannula will be calculated as the sum of all the individual 
durations of respiratory failure therapy type equal to “Oxygen via High Flow Nasal Cannula” 
between Days 1 and 28. For any subjects who have respiratory failure therapy type equal to 
“Oxygen via High Flow Nasal Cannula” prior to start of study treatment which is ongoing at start 
of study treatment, the duration will only be counted from the date of study drug administration. 
Subjects who did not have respiratory failure therapy equal to “Oxygen via High Flow Nasal 
Cannula” between Days 1 and 28 will have missing duration of time requiring O2 nasal cannula 
values. 
ICU length of stay will be calculated as the ICU discharge date minus the ICU admission date 
+ 1. If the subject was not discharged from the ICU, the stop date will be defined as the date of 
study discontinuation/completion. For any subjects who have an ICU record prior to start of 
study treatment which is ongoing at start of study treatment, the duration will only be counted 
from day of start of study treatment. Subjects who were not admitted to the ICU will have 
missing ICU length of stay values.  
Hospital length of stay will be calculated as the hospital discharge date minus the hospital 
admission date + 1. If the subject was not discharged from the hospital, the stop date will be 
defined as the date of study discontinuation/completion. For any subjects who have a hospital 
record prior to start of study treatment which is ongoing at start of study treatment, the duration 
will only be counted from day of start of study treatment.  
8.8.5 Pulse Oximetry 
The pulse oximetry collection date, collection time, and result will be recorded in the eCRF.  
Time to return to room air with resting pulse oximeter >93% will be derived as the duration of 
respiratory failure (i.e., the latest stop date for any respiratory failure therapy minus the earliest 
start date for any respiratory failure therapy start date + 1) + the duration of pulse oximetry 
≤93% after the end of respiratory failure (i.e, the date of first pulse oximetry >93% post 
respiratory failure minus the latest stop date of any respiratory failure therapy type). If the 
subject did not return to room air or did not attain pulse oximetry >93%, duration of pulse 
oximetry ≤93% after the end of respiratory failure will be set to zero and the stop date of any 
respiratory therapy will be defined as the date of study discontinuation/completion. Subjects who 
did not have any respiratory failure therapy will have missing time to return to room air values. 
Pulse oximetry change from baseline values will be calculated as the assessment value minus the 
baseline value. 
8.8.6 Sequential Organ Failure Assessment (SOFA) Score 
The SOFA scale is a simple and objective tool to calculate both the number and the severity of 
organ dysfunction in the following 6 organ systems: respiration, coagulation, liver, 


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cardiovascular, central nervous system, and renal, and the scale can measure individual or 
aggregate organ dysfunction [Vincent et al, 1996]), see Table 1 The individual organ system 
scores are assessed using data collected from ABG tests, laboratory tests, vital signs, 
concomitant medications, and the Glasgow Coma Scale; see Table 1 for derivations. For the 
cardiovascular assessment, mean arterial pressure (MAP) will be calculated as the sum of the 
systolic blood pressure (SBP) and 2 times the diastolic blood pressure (DBP) divided by 3. 
The Glasgow Coma Scale assessment date and overall score will be recorded in the eCRF.  
SOFA total scores will be derived for subjects where the required data are available. Subjects 
who did not have the required data will have missing SOFA score values. The SOFA total score 
is calculated as the sum of the 6 organ system scores and ranges from 6 to 24. SOFA total score 
change from baseline values will be calculated as the assessment value minus the baseline value.  
 Table 1: 
The Sequential Organ Failure Assessment (SOFA) 
SOFA Scale 
1 
2 
3 
4 
Respiration 
PaO2/FiO2 (mmHg) 
<400 
<300 
<200 (with  
respiratory support) 
<100 (with respiratory 
support) 
Coagulation 
Platelets × 103/mm3 
<150 
<100 
<50 
<20 
Liver 
Bilirubin (mg/dL) b 
1.2 - 1.9 
2.0 - 5.9 
6.0 - 11.9 
>12.0 
Cardiovasculara 
Hypotension 
MAP 
<70 
mmHg 
Dopamine≤5 or 
dobutamine (any 
dose) 
Dopamine>5 or 
epinephrine≤0.1 or 
norepinephrine≤0.1 
Dopamine>15 or 
epinephrine>0.1 or 
norepinephrine>0.1 
Central Nervous System 
Glasgow Coma Scale 
13 - 14 
10 - 12 
6 - 9 
<6 
Renal 
Creatinine (mg/dL) or 
urine output (mL/day) b 
1.2 - 1.9 
2.0 - 3.4 
3.5 - 4.9 or <500 
>5.0 or <200 
a MAP: mean arterial pressure; PaO2/FiO2: partial pressure of arterial oxygen/percentage of 
inspired oxygen.  
b If value <1.2, SOFA Scale = 0. 
8.8.7 Aspirate Viral Load 
The aspirate viral load test date and result will be recorded in the eCRF.  
Viral load change from baseline values will be calculated as the assessment value minus the 
baseline value. 


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8.9 Safety Endpoints 
8.9.1 Adverse Events 
AEs are collected from the time of the informed consent is signed until the follow-up call is 
completed. For each AE, the following data will be recorded in the eCRF: verbatim text, whether 
AE is a new infection (Yes/No), site of infection, source of culture, whether AE is an 
anaphylactic reaction (Yes/No), start date, stop date (or ongoing), outcome, relationship to study 
drug, CTCAE grade, whether treatment was required (Yes/No), whether AE caused permanent 
discontinuation from study (Yes/No), whether AE was serious (Yes/No), and seriousness criteria. 
The verbatim text will be coded by using MedDRA version 21.0 or later.  
Source of culture will be recorded as “BAL”, “Tracheal Aspirate”, “Sputum”, “Blood”, “Urine”, 
or “Other”. Outcome will be recorded as “Recovered/Resolved”, “Recovering/Resolving”. “Not 
Recovered/Not Resolved”, “Recovered/Resolved With Sequelae”, “Fatal”, or “Unknown”. 
Relationship to investigational product will be recorded as “Not Related”, “Possibly Related”, or 
“Probably Related”. CTCAE grade will be recorded as “Grade 1”, “Grade 2”, “Grade 3”, “Grade 
4”, or “Grade 5”. Seriousness criteria will be recorded as “Death”, “Life-threatening adverse 
experience”, “Persistent or significant disability/incapacitation”, “Inpatient hospitalization or 
prolongation of existing hospitalization”, “Congenital anomaly/birth defect”, or “Other important 
Medical Event”. Descriptions for investigator assessments of CTCAE grading and relationship to 
study drug are shown in Table 2 and Table 3, respectively. 
Treatment emergent AEs (TEAEs) are defined as those AEs occurring or worsening after 
administration of study drug on Day 1 and reported up to Day 28. Imputation rules for partial or 
missing start/stop date for AEs are detailed in Appendix 3. Imputations done for partial or 
missing start/stop dates will be used to classify events as treatment-emergent.  
 
 


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Table 2: 
Assessment of CTCAE Grade 
CTCAE Grade 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; or clinical or diagnostic 
observations only; or intervention not indicated 
Grade 2 
Moderate; or minimal, local or non-invasive intervention indicated; or 
limiting age-appropriate instrumental activities of daily living (ADL) 
Grade 3 
Severe or medically significant but not immediately life-threatening; or 
hospitalization or prolongation of hospitalization indicated; or disabling; 
or limiting self-care ADL 
Grade 4 
Life-threatening consequences 
Grade 5 
Death related to AE 
CTCAE version 5.0 used for grade assessments. 
 
Table 3: 
Assessment of Relationship to Investigational Product 
Relationship 
Description 
Not Related 
Exposure to investigational product has not occurred. 
OR 
The administration of investigational product and the occurrence of the 
AE are not reasonably related in time 
OR 
The AE is considered likely to be related to an etiology other than the 
Possibly Related 
The administration of the investigational product and the occurrence of 
the AE are reasonably related in time. 
AND 
The AE could not be explained equally well by factors or causes other 
than exposure to investigational product. 
Probably Related The administration of investigational product and the occurrence of the AE 
are reasonably related in time. 
AND 
The AE is more likely explained by exposure to investigational product than 
by other factors or causes. 


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8.9.2 Electrocardiograms 
A standard 12-lead ECG is considered standard of care and will be performed daily for those 
who are not being assessed by cardiac monitor. Electronic ECG tracings will be analyzed per the 
site’s practice. In addition, the investigator’s assessment of the ECG tracing as normal or 
abnormal must be documented, and if abnormal, his/her determination of whether the 
abnormality is clinically significant or not will be documented on the tracing. All ECG values 
which, in the investigator’s opinion, show clinically relevant or pathological changes during or 
after termination of the treatment are to be discussed with the Sponsor Medical Monitor and 
reported as AEs. 
The ECG assessment date, time, and interpretation will be recorded in the eCRF. The ECG 
interpretation will be recorded as “Normal”, “Abnormal Not Clinically Significant”, or 
“Abnormal Clinically Significant”. 
8.9.3 Physical Examination/Chest CT/CXR 
A complete physical examination including Chest CT/CXR is considered standard of care and 
will be performed per the site’s practice. Any clinically significant findings are to be reported 
as Medical History or AE depending on timing. For physical exam, the exam date and whether 
there were any clinically significant abnormalities (Yes/No) will be recorded in the eCRF. For 
chest CT/CXR exam, the exam date, test, and whether there were any clinically significant 
abnormalities (Yes/No) will be recorded in the eCRF. CT/CXR test will be recorded as “CT 
Scan” or “CXR”. 
8.9.4 Laboratory Tests 
Laboratory samples are considered standard of care and will be performed per the site’s practice. 
Laboratory specimens will be analyzed at the hospital laboratory per their collection and 
processing requirements. 
For all samples collected, the following data will be recorded in the eCRF: test category (i.e., 
Chemistry, Hematology, and Urinalysis), laboratory name, collection date, collection time, 
laboratory result, unit, and whether abnormal result is clinically significant (Yes/No). For 
pregnancy tests, occurrence of pregnancy test, method, collection date, and result will be 
recorded in the eCRF. Occurrence of pregnancy test will be recorded as “No”, “Yes”, or “N/A 
Subject Male”. Method will be recorded as “Serum” or “Urine”. Result will be recorded as 
“Negative” or “Positive”. 
Laboratory tests collected include: 
Chemistry – albumin (g/L), ALT (U/L), AST (U/L), alkaline phosphatase (U/L), direct bilirubin 
(umol/L), total bilirubin (umol/L), calcium (mmol/L), serum creatinine (umol/L), glucose 
(mmol/L), chloride (mmol/L), potassium (mmol/L), sodium (mmol/L), BUN (mmol/L), 
bicarbonate (mmol/L), LDH (U/L), creatinine kinase (U/L), amylase (U/L), CRP (mg/L), lactate 
or lactic acid (mmol/L). 
Hematology – RBC (cells/L), hematocrit (fraction_of_one), hemoglobin (g/L), platelets (cells/L), 
WBC (cells/L), eosinophils (cells/L), neutrophils) (cells/L), lymphocytes (cells/L), basophils 


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(cells/L), monocytes (cells/L), %eosinophils (fraction_of_one), %neutrophils (fraction_of_one), 
%lymphocytes (fraction_of_one), %basophils (fraction_of_one), %monocytes (fraction_of_one). 
Urinalysis – protein, leuckocytes (cells/uL), pH, specific gravity, glucose (mmol/L), ketones, 
occult blood, bilirubin, nitrite, urobilinogen. 
Laboratory results of chemistry and hematology will be graded according to laboratory 
CTCAE version 5.0 for each laboratory parameter defined in Appendix 5.Laboratory 
CTCAE grading has 5 levels (grade 0 to grade 4). In addition, liver function tests will 
be assessed for meeting potentially clinically important (PCI) criteria as defined in 
Table 3. For a combined PCI criterion to be fulfilled, all conditions have to be fulfilled 
at the same laboratory assessment. 
Table 4: 
Liver Function Potentially Clinically Important Criteria 
Parameter 
Criterion 
ALT 
>3 × ULN; >5 × ULN; >10 × ULN 
AST 
TBL 
>3 × ULN; >5 × ULN; >10 × ULN 
>1 x ULN 
ALT and TBL 
ALT >3 × ULN and TBL >2 × ULN 
AST and TBL 
ALT and AST and 
TBL 
AST >3 × ULN and TBL >2 × ULN 
ALT or AST>3 x ULN and TBL>2 x ULN and ALP>1.5 x ULN 
(Hy’s Law criteria) 
ALT = alanine aminotransferase, AST = aspartate aminotransferase, TBL = total bilirubin, ALP 
= alkaline phosphatase, ULN = upper limit of normal. 
 
The PCS laboratory criteria are provided in Table 5. 
 
 


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Table 5: 
PCS Laboratory Criteria 
Laboratory Parameter 
SI Unit 
Lower Limit 
Upper Limit 
Chemistry 
Creatinine 
umol/L 
 
>194.5 
Sodium 
mmol/L 
≤130 
>150 
Potassium 
mmol/L 
<3.0 
>5.5 
Total bilirubin 
umol/L 
 
>1.5 × ULN 
ALT 
U/L 
 
>3 × ULN 
AST 
U/L 
 
>3 × ULN 
Hematology 
Hemoglobin 
g/L 
<0.8 × LLN and 
>20% decrease from 
baseline 
>1.3 × ULN and 
>30% increase from 
baseline 
Leukocytes 
× 10/9L 
≤2.8 
≥16.0 
Lymphocytes 
× 109/L 
<0.5 
>20 
Neutrophils 
× 109/L 
<1.0 
 
Platelets 
× 109/L 
≤75 
≥700 
ALT = alanine aminotransferase, AST = aspartate aminotransferase, GGT = gamma-glutamyl 
transferase, PCS = potentially clinically significant, LLN=lower limit of normal, ULN=upper 
limit of normal. 
 
Laboratory change from baseline values will be calculated as the post-baseline assessment value 
minus the baseline value. 
 
8.9.5 Vital Signs 
Blood pressure, pulse rate, respiratory rate, temperature, body weight, and height are 
considered standard of care and will be performed per the site’s practice. Additional blood 
pressure and pulse rate measurements may be performed, as determined by the investigator, to 
ensure appropriate monitoring of subject safety and accurate recording of vital sign 
measurements. Any changes from baseline which are deemed clinically significant by the 
investigator are to be recorded as an AE. 
Vital signs assessment date, assessment time, systolic blood pressure (BP), diastolic BP, heart 
rate, respiration rate, body temperature, body temperature unit, weight, weight unit, height, and 
height unit will be recorded in the eCRF. Body temperature unit will be recorded as “C” or “F”. 
Weight unit will be recorded as “kg” or “lb”. Height unit will be recorded as “cm” or “in”. Body 
mass index (BMI) will be calculated in kg/m2 as weight in kg divided by height squared in cm2 
multiplied by 10,000 in cm2/m2. 
Change from baseline values will be calculated as the reported vital sign value minus the 
baseline value. 
PCS criteria will be used to assess PCS vital sign occurrences – see Table 6. 


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Table 6: 
Vital Signs PCS Criteria 
Parameter 
PCS Criterion 
Systolic blood pressure 
 
 
Diastolic blood pressure 
 
 
Pulse Rate 
≤90 mmHg and decrease of >20 mmHg from Baseline 
>180 mmHg and increase of >25 mmHg from Baseline 
 
≤50 mmHg and decrease of ≥15 mmHg from Baseline 
≥105 mmHg and increase of ≥15 mmHg from Baseline 
 
≤50 bpm 
>130 bpm 
 
 
8.10 
Pharmacokinetic (PK) Endpoints 
Blood samples for PK analysis will be collected on Day 2 at 24 hours post dose and at any time 
on Days 8, 14, and 28.  
The occurrence of PK sample collection (Yes/No), collection date, and collection time will be 
recorded in the eCRF. Data transferred from the pharmacokinetics vendor will be combined with 
the eCRF data prior to analysis. 
8.11 
Pharmacodynamic (PD) Endpoints 
 
8.11.1 LIGHT and InflammationMAP 
The occurrence of LIGHT and InflammationMAP sample collection (Yes/No), collection date, 
and collection time will be recorded in the eCRF.  
The derivation of any LIGHT and InflammationMAP endpoints will be described separately. 
8.11.2 Anti-drug Antibody (ADA) 
Blood samples for ADA analysis will be collected at any time on Days 8, 14, and 28. 
Additionally, a sample will be collected when an immunologically related adverse event is 
reported.  
The occurrence of ADA sample collection (Yes/No), collection date, and collection time will be 
recorded in the eCRF.  
The derivation of any ADA endpoints will be described separately. 
8.12 
Visit Windows/Unscheduled Visits 
Schedules of assessments and procedures are included in Appendix 1. For analysis purposes, 
analysis windows will be used to summarize visits as described in Table 7. If 2 or more visits 
occur within the same analysis window, data from the visit with the “worst” or “most extreme” 
value will be used in summaries and/or analyses – see  Appendix 6; all data will be displayed in 
subject listings. 


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Table 7: 
Analysis Windows 
Study Visit 
Analysis Window (Days) 
 Day 1 (Baseline) 
≤1 
 Day 2 
2 – 3 
 Day 5 
4 – 6 
 Day 8 
7 – 8 
 Day 9 
9 – 12 
 Day 14 
13 – 17 
 Day 28/ET 
18 – 28 
 Safety Follow-up Phone Call 
  Day 60 
>28 
9 
OVERALL STATISTICAL CONSIDERATIONS 
9.1 General Conventions 
Efficacy and safety variables will be summarized using descriptive statistics. Descriptive 
statistics for continuous data will include number of subjects (n), mean, standard deviation (SD), 
median, minimum, and maximum. Summaries of change from baseline variables will include only 
subjects who have both a baseline value and corresponding value at the timepoint of interest. 
Descriptive statistics for categorical data will include frequency and percentage.  
Listings will be provided for all collected study data. 
The primary (and key secondary) efficacy analyses will be conducted after all subjects have 
completed up to the 28 day/ET assessments. The timing of the primary endpoint analysis 
has been chosen to allow the active treatment to take effect and to support decision making 
concerning the continued development. The follow-up period is chosen to assess potential 
relapse of symptoms and long-term safety. Top-line results will be issued, to a pre-determined 
Sponsor group, after the 28-day/ET “soft” database lock. The final analysis and summarization 
will be performed after all subjects have completed the EoS visit at Day 60. At the time of the 
soft lock, only the sponsor lead physician and lead statistician will receive patient-level treatment 
assignment data; all other sponsor staff will be “group unblinded” (i.e., no patient listings 
showing actual treatment assignment will be provided). Data related to ongoing AEs, 
medications, and endpoints not available for inclusion in the top-line analyses will be subject to 
change prior to the final database lock. Subjects, investigators, blinded site personnel, 
and monitors will not have access to any “group unblinded” summaries and will remain 
blinded to the individual treatment assignment until the end of the trial. All other sponsor staff 
(study statistician, study programmer, clinical trial team, decision boards etc.) will stay blinded to 
individual treatment assignments (except in the case of a safety event necessitating 
unblinding) until after final database lock, for the analysis of the primary endpoint at 
Day 28/ET. Blinded study monitors will remain blinded throughout the study; unblinded study 
monitors will review pharmacy/IP documentation.  


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All unblinded personnel will otherwise keep randomization lists and data or information that 
could unblind other study team members confidential and secure until “soft” database lock for 
the primary endpoint at Day 28/ET. 
Following final database lock, all roles may have access to unblinded data and/or summaries.  
The clinical trial team is allowed to share unblinded group results with other sponsor staff 
(eg, decision boards) as required for internal decision making on the study or the project at the 
time of the primary analysis at Day 28/ET, while the follow-up period is ongoing for some 
subjects. 
9.2 Handling of Missing Data 
Imputation rules for partial or missing start/stop date for AEs are detailed in Appendix 3. 
Imputations done for partial or missing start/stop dates will only be used to classify events as 
treatment-emergent, while the listings will display the dates as collected on the case report form. 
For these date imputations, an estimated study day will be determined based on the imputation 
rules and will be flagged as such in the listings. 
Imputation rules for partial or missing start/stop date for prior and concomitant medications and 
medical procedures are detailed in Appendix 4. Imputations done for partial or missing start/stop 
dates will only be used to classify medications or medical procedures as concomitant, while the 
listings will display the dates as collected on the case report form. 
Other than above no imputation of missing data will be performed. 
9.3 Interim Analysis 
No formal interim analysis is planned for this study. 
10 STATISTICAL ANALYSIS METHODS 
Descriptive statistics for continuous data will include number of subjects (n), mean, standard 
deviation (SD), median, minimum, and maximum. Summaries of change from baseline variables 
will include only subjects who have both a baseline value and corresponding value at the 
timepoint of interest. Descriptive statistics for categorical data will include frequency and 
percentage. Where appropriate, descriptive statistics may be presented with 90% confidence 
intervals (CIs). 
The minimum and maximum will be reported with the same degree of precision (i.e., the same 
number of decimal places) as the recorded data. Measures of location (e.g., mean and median) 
will be reported to 1 degree of precision more than the recorded data, and measures of spread 
(e.g., standard deviation) will be reported to 2 degrees of precision more than the recorded data. 
Percentages will be displayed with one decimal place and percentages for zero counts will be 
omitted from the presented results. 
Any changes to the analyses that are not included in this SAP will be documented in the CSR. 


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All inferential analyses will use a one-sided alpha of 0.05 to assess statistical significance. 
10.1 
Subject Disposition 
The number of subjects randomized, completed, completing prior to Day 28, completing the 
Day 60 phone call, and discontinued from the study will be summarized by treatment group and 
overall. For those subjects who discontinued the study prematurely, the reason for 
discontinuation will be summarized by treatment group and overall. In addition, the number 
of subjects in each analysis set will also be summarized by treatment and overall.  
In addition, screen failures and reasons for exclusion, will be summarized for all subjects 
screened. 
10.2 
Demographics and Baseline Characteristics 
Demographic and other baseline characteristics will be summarized by treatment group and 
overall using descriptive statistics.  
10.3 
Protocol Deviations 
Reported protocol deviations will be categorized to a deviation category, and mapped to a 
deviation term. Subjects having important protocol deviations will be summarized using counts 
and percentages by deviation category and coded deviation term for the Randomized Analysis 
Set. Subjects will be only counted once within each deviation category and coded deviation term. 
Both important and non-important PDs will be included in subject listings. 
10.4 
Medical History 
Number and percent of patients reporting any medical history by SOC and PT for the  
Randomized Analysis Set will be provided. A patient with multiple medical conditions will 
be counted once per SOC and PT. For computing percentages, the denominator will be the 
number of patients in the  Randomized Analysis Set. The summary table will be sorted by 
descending order of frequency of SOC (then alphabetically for ties), then by descending 
order of frequency of PT within each SOC (then alphabetically for ties), in the CERC-002 
treatment group. 
10.5 
Prior and Concomitant Medications 
Analysis of prior and concomitant medications use will be performed in the following 
manner: 
• Pre-administration (prior) medications: Medications that were administered within 7 days 
prior to the administration of CERC-002 or placebo, regardless if stopped after the 
administration of study drug, will be included for the summary of prior medications. The 
number and percentage of subjects reporting the use of prior medications by ATC Level 3 
and preferred name will be summarized for the Safety Analysis Set. For computing 
percentages, the denominator will be the number of subjects in the Safety Analysis Set.  
• Concomitant medications: Concomitant medications that were administered following the 
administration of CERC-002 or placebo through end of study, regardless if concomitant 
medication initiation was before or after the administration of study drug, will be included 


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for the summary of concomitant medications/procedures. The number and percentage of 
subjects reporting the use of concomitant medications by ATC Level 3 and preferred name 
will be summarized for the Safety Analysis Set. For computing percentages, the denominator 
will be the number of subjects in the Safety Analysis Set. 
10.6 
Concomitant Procedures 
Concomitant procedures are defined as procedures that were reported after study drug 
administration. Concomitant procedures will be listed by subject. 
 
10.7 
Pharmacokinetics 
For all PK variables, descriptive statistics will be presented by collection timepoint 
(where applicable) using the PK Analysis Set. The following statistics will be calculated for 
plasma concentrations: number of subjects, number of subjects with concentrations below the 
level of quantification (BLQ), arithmetic mean, standard deviation, coefficient of variation, 
median, minimum, and maximum. 
For descriptive summaries, plasma concentrations reported as BLQ will be set to zero. 
10.8 
Immunogenicity  
ADA levels will be reported separately. 
10.9 
Pharmacodynamics  
LIGHT levels and inflammatory biomarker patterns (InflammationMAP) will be reported 
separately. 
10.10 Treatment Compliance and Exposure 
Exposure to investigational product will be summarized by treatment group using 
descriptive statistics. 
11 EFFICACY PARAMETERS 
11.1 
Primary Analysis 
The proportion of subjects alive and free of respiratory failure through Day 28/ET will be 
presented by treatment group. In addition, the proportion of subjects alive and free of respiratory 
failure at Day 28/ET in the CERC-002 group will be compared to that in the placebo group using 
logistic regression methods. The logistic regression model will include terms for treatment 
group. The comparison of interest will be the difference between the CERC-002 and placebo 
treatment groups. Model based point estimate (i.e., odds ratio), 90% confidence interval, and 
one-sided p-value will be reported. SAS Proc Logistic will be run with the Wald chi-square 
statistic used to assess the statistical significance of the treatment effect.  
11.2 
Secondary Analyses 
The proportion of subjects alive at Day 28/ET will be presented by treatment group. In 
addition, the proportion of subjects alive at Day 28/ET in the CERC-002 group will be 
compared to that in the placebo group using similar logistic regression methods as described for 
the primary endpoint. 


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For continuous variables collected at multiple post-baseline timepoints, mixed model repeated 
measures (MMRM) methods will be used to compare treatment groups over time. The MMRM 
model will include the corresponding change from baseline as the dependent variable and 
baseline, treatment, timepoint, and timepoint*treatment interaction as fixed effects. An 
unstructured residual covariance matrix between visits within subject will be assumed if 
possible; otherwise, another appropriate covariance structure will be used. Model based point 
estimates (i.e., least square [LS] means for each treatment group and the treatment difference), 
90% confidence interval for the difference, and p-value will be reported for each visit.  
For time to event and duration of response (days) endpoints, the Wilcoxon rank sum test will be 
used to compare treatment groups, with the Hodges-Lehmann estimator used to obtain the 
median difference and associated 90% CIs.  
If the data warrants, Kaplan-Meier analyses of time to event endpoints (invasive ventilation, 
return to room air with resting pulse oximeter >93%) may be performed to compare treatment 
groups.  
Dichotomous variables will be analyzed using logistic regression as described for the primary 
analysis.  
No adjustment for multiple testing will be done.  
Key secondary efficacy analyses (see Appendix 2) will be included in the top-line outputs 
generated after the soft-lock at Day 28/ET (see Section 9.1). 
11.3 
Sensitivity Analyses 
No sensitivity analyses are planned. If a large number of subjects (eg, 20% or more) has major 
protocol violations, a Per Protocol Analysis Set may be defined and used to re-run the primary 
and key secondary efficacy analyses. Subjects in the Per Protocol Analysis Set will be 
categorized according to treatment actually received. 
11.4 
Exploratory Analyses 
Viral load in nasopharyngeal aspirates will be summarized by treatment group and time point. 
11.5 
Interim Analysis 
No formal interim analysis is planned for this study. 
11.6 
Subgroup Analyses 
The following subgroups will be included in the analysis of the primary efficacy parameter and 
may be used for key secondary efficacy data. 
• Age group (<60, ≥60 years) 
• Concomitant corticosteroid use (yes, no) 


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12 SAFETY AND TOLERABILITY 
12.1 
Adverse Events 
AEs will be recorded from the time a subject has signed the informed consent until end of study. 
Each verbatim AE term will be coded to a system organ class (SOC) and preferred term (PT) 
using the Medical Dictionary for Regulatory Activities (MedDRA) dictionary version 21.0 or 
later. 
The overall incidence of subjects having at least one AE will be summarized by treatment 
group. The incidence of TEAEs will be summarized by treatment group, system organ class 
and preferred term. Each subject will be counted only once per SOC and preferred term.  
AE incidence will be presented as the number and percentage of subjects with a specific AE.  
If there is more than one occurrence of an event, the event with the worst severity or the highest 
rated causality category will be summarized. 
Summaries of AEs by SOC and PT will be sorted alphabetically for SOC within CERC-002, then 
by descending order of frequency of PT within each SOC (then alphabetically for ties). 
Summaries of AEs by PT will be sorted by descending order of frequency of PT, then 
alphabetically for ties. 
Overall Summary of AEs 
An AE overview containing the number of unique subjects and percentages will be provided for 
the following categories: 
• Any AEs 
• Any serious AEs 
• Any TEAEs 
• Any study drug related TEAEs 
• Any TEAEs leading to infection 
• Any TEAEs leading to study discontinuation 
• Any study drug related TEAEs leading to study discontinuation 
• Any TEAEs by maximum CTCAE grade (mild, moderate, severe or medically significant, 
life-threatening, or death) 
• Any serious TEAEs 
• Any study drug related serious TEAEs 
• Any TEAEs leading to death 
• Any serious TEAEs by maximum CTCAE grade (mild, moderate, severe or medically 
significant, life-threatening, or death) 
Summary of AEs by SOC and PT 
The following will be summarized by SOC and PT: 


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• Incidence of serious AEs  
• Incidence of TEAEs 
• Incidence of study drug related TEAEs 
• Incidence of TEAEs leading to infection 
• Incidence of TEAEs leading to study discontinuation.  
• Incidence of study drug related to TEAEs leading to study discontinuation 
• Incidence of TEAEs by worst severity (mild, moderate, severe or medically significant, life-
threatening, or death) 
• Incidence of Serious TEAEs 
• Incidence of study drug related serious TEAEs 
• Incidence of TEAEs leading to death 
• Incidence of serious TEAEs by worst severity (mild, moderate, severe or medically 
significant, life-threatening, or death) 
Data listings of all AEs (including TEAEs and non-TEAEs), all serious AEs (including serious 
TEAEs and serious non-TEAEs), and TEAEs leading to death will be provided. 
12.2 
Electrocardiograms 
All ECG results will be listed by subject 
12.2 
Laboratory Tests 
 
12.3.1 Laboratory Values and Changes Over Time 
Observed values of continuous chemistry, hematology, and urinalysis (specificity and pH) 
laboratory parameters at selected timepoints, and change from baseline in these parameters at 
each postbaseline time point, will be summarized descriptively. All laboratory test data will be 
listed by subject. 
12.3.2 Shift from Baseline to Post-Baseline Laboratory Results 
Shift tables for hematology and chemistry laboratory parameters, using laboratory CTCAE 
version 5.0 grading showing changes from baseline to post-baseline values will be summarized 
using counts and percentages. For a specific laboratory parameter, subjects with both baseline 
and a postbaseline value will be included for shift summaries. For computing percentages, the 
denominator will be the number of subjects in the treatment group. 
The number and percentage of subjects meeting criteria for abnormal liver function tests (LFTs) 
will be summarized by treatment group and time point. For computing percentages, the 
denominator will be the number of subjects with a postbaseline value for the specific laboratory 
parameter and the respective time point. Error! Reference source not found.Only subjects with 
newly occurring values (at least one postbaseline measurement and meeting the criterion but not 
meeting the criterion at baseline) will be counted.  


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12.3.3 Potentially Clinically Significant Laboratory Values 
The number and percentage of subjects meeting PCS criteria for laboratory values at selected 
timepoints will be presented by treatment group. For computing percentages, the denominator 
will be the number of subjects with a postbaseline value for the specific laboratory parameter, 
except for hemoglobin that requires subjects with a baseline and a post-baseline value at the 
respective time point.  
12.4 
Vital Signs 
12.4.1 Vital Sign Values and Changes Over Time 
Observed values of SBP, DBP, respiratory rate, temperature, and body weight at baseline, and at 
selected post-baseline timepoints, and change from baseline in these parameters at each post-
baseline time point, will be summarized descriptively by treatment group. 
12.4.2 Potentially Clinically Significant Vital Sign Values 
The number and percentage of subjects meeting PCS criteria for SBP and DBP at selected 
timepoints will be presented by treatment group. For computing percentages, the denominator 
will be the number of subjects with a postbaseline value for the specific vital sign parameter and 
the respective time point. The PCS criteria are shown in Table 6. 
 
 


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13 OTHER RELEVANT DATA ANALYSES/SUMMARIES 
Not applicable. 
14 DATA MONITORING COMMITTEE 
An external, independent DMC comprising physicians, scientists and a biostatistician will 
review the study data at intervals defined in the DMC charter and will monitor the trial for 
safety signals. 
Safety monitoring will be performed continuously throughout the study in accordance with 
the protocol and DMC charter. The DMCs role is to protect the interests of the subjects in the 
study and those still to be entered in the study by reviewing cumulative data. The DMCs 
meeting schedule may be adjusted based on recommendations made by the DMC, the 
amount of incremental safety data, and other practical considerations. The data provided to the 
DMC may not be monitored and will not be considered “clean” until the database is locked at 
the completion of the study. 
A set of blinded (aggregate data only) and unblinded outputs (by treatment) will be generated for 
the DMC. These outputs are defined in the DMC Charter and are a subset of those to be 
generated for the CSR at the end of the study. No unblinded outputs will be available to the study 
team prior to all subjects have completed Day 28 assessments. 
15 CHANGES TO PLANNED ANALYSES  
15.1 
Changes to Analyses Specified in Protocol 
In Section 10.3.1 of the protocol, an AE is defined as treatment-emergent “if it occurs after the 
first dose of investigational product and within 30 days of a subject’s last dose of investigational 
product.”  This text has been modified in SAP Section 8.9.1 to more accurately describe the 
derivation given that only a single dose of study drug is to be administered.  
The proportion of subjects with any use of invasive ventilation through Day 28/ET was added as 
a secondary endpoint to supplement the time to invasive ventilation endpoint as defined in 
Section 7.2.2 of the protocol. This endpoint also closely matches that used in other ongoing 
COVID-19 studies.  
The duration of time requiring O2 nasal cannula is confirmed as a secondary endpoint in SAP 
Section 8.8.4. This endpoint was mentioned in the Endpoints and Criteria for Evaluation 
sections of the protocol synopsis, but was inadvertently omitted in Section 7.2.2 of the protocol. 
15.2 
Changes to Approved Prior Versions of the SAP 
Not applicable. 
 


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16 REFERENCES 
1. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) 
score to describe organ dysfunction/failure. On behalf of the Working Group on 
Sepsis -Related Problems of the European Society of Intensive Care Medicine. Intensive 
Care Med. 1996;22(7):707–710. 


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17 APPENDICES 


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Appendix 1 
Schedule of Assessments  
Procedure 
Baselin
e 
(Day 1) 
Day 
2 
Day 
5 
Day 
8 
Day 
9 
Day 
14 
Day 
28/ET1 
Safety 
Follow-up 
Phone Call 
Day 602 
Informed consent and 
assent (as applicable) 
X 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
Concomitant 
medications3 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events4 
X 
X 
X 
X 
X 
X 
X 
X 
Viral load in 
nasopharyngeal 
aspirates9  
X 
 
X 
 
 
 
 
 
ECG7 
X 
X 
X 
X 
X 
X 
X 
 
Pregnancy test10 
X 
 
 
 
 
 
 
 
PK  
 
X6 
 
X 
 
X 
X 
 
LIGHT and 
InflammationMAP 
X5 
X6 
X 
X 
X 
X 
X 
 
ADA8 
 
 
 
X 
 
X 
X 
 
Investigational 
product 
administration 
X 
 
 
 
 
 
 
 
Abbreviations: ADA = antidrug antibodies; ECG = electrocardiogram; ET = early termination; 
InflammationMAP = inflammatory biomarker patterns; LIGHT = Lymphotoxin-like, exhibits 
Inducible expression, and competes with Herpes Virus Glycoprotein D for Herpesvirus Entry 
Mediator, a receptor expressed by T lymphocytes; PK = pharmacokinetics. 
1. Day 28 is to be conducted as a follow-up call for subjects who are discontinued from the study 
and for subjects who are discharged prior to the Day 28 visit. Additionally, if a subject is 
discontinued from the study or is discharged from the hospital prior to Day 28, the Day 28/ET 
visit procedures should be performed. No further visits will be required to be performed with 
the exception of the Day 28 and Day 60 follow-up calls. 


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2. A safety follow-up call to be conducted approximately 52 days after the last dose of 
investigational product. 
3. Concomitant medications to be collected throughout the study period.  
4. Adverse events to be collected throughout the study period.  
5. Sample to be collected prior to investigational product administration.  
6. Sample to be collected 24 hours (± 2 hours) post Day 1 dosing.  
7. An ECG will be collected daily when a subject is not being assessed by cardiac monitoring. 
8. An ADA sample will be collected at Days 8, 14, 28/ET. Additionally, a sample is to be 
collected when an immunologically related adverse event is reported (e.g., a skin reaction, lupus-
like syndrome, unexplained thrombocytopenia). 
9. If the site is unable to do a quantitative test in order to obtain viral load, the viral load samples 
to be collected at Days 1 and 5 are not required to be collected. 
10. For females of childbearing potential. A subject is not considered to be of childbearing 
potential if they are post-menopausal (12 consecutive months of spontaneous amenorrhea and ≥ 
age 51 years, and/or surgically sterile (having undergone one of the following surgical acts:  
hysterectomy, bilateral tubal ligation, bilateral oophorectomy or bilateral salpingectomy) and at 
least 6 weeks post-sterilization. 
 


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Appendix 2 
Summary of Efficacy Analyses 
Parameter 
Analysis Set 
Statistical Method 
Interpretation 
Alive and free of 
respiratory failure up 
to Day 28/ET 
Full 
Logistic regression; 
CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Primary analysis 
The proportion of 
subjects with any use 
of invasive ventilation 
through Day 28/ET 
 
Full 
Logistic regression; 
CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Key Secondary analysis 
Alive at the Day 
28/ET visit 
Full 
Logistic regression; 
CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Key Secondary analysis 
Time to invasive 
ventilation at defined 
study milestones 
(days) 
Full 
Wilcoxon rank sum 
test; CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Key Secondary analysis 
Duration of invasive 
ventilation (days) 
Full 
Wilcoxon rank sum 
test; CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Key Secondary analysis 
Time to return to room 
air with resting pulse 
oximeter>93% (days) 
Full 
Wilcoxon rank sum 
test; CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Key Secondary analysis 
Intensive care unit 
(ICU) length of stay 
(days) 
Full 
Wilcoxon rank sum 
test; CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Secondary analysis 
Hospital length of stay 
(days) 
Full 
Wilcoxon rank sum 
test; CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Secondary analysis 
Change in partial 
pressure of arterial 
oxygen/percentage of 
inspired oxygen 
(PaO2/FiO2) ratio at 
defined study 
milestones 
Full 
 
MMRM 
ANCOVA; CERC-
002 vs. Placebo; 
alpha = 0.05 one-
sided 
Key Secondary analysis 
 
 
 


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Parameter 
Analysis Set 
Statistical Method 
Interpretation 
Peak PaO2/FiO2 ratio 
Full 
MMRM 
ANCOVA; CERC-
002 vs. Placebo; 
alpha = 0.05 one-
sided 
 Secondary analysis 
Partial pressure of 
oxygen (PO2) change 
from baseline to end 
of study 
Full 
ANCOVA; CERC-
002 vs. Placebo; 
alpha = 0.05 one-
sided 
Key Secondary analysis 
Change in Sequential 
Organ Failure 
Assessment (SOFA) 
score from baseline to 
defined study 
milestones 
Full 
MMRM 
ANCOVA; CERC-
002 vs. Placebo; 
alpha = 0.05 one-
sided 
Secondary analysis 
Change in body 
temperature from 
baseline to defined 
study milestones 
Full 
MMRM 
ANCOVA; CERC-
002 vs. Placebo; 
alpha = 0.05 one-
sided 
Secondary analysis 
Duration of time 
requiring O2 nasal 
canula (days) 
Full 
Wilcoxon rank sum 
test; CERC-002 vs. 
Placebo; alpha = 
0.05 one-sided 
Secondary analysis 
Viral load in 
nasopharyngeal 
aspirates 
Full 
Descriptive 
Exploratory analysis 
 
 


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Appendix 3 
Imputation Rules for Missing or Partial Dates for AEs  
Date 
Situation 
Imputation Rule 
AE Start Date 
Only month and year are known and month 
and year are prior to first dose date  
Use the first day of the 
month 
Only month and year are known and month 
and year are the same as first dose date 
Use the first administration 
date 
Only month and year are known and month 
and year are after first dose date 
Use the first day of the 
month 
Only year is known and year is before first 
dose date 
Use Jan 1 of that year 
Only year is known and year is after first 
dose date 
Use Jan 1 of that year 
AE End Date 
Only month and year are known and month 
and year are prior to last dose date  
Use the last day of the month 
Only month and year are known and month 
and year are the same as last dose date 
Use the last observed date 
Only month and year are known and month 
and year are after last dose date 
Use the last day of the month 
Only year is known and year is before last 
dose date 
Use Dec 31 of that year 
The estimated stop date is before a complete 
or imputed AE start date 
Use the last day of the month 
of the AE start date 
AE = adverse event. 
Note: The imputation of end date must be later than start date. 
 
 


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Appendix 4 
Imputation Rules for Missing or Partial Dates for Prior and 
Concomitant Medications and Medical Procedures 
Imputation rules for missing or partial dates (D = day, M = month, Y = year, T = time) 
Parameter 
Missing 
Additional conditions 
Imputation Rule 
Start date  
D only 
M and Y same as M and Y of 
administration of study drug 
Date of administration of study 
drug 
M and/or Y not same as M and Y 
of administration of study drug 
First day of month 
M and D Y same as Y of administration of 
study drug 
Date of administration of study 
drug 
Y not same as Y of administration 
of study drug 
Use Jan 01 of Y 
M, D, 
and Y 
None--date completely missing 
Date of administration of study 
drug 
Stop date  
D only 
M and Y same as M and Y of last 
observation 
Date of last observation 
M and/or Y not same as M and Y 
of last observation 
Last day of month 
M and D Y same as Y of last observation 
Date of last observation 
Y not same as Y of last 
observation 
Use Dec 31 of Y 
M, D, 
and Y 
None--date completely missing 
Date of last observation 
 
 


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Appendix 5 
Laboratory CTCAE Grade Version 5.0 Criteria 
Lab 
Parameter 
SI Unit 
CTCAE Grade v5.0 
Grade 
0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
decreased 
(Anemia) 
g/L 
≥LLN 
100 – 
<LLN 
80 – <100 
<80 
 
Hemoglobin 
increased  
g/L 
≤ULN 
>ULN – 2 
x ULN 
>2 x ULN 
– 4 x ULN 
>4 x ULN 
 
Hypoglycemi
a (Glucose 
decreased) 
mmol/L 
≥LLN 
3.0525 –  
<LLN  
2.22 –  
<3.0525  
1.665 –  
<2.22   
<1.665  
Glucose 
(hyperglycemi
a) 
mmol/L 
LLN – 
ULN 
>ULN – 
8.88 
>8.88 – 
13.875 
>13.875 –
27.75 
>27.75 
Albumin 
g/L 
≥LLN 
<LLN – 
30 
<30 – 20 
<20 
Life-
threatening 
consequenc
es; urgent 
intervention 
indicated 
Alkaline 
phosphatase 
 
≤ULN 
>ULN – 
2.5 × ULN 
>2.5 – 5.0 
ULN 
>5.0 – 20.0 
ULN 
>20.0 x 
ULN 
Alanine 
aminotransfer
ase increased 
U/L 
≤ULN 
>ULN – 
3 × ULN 
>3 × ULN 
– 
 5 × ULN 
>5 × ULN – 
20 × ULN 
>20 × ULN 
Aspartate 
aminotransfer
ase increased 
U/L 
≤ULN 
>ULN – 
3 × ULN 
>3 × ULN 
– 
 5 × ULN 
>5 × ULN – 
20 × ULN 
>20 × ULN 
Blood 
bilirubin 
increased 
umol/L 
≤ULN 
>ULN – 
1.5 × ULN 
>1.5 × 
ULN – 3 
× ULN 
>3 × ULN – 
10 × ULN 
> 10 × ULN 
Creatinine 
increased 
umol/L 
≤ULN 
>ULN – 
1.5 × ULN 
>1.5 × 
ULN – 3 
× ULN 
>3 × ULN – 
6 × ULN 
> 6 × ULN 
Calcium 
(hypocalcemi
a) 
mmol/L 
LLN – 
ULN 
<LLN – 
2.0 
<2.0 – 1.8 
<1.8 – 1.5 
<1.5 
Calcium 
(hypercalcemi
a) 
mg/dL 
LLN – 
ULN 
>ULN – 
2.9 
>2.9 – 3.1 
>3.1 – 3.4 
>3.4 
 
 
 
 
 
 
 


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Lab 
Parameter 
SI Unit 
CTCAE Grade v5.0 
Grade 
0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Eosinophils 
increased 
× 109/L 
≤ULN 
>ULN and 
>Baseline 
Lymphocyte 
count 
decreased 
× 109/L 
≥LLN 
0.8 –  
<LLN 
0.5 –  
<0.8 
0.2 – <0.5 
<0.2 
Lymphocyte 
count 
increased 
× 10
9/L 
 4  
 
 
>4 - 20 
>20 
 
Neutrophil 
count 
decreased 
× 10
9/L 
≥LLN 
≤LLN 
≤1.5 
0.5 – <1.0 
<0.5 
Platelet count 
decreased 
× 10
9/L 
≥LLN 
75 –  
<LLN 
50– <75 
25 – <50 
<25 
White blood 
cell decreased 
× 109/L 
≥LLN 
3 – <LLN 
2 – <3 
1 – <2 
<1 
White blood 
cell increased 
(eukocytosis) 
× 109/L 
≤10  
 
 
 
>10 
 
Hyperkalemia 
(Potassium 
increased) 
mmol/L 
≤ULN 
>ULN – 
5.5  
>5.5 – 6.0  
>6.0 – 7.0  
>7.0  
Hypokalemia 
(Potassium 
decreased) 
mmol/L 
≥LLN 
3.0 –  
<LLN  
Symptoma
tic with 
3.0 – 
 <LLN  
2.5 – <3.0  
<2.5  
Hypernatremi
a (Sodium 
increased) 
mmol/L 
≤ULN 
>ULN – 
150  
>150 – 
155  
>155 – 160  
>160  
Hyponatremia 
(Sodium 
decreased) 
mmol/L 
≥LLN 
130 – 
<LLN   
125 –  
<130  
120 – <125  
<120  
 


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Appendix 6 
Identification of Extreme Value at Visits 
Parameter 
Analysis Value for 
Summarization/Analysis 
Efficacy 
 
Change in partial pressure of arterial 
oxygen/percentage of inspired oxygen 
(PaO2/FiO2) ratio  
Lowest level  
PaO2/FiO2 ratio 
Lowest ratio  
FIO2 
Lowest 
O2CT 
Lowest 
Partial pressure of oxygen (PO2) change from 
baseline 
Lowest 
PCO2 
Lowest 
Change in Sequential Organ Failure 
Assessment (SOFA) scale 
Highest score 
Change in body temperature 
Highest  
Viral load in nasopharyngeal aspirates 
Will only be done twice in the protocol 
Pulse Oximetry 
Lowest level 
Arterial Blood Gas (ABG) 
Out of this will get PO2 – lowest 
Glasgow Coma Scale 
Lowest 
Vital signs 
 
SBP 
Lowest 
DBP 
Lowest 
Pulse rate 
Highest  
Respiratory rate 
Highest 
Weight 
Will only be done once per day 
Body temperature 
Highest 
Laboratory Parameters 
 
Albumin 
Lowest (prob only once per day) 
ALT 
Highest (prob only once per day) 


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AST 
Highest (prob only once per day) 
Alkaline phosphatase 
Highest (prob only once per day) 
Direct bilirubin 
Highest (prob only once per day) 
Total bilirubin 
Highest (prob only once per day) 
Calcium 
Highest (prob only once per day) 
Serum creatinine 
Highest (prob only once per day) 
Glucose 
Highest  
Chloride 
Highest (prob only once per day) 
Potassium 
Lowest (prob only once per day) 
Sodium 
Highest (prob only once per day) 
BUN 
Highest (prob only once per day) 
Bicarbonate 
Highest (prob only once per day) 
LDH 
Highest (prob only once per day) 
Creatinine kinase 
Highest (prob only once per day) 
Amylase 
Highest (prob only once per day) 
CRP 
Highest (prob only once per day) 
Lactate 
Highest (prob only once per day) 
RBC 
Lowest (prob only once per day) 
Hematocrit 
Lowest (prob only once per day) 
Hemoglobin 
Lowest (prob only once per day) 
Platelets 
Lowest (prob only once per day) 
WBC 
Either waya (prob only once per day) 
Neutrophils 
Either waya (prob only once per day) 
Eosinophils 
Highest (prob only once per day) 
Lymphocytes 
Either waya (prob only once per day) 
Basophils 
Either waya (prob only once per day) 
Monocytes 
Highest (prob only once per day) 


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Protein 
Lowest (prob only once per day) 
Leukocytes 
Either waya (prob only once per day) 
pH 
Either waya (prob only once per day) 
Specific gravity 
Either waya (prob only once per day) 
Urine glucose 
Highest (prob only once per day) 
Urine protein 
Lowest (prob only once per day) 
Urine WBC 
Either waya (prob only once per day) 
Occult blood 
Highest (prob only once per day) 
Ketones 
Highest (prob only once per day) 
Urine bilirubin 
Highest (prob only once per day) 
Urine nitrite 
Highest (prob only once per day) 
Urobilinogen 
Highest (prob only once per day) 
 
a Maximum absolute difference between observed value and low normal and high normal limits; 
if equal, high value will be chosen; if normal limits not available, value most different from 
baseline value will be chosen; if baseline missing or if equal, high value will be chosen.