Conditions: Respiratory Distress Syndrome, Adult
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 39
Healthy volunteers: no

Brief summary:
To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-2 Infection by assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 22. Respiratory failure is defined as non-invasive ventilation or high-flow oxygen, intubation and mechanical ventilation, or ventilation with additional organ support (e.g., pressors, RRT, ECMO).

Detailed description:
This study is a multicenter, randomized, placebo-control, efficacy and safety study of VERU-111 for the treatment of COVID-19. Subjects will receive either 18 mg of VERU-111 or matching placebo orally or through nasogastric tube daily for to 21 days or until the subject is discharged from the hospital, whichever comes first.

The primary efficacy endpoint of the study will be the proportion of subjects that are alive without respiratory failure at Day 22. Respiratory failure is defined as non-invasive ventilation or high-flow oxygen, intubation and mechanical ventilation, or ventilation with additional organ support (e.g., pressors, RRT, ECMO).

The total study duration for a subject from screening to follow up visit is planned to be 62 days.

An evaluation of the effect of VERU-111 on SARS-CoV-2 (COVID-19) compared to the placebo control will be evaluated after the last subject has completed Day 22. This will allow for the decision to move to Phase 3 more quickly if the Phase 2 portion of the study shows a clinically relevant difference in the proportion of subjects that are alive without respiratory failure at Day 22 in the VERU-111 treated groups compared to the Placebo treatment group and VERU-111 is well tolerated in the study.

Arms:
arm 1: Veru-111 18mg capsules arm 2: Placebo capsules

Interventions: intervention 1: Veru-111
Intervention descriptions: intervention 1: Respiratory Distress Syndrome, Adult

Protocol document:
SAP_002.pdf: 
Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
REF: Worldwide-TMP-QA-001f-1.3 
 
Page 1 of 36 
Statistical Analysis Plan 
Title: Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for the 
Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 
in Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS) 
Protocol Number: V0211901 
Protocol Version: 1.0 / 23-APR-2020 
2.0 / 05-MAY-2020 
3.0 / 12-MAY-2020 
4.0 / 04-JUN-2020 
5.0 / 17-JUN-2020 
6.0 / 10-JUL-2020 
7.0 / 25-SEP-2020 
 
SAP Version 2.0 
SAP Issue Date: 09-FEB-2021 
SAP Author: Tuomas Kemppainen, MSc 
 
Previous SAP Versions 
 Version 1.0 / 04-JAN-2021 
Version 2.0 / 04-FEB-2021 
 
 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
REF: Worldwide-TMP-QA-001f-1.3 
 
Page 2 of 36 
SAP Amendments before database lock 
Version  Issue Date 
Section 
Revision / Addition 
Rationale 
1.0 
04-JAN-2021 
 
 
First version 
2.0 
04-FEB-2021 
6.1.3 
 
 
6.12.1 
 
6.12.2.1 
 
 
 
 
 
 
6.12.2.4 
6.12.2.5 
 
6.12.2.9 
11 
ITT population updated to 
include all randomized 
subjects. 
Added responder rate 
analysis. 
Updated baseline 
definition for WHO 
Ordinal Scale and added 
note that LOCF will be 
used for all missing data. 
Added also sensitivity 
analysis 
Added sensitivity analysis. 
Added responder rate 
analysis. 
Added sensitivity analysis. 
Updated list of outputs 
with the above additions. 
Updates based on FDA 
feedback on the SAP. 
3.0 
09-FEB-2021 
6.1.5 
Updated EE population. 
Update during subject 
evaluability. 
 
 
 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
REF: Worldwide-TMP-QA-001f-1.3 
 
Page 3 of 36 
Table of Contents 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................... 5 
1 
INTRODUCTION ............................................................................................... 6 
2 
STUDY OBJECTIVES ....................................................................................... 6 
2.1 
Primary Objective ........................................................................................................... 6 
2.2 
Secondary Objectives...................................................................................................... 7 
2.3 
Safety Objectives ............................................................................................................ 7 
3 
ENDPOINTS ....................................................................................................... 7 
3.1 
Primary Endpoint ............................................................................................................ 7 
3.2 
Secondary Endpoints ...................................................................................................... 8 
4 
SAMPLE SIZE ..................................................................................................10 
5 
RANDOMIZATION .........................................................................................10 
6 
PLANNED ANALYSES ...................................................................................10 
6.1 
Analysis Populations ..................................................................................................... 10 
6.1.1 
Enrolled Population ................................................................................................ 10 
6.1.2 
Randomized Population .......................................................................................... 10 
6.1.3 
Intent-to-Treat (ITT) Population ............................................................................. 10 
6.1.4 
Modified Intent-to-Treat (mITT) Population .......................................................... 10 
6.1.5 
Efficacy Evaluable (EE) Population ....................................................................... 11 
6.2 
Derived Data ................................................................................................................. 11 
6.2.1 
Baseline ................................................................................................................... 11 
6.2.2 
Duration / Study Day / Time ................................................................................... 11 
6.2.3 
Conventions for Missing and Partial Dates ............................................................ 11 
6.2.4 
Missing / Partial Start / Stop Date of Concomitant Medications ............................ 11 
6.2.5 
Missing Last Dates of Study Drug Dosing ............................................................. 12 
6.2.6 
Missing Diagnosis Dates......................................................................................... 12 
6.2.7 
Exposure to Study Drug .......................................................................................... 13 
6.2.8 
Inexact Values ......................................................................................................... 13 
6.2.9 
Unscheduled Visits ................................................................................................. 13 
6.3 
Conventions .................................................................................................................. 13 
6.3.1 
Decimal Places ........................................................................................................ 14 
6.4 
Subject Disposition ....................................................................................................... 14 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
REF: Worldwide-TMP-QA-001f-1.3 
 
Page 4 of 36 
6.5 
Protocol Deviations ....................................................................................................... 14 
6.6 
Baseline Comparability ................................................................................................. 15 
6.7 
Medical History ............................................................................................................ 15 
6.8 
Prior and Concomitant Medications ............................................................................. 15 
6.9 
Exposure to Study Drug ................................................................................................ 16 
6.10 
Treatment Compliance .................................................................................................. 16 
6.11 
Dosing of Standard of Care........................................................................................... 16 
6.12 
Efficacy Analyses ......................................................................................................... 16 
6.12.1 
Primary Endpoint .................................................................................................... 16 
6.12.2 
Secondary Endpoints .............................................................................................. 18 
6.12.3 
Exploratory Endpoints ............................................................................................ 23 
6.12.4 
Multiplicity ............................................................................................................. 23 
6.13 
Pharmacokinetic Analyses ............................................................................................ 23 
6.14 
Pharmacodynamic Analyses ......................................................................................... 24 
6.15 
Safety Analyses ............................................................................................................. 24 
6.15.1 
Adverse Events ....................................................................................................... 24 
6.15.2 
Laboratory Data ...................................................................................................... 25 
6.15.3 
Vital Signs ............................................................................................................... 26 
6.15.4 
Physical Examination.............................................................................................. 26 
6.15.5 
Electrocardiogram Data .......................................................................................... 26 
6.15.6 
Chest X-Ray / Computed Tomography (CT).......................................................... 27 
6.15.7 
Pregnancy Test ........................................................................................................ 27 
7 
INTERIM ANALYSIS ......................................................................................27 
8 
DATA SAFETY MONITORING BOARD ANALYSIS .................................27 
9 
CHANGES TO PLANNED PROTOCOL ANALYSIS ...................................27 
10 REFERENCES ..................................................................................................29 
11 LIST OF TABLES, FIGURES AND LISTINGS .............................................30 
 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
REF: Worldwide-TMP-QA-001f-1.3 
 
Page 5 of 36 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
ARDS 
Acute Respiratory Distress Syndrome 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
COVID-19 
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) 
CSR 
Clinical Study Report 
CT 
Computed Tomography 
ECG 
Electrocardiogram 
ECMO 
Extracorporeal Membrane Oxygenation 
eCRF 
Electronic Case Report Form 
ICU 
Intensive Care Unit 
ITT 
Intent-to-Treat 
MedDRA 
Medical Dictionary of Regulated Activities 
mITT 
Modified Intent-to-Treat 
MMRM 
Mixed Model for Repeated Measures 
PRN 
Pro re nata – As Needed 
RRT 
Renal Replacement Therapy 
SAE 
Serious Adverse Event 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
SpO2 
Capillary Oxygen Saturation 
TEAE 
Treatment Emergent Adverse Event 
WHO 
World Health Organization 
 
 
 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
REF: Worldwide-TMP-QA-001f-1.3 
 
Page 6 of 36 
1 INTRODUCTION 
This document details the planned statistical analyses for Veru Inc., protocol “V0211901” study 
titled “Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for the Treatment of Severe 
Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Patients at High Risk for Acute 
Respiratory Distress Syndrome (ARDS)”. 
The proposed analyses are based on the contents of the final version of the protocol (version 7.0, 
dated 25-SEP-2020). IND number: 149282. 
This study is a multicenter, randomized, double-blind, placebo-control, efficacy and safety study 
of VERU-111 for the treatment of COVID-19. 
This study consists of two treatment arms: VERU-111 18 mg treated group, and Placebo treated 
Group. Subjects will be randomized in a 1:1 fashion. 
Subjects in the VERU-111 treatment group will receive standard of care, plus oral daily VERU-
111 18 mg for 21 days or until released from hospital. 
Subjects in the Placebo treatment group will receive standard of care, plus a placebo capsule for 
21 days or until released from hospital. 
VERU-111 18 mg dose will be supplied as capsules containing 18 mg of VERU-111. Capsules 
will be supplied in bottles containing 21 capsules in each bottle. Subjects will take one VERU-111 
capsule per day. 
Placebo capsules containing zero (0) mg VERU-111 drug substance will be supplied in bottles 
containing 21 capsules each. The placebo capsules will contain only anhydrous lactose, USP. 
These capsules are identically appearing to the VERU-111 capsules. Subjects will take one 
Placebo capsule per day. 
2 STUDY OBJECTIVES 
2.1 Primary Objective 
To demonstrate the efficacy of VERU-111 in the treatment of SARS-CoV-2 infection by 
assessing its effect on the proportion of subjects that are alive without respiratory failure at Day 
29. Respiratory failure is defined as endotracheal intubation and mechanical ventilation, 
extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
REF: Worldwide-TMP-QA-001f-1.3 
 
Page 7 of 36 
positive pressure ventilation, clinical diagnosis of respiratory failure with initiation of none of 
these measures only when clinical decision making is driven solely by resource limitation. 
2.2 Secondary Objectives 
Secondary objectives of the study are: 
1. World Health Organization (WHO) Ordinal Scale for Clinical Improvement (8-point 
ordinal scale) at Day 15, Day 22, and Day 29 
a. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 15 
b. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 22 
c. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 29 
d. Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for 
Clinical Improvement at Day 15 
e. Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for 
Clinical Improvement at Day 22 
f. Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for 
Clinical Improvement at Day 29 
2. Proportion of subjects with normalization of fever and oxygen saturation through Day 15, 
Day 22, and Day 29 
3. Days on mechanical ventilation 
4. All-cause mortality at Day 15, Day 22, and Day 29 
5. Proportion of subjects alive and free of respiratory failure at Day 15, Day 22 
6. Proportion of subjects alive and discharged from the ICU at Day 15, Day 22, and Day 29 
7. Proportion of subjects alive and discharged from hospital at Day 15, Day 22, and Day 29 
8. Days in Intensive Care Unit (ICU) 
9. Days in hospital 
10. Proportion of subjects on mechanical ventilation at Day 15, Day 22, and Day 29 
11. Assess the pharmacokinetics of VERU-111 on Day 15. 
2.3 Safety Objectives 
To assess the safety and tolerability of VERU-111. 
3 ENDPOINTS 
3.1 Primary Endpoint 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
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Page 8 of 36 
The primary endpoint for the study is the proportion of subjects that are alive without respiratory 
failure at Day 29. Respiratory failure is defined as endotracheal intubation and mechanical 
ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, 
noninvasive positive pressure ventilation, clinical diagnosis of respiratory failure with initiation 
of none of these measures only when clinical decision making is driven solely by resource 
limitation. 
3.2 Secondary Endpoints 
The secondary endpoints on this study are: 
1. WHO Ordinal Scale for Clinical Improvement (8-point ordinal scale): 
Patient State 
Descriptor 
Score 
Uninfected 
No clinical or virological evidence 
of infection 
0 
Ambulatory 
No limitation of activities 
1 
 
Limitation of activities 
2 
Hospitalized, Mild disease 
Hospitalized, no oxygen therapy 
3 
 
Oxygen by mask or nasal prongs 
4 
Hospitalized, Severe 
disease 
Non-invasive ventilation or high-
flow oxygen 
5 
 
Intubation and mechanical 
ventilation 
6 
 
Ventilation + additional organ 
support – pressors, Renal 
Replacement Therapy (RRT), 
Extracorporeal Membrane 
Oxygenation (ECMO) 
7 
Death 
Death 
8 
 
2. Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for Clinical 
Improvement at Day 15 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
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This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
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Page 9 of 36 
3. Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for Clinical 
Improvement at Day 22 
4. Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for Clinical 
Improvement at Day 29 
5. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 15 
6. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 22 
7. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 29 
8. Proportion of subjects with normalization of fever and oxygen saturation through Day 15. 
This will be a composite of fever normalization maintained for at least 24 hours AND 
peripheral capillary oxygen saturation (SpO2) >94% sustained for 24 hours. 
9. Proportion of subjects with normalization of fever and oxygen saturation through Day 22. 
This will be a composite of fever normalization maintained for at least 24 hours AND 
peripheral capillary oxygen saturation (SpO2) >94% sustained for 24 hours. 
10. Proportion of subjects with normalization of fever and oxygen saturation through Day 29. 
This will be a composite of fever normalization maintained for at least 24 hours AND 
peripheral capillary oxygen saturation (SpO2) >94% sustained for 24 hours. 
11. Days on mechanical ventilation 
12. All-cause mortality at Day 15 
13. All-cause mortality at Day 22 
14. All-cause mortality at Day 29 
15. Proportion of subjects alive and free of respiratory failure at Day 15 
16. Proportion of subjects alive and free of respiratory failure at Day 22 
17. Proportion of subjects alive and discharged from the ICU at Day 15 
18. Proportion of subjects alive and discharged from the ICU at Day 22 
19. Proportion of subjects alive and discharged from the ICU at Day 29 
20. Proportion of subjects alive and discharged from hospital at Day 15 
21. Proportion of subjects alive and discharged from hospital at Day 22 
22. Proportion of subjects alive and discharged from hospital at Day 29 
23. Days in ICU 
24. Days in hospital 
25. Proportion of subjects on mechanical ventilation at Day 15 
26. Proportion of subjects on mechanical ventilation at Day 22 
27. Proportion of subjects on mechanical ventilation at Day 29 
28. Pharmacokinetics of VERU-111 on Day 15. 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
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Page 10 of 36 
4 SAMPLE SIZE 
In the Phase 2, there are no power calculations done to determine the sample size. The Phase 2 
study is intended as a proof-of-concept study only. 
5 RANDOMIZATION 
Approximately, 40 subjects are planned to be randomized at a 1:1 ratio into two treatment arms 
(20 subjects in the VERU-111 treated group and 20 subjects in the Placebo treated group). 
The subjects with documented evidence of COVID-19 infection (by standard diagnostic method) 
with symptoms for less than 8 days will be enrolled. Subjects will be at high risk for the 
development of ARDS. 
6 PLANNED ANALYSES 
No statistical analysis plan (SAP) prepared in advance of the data can be absolutely definitive and 
the final Clinical Study Report (CSR) may contain additional tables or statistical tests if warranted 
by the data obtained. The justification for any such additional analyses will be fully documented 
in the final CSR. 
6.1 Analysis Populations 
Subjects excluded from the analysis populations and the reason for their exclusion will be listed in 
Appendix 16.2 of the CSR. 
6.1.1 
Enrolled Population 
All subjects who gave informed consent. 
6.1.2 
Randomized Population 
All enrolled subjects who were randomized to study treatment. 
6.1.3 
Intent-to-Treat (ITT) Population 
All randomized subjects regardless whether the subject took the study drug or not. The ITT 
population will be used as the safety population. 
6.1.4 
Modified Intent-to-Treat (mITT) Population 
All enrolled subjects who have taken at least 7 doses of study drug. 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
prior approval from Worldwide Quality Assurance or in compliance with Worldwide Standard Operating Procedures. 
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Page 11 of 36 
6.1.5 
Efficacy Evaluable (EE) Population 
All ITT subjects excluding those subjects who were identified as non-compliant to study 
procedures. These subjects will be identified together with reason for exclusion in the subject 
evaluability form which will be signed prior to the database lock. 
6.2 Derived Data 
This section describes the derivations required for statistical analysis. Unless otherwise stated, 
variables derived in the source data will not be re-calculated. 
6.2.1 
Baseline 
Baseline is defined as the last non-missing value (either scheduled, unscheduled or repeat) before 
the subject receives the first dose of study drug. 
6.2.2 
Duration / Study Day / Time 
Study day will be calculated as the number of days from first dose of study drug. 
 date of event – date of first dose of study drug + 1, for events on or after first dose 
 date of event – date of first dose of study drug, for events before first dose 
6.2.3 
Conventions for Missing and Partial Dates 
All rules explained below for partial / missing dates will be followed unless contradicted by any 
other data recorded on the electronic Case Report Form (eCRF). 
All dates presented in the individual subject listings will be as recorded on the eCRF (i.e., not 
completed as per the below rules). 
6.2.4 
Missing / Partial Start / Stop Date of Concomitant Medications 
Missing and partial start and stop date will be imputed for analysis purposes as follows. 
Partial or missing stop date will be imputed as follows: 
If the stop date is completely missing and the event has resolved, or the subject has stopped taking 
the concomitant medication, the stop date will be imputed as the date of the subject’s last clinic 
visit in the study. 
 If only the year is known, the stop date will be imputed as “31-Dec” of that year or as the 
date of the subject’s last clinic visit in the study if in the same year. 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
Veru Inc. 
Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
QMD Ref: Worldwide-TMP-ST-005-7.0 Effective: 12Aug2019 
Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
This document is the property of Worldwide Clinical Trials Inc. and may not be duplicated, copied, altered or removed from company without 
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Page 12 of 36 
 If the month and year are known, the stop date will be imputed as the last day of that month 
unless the stop date corresponds to the same month as the subject’s last clinic visit in which 
case the date of subject’s last clinic visit in the study will be used instead. 
Missing start date will be imputed as follows: 
 If the stop date occurs on or after the start of study drug or the event / concomitant 
medication is ongoing, the start date will be imputed as the date of the first dose of study 
drug. 
 If the stop date occurs before the start of study drug, the start date of the event / concomitant 
medication will be imputed as the subject’s screening date or the stop date of the event / 
concomitant medication whichever the earlier. 
Partial start date (year present, but month and day missing) 
 If the stop date occurs on or after the start of study drug or the event / concomitant 
medication is ongoing, and the year is the same as the year of first dosing the start date will 
be imputed as “01-Jan” of the same year or the date of the first dose of study drug 
whichever is latest. If the year is different from the year of first dosing “01-Jan” will be 
used. 
 If the stop date occurs before the start of study drug, the start date of the event / concomitant 
medication will be imputed as the “01-Jan” of the same year. 
Partial start date (month and year present, but day missing) 
 If the stop date occurs on or after the start of study drug or the event / concomitant 
medication is ongoing, the start date will be imputed as the first day of the same month and 
year unless this partial start date is in same month as the first dose of study drug in which 
case the date of first dose of study drug will be used. 
 If the stop date occurs before the start of study drug, the start date will be imputed as the 
first day of the month and year of the partial stop date. 
If the start time is missing it will be imputed only in the case where the start date of the concomitant 
medication / event corresponds to the date of the first dose of study drug. The time will be imputed 
as the same time as the first dose of study drug. In all other cases the time will not be imputed. 
6.2.5 
Missing Last Dates of Study Drug Dosing 
Missing dates for study drug dosing will not be imputed. 
6.2.6 
Missing Diagnosis Dates 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
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Protocol Number: 
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STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
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Governing QMD: Worldwide-SOP-ST-001 
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Page 13 of 36 
If the month and year are present but the day is missing, the diagnosis date will be set to first day 
of the relevant month. If only the year is recorded the diagnosis date will be set as “01-Jan” for 
that year. 
6.2.7 
Exposure to Study Drug 
Exposure to study drug will be calculated as the date of last dosing minus the first day of dosing + 
1. The exposure calculation will not take into account breaks in therapy. 
6.2.8 
Inexact Values 
In the case where a variable is recorded as “> x”, “≥ x”, “< x” or “≤ x”, a value of x will be taken 
for analysis purposes. 
6.2.9 
Unscheduled Visits 
Only scheduled post-baseline values will be tabulated. Post-baseline repeat / unscheduled 
assessments will be disregarded, although these post-baseline assessments will be listed in the 
relevant appendices to the CSR. 
6.3 Conventions 
All data listings, summaries, figures and statistical analyses will be generated using SAS version 
9.4 or higher1. 
Summaries will be presented by treatment group. Treatment group labels will be displayed as 
follows: 
 VERU-111 18 mg 
 Placebo 
Listings will be sorted in the following order treatment group, subject, parameter, and visit unless 
otherwise stated. All data will be listed, subjects who were not randomized will be displayed after 
the randomized treatment groups. 
Continuous variables will be summarized by the number of non-missing observations, mean, 
median, standard deviation, and minimum and maximum. 
Categorical variables will be summarized by presenting the frequency and percent. Percentages 
will be based on the number of non-missing observations or the subject population unless 
otherwise specified. For each variable, all categories will be shown. Zero frequencies (but not the 
percent) within a category will be presented. 


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6.3.1 
Decimal Places 
Decimal places for derived data described in section 6.2 will be determined by the scale of 
measurement unless otherwise stated. No decimal places will be displayed if the smallest 
calculated value is ≥ 100; 1 decimal place will be displayed when the smallest value is within the 
interval (10, 100), with 10 being inclusive; 2 decimal places will be displayed when the smallest 
value is within (1, 10), with 1 being inclusive; and so on for even smaller scales of measurement.  
Derived data where it is known in advance the result will be an integer for example day, month, 
year, number of days and total scores (for rating scales) will be presented with zero decimal places.  
Means, medians and percentiles will be displayed to one more decimal place than the data, 
dispersion statistics (e.g. standard deviation) will have two more decimal places, and the minimum 
and maximum will be displayed to the same number of decimal places as reported in the raw data. 
Percentages will be displayed with one decimal place. 
P-values will be quoted to 3 decimal places. P-values < 0.001 will be presented as p<0.001. Where 
this value is less than 0.05, 0.01 or 0.001, attention will be drawn to this fact using the conventional 
“*”, “**” or “***” annotation, respectively. 
6.4 Subject Disposition 
Subject disposition will be summarized as follows: 
 The number of subjects, who entered the study, were randomized and who are in each 
analysis population will be summarized by treatment group and overall for the enrolled 
population. 
 The number of subjects who failed screening and the reasons for failure will be tabulated 
for enrolled population. 
 The number of early withdrawals and the reasons for withdrawals will be tabulated by 
treatment group and overall for the ITT population. 
 The number of subjects present at each scheduled visit will be summarized by treatment 
group for the ITT population.  
6.5 Protocol Deviations 
Protocol deviations will be summarized and listing of protocol deviations will be provided within 
Appendix 16.2 of the CSR.  


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6.6 Baseline Comparability 
The comparability of treatment groups with respect to subject demographics and baseline 
characteristics will be assessed in a descriptive manner, but no formal statistical testing will be 
performed. 
Standard continuous or categorical variable summaries will be presented by randomized treatment 
group for the following variables based on the ITT population: 
 Age (years) at Informed Consent 
 Age category (<60 years, >=60 years) 
 Sex (Female, Male) 
 Fertility Status for Women (Childbearing Potential, Post-menopausal, Surgically Sterile) 
 Ethnicity (Hispanic or Latino, Not Hispanic or Latino) 
 Race (American Indian or Alaska Native, Asian, Black or African American, Native 
Hawaiian or Other Pacific Islander, White) 
 Weight (kg) at Screening 
 Height (cm) at Screening 
 Body Mass Index (BMI) (kg/m2) at Screening. 
6.7 Medical History 
Separate tabulations of previous and ongoing conditions will be presented by randomized 
treatment group and overall for the ITT population. Previous conditions are all conditions which 
ended before the first dose of study drug. Ongoing conditions are all conditions which were 
ongoing at the time of the first dose of study drug. 
Conditions will be presented by Medical Dictionary of Regulated Activities (MedDRA, version 
23.0 updated) primary system organ class and preferred term. 
6.8 Prior and Concomitant Medications 
Separate tabulations will be produced for prior and concomitant medications presented by 
randomized treatment group and overall for the ITT population. Prior medications are defined as 
all medications ending before the date of first dose of study drug. Concomitant medications are 
defined as medications taken on or after the date of first dose of study drug. 


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Prior and Concomitant medication verbatim terms (as recorded on the CRFs) will be mapped to 
Anatomical Therapeutic Chemical (ATC) Level 2 and Drug Reference Names using the WHO 
dictionary (version B3 Mar 2020). 
Concomitant medications will be summarized using ATC Level 2 and preferred term. 
6.9 Exposure to Study Drug 
Extent of exposure (number of days of exposure to study drug) will be presented by randomized 
treatment group for the ITT population. 
6.10 Treatment Compliance 
All subjects will receive standard of care plus oral daily VERU-111 or Placebo. Subjects will 
take one capsules per day. 
Overall study drug compliance (%) will be summarized using descriptive statistics by treatment 
group and overall. Additionally, compliance (%) will be summarized as frequencies in ‘<80%’ 
and ‘>=80%’ categories. 
Overall study drug compliance will be calculated as follows: 
100 ∗
𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑎𝑝𝑠𝑢𝑙𝑒𝑠 𝑡𝑎𝑘𝑒𝑛
𝑝𝑙𝑎𝑛𝑛𝑒𝑑 𝑡𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑎𝑝𝑠𝑢𝑙𝑒𝑠 
where planned number of capsules is 1 capsules/day in both VERU-111 and placebo groups. 
Planned number of capsules will be calculated as last dose date – randomization date +1. 
6.11 Dosing of Standard of Care 
The number and percentage of subjects using remdesivir or dexamethasone (or both) will be 
summarized by treatment group. 
All standard of care information will be listed. 
6.12 Efficacy Analyses 
All statistical tests will be performed using a two-tailed 5% overall significance level, unless 
otherwise stated. All comparisons between treatments will be reported with 95% confidence 
intervals for the difference. 
6.12.1 
Primary Endpoint 


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The primary endpoint for the study is the proportion of subjects that are alive without respiratory 
failure at Day 29. Respiratory failure is defined as endotracheal intubation and mechanical 
ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, 
noninvasive positive pressure ventilation, clinical diagnosis of respiratory failure with initiation 
of none of these measures only when clinical decision making is driven solely by resource 
limitation. 
This analysis will compare the percentage of subjects that are alive without respiratory failure on 
Day 29 (responder). 
Responders are subjects who have Grade 0-4 on the WHO Ordinal Scale for Clinical 
Improvement on Day 29. If subject was discharged from the hospital prior to Day 29 and WHO 
Ordinal Scale for Clinical Improvement is not collected at Day 29 then the last available 
observation before or at the time of discharge will be carried forward. 
Non-responders are subjects who died before Day 29 or has Grade 5, 6, 7, or 8 on the WHO 
Ordinal Scale for Clinical Improvement on Day 29. 
The number and percentage of responders will be summarized by treatment group. Responders 
will be analyzed using a logistic regression model. This model will include treatment as a factor, 
and study site, remdesivir use (No/Yes), dexamethasone use (No/Yes) and WHO Ordinal Scale 
for Clinical Improvement at baseline as a covariates. Odds ratios, standard errors, 95% 
confidence intervals and p-values for the treatment difference will be presented. 
The primary analysis will be performed on the ITT population. A sensitivity analysis will be 
performed repeating the analysis on the EE population. 
Example SAS code for the analysis is as follows: 
proc logistic data=XXX order=internal; 
class response trt01pn site remdesivir dexamethasone; 
model response=trt01pn site remdesivir dexamethasone who_base /  
               clodds=both firth; 
estimate 'Treatment A vs. Treatment B' trt01pn 1 -1 / cl e exp; 
lsmeans trt01pn / cl exp diff; 
ods output modelanova=modelanova1 lsmeans=lsmeans1 diffs=diffs1; 
run; 
Responder rates and differences between treatment groups in responder rates will be calculated 
as sensitivity analysis for primary endpoint. Wald method will be used for 95% confidence 
intervals and testing of treatment differences. 


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Page 18 of 36 
Example SAS code for the analysis is as follows: 
proc freq data=XXX order=internal; 
tables avisitn*trt01pn*avalc / riskdiff(column=2 equal var=null cl=wald); 
exact riskdiff barnard(column=2); 
ods output riskdiffcol2=riskdiff1 pdiffcls=waldci1 pdifftest=waldtest1 
barnardstest=barnard1; 
run; 
6.12.2 
Secondary Endpoints 
6.12.2.1 Change in mean WHO Ordinal Scale for Clinical Improvement at Day 15, Day 22 
and Day 29 
The mean change in WHO Ordinal Scale for Clinical Improvement from baseline to Day 15, Day 
22 and Day 29 will be assessed. 
Baseline for WHO Ordinal Scale is the last available record up to and including Day 1. If subject 
died or was discharged from the hospital prior to Day 15, 22 or 29 and WHO Ordinal Scale for 
Clinical Improvement is not collected or record is otherwise missing at those timepoints then the 
last available observation before or at the time of death/discharge will be carried forward. 
Analysis will be performed using two different approaches, including the LOCF values and 
excluding LOCF values. Further, these analyses will be repeated using separate baseline 
definition. As the time of WHO Ordinal Scale is collected it cannot be definitely confirmed if 
Day 1 record was taken before or after start of study treatment. Sensitivity analysis will be 
performed using the WHO Ordinal Scale from Screening record. 
Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) will be 
summarized for absolute values and change from baseline by treatment group and visit. 
Change from baseline will be analyzed using mixed model for repeated measures (MMRM) 
including treatment, visit and treatment-by-visit interaction as fixed effects, and study site, 
remdesivir use (No/Yes), dexamethasone use (No/Yes) and WHO Ordinal Scale for Clinical 
Improvement at baseline as covariates. The resulting F-tests will be based on Kenward-Roger’s 
adjusted degrees of freedom. Subject effect will be assumed to be random and an unstructured 
covariance structure will be used for within subject variation. If this model does not converge 
then the following covariance matrices will be used in order until the model converges: Toeplitz, 
first-order autoregressive, and compound symmetry. Least squares means, standard errors, 95% 
confidence intervals and p-values for treatments and treatment differences at each visit (study 
days 15, 22, 29, 45 and 60) will be presented. 


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Example SAS code for the analysis is as follows: 
proc mixed data=XXX order=internal; 
class usubjid trt01pn avisitn siteid remdesivir dexamethasone; 
model response=trt01pn avisitn trt01pn*avisitn site remdesivir  
               dexamethasone who_base / ddfm=kr; 
repeated avisitn / type=un subject=usubjid; 
lsmeans trt01pn trt01pn*avisitn / diff cl e; 
ods output tests3=tests lsmeans=lsmeans diffs=diffs 
convergencestatus=converge; 
run; 
6.12.2.2 Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for 
Clinical Improvement at Day 15, Day 22, and Day 29 
As the primary endpoint will be using WHO scale to define responders/non-responders this 
analysis specified in the protocol would be corresponding to the primary endpoint. Primary 
endpoint analysis table will include Days 15, 22 and 29 which makes this analysis redundant. 
Therefore this secondary endpoint will be dropped out. 
6.12.2.3 Proportion of subjects with normalization of fever and oxygen saturation through 
Day 15, Day 22, and Day 29. 
The percentage of subjects with normalization of fever and oxygen saturation through Day 15, 
Day 22 and Day 29 (inclusive) will be summarized. A subject will be considered as a treatment 
success if fever normalization (body temperature < 37.0 °C) maintained for at least 24 hours 
AND peripheral capillary oxygen saturation (SpO2) >94% sustained for 24 hours is observed. 
This analysis will compare the percentage of subjects that meet the composite endpoint at Day 
15, Day 22, and Day 29. 
Evaluation of the responder status will include all vital sign data and vital sign log data, and 
responder status will be evaluated at study days 15, 22 and 29 by checking if subject had normal 
temperature and SpO2 at least for the last 24 hours. 
Responders are subjects who have fever normalization maintained for at least 24 hours AND 
peripheral capillary oxygen saturation (SpO2) >94% sustained for 24 hours is observed at the 
time of the visit. 
Non-responders are subjects who died before the visit or do not meet both criteria of the endpoint 
(fever normalization and SpO2>94%) at the time of the visit. 
These endpoints will be analyzed using the same methodology as for the primary endpoint.  


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Separate analysis will be performed for each visit. 
6.12.2.4 Days on mechanical ventilation 
Mechanical ventilation is defined as subject having ‘Intubation and mechanical ventilation’ or 
‘Ventilation + additional organ support – pressors, RRT, ECMO’. 
‘Days on mechanical ventilation’ will be summarized using descriptive statistics (n, mean, 
standard deviation, median, minimum and maximum) by treatment group. 
‘Days on mechanical ventilation’ will be the number of days on mechanical ventilation up to 
Day 29. If subject dies early in the study and was on mechanical ventilation at the time of the 
death then it is assumed that subject was on mechanical ventilation up to Day 29. A sensitivity 
analysis will be performed assigning the worst possible endpoint score for deaths (i.e., 
considered to be on mechanical ventilation from baseline up to Day 29 and setting days on 
mechanical ventilation to 29). 
Treatment comparison will be based on analysis of covariance (ANCOVA) model including 
treatment as a factor, and study site, remdesivir use (No/Yes), dexamethasone use (No/Yes) and 
WHO Ordinal Scale for Clinical Improvement at baseline as covariates. Treatment difference, 
standard error, 95% confidence interval and p-value will be presented. 
Example SAS codes for the analysis are as follows: 
proc mixed data=XXX order=internal; 
class trt01pn site remdesivir dexamethasone; 
model response=trt01pn site remdesivir dexamethasone who_base /  
               ddfm=kr; 
lsmeans trt01pn / cl diff; 
ods output tests3=tests lsmeans=lsmeans diffs=diffs 
run; 
6.12.2.5 All-cause mortality at Day 15, Day 22, and Day 29 
The number and percentage for all-cause mortality will be summarized by treatment group and 
visit. 
These endpoints will be analyzed using the same methodology as for the primary endpoint.  
Responders are subjects who are alive at the time of the visit. 
Non-responders are subjects who died before the visit. 
Separate analysis will be performed for each visit. 


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Responder rates and differences between treatment groups in responder rates will be calculated 
as sensitivity analysis using the same methodology as for the primary endpoint. 
6.12.2.6 Proportion of subjects alive and free of respiratory failure at Day 15, and Day 22 
These endpoints will be analyzed using the same methodology as for the primary endpoint.  
Separate analysis will be performed for each visit. 
This will be the same analysis as for primary endpoint but just repeated for days 15 and 22. 
6.12.2.7 Proportion of subjects alive and discharged from the ICU at Day 15, Day 22, and Day 
29 
The percentage of subjects alive and discharged from the ICU through Day 15, Day 22 and Day 
29 (inclusive) will be summarized. 
This analysis will compare the percentage of subjects that are alive and discharged from the ICU 
(responder) at Day 15, Day 22, and Day 29. 
Responders are subjects who are alive and have been discharged from the hospital or not in the 
ICU at the time of the visit. 
Non-responders are subjects who died before the visit or are in the ICU at the time of the visit. 
This endpoint will be analyzed using the same methodology as for the primary endpoint.  
Separate analysis will be performed for each visit. 
6.12.2.8 Proportion of subjects alive and discharged from hospital at Day 15, Day 22, and Day 
29 
The percentage of subjects alive and discharged from the hospital through Day 15, Day 22 and 
Day 29 (inclusive) will be summarized. 
This analysis will compare the percentage of subjects that are alive and discharged from the 
hospital (responder) at Day 15, Day 22, and Day 29. 
Responders are subjects who are alive and have been discharged from the hospital at the time of 
the visit. 
Non-responders are subjects who died before the visit or are in the hospital at the time of the 
visit. 
This endpoint will be analyzed using the same methodology as for the primary endpoint.  


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Separate analysis will be performed for each visit. 
6.12.2.9 Days in ICU 
‘Days in ICU’ will be summarized using descriptive statistics (n, mean, standard deviation, 
median, minimum and maximum) by treatment group. 
‘Days in ICU’ will be the number of days in ICU up to Day 29. If subject dies early in the study 
and is in the ICU at the time of the death then it is assumed that subject was in the ICU up to Day 
29. 
‘Days in ICU’ will be analyzed using the same methodology as for ‘Days in mechanical 
ventilation’ and the same sensitivity analysis will be performed. 
6.12.2.10 
Days in hospital 
‘Days in hospital’ will be summarized using descriptive statistics (n, mean, standard deviation, 
median, minimum and maximum) by treatment group. 
‘Days in hospital’ will be the number of days in hospital up to Day 29. If subject dies early in the 
study and is in the hospital at the time of the death then it is assumed that subject was in the 
hospital up to Day 29. 
‘Days in hospital’ will be analyzed using the same methodology as for ‘Days in mechanical 
ventilation’. 
6.12.2.11 
Proportion of subjects on mechanical ventilation at Day 15, Day 22, and Day 29 
The percentage of subjects on mechanical ventilation through Day 15, Day 22 and Day 29 
(inclusive) will be summarized. 
This analysis will compare the percentage of subjects that are NOT on mechanical ventilation 
(responder) at Day 15, Day 22, and Day 29. 
Responders are subjects who have been discharged from the hospital or are not on mechanical 
ventilation at the time of the visit. 
Non-responders are subjects who died before the visit or are on the mechanical ventilation at the 
time of the visit. 
This endpoint will be analyzed using the same methodology as for the primary endpoint.  
Separate analysis will be performed for each visit. 


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6.12.3 
Exploratory Endpoints 
6.12.3.1 Area under curve (AUC) of WHO Ordinal Scale for Clinical Improvement 
Area under curve (AUC) of WHO Ordinal Scale for Clinical Improvement will be calculated 
from baseline up to Day 15 using trapezoidal rule. For each subject all available measurements 
up to study day 15 are included in the calculations. If subject does not have record on Day 15 
then the last observation carried forward (LOCF) will be used. If a patient dies on Day 10, then 
they would be an 8 from Day 10 to Day 15. If the patient is discharged as a 2 on Day 5 then they 
would be a 2 from Day 5 to Day 15. 
Actual collection times will be used in the calculations. 
AUC will be summarized by treatment group and listed together with WHO Ordinal Scale for 
Clinical Improvement. 
6.12.3.2 Oxygen Use 
Oxygen use will be summarized by treatment group as shift (decrease, no change, increase) from 
baseline (last oxygen dose prior to the date of treatment start) at study days 3, 9, 15, 22 and 29. 
This information will be derived from concomitant medication data for oxygen. 
6.12.4 
Multiplicity 
All secondary endpoints and the supportive analyses will be considered as descriptive evidence of 
efficacy and will be analyzed without any procedures to account for multiple comparisons. 
6.13 Pharmacokinetic Analyses 
The pharmacokinetics of VERU-111 will be assessed on Day 15. Plasma samples for 
pharmacokinetic assessment will be taken at baseline (prior to dosing on Day 15) and at 4 hours 
(±2 hours), 12 hours (±2 hours) after dosing on Day 15, and at 24 hours (±2 hours) after dosing 
on Day 15 (prior to dosing on Day 16). 
The following parameters will be estimated through standard methodology with this limited 
sampling schedule: 
 AUC0-t  
Area Under Concentration Curve from time 0 to time t. 
 Cmax 
 
Maximum Concentration 
 Tmax 
 
Time to Cmax 
 kel 
 
Elimination Rate Constant 


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 Cl/F 
 
Clearance 
 T½, 
 
Half-Life 
 Vd/F 
 
Volume of Distribution 
The limited sampling schedule is used due to limitations on study personnel entering the 
subject’s room during the day. If the sample is missed due to restrictions in entering the room, 
then this sample will be listed as missing. 
PK concentrations will be summarized using descriptive statistics (n, mean, standard deviation, 
CV(%), geometric mean, median, minimum and maximum) for absolute values by treatment 
group and visit. Mean plots by treatment and individual subject curves will be displayed on 
linear and semi-logarithmic scale (time on linear scale, concentration on logarithmic scale) for 
concentration data. 
PK parameters will be summarized using descriptive statistics (n, mean, standard deviation, 
median, minimum and maximum) for absolute values by treatment group. 
All PK concentration and PK parameter data will be listed. 
6.14 Pharmacodynamic Analyses 
Not applicable. 
6.15 Safety Analyses 
The safety analyses will be presented by the treatment received for the ITT Population. 
6.15.1 
Adverse Events 
A treatment emergent adverse event (TEAE) is defined as: 
 Any AE that has an onset on or after the first dose of study drug and before last dose of 
study drug + 7 days. 
 Any pre-existing AE that has worsened in severity on or after the first dose of study drug 
and before the last dose of study drug + 7 days. 
A treatment-related AE is defined as an AE with causality collected as ‘POSSIBLY RELATED’, 
‘PROBABLY RELATED’ or ‘RELATED’ in the CRF. If an AE has missing relationship it is 
assumed to be ‘RELATED’ to the study drug for analysis purposes. 


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If an AE has missing standard toxicity grade it is assumed to be ‘GRADE 3 (SEVERE)’ for 
analysis purposes. 
AEs will be summarized according to the MedDRA (version 23.0 updated) system organ class and 
preferred term. 
The following tables will be presented for AEs: 
 Overall incidence and the number of events in the following categories: 
o TEAEs 
o Treatment-Related TEAEs 
o Serious TEAEs 
o Treatment-Related Serious TEAEs 
 For the above AE categories tables including incidence and number of events will be 
presented by system organ class and preferred term 
 TEAEs by system organ class, preferred term and maximum toxicity grade (incidence, no 
event counts) 
 TEAEs by system organ class, preferred term and strongest relationship grade (incidence, 
no event counts) 
 Listing of Deaths (presented in the Table section of the appendices) 
 Listing of Serious TEAEs (presented in the Table section of the appendices). 
In counting the number of AEs reported, a continuous event (i.e. reported more than once and 
which did not cease), will be counted only once; non-continuous AE reported several times by the 
same subject will be counted as multiple events. 
All AEs will be listed. 
6.15.2 
Laboratory Data 
Laboratory data will be collected in local labs and the units need to be made consistent before 
presenting in summary tables. 
Descriptive statistics of the observed values and change from baseline (continuous data) will be 
presented by treatment group and visit for each chemistry, hematology and urinalysis parameter.  
Each measurement (continuous data) will be classed as below, within, or above normal range, 
based on ranges supplied by the laboratory used. Shift tables in relation to the normal range from 
baseline to each timepoint will be presented. 


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Page 26 of 36 
A listing of any clinically significant laboratory measurements recorded throughout the study will 
be presented in tables section. 
All laboratory data will be listed. 
6.15.3 
Vital Signs 
Descriptive statistics for observed values and changes from baseline in the following vital signs 
will be presented by treatment group and visit: 
 Systolic blood pressure (mmHg) 
 Diastolic blood pressure (mmHg) 
 Pulse rate (bpm) 
 Respiration rate (breath / min) 
 Body weight (kg) 
 Body temperature (degrees Celsius) 
 SpO2 (%) 
Vital Signs log will be collected every 12 hours during study days 1-21. When study day has more 
than one record then summary table will use the average within the day. 
Data for body temperature and SpO2 log will be presented in plot where individual subjects will 
be overlaid in one figure (spaghetti plot) by treatment group. 
All vital sign data will be listed. 
6.15.4 
Physical Examination 
Shift tables for each body system from baseline to worst post-baseline record will be presented 
(Normal, Abnormal NCS and Abnormal CS). NCS = Abnormal Not Clinically Significant, CS = 
Clinically Significant. 
All physical examination data will be listed. 
6.15.5 
Electrocardiogram Data 
Descriptive statistics for observed values and changes from baseline in the following ECG 
variables will be tabulated at each follow-up visit: 
 Heart rate (bpm) 
 PR interval (ms) 


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Page 27 of 36 
 RR interval (ms) 
 QRS duration (ms) 
 QT interval (ms) 
 QTc interval (ms) 
 QTc interval (ms) [Bazett’s formula - QTcB] 
 QTc interval (ms) [Fridericia’s formula - QTcF] 
Shift tables in relation to the overall interpretation (Normal, Abnormal NCS and Abnormal CS) 
from baseline to worst post-baseline record will be presented. 
All ECG data will be listed. 
6.15.6 
Chest X-Ray / Computed Tomography (CT) 
Shift tables for chest X-ray / CT from baseline to each timepoint will be presented (Normal, 
Abnormal). 
All chest X-ray / CT data will be listed. 
6.15.7 
Pregnancy Test 
Pregnancy test data will be listed only. 
7 INTERIM ANALYSIS 
Interim analysis was planned in the protocol but will not be performed. 
8 DATA SAFETY MONITORING BOARD ANALYSIS 
Data safety monitoring board (DSMB) will meet on a bi-weekly basis to: 
 Review aggregate and individual subject data related to safety, data integrity and overall 
conduct of the trial. 
 Provide recommendations to continue or terminate the trial depending upon these 
analyses. 
9 CHANGES TO PLANNED PROTOCOL ANALYSIS 
In the statistical models the use of remdesivir and dexamethasone were added as covariates. 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
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Protocol Number: 
V0211901 
STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
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Page 28 of 36 
Secondary endpoint ‘Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal 
Scale for Clinical Improvement at Day 15, Day 22, and Day 29’ will be excluded from the SAP 
as it would be the same as primary endpoint and corresponding endpoints for Days 15 and 22. 
Interim analysis will not be performed. 
ITT Population was updated to include all randomized subjects regardless whether the subject 
too study drug or not. This will not have impact on the populations as all randomized subjects 
were treated. 
Efficacy Evaluable (EE) Population was added. 
 
 


Worldwide Clinical Trials Controlled Quality Management Document 
 
Sponsor: 
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Protocol Number: 
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STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
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Governing QMD: Worldwide-SOP-ST-001 
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Page 29 of 36 
10 REFERENCES 
1. SAS Institute Inc., Cary, NC, 27513, USA 
 
 
 


Worldwide Clinical Trials Controlled Quality Management Document 
 
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Protocol Number: 
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STATISTICAL ANALYSIS PLAN. PHASE 2-3-4 
 
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Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
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Page 30 of 36 
11 LIST OF TABLES, FIGURES AND LISTINGS 
The following table includes details of the tables, figures and listings to be included within each 
section of the eCTD. The eCTD section is shown in bold. The following validation methods maybe 
used:  
 Independent programming of numbers and manual review of format (IP) 
 Independent programming by statistician of numbers and manual review of format (Stat 
IP) 
 Manual review (MR) 
 Code review (CR) 
Table 
Number 
Table Title 
Included in 
Preliminary 
Analysis 
Included 
in DSMB 
(Table 
No.) 
Validation 
Method 
Shell 
Number 
(if 
repeat) 
14.1  
Demographics Data 
 
 
 
 
14.1.1  
Disposition 
 
 
 
 
14.1.1.1 
Subject Enrollment (Enrolled Population) 
 
Yes (O1, 
S1) 
IP 
 
14.1.1.2 
Screen Failures (Enrolled Population) 
 
 
IP 
 
14.1.1.3 
Inclusion/Exclusion Criteria Violations (Enrolled Population) 
 
 
IP 
 
14.1.1.4 
Analysis Populations (Enrolled Population) 
 
 
IP 
 
14.1.1.5 
Subject Disposition (Randomized Population) 
 
Yes (S2) 
IP 
 
14.1.1.6 
Protocol Deviations (ITT Population) 
 
Yes (S3) 
IP 
 
14.1.2  
Demographics 
 
 
 
 
14.1.2.1 
Demographics (ITT Population) 
 
Yes (S4) 
IP 
 
14.1.2.2 
Demographics (EE Population) 
 
 
IP 
14.1.2.1 
14.1.2.3 
Baseline Condition (ITT Population) 
 
Yes (S5) 
IP 
 
14.1.2.4 
Baseline Condition (EE Population) 
 
 
IP 
14.1.2.3 
14.1.3-
14.1.4 
Baseline Characteristics 
 
 
 
 
14.1.3.1 
Previous Medical History by System Organ Class and Preferred 
Term (ITT Population) 
 
 
IP 
 
14.1.3.2 
Ongoing Medical History by System Organ Class and Preferred 
Term (ITT Population) 
 
 
IP 
14.1.3.1 
14.1.4.1 
Prior Medications by ATC Level 2 and Preferred Term (ITT 
Population) 
 
 
IP 
 
14.1.4.2 
Concomitant Medications by ATC Level 2 and Preferred Term 
(ITT Population) 
 
 
IP 
14.1.4.1 
14.1.5 
Extent of Exposure, Dosage Information, And Compliance 
 
 
 
 
14.1.5.1 
Treatment Exposure (ITT Population) 
 
 
IP 
 
14.1.5.2 
Treatment Compliance (ITT Population) 
 
 
IP 
 


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Page 31 of 36 
Table 
Number 
Table Title 
Included in 
Preliminary 
Analysis 
Included 
in DSMB 
(Table 
No.) 
Validation 
Method 
Shell 
Number 
(if 
repeat) 
14.1.5.3 
Standard of Care (ITT Population) 
 
 
IP 
 
14.2  
Efficacy Data 
 
 
 
 
14.2.1 
Primary Efficacy Endpoint 
 
 
 
 
14.2.1.1 
Proportion of Subjects Alive and Free of Respiratory Failure by 
Visit (ITT Population) 
Yes 
 
IP 
 
14.2.1.2 
Logistic Regression for Proportion of Subjects Alive and Free 
of Respiratory Failure by Visit (ITT Population) 
Yes 
 
Stat IP 
 
14.2.1.2a 
Responder Rates for Proportion of Subjects Alive and Free of 
Respiratory Failure by Visit (ITT Population) 
 
 
Stat IP 
 
14.2.1.3 
Proportion of Subjects Alive and Free of Respiratory Failure by 
Visit (EE Population) 
 
 
IP 
14.2.1.1 
14.2.1.4 
Logistic Regression for Proportion of Subjects Alive and Free 
of Respiratory Failure by Visit (EE Population) 
 
 
Stat IP 
14.2.1.2 
14.2.2-
14.2.11 
Secondary Efficacy Endpoints 
 
 
 
 
14.2.2.1 
Descriptive Statistics for WHO Ordinal Scale for Clinical 
Improvement by Visit - With LOCF values (ITT Population) 
Yes 
 
IP 
 
14.2.2.2 
Mixed Model for Repeated Measures (MMRM) for Change 
from Baseline in WHO Ordinal Scale for Clinical Improvement 
- With LOCF values (ITT Population) 
Yes 
 
Stat IP 
 
14.2.2.3 
Descriptive Statistics for WHO Ordinal Scale for Clinical 
Improvement by Visit - Without LOCF values (ITT Population) 
 
 
IP 
14.2.2.1 
14.2.2.4 
Mixed Model for Repeated Measures (MMRM) for Change 
from Baseline in WHO Ordinal Scale for Clinical Improvement 
- Without LOCF values (ITT Population) 
 
 
Stat IP 
14.2.2.2 
14.2.2.5 
Descriptive Statistics for WHO Ordinal Scale for Clinical 
Improvement by Visit - With LOCF values - Screening as 
Baseline (ITT Population) 
Yes 
 
IP 
14.2.2.1 
14.2.2.6 
Mixed Model for Repeated Measures (MMRM) for Change 
from Baseline in WHO Ordinal Scale for Clinical Improvement 
- With LOCF values - Screening as Baseline (ITT Population) 
Yes 
 
Stat IP 
14.2.2.2 
14.2.2.7 
Descriptive Statistics for WHO Ordinal Scale for Clinical 
Improvement by Visit - Without LOCF values - Screening as 
Baseline (ITT Population) 
 
 
IP 
14.2.2.1 
14.2.2.8 
Mixed Model for Repeated Measures (MMRM) for Change 
from Baseline in WHO Ordinal Scale for Clinical Improvement 
- Without LOCF values - Screening as Baseline (ITT 
Population) 
 
 
Stat IP 
14.2.2.2 
14.2.2.9 
Area Under Curve of WHO Ordinal Scale for Clinical 
Improvement (ITT Population) 
 
 
IP 
 
14.2.3.1 
Proportion of Subjects with Fever Normalization and 
SpO2>94% by Visit (ITT Population) 
 
 
IP 
14.2.1.1 


Worldwide Clinical Trials Controlled Quality Management Document 
 
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Table 
Number 
Table Title 
Included in 
Preliminary 
Analysis 
Included 
in DSMB 
(Table 
No.) 
Validation 
Method 
Shell 
Number 
(if 
repeat) 
14.2.3.2 
Logistic Regression for Proportion of Subjects with Fever 
Normalization and SpO2>94% by Visit (ITT Population) 
 
 
Stat IP 
14.2.1.2 
14.2.3.3 
Shift from Baseline in Oxygen Use (ITT Population) 
 
 
IP 
 
14.2.4.1 
Descriptive Statistics for Days on Mechanical Ventilation (ITT 
Population) 
Yes 
 
IP 
 
14.2.4.2 
Analysis of Covariance (ANCOVA) for Days on Mechanical 
Ventilation (ITT Population) 
Yes 
 
Stat IP 
 
14.2.4.3 
Descriptive Statistics for Days on Mechanical Ventilation - 
Death Assigned to Worst Possible Outcome (ITT Population) 
Yes 
 
IP 
 
14.2.4.4 
Analysis of Covariance (ANCOVA) for Days on Mechanical 
Ventilation - Death Assigned to Worst Possible Outcome (ITT 
Population) 
Yes 
 
Stat IP 
 
14.2.5.1 
Frequency Table for All-Cause Mortality by Visit (ITT 
Population) 
 
 
IP 
14.2.1.1 
14.2.5.2 
Logistic Regression for All-Cause Mortality by Visit (ITT 
Population) 
 
 
Stat IP 
14.2.1.2 
14.2.5.2a 
Responder Rates for All-Cause Mortality by Visit (ITT 
Population) 
 
 
Stat IP 
14.2.1.2a 
14.2.6.1 
Proportion of Subjects Alive and Discharged from the ICU by 
Visit (ITT Population) 
 
 
IP 
14.2.1.1 
14.2.6.2 
Logistic Regression for Proportion of Subjects Alive and 
Discharged from the ICU by Visit (ITT Population) 
 
 
Stat IP 
14.2.1.2 
14.2.7.1 
Proportion of Subjects Alive and Discharged from the Hospital 
by Visit (ITT Population) 
Yes 
 
IP 
14.2.1.1 
14.2.7.2 
Logistic Regression for Proportion of Subjects Alive and 
Discharged from the Hospital by Visit (ITT Population) 
Yes 
 
Stat IP 
14.2.1.2 
14.2.8.1 
Descriptive Statistics for Days in ICU (ITT Population) 
Yes 
 
IP 
14.2.5.1 
14.2.8.2 
Analysis of Covariance (ANCOVA) for Days in ICU (ITT 
Population) 
Yes 
 
Stat IP 
14.2.5.2 
14.2.8.3 
Descriptive Statistics for Days in ICU - Death Assigned to 
Worst Possible Outcome (ITT Population) 
Yes 
 
IP 
14.2.5.1 
14.2.8.4 
Analysis of Covariance (ANCOVA) for Days in ICU - Death 
Assigned to Worst Possible Outcome (ITT Population) 
Yes 
 
Stat IP 
14.2.5.2 
14.2.9.1 
Descriptive Statistics for Days in Hospital (ITT Population) 
 
 
IP 
14.2.1.1 
14.2.9.2 
Analysis of Covariance (ANCOVA) for Days in Hospital (ITT 
Population) 
 
 
Stat IP 
14.2.5.2 
14.2.10.1 
Proportion of Subjects on Mechanical Ventilation by Visit (ITT 
Population) 
 
 
IP 
14.2.1.1 
14.2.10.2 
Logistic Regression for Proportion of Subjects on Mechanical 
Ventilation by Visit (ITT Population) 
 
 
Stat IP 
14.2.1.2 
14.3  
Safety Data 
 
 
 
 
14.3.1  
Displays of Adverse Events 
 
 
 
 


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Protocol Number: 
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Table 
Number 
Table Title 
Included in 
Preliminary 
Analysis 
Included 
in DSMB 
(Table 
No.) 
Validation 
Method 
Shell 
Number 
(if 
repeat) 
14.3.1.1.1 
Overall Summary of Adverse Events (ITT Population) 
 
Yes (S6) 
IP 
 
14.3.1.2.1 
TEAEs by System Organ Class and Preferred Term (ITT 
Population) 
 
Yes (S7) 
IP 
 
14.3.1.2.2 
Treatment-Related TEAEs by System Organ Class and Preferred 
Term (ITT Population) 
 
Yes (S8) 
IP 
14.3.1.2.1 
14.3.1.2.3 
Serious TEAEs by System Organ Class and Preferred Term (ITT 
Population) 
 
Yes (S9) 
IP 
14.3.1.2.1 
14.3.1.2.4 
Treatment-Related Serious TEAEs by System Organ Class and 
Preferred Term (ITT Population) 
 
Yes (S10) 
IP 
14.3.1.2.1 
14.3.1.3.1 
TEAEs by System Organ Class, Preferred Term and Maximum 
Toxicity Grade (ITT Population) 
 
 
IP 
 
14.3.1.3.2 
TEAEs by System Organ Class, Preferred Term and Strongest 
Relationship to Study Treatment (ITT Population) 
 
 
IP 
14.3.1.3.1 
14.3.2  
Listings of Deaths, Other Serious and Significant Adverse 
Events 
 
 
 
 
14.3.2.1 
Listing of Deaths (ITT Population) 
 
Yes (S11) 
IP 
 
14.3.2.2 
Listing of Serious TEAEs (ITT Population) 
 
 
IP 
14.3.2.1 
14.3.3  
Narratives of Deaths, Other Serious and Certain Other 
Significant Adverse Events 
 
 
 
 
 
Not applicable 
 
 
 
 
14.3.4  
Abnormal Laboratory Values 
 
 
 
 
14.3.4.1 
Listing of Abnormal Laboratory Values (ITT Population) 
 
 
IP 
 
14.3.5 
Laboratory Data 
 
 
 
 
14.3.5.1.1 
Hematology Descriptive Statistics (ITT Population) 
 
Yes (S12) 
IP 
14.2.2.1 
14.3.5.1.2 
Hematology Shift Table (ITT Population) 
 
 
IP 
 
14.3.5.2.1 
Chemistry Descriptive Statistics (Safety Population) 
 
Yes (S13) 
IP 
14.2.2.1 
14.3.5.2.2 
Chemistry Shift Table (ITT Population) 
 
 
IP 
14.3.5.1.2 
14.3.5.3.1 
Urinalysis Descriptive Statistics (Continuous) (ITT Population) 
 
Yes (S14) 
IP 
14.2.2.1 
14.3.5.3.2 
Urinalysis Descriptive Statistics (Categorical) (ITT Population) 
 
Yes (S15) 
IP 
 
14.3.5.3.3 
Urinalysis Shift Table (ITT Population) 
 
 
IP 
14.3.5.1.2 
14.3.6 
Vital Signs 
 
 
 
 
14.3.6.1.1 
Vital Signs Descriptive Statistics (ITT Population) 
 
 
IP 
14.2.2.1 
14.3.7 
Physical Examination 
 
 
 
 
14.3.7.1.1 
Physical Examination Shift Table (ITT Population) 
 
 
IP 
14.3.5.1.2 
14.3.8 
ECG 
 
 
 
 
14.3.8.1.1 
ECG Descriptive Statistics (ITT Population) 
 
 
IP 
14.2.2.1 
14.3.8.1.2 
ECG Shift Table (ITT Population) 
 
 
IP 
14.3.5.1.2 
14.3.9 
Other Safety 
 
 
 
 
14.3.9.1.1 
Chest X-Ray / CT Shift Table (ITT Population) 
 
 
IP 
14.3.5.1.2 
14.4  
Pharmacokinetics 
 
 
 
 


Worldwide Clinical Trials Controlled Quality Management Document 
 
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Protocol Number: 
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Governing QMD: Worldwide-SOP-ST-001 
Confidentiality Statement 
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Table 
Number 
Table Title 
Included in 
Preliminary 
Analysis 
Included 
in DSMB 
(Table 
No.) 
Validation 
Method 
Shell 
Number 
(if 
repeat) 
14.4.1.1 
Pharmacokinetic Concentrations Descriptive Statistics (ITT 
Population) 
 
 
IP 
 
14.4.2.1 
Pharmacokinetic 
Parameters 
Descriptive 
Statistics 
(ITT 
Population) 
 
 
IP 
 
 
 
 


Worldwide Clinical Trials Controlled Quality Management Document 
 
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Protocol Number: 
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Figure 
Number 
Figure Title 
Included 
in 
DSMB 
Validation 
Method 
Shell 
Number 
(if 
repeat) 
14.2 
Efficacy Figures 
 
 
 
14.2.1.1 
Mean Profile for WHO Ordinal Scale for Clinical Improvement (ITT 
Population) 
 
IP 
 
14.2.1.2 
Mean Change from Baseline Profile for WHO Ordinal Scale for 
Clinical Improvement (ITT Population) 
 
IP 
14.2.1.1 
14.3 
Safety Figures 
 
 
 
14.3.1.1 
Individual Body Temperature versus Time by Treatment Group (ITT 
Population) 
 
IP 
 
14.3.2.1 
Individual SpO2 versus Time by Treatment Group (ITT Population) 
 
IP 
14.3.1.1 
14.4 
Pharmacokinetic Figures 
 
 
 
14.4.1.1 
Pharmacokinetic Concentrations, Individual Profiles on Linear and 
Semi-Logarithmic Scales (ITT Population) 
 
IP 
 
14.4.1.2 
Pharmacokinetic Concentrations, Mean Profiles on Linear and Semi-
Logarithmic Scales (ITT Population) 
 
IP 
 
 
 


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Listing 
Number 
Listing Title 
Included 
in DSMB 
Validation 
Method 
Shell 
Number 
(if 
repeat) 
16.2  
Subject Data Listings 
 
 
 
16.2.1  
Discontinued Subjects 
 
 
 
16.2.1.1 
Screen Failures (Enrolled Population) 
 
IP 
 
16.2.1.2 
Inclusion/Exclusion Criteria Violations (Enrolled Population) 
 
IP 
 
16.2.1.3 
Study Completion (ITT Population) 
 
IP 
 
16.2.2 
Protocol Deviations 
 
 
 
16.2.2.1 
Protocol Deviations (ITT Population) 
Yes (LS7) 
IP 
 
16.2.3 
Subjects Excluded from The Efficacy Analyses 
 
 
 
16.2.3.1 
Analysis Populations (ITT Population) 
 
IP 
 
16.2.4 
Demographic Data 
 
 
 
16.2.4.1 
Demographics (ITT Population) 
Yes (LS1) 
IP 
 
16.2.4.2 
Medical History (ITT Population) 
Yes (LS2) 
IP 
 
16.2.4.3 
Prior and Concomitant Medications (ITT Population) 
 
IP 
 
16.2.5  
Compliance and / or Drug Concentration Data 
 
 
 
16.2.5.1 
Drug Accountability (ITT Population) 
 
IP 
 
16.2.5.2 
Dosing (ITT Population) 
 
IP 
 
16.2.5.3 
Standard of Care (ITT Population) 
 
IP 
16.2.4.3 
16.2.5.4 
Pharmacokinetic Concentrations (ITT Population) 
 
IP 
 
16.2.5.5 
Pharmacokinetic Parameters (ITT Population) 
 
IP 
 
16.2.6  
Individual Efficacy Response Data 
 
 
 
16.2.6.1 
Responder Endpoints (ITT Population) 
 
IP 
 
16.2.6.2 
WHO Ordinal Scale for Clinical Improvement (ITT Population) 
 
IP 
 
16.2.6.3 
‘Days on/in’ Endpoints (ITT Population) 
 
IP 
 
16.2.7  
Adverse Event Listings 
 
 
 
16.2.7.1 
Adverse Events (ITT Population) 
Yes (LS3) 
IP 
 
16.2.8  
Individual Laboratory Measurements and Other Safety 
 
 
 
16.2.8.1 
Hematology (ITT Population) 
Yes (LS4) 
IP 
 
16.2.8.2 
Serum Chemistry (ITT Population) 
Yes (LS5) 
IP 
 
16.2.8.3 
Urinalysis (ITT Population) 
Yes (LS6) 
IP 
 
16.2.8.4 
Pregnancy Test (ITT Population) 
 
IP 
 
16.2.8.5 
Vital Signs (ITT Population) 
 
IP 
 
16.2.8.6 
Physical Examination (ITT Population) 
 
IP 
 
16.2.8.7 
ECG (ITT Population) 
 
IP 
 
16.2.8.8 
Chest X-Ray / CT (ITT Population) 
 
IP 
 
 

Prot_000.pdf: 
Veru Inc 
CONFIDENTIAL 
Protocol V0211901 – FINAL Version 7.0 
FINAL: Amendment 6 (Version 7) 25 September 2020
 
 
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CLINICAL TRIAL PROTOCOL: V0211901 
 
Protocol Number: 
V0211901 
Protocol Date: 
Original Protocol/ 23 April 2020 
 
 
 
Amendment 1 (version 2.0)/ 5 May 2020 
 
 
 
Amendment 2 (version 3.0)/12 May 2020 
 
 
 
Amendment 3 (version 4.0)/4 June 2020 
 
 
 
Amendment 4 (version 5.0)/17 June 2020 
 
 
 
Amendment 5 (version 6.0)/10 July 2020 
 
 
 
Amendment 6 (version 7.0)/25 September 2020 
 
 
 
 
Protocol Title: 
Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for the 
Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 
(SARS-CoV-2) in Patients at High Risk for Acute Respiratory Distress 
Syndrome (ARDS). 
IND number:  
149282 
EudraCT number: Not Applicable 
Clinical Phase: 
2 
Study Sponsor: 
Veru Inc. 
48 NW 25th St 
Suite 102 
Miami, FL 33127 
Telephone: (305) 509-6986 
 
CONFIDENTIAL 
This document is a confidential communication of Veru Inc. All information and data 
contained within this document is confidential. Acceptance of this document constitutes the 
agreement by the recipient that no information contained herein may be divulged or disclosed 
to third parties without prior written approval. 


Veru Inc 
CONFIDENTIAL 
Protocol V0211901 – FINAL Version 7.0 
FINAL: Amendment 6 (Version 7) 25 September 2020
 
 
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TABLE OF CONTENTS 
1.0 
LIST OF ABBREVIATIONS ...................................................................... 5 
2.0 
PHASE 2 PROTOCOL SUMMARY ........................................................... 6 
3.0 
INTRODUCTION .................................................................................... 10 
3.1 
Background ............................................................................................... 10 
3.2 
Target Indication and Pharmacologic Activity ............................................... 13 
3.3 
Study Rationale .......................................................................................... 13 
4.0 
STUDY OBJECTIVES ............................................................................. 14 
4.1 
Primary Objectives ..................................................................................... 14 
4.2 
Secondary Objectives ................................................................................. 14 
4.3 
Safety Objective ......................................................................................... 15 
5.0 
STUDY DESIGN ...................................................................................... 15 
5.1 
Treatment Groups and Allocation of Subjects ................................................ 15 
5.2 
Study Duration ........................................................................................... 15 
5.3 
Efficacy Endpoints ..................................................................................... 16 
5.3.1 
Primary Endpoint ....................................................................................... 16 
5.3.2 
Secondary Endpoints .................................................................................. 16 
6.0 
SUBJECT POPULATION ........................................................................ 17 
6.1 
Number of Subjects .................................................................................... 17 
6.2 
Selection Criteria ........................................................................................ 17 
6.2.1 
Inclusion Criteria ........................................................................................ 17 
6.2.2 
Exclusion Criteria ....................................................................................... 18 
7.0 
STUDY MEDICATION ............................................................................ 19 
7.1 
Enrollment and Blinding ............................................................................. 19 
7.2 
Drug Supply .............................................................................................. 20 
7.2.1 
VERU-111 Capsules ................................................................................... 20 
7.2.2 
Placebo Control .......................................................................................... 20 
7.2.3 
Drug Accountability ................................................................................... 20 
7.3 
Drug Administration ................................................................................... 20 
8.0 
STUDY PROCEDURES ........................................................................... 21 
8.1 
Screening .................................................................................................. 21 
8.2 
Enrollment ................................................................................................. 21 
8.3 
Day 1 ........................................................................................................ 21 
8.4 
Day 2 through Day 21 ................................................................................. 22 
8.5 
Day 3, Day 9, and Day 15 ........................................................................... 22 
8.6 
Day 22 ± 3 days (these assessments will also be done at Early Termination or 
Discontinuation from the study) ................................................................... 23 
8.7 
Day 29 ± 3 days ......................................................................................... 23 


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8.8 
Follow up visits at Day 45 (± 3 days) and Day 60 (± 3 days) (can be 
conducted via phone/teleconference) ............................................................ 23 
8.9 
Subject Stopping Rules ............................................................................... 24 
8.10 
Early Discontinuation of Study Treatment ..................................................... 24 
8.11 
Adverse Events .......................................................................................... 25 
8.11.1 
Intensity of Adverse Events ......................................................................... 26 
8.11.2 
Test Medication Causality ........................................................................... 26 
8.11.3 
Serious Adverse Events ............................................................................... 27 
8.11.4 
Initial Reports ............................................................................................ 28 
8.11.5 
Precautions ................................................................................................ 28 
8.11.6 
Reporting of Adverse Events Associated with Study Drug Overdose, Misuse, 
Abuse or Medication Error .......................................................................... 28 
8.12 
Concomitant Medications and Concomitant Therapies ................................... 29 
8.13 
Prohibited Medications ............................................................................... 29 
8.14 
Withdrawal of Subjects ............................................................................... 29 
9.0 
STATISTICAL ANALYSIS ...................................................................... 29 
9.1 
Sample Size Calculation .............................................................................. 29 
9.2 
Populations ................................................................................................ 30 
9.3 
Efficacy Analyses ....................................................................................... 30 
9.3.1 
Primary Endpoint ....................................................................................... 30 
9.4 
Secondary Analyses .................................................................................... 30 
9.4.1 
Secondary Endpoints .................................................................................. 30 
9.4.1.1 
Mean change from baseline in WHO Ordinal Scale for Clinical Improvement at 
Day 15, Day 22 and Day 29 ......................................................................... 30 
9.4.1.2 
Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for 
Clinical Improvement at Day 15, Day 22, and Day 29 .................................... 31 
9.4.1.3 
Proportion of subjects with normalization of fever and oxygen saturation through 
Day 15, Day 22, and Day 29. ....................................................................... 31 
9.4.1.4 
Days on mechanical ventilation .................................................................... 31 
9.4.1.5 
All-cause mortality at Day 15, Day 22, and Day 29 ........................................ 32 
9.4.1.6 
Proportion of patients alive and free of respiratory failure at Day 15, and Day 2232 
9.4.1.7 
Proportion of patients alive and discharged from the ICU at Day 15, Day 22, and 
Day 29 ...................................................................................................... 32 
9.4.1.8 
Proportion of patients alive and discharged from hospital at Day 15, Day 22, and 
Day 29 ...................................................................................................... 33 
9.4.1.9 
Days in ICU ............................................................................................... 33 
9.4.1.10 
Days in hospital.......................................................................................... 33 
9.4.1.11 
Proportion of subjects on mechanical ventilation at Day 15, Day 22, and Day 2933 
9.4.1.12 
Mean change from baseline in C-reactive protein at Day 9 .............................. 33 


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9.5 
Interim Analysis ......................................................................................... 34 
9.6 
Pharmacokinetic Analysis ........................................................................... 34 
9.6.1 
Plasma Sample Labels ................................................................................ 35 
9.7 
Safety Analysis .......................................................................................... 35 
9.7.1 
Data Safety Monitoring Board ..................................................................... 35 
10.0 
ADMINISTRATION PROCEDURES ....................................................... 36 
10.1 
Study Conduct and Compliance ................................................................... 36 
10.2 
Informed Consent ....................................................................................... 36 
10.3 
Protocol Amendments ................................................................................. 37 
10.4 
Protocol Deviations .................................................................................... 38 
10.5 
Data Handling and Recordkeeping ............................................................... 38 
10.5.1 
Data Handling ............................................................................................ 38 
10.5.2 
Data Entry ................................................................................................. 38 
10.5.3 
Medical Information Coding ........................................................................ 38 
10.5.4 
Data Validation .......................................................................................... 38 
10.5.5 
Record Keeping ......................................................................................... 39 
10.6 
Data Quality .............................................................................................. 39 
10.7 
Regulatory Approval .................................................................................. 39 
10.8 
Publication Policy ...................................................................................... 39 
10.9 
Clinical Study Report .................................................................................. 40 
10.10 
Contractual and Financial Details ................................................................. 40 
10.11 
Insurance and Indemnity ............................................................................. 40 
11.0 
REFERENCES ......................................................................................... 41 
12.0 
APPENDICES .......................................................................................... 43 
12.1 
Appendix A: Clinical Laboratory Tests (local laboratory) ............................... 43 
12.2 
Appendix B: Schedule of Study Evaluations.................................................. 44 
 


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1.0 
LIST OF ABBREVIATIONS 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ARDS 
Acute respiratory distress syndrome 
AST 
Aspartate aminotransferase 
BUN 
Blood urea nitrogen 
ECMO 
Extracorporeal membrane oxygenation 
eCRF 
Electronic Case report form 
ECOG 
Eastern Cooperative Oncology Group 
GCP 
Good clinical practice 
GGT 
Gamma-glutamyl transferase 
IMP 
Investigational medicinal product 
IRB 
Institutional review board 
IUD 
Intrauterine device 
IUS 
Intrauterine system 
LDH 
Lactate dehydrogenase 
LDL 
Low density lipoprotein 
LMWH 
Low molecular weight heparin 
MedDRA 
Medical dictionary of regulatory activities 
NSAID 
Nonsteroidal anti-inflammatory drug 
OTC 
Over the Counter 
PRN 
Pro re nata – As Needed 
RRT 
Renal replacement therapy 
SAE 
Serious adverse event 
 
 
 
 
 
 
 


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2.0 
PHASE 2 PROTOCOL SUMMARY 
Study 
Number: 
 
V0211901 
Title: 
Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for the 
Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-
CoV-2) in Patients at High Risk for Acute Respiratory Distress Syndrome 
(ARDS) 
 
Primary 
Objectives: 
To demonstrate the efficacy of VERU-111 in the treatment of SARS-Cov-
2 Infection by assessing its effect on the proportion of subjects that are 
alive without respiratory failure at Day 29. Respiratory failure is defined as 
endotracheal intubation and mechanical ventilation, extracorporeal 
membrane oxygenation, high-flow nasal cannula oxygen delivery, 
noninvasive positive pressure ventilation, clinical diagnosis of respiratory 
failure with initiation of none of these measures only when clinical 
decision making is driven solely by resource limitation. 


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FINAL: Amendment 6 (Version 7) 25 September 2020
 
 
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Secondary 
Objectives: 
The secondary objectives/endpoints on this study are: 
1. WHO Ordinal Scale for Clinical Improvement (8-point ordinal 
scale) at Day 15, Day 22, and Day 29  
Patient State 
Descriptor 
Score 
Uninfected 
No clinical or virological evidence 
of infection 
0 
Ambulatory 
No limitation of activities 
1 
 
Limitation of activities 
2 
Hospitalized, Mild disease 
Hospitalized, no oxygen therapy 
3 
 
Oxygen by mask or nasal prongs 
4 
Hospitalized, Severe 
disease 
Non-invasive ventilation or high-
flow oxygen 
5 
 
Intubation and mechanical 
ventilation 
6 
 
Ventilation + additional organ 
support – pressors, RRT, ECMO 
7 
Death 
Death 
8 
 
2. Proportion of subjects with normalization of fever and oxygen 
saturation through Day 15, Day 22, and Day 29 
3. Days on mechanical ventilation 
4. Percentage of subjects discharged from hospital by Day 15 (and 
Day 22) 
5. All-cause mortality at Day 15, Day 22, and Day 29 
6. Proportion of patients alive and free of respiratory failure at Day 
15, and Day 22 
7. Proportion of patients alive and discharged from the ICU at Day 15, 
Day 22, and Day 29 
8. Proportion of patients alive and discharged from hospital at Day 15, 
Day 22, and Day 29 
9. Days in ICU 
10. Days in hospital 
11. Proportion of subjects on mechanical ventilation at Day 15, Day 22, 
and Day 29 
12. Assess the pharmacokinetics of VERU-111 on Day 15 
13. Assess the effect of VERU-111 on C-reactive protein (change from 
baseline) 
 


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Safety 
Objective: 
To assess the safety and tolerability of VERU-111 
Design: 
This study is a multicenter, randomized, placebo-control, efficacy and 
safety study of VERU-111 for the treatment of COVID-19. Subjects will 
receive either 18 mg of VERU-111 or matching placebo orally or through 
nasogastric tube daily for up to 21 days or until the subject is discharged 
from the hospital, whichever comes first. 
The primary efficacy endpoint of the study will be the proportion of 
subjects that are alive without respiratory failure at Day 29. Respiratory 
failure is defined as endotracheal intubation and mechanical ventilation, 
extracorporeal membrane oxygenation, high-flow nasal cannula oxygen 
delivery, noninvasive positive pressure ventilation, clinical diagnosis of 
respiratory failure with initiation of none of these measures only when 
clinical decision making is driven solely by resource limitation. 
The total study duration for a subject from screening to follow up visit is 
planned to be 62 days. 
An evaluation of the effect of VERU-111 on SARS-CoV-2 (COVID-19) 
compared to the placebo control will be evaluated after the last subject has 
completed Day 22. This will allow for the decision to move to Phase 3 
more quickly if the Phase 2 portion of the study shows a clinically relevant 
difference in the proportion of subjects that are alive without respiratory 
failure at Day 22 in the VERU-111 treated groups compared to the Placebo 
treatment group and VERU-111 is well tolerated in the study. 
Due to the unexpectedly slow recruitment into this study, Veru is 
conducting an interim analysis after the first 24 subjects have completed 
Day 15 or have discontinued from the study. 
Subjects: 
Approximately, 40 subjects are planned to be randomized at a 1:1 ratio into 
two treatment arms (20 subjects in the VERU-111 treated group and 20 
subjects in the Placebo treated group).  
The subjects with documented evidence of COVID-19 infection will be 
enrolled.  
Treatments: 
Subjects in the VERU-111 treatment groups will receive standard of care, 
plus oral daily VERU-111 18 mg for 21 days or until released from 
hospital. 
Subjects in the Placebo treatment group will receive standard of care, plus 
a placebo capsule for 21 days or until released from hospital. 


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Procedures: 
 
Potential study participants will undergo a series of screening evaluations 
within 2 days prior to randomization.  Subjects who give written informed 
consent and satisfy the selection criteria will be enrolled into the study.   
The temperature and SpO2 levels will be taken every 12 hours starting at 
baseline. 
Safety evaluations including assessment of adverse events (Days 1-21, Day 
29, Day 45, and Day 60), 12-lead electrocardiogram (single) (baseline, Day 
15, Day 22, and Day 29) and clinical laboratory results: urinalysis 
(baseline, Day 22, and Day 29), hematology (baseline, Day 3, Day 9, Day 
15, Day 22, and Day 29), and serum chemistry (baseline, Day 3, Day 9, 
Day 15, Day 22 and Day 29). 


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3.0 
INTRODUCTION 
3.1 
Background 
Over the last 20 years, a number of viral epidemics have posed a serious global public health 
risk including Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2002-2003, 
H1N1 Influenza in 2009, and the Middle East Respiratory Syndrome coronavirus (MERS-
CoV) in 2012. Around December 2019, a new viral acute severe respiratory illness emerged. 
In February 2020, the World Health Organization (WHO) announced that this illness is 
caused by a coronavirus termed COVID-19. As it was related to SARS-CoV, it was 
eventually named by the International Committee on Taxonomy of Viruses (ICTV) as SARS-
CoV-2 (Cascella 2020). The disease resulting from SARS-Cov-2 infection is called, 
Coronavirus Disease 2019 (COVID-19). Infection with SARS-CoV-2 and the resulting 
COVID-19 disease has been declared a global pandemic with over 2,107,450 cases and 
136,992 deaths worldwide as of 18 April 2020 and counting (April 18, 2020; 
Worldometers.info). 
SARS-CoV-2 is an enveloped, nonsegmented, positive-sense, single stranded RNA virus with 
an unusually large RNA genome, a nucleocapsid, and club-like spikes (S protein) that project 
from their surface and from which they are named.  It belongs to the betacoronavirus 
category which includes SARS-CoV and MERS-CoV. These viruses have been responsible 
for epidemics with variable severity with both respiratory and extra-respiratory clinical 
manifestations, highly contagious, and mortality rates between 10-35% (Cascella 2020). The 
coronavirus superfamily (Coronaviridae) includes several human pathogens with large RNA 
genomes, e.g., influenza and viral encephalitis and they are classified into alpha, beta, delta 
and gamma coronavirus families and then further divided into Lineages A, B, C and D. 
SARS-CoV-2 is a Lineage B betacoronavirus (Gorbalenya 2020). 
Viruses have efficient mechanisms that take control of their host’s cellular machinery to carry 
out viral replication, assembly and to exit from the cell to spread infectious virions. Given the 
spatial distances between the point of virion entry at the plasma membrane to the location in 
the cell where RNA replication (nucleus) and viral assembly occur in the ER and Golgi and 
then the newly generated virions have to travel back out to the plasma membrane to egress out 
of the cell, it is no wonder that the virus’s most critical task is to hijack the host’s internal 
transportation system, the cytoskeleton (Ward 2011). The cytoskeleton has three major types 
of protein filaments: microfilaments (actin), microtubules (tubulin), and intermediate 
filaments. The principal ones involved in viral replication and trafficking (transport) are 
microtubules and actin since these are the two main filament systems involved in cellular 
transport (Ward 2011). 
Microtubules are important for cell shape, transport, motility, and cell division (Heald 2002). 
Microtubules are dynamic long polar fibers/filaments that result from the polymerization of  
and   tubulin heterodimer subunits with a positive end located at the plasma membrane and a 
minus end facing the nucleus at the microtubule organizing center (MTOC). From the MTOC, 
microtubule fibers radiate out from the nuclear area towards the periphery of the cell. 
Microtubules are dynamic network systems, meaning that, they undergo rapid polymerization 


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(add  and   tubulin subunits heterodimers) to grow, and subsequent rapid depolymerization 
(remove  and   tubulin subunits heterodimers) to shrink. This “dynamic” growing and 
shrinking serves the constantly changing transportation requirements of the cell. Large 
macromolecules, like viruses, engage with specialized motor proteins (kinesins and dyneins) 
(Dohner 2005; Biswas 2014; Han 2012; Hara 2009). Kinesins and dyneins attach, carry, and 
move the virus cargo up and down these microtubule tracks to travel long distances to reach 
the different compartments within the cell (Ward 2011; Simpson 2020; Cooper 2000). 
Microtubule based transportation is a critical aspect of viral replication (Naghavi 2017; 
Dohner 2005). In fact, viral infection or expression of viral proteins alters the organization of 
the microtubular networks to serve their need to replicate and spread infectious virion. 
Microtubules not only facilitate infection, but microtubules are actively manipulated by 
viruses (Naghavi 2017).  Furthermore, microtubule inhibiting agents that disrupt microtubule 
networks suppress viral infection (Rudiger 2016). 
Virus-cell surface interactions, virus entry and internalization-  
Although microtubules are located within the cell, they are able to influence the viral infection 
from the onset. Viruses utilize specific sites and proteins to attached to the cell surface. The 
spatial organization of these surface receptors and entry factors are controlled in part by the 
polarization of the microtubular array (Naghavi 2017). When added early, nocodazole, a 
microtubule depolymerizing drug, decreased mouse hepatitis coronavirus virus infection by 
affecting plasma membrane entry by endocytosis (Burkard 2014). There are apparently other 
ways that entry and internalization may occur as human coronavirus NL63 internalization and 
vesicle entry was not affected by nocodazole (Milewska 2018). 
In the case of SARS-CoV, the first stage of interaction with the microtubule cytoskeleton 
occurs when the Spike (S) protein mediated attachment to the cell surface (Ren 2015). After 
binding, the virus particles actively rearrange the cytoskeleton by regulating the 
FAK/Cofilin/Rac/Cdc42 pathway (Lv 2019).  
Virus intracellular transport via microtubules to the perinuclear region- 
Many viruses require microtubules at cell entry for efficient nuclear targeting (Dohner 2005). 
Vesicular transport occurs via microtubule trafficking and the corresponding specialized 
motor proteins. In the case of the Mouse Hepatitis Coronavirus Virus, the early secretory 
pathway is important in the formation of the replication complex (Knoops 2010; Oostra 
2007). Intracellular transport of the endocytosed vesicles containing coronavirus utilizes S-
protein bound to  - tubulin on microtubules to locate to the perinuclear region of the cell.  
Viruses can also modulate microtubular dynamics to promote rapid transport to nucleus 
(Naghavi 2017; Suomalainen 2001).  Coronaviruses may also have interactions of S proteins 
with the specialized motor proteins like kinesins and dyneins (Rudiger 2016).  
Virion replication and assembly and egress of infectious viral particles out of the cell- 
Virus particle assembly occurs in the ER-Golgi intermediate compartment (ERGIC) and is 
orchestrated by the M protein. M provides the scaffold for virion morphogenesis and M-S and 
M-N interactions facilitate the recruitment of structural components to the assembly site. 


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Coronavirus particles budding into the ERGIC are transported in smooth walled vesicles and 
trafficked via microtubules for release by exocytosis. Host factors, specifically, the 
interactions between the cytoskeleton and other structural proteins are essential in this 
process. Interactions between tubulin and the cytosolic domain of the S protein of human 
coronavirus-229E, human coronavirus-NL63, and TGEV are required for successful assembly 
and release of viral particles (Reviewed in Fung 2019). RNA viruses utilize diverse structures 
within the cytoskeleton for their replication which rely on microtubules to form and function 
(Naghavi 2017). Nocodazole, a microtubule depolymerizing agent, blocks the movement and 
fusion of capsids and nucleoprotein particles to the budding ER/Golgi compartments to form 
virions as well as the secretory microtubule trafficking to egress new virions resulting in 
reduced virus yields (Eichwald 2012; Criglar 2014; Dohner 2005).   
To evaluate early assembly events, alpha (HCoV-229E, HCoV-NL63, and TGEV) and beta 
(SARS-CoV) coronaviruses S proteins were treated with nocodazole. The pharmacological 
action of nocodazole is the inhibition of tubulin polymerization. Untreated cells had long and 
filamentous tubulin structures (microtubules) and the S protein accumulated near the nucleus 
(ERGIC) and less S protein distributed in the cytosol, whereas the nocodazole treated cells 
had dispersed and patchy tubulin fragments and the S proteins were “differentially 
distributed”, or scattered throughout the cytoplasm (Rudiger 2016). Also, following 
nocodazole treatment, M protein amount was decreased and there was a reduced 
colocalization of S and M proteins (Rudiger 2016). Nocodazole treatment resulted in both a 
significant reduction in viral particles and these particles had very little S protein, and thus, 
the virions were less infectious as well (Rudiger 2016). In fact, nocodazole treatment at all 
time points resulted in significantly lower virus titers in cell culture supernatant versus 
untreated infected cells (Rudiger 2016).  
In summary, tubulin interacts with the cytoplasmic domain of alphacoronavirus and 
betacoronavirus SARS-CoV spike S proteins.  Rudiger et al. (2016) conclude that the 
reduction in infectious virus titer following treatment with a drug that causes microtubule 
depolymerization is mainly because there is less S protein present at the assembly site due to 
impaired S protein-microtubule transport and that the incorporation process of S protein itself 
into virions is tubulin-dependent. Furthermore, disruption of microtubule trafficking impaired 
the egress of these poorly assembled virions with less surface spike S proteins, less infectious, 
out of the cell. A microtubule depolymerizing agent may be effective in treating in treating 
coronavirus infection to disrupt microtubule trafficking critical for virus replication cycle. 
Colchicine-like Activity 
The central mechanism of colchicine clinical anti-inflammatory and anti-viral activities is 
based on its ability to bind the “colchicine binding” sites on alpha and beta tubulin which 
when incorporated into microtubule block subsequent microtubule polymerization 
(Slobodnick 2018). Inhibition of tubulin polymerization is responsible for the effects of 
colchicine on cell migration, cytokine release, and intracellular trafficking (antiviral) and 
disruption of inflammatory cell activities seen for acute gout and familial Mediterranean 
fever. Colchicine modulates leucocyte mediated inflammatory activities including inhibition 
of leucocyte production of superoxides and release of various cytokines and pyrogens 


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(Slobodnick 2018). Colchicine-like agents may be useful to treat the “cytokine storm” seen 
with SARS-CoV 2. IL-18 is a member of the IL-1 cytokine family and unopposed elevated 
levels of IL-18 concentrations have been associated with macrophage activation syndrome 
and poor clinical outcomes in severe inflammatory and septic shock conditions (Verweyen 
2020). Interestingly, colchicine abrogates IL-1 and IL-18 overexpression by reducing its 
transcription to reduce severe inflammation and septic shock. Verweyen et al. (2020) also 
showed that colchicine as well as nocodazole abrogated IL18 expression confirming that 
microtubule depolymerization is the mechanism. 
3.2 
Target Indication and Pharmacologic Activity 
VERU-111 is orally bioavailable bis-indole that binds the “colchicine binding site” of  and  
tubulin and inhibits tubulin polymerization at low nanomolar concentrations. VERU-111 is 
neither a substrate for MDRs including P-gp, MRPs, and BCRP, nor CYP3A4. VERU-111 
also decreases the transcription of I, III, and IV-tubulin isoforms (Li 2012). VERU-111 
was initially developed as an antiproliferative agent to treat malignancy. In preclinical animal 
models and confirmed in a Phase 1b/2 study in 39 men with metastatic prostate cancer, 
VERU-111 has a good safety profile as it does not cause neutropenia or myelosuppression 
and is well tolerated (clinical data on file at Veru Inc., Li 2012; Chen 2012). The Phase 1b 
study is ongoing with some men being treated with high daily doses of VERU-111 for greater 
than a year. In vivo, VERU-111 disrupts the microtubule filaments similar to nocodazole and 
colchicine, the central mechanism that contributes to both their antiviral and anti-
inflammatory activities. 
3.3 
Study Rationale 
Based on VERU-111’s mechanistic similarities to other microtubular depolymerizing agents 
as well as its preclinical and clinical experience, VERU-111 could have a two-pronged 
approach to the treatment of SARS-CoV-2 (COVID-19) virus infection and the debilitating 
and sometimes lethal respiratory effects of the virus.  
1. As an antiviral, it would have direct effects on S protein-microtubule trafficking with 
the potential to reduce the production of infectious virions particularly affecting viral 
replication and assembly and virion egress.  
2. As an anti-inflammatory agent, it may reduce virally induced severe inflammation in 
the respiratory system and reduce the incidence of cytokine storm and septic shock 
that can occur in subjects that progress. 
VERU-111 appears to be an appropriate candidate to enter clinical development for the 
treatment of SARS-CoV-2 (COVID-19) infection. In the absence of an effective treatment 
and the progression of the ongoing global pandemic and potentially future similar viral 
epidemic infections, Veru is initiating a Phase 2 clinical development program of VERU-111 
for the treatment of SARS-CoV-2 infection (COVID-19). 


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4.0 
STUDY OBJECTIVES 
4.1 
Primary Objectives 
To demonstrate the efficacy of VERU-111 in the treatment of SARS-CoV-2 infection by 
assessing its effect on the proportion of subjects that are alive without respiratory failure at 
Day 29. Respiratory failure is defined as endotracheal intubation and mechanical ventilation, 
extracorporeal membrane oxygenation, high-flow nasal cannula oxygen delivery, noninvasive 
positive pressure ventilation, clinical diagnosis of respiratory failure with initiation of none of 
these measures only when clinical decision making is driven solely by resource limitation. 
4.2 
Secondary Objectives 
The secondary objectives/endpoints on this study are: 
1. WHO Ordinal Scale for Clinical Improvement (8-point ordinal scale) at Day 15, Day 
22, and Day 29  
Patient State 
Descriptor 
Score 
Uninfected 
No clinical or virological evidence 
of infection 
0 
Ambulatory 
No limitation of activities 
1 
 
Limitation of activities 
2 
Hospitalized, Mild disease 
Hospitalized, no oxygen therapy 
3 
 
Oxygen by mask or nasal prongs 
4 
Hospitalized, Severe 
disease 
Non-invasive ventilation or high-
flow oxygen 
5 
 
Intubation and mechanical 
ventilation 
6 
 
Ventilation + additional organ 
support – pressors, RRT, ECMO 
7 
Death 
Death 
8 
a. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 15 
b. Proportion of subjects that progress to Grade 5, 6, 7, or 8 on the WHO Ordinal 
Scale for Clinical Improvement at Day 15 
c. Proportion of subjects that progress to Grade 5, 6, 7, or 8 on the WHO Ordinal 
Scale for Clinical Improvement at Day 22 
d. Proportion of subjects that progress to Grade 5, 6, 7, or 8 on the WHO Ordinal 
Scale for Clinical Improvement at Day 29 


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e. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 22 
f. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 29 
2. Proportion of subjects with normalization of fever and oxygen saturation through Day 
15, Day 22, and Day 29 
3. Days on mechanical ventilation 
4. Percentage of subjects discharged from hospital by Day 15 (and Day 22) 
5. All-cause mortality at Day 15, Day 22, and Day 29 
6. Proportion of patients alive and free of respiratory failure at Day 15, and Day 22 
7. Proportion of patients alive and discharged from the ICU at Day 15, Day 22, and Day 
29 
8. Proportion of patients alive and discharged from hospital at Day 15, Day 22, and Day 
29 
9. Days in ICU 
10. Days in hospital 
11. Proportion of subjects on mechanical ventilation at Day 15, Day 22, and Day 29 
12. Assess the pharmacokinetics of VERU-111 on Day 15 
13. Assess the effect of VERU-111 on C-reactive protein from baseline to Day 9 
4.3 
Safety Objective 
To assess the safety and tolerability of VERU-111 
5.0 
STUDY DESIGN 
5.1 
Treatment Groups and Allocation of Subjects 
This randomized, placebo-control clinical study consists of two treatment arms: VERU-111 
18 mg treated group, and Placebo treated group. Subjects will be randomized in a 1:1 fashion 
to the VERU-111 treated group and Placebo treated group, respectively. 
All patients will receive standard of care for the treatment of SARS-CoV-2 infection 
(COVID-19). 
5.2 
Study Duration 
The study will require that each subject in the VERU-111 treated groups receive 18 mg daily 
oral dose of VERU-111 or placebo for up to 21 days (Day 21) with final on study efficacy 
assessments done on Day 29 with safety assessments continuing to Day 60 of the study. The 
total duration of the study for a subject in the study from screening to follow-up visit 
(approximately Day 60 on study) will be approximately 62 days.   


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5.3 
Efficacy Endpoints 
5.3.1 
Primary Endpoint 
The primary endpoint for the study is the proportion of subjects that are alive without 
respiratory failure at Day 29. Respiratory failure is defined as endotracheal intubation and 
mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula 
oxygen delivery, noninvasive positive pressure ventilation, clinical diagnosis of respiratory 
failure with initiation of none of these measures only when clinical decision making is driven 
solely by resource limitation. 
5.3.2 
Secondary Endpoints 
The secondary endpoints on this study are: 
1. WHO Ordinal Scale for Clinical Improvement (8-point ordinal scale) 
Patient State 
Descriptor 
Score 
Uninfected 
No clinical or virological evidence 
of infection 
0 
Ambulatory 
No limitation of activities 
1 
 
Limitation of activities 
2 
Hospitalized, Mild disease 
Hospitalized, no oxygen therapy 
3 
 
Oxygen by mask or nasal prongs 
4 
Hospitalized, Severe 
disease 
Non-invasive ventilation or high-
flow oxygen 
5 
 
Intubation and mechanical 
ventilation 
6 
 
Ventilation + additional organ 
support – pressors, RRT, ECMO 
7 
Death 
Death 
8 
1. Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for 
Clinical Improvement at Day 15 
2. Proportion of subjects that progress to Grade 5, 6, 7, or 8 on the WHO Ordinal Scale 
for Clinical Improvement at Day 22 
3. Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for 
Clinical Improvement at Day 29 
4. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 15. 
5. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 22 
6. Change in mean WHO Ordinal Scale for Clinical Improvement at Day 29 


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7. Proportion of subjects with normalization of fever and oxygen saturation through Day 
15. This will be a composite of fever normalization maintained for at least 24 hours 
AND peripheral capillary oxygen saturation (SpO2) >94% sustained for 24 hours. 
8. Proportion of subjects with normalization of fever and oxygen saturation through Day 
22. This will be a composite of fever normalization maintained for at least 24 hours 
AND peripheral capillary oxygen saturation (SpO2) >94% sustained for 24 hours. 
9. Proportion of subjects with normalization of fever and oxygen saturation through Day 
29. This will be a composite of fever normalization maintained for at least 24 hours 
AND peripheral capillary oxygen saturation (SpO2) >94% sustained for 24 hours. 
10. Days on mechanical ventilation  
11. All-cause mortality at Day 15 
12. All-cause mortality at Day 22 
13. All-cause mortality at Day 29 
14. Proportion of patients alive and free of respiratory failure at Day 15 
15. Proportion of patients alive and free of respiratory failure at Day 22 
16. Proportion of patients alive and discharged from the ICU at Day 15 
17. Proportion of patients alive and discharged from the ICU at Day 29 
18. Proportion of patients alive and discharged from hospital at Day 15 
19. Proportion of patients alive and discharged from hospital at Day 22 
20. Proportion of patients alive and discharged from hospital at Day 29 
21. Days in ICU 
22. Days in hospital 
23. Proportion of subjects on mechanical ventilation at Day 15 
24. Proportion of subjects on mechanical ventilation at Day 22 
25. Proportion of subjects on mechanical ventilation at Day 29 
26. Pharmacokinetics of VERU-111 on Day 15 
27. Change in mean C-reactive protein from baseline to Day 9. 
6.0 
SUBJECT POPULATION 
6.1 
Number of Subjects 
Approximately, 40 subjects are planned to be randomized at a 1:1 ratio into two treatment 
arms (20 subjects in the VERU-111 treated group and 20 subjects in the Placebo treated 
group).  
The subjects with documented evidence of COVID-19 infection (by standard diagnostic 
method) will be enrolled. Subjects will be at high risk for the development of ARDS. 
6.2 
Selection Criteria 
6.2.1 Inclusion Criteria 
Subjects accepted for this study must: 
1. 
Provide informed consent  
2. 
Be able to communicate effectively with the study personnel 
3. 
Aged ≥18 years 


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4. 
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection confirmed by 
polymerase chain reaction (PCR) test 
5. 
Patients at high risk for ARDS, with known comorbidities for being at high risk, such as, 
Asthma (moderate to severe), Chronic Lung Disease, Diabetes, Chronic Kidney Disease 
being treated with dialysis, Severe Obesity (BMI ≥40), 65 years of age or older, primarily 
reside in a nursing home or long-term care facility, or immunocompromised. 
6. 
Peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air at screening. If patient 
is on oxygen therapy at the time of presentation for screening and the SpO2 levels were 
≤94% prior to introduction to oxygen therapy with proper documentation example EMT 
notes or ER/ED notes, then the patient is considered to have met this inclusion criterion. 
If patient is on oxygen therapy at the time of presentation for screening and the SpO2 
levels prior to introduction to oxygen therapy are unknown, the patient may be 
considered to have met this inclusion criterion if oxygen therapy is removed and the 
SpO2 levels fall to ≤94%, then the patient is considered to have met this inclusion 
criterion. However, removal of the oxygen therapy should only be done if it is considered 
medically reasonable. 
7. 
Subjects must agree to use acceptable methods of contraception 
• If subject is female or the male subject’s partner could become pregnant, use 
acceptable methods of contraception from the time of the first administration of 
study medication until 6 months following administration of the last dose of 
study medication. Acceptable methods of contraception are as follows: Condom 
with spermicidal foam/gel/film/cream/suppository [i.e., barrier method of 
contraception], surgical sterilization (vasectomy with documentation of 
azospermia) and a barrier method {condom used with spermicidal 
foam/gel/film/cream/suppository}, the female partner uses oral contraceptives 
(combination estrogen/progesterone pills), injectable progesterone or subdermal 
implants and a barrier method (condom used with spermicidal 
foam/gel/film/cream/suppository) 
• If female subject or the female partner of a male subject has undergone 
documented tubal ligation (female sterilization), a barrier method (condom used 
with spermicidal foam/gel/film/cream/suppository) should also be used 
• If female subject or the female partner of a male subject has undergone 
documented placement of an intrauterine device (IUD) or intrauterine system 
(IUS), a barrier method (condom with spermicidal 
foam/gel/film/cream/suppository) should also be used 
8. Subject is willing to comply with the requirements of the protocol through the end of the 
study 
6.2.2 Exclusion Criteria 
Any of the following conditions are cause for exclusion from the study: 
1. Known hypersensitivity or allergy to colchicine 
2. Participation in any other clinical trial of an experimental treatment for COVID-19. 
Convalescent plasma and remdesivir are allowed in this study. 


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3. Concurrent treatment with other experimental agents with actual or possible direct acting 
antiviral activity against COVID-19 is prohibited < 24 hours prior to study drug dosing 
(except standard of care). Remdesivir and convalescent plasma are allowed in the study. 
4. Requiring ventilation + additional organ support – pressors, RRT, ECMO (WHO Ordinal 
Scale for Clinical Improvement – Score of 7) and patients requiring ventilation with a 
WHO Ordinal Scale for Clinical Improvement – Score of 6 for >5 days at screening.  
• Patients on ventilation with a WHO Ordinal Scale for Clinical Improvement 
Score of 5 (non-invasive ventilation or high-flow oxygen) are allowed into the 
study. 
• Patients on ventilation with a WHO Ordinal Scale for Clinical Improvement 
Score of 6 (intubation and mechanical ventilation) for less than five (5) days are 
allowed into the study.  
5. Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) >2 X upper limit of 
normal (ULN) 
6. Total bilirubin > ULN 
7. Creatinine clearance < 60 mL/min 
8. Documented medical history of liver disease, including but not limited to, prior diagnosis 
of hepatitis of any etiology, cirrhosis, portal hypertension, or confirmed or suspected 
esophageal varices 
9. Moderate to severe renal impairment 
10. Hepatic impairment 
11. History of hepatitis 
12. Any comorbid disease or condition (medical or surgical) which might compromise the 
hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or 
central nervous system; or other conditions that may interfere with the absorption, 
distribution, metabolism or excretion of study drug, or would place the subject at increased 
risk 
13. Participants must agree to refrain from prolonged exposure to the sun or agree to use at 
least SPF 50 on all exposed skin and protective clothing during prolonged sun exposure 
throughout participation in this study and/or treatment with VERU-111. 
7.0 
STUDY MEDICATION 
7.1 
Enrollment and Blinding 
The study will be a randomized, double-blind, placebo-controlled study. The study will be 
unblinded when the last patient has completed the Day 29 assessments. 
An emergency code break will be available to the investigator / pharmacist / investigational 
drug storage manager. This code break option in IWRS may only be disclosed in emergency 
situations when the identity of the trial drug must be known to the investigator in order to 
provide appropriate medical treatment or if required to assure safety of trial participants. If the 
code break for a patient is opened, the sponsor and CRO will be informed immediately via 
IWRS notification. The reason for the IWRS unblinding of the subject must be documented 
on the appropriate eCRF page along with the date and the initials of the person who broke the 
code. 


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7.2 
Drug Supply 
7.2.1 VERU-111 Capsules 
VERU-111 18 mg dose will be supplied as capsules containing 18 mg of VERU-111. 
Capsules will be supplied in bottles containing 21 capsules in each bottle. Patients will take 
one VERU-111 capsule per day.  
The VERU-111 capsules should be stored at controlled room temperature, 20°C to 25°C 
(68°F to 77°F) with excursions permitted between 15°C to 30°C (59°F to 86°F). 
7.2.2 Placebo Control 
Placebo capsules contain zero (0) mg VERU-111 drug substance will be supplied in bottles 
containing 21 capsules each. The placebo capsules will contain only anhydrous lactose, USP. 
These capsules are identically appearing to the VERU-111 capsules. Patients will take one 
Placebo capsule per day. 
The Placebo capsules should be stored at controlled room temperature, 20°C to 25°C (68°F to 
77°F) with excursions permitted between 15°C to 30°C (59°F to 86°F). 
7.2.3 Drug Accountability 
Subjects should not take a replacement dose if a dose is missed. Study medication should not 
be taken more than once a day. 
The pharmacists or other site personnel as delegated by the Investigator are responsible for 
accountability of all used and unused study drug supplies. A study drug dosing log should be 
kept current and should contain the dates and times drug dosing the subject, the subject’s 
identification (i.e., subject number), the initials of the dispensing persons. Veru Inc., shall be 
immediately notified of any unexpected occurrences during the dispensing or dosing of study 
drug. 
7.3 
Drug Administration 
Study drug should be taken daily at approximately the same time every day with 
approximately 240 mL (a full glass) of non-alcoholic liquid (drink). Dosing should occur 
within 30 minutes to 1 hour prior to the start of the morning meal.  Subjects will take the 
entire daily dose at once. In subjects with a nasogastric feeding tube, the contents of the 
capsules may be emptied into the tube and appropriately flushed through the tube. 


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8.0 
STUDY PROCEDURES 
8.1 
Screening 
Potential subjects will be screened for this study in the 2 days prior to enrollment. The 
following activities will be conducted at screening: 
1. 
Signed informed consent and HIPAA form will be obtained prior to any study-specific 
procedures and a copy of the signed consent form will be given to the subject. 
2. 
Assess subject eligibility for inclusion into this study based on protocol 
inclusion/exclusion criteria. 
3. 
Medical history will be obtained, including diagnosis of COVID-19 infection (date of 
diagnosis), details and dates of treatments received, documentation of symptoms 
related to COVID-19 infection. 
4. 
The use of any medications will be recorded. This will include medications currently 
being taken and those taken since COVID-19 symptoms started. Over-the-counter 
(OTC) medications as well as medications taken on an as-needed basis (PRN) should 
be recorded. 
5. 
Pregnancy test (female subjects only) 
6. 
Vital signs (temperature/pulse/supine, if possible, blood pressure) 
7. 
SpO2 
8. 
Physical examination including height and weight 
9. 
Electrocardiogram- 12 lead (single) 
10. 
Clinical Laboratory Tests 
• Hematology (Appendix A) 
• Serum chemistry (Appendix A) 
• Urinalysis 
8.2 
Enrollment 
Enrollment should be done after the subject has completed the screening assessments and 
after it has been determined that the subject meets all the inclusion and exclusion criteria. 
Subject will be randomized into one of two treatment groups. 
8.3 
Day 1 
The Day 1 visit assessments will serve as the baseline assessments. 
1. 
The medical history should be reviewed and updated to include any changes occurring 
since the screening visit. This will include the following: 
a. Number of days from onset of COVID-19 symptoms to Day 1 


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b. Specific reason for hospitalization 
2. 
Assessment of eligibility 
3. 
Vital signs (temperature/pulse/supine, if possible, blood pressure) 
4. 
SpO2 
5. 
Physical examination (including weight) 
6. 
Chest X-ray or Computed Tomography (CT) scan 
7. 
Clinical Laboratory Tests 
a. Hematology (Appendix A) 
b. Serum chemistry (Appendix A) 
c. Urinalysis 
8. 
Record the usage of any concomitant medications and ongoing treatments. 
9. 
Adverse events (ongoing on Day 1) 
10. 
First dose of study drug 
11. 
Temperature and SpO2 every 12 hours after dosing 
8.4 
Day 2 through Day 21 
The following assessments will be conducted on each of Day 2 to Day 21 
1. 
Temperature and SpO2 every 12 hours 
2. 
Vital signs (temperature/pulse/supine, if possible, blood pressure) 
3. 
Record the usage of any concomitant medications and ongoing treatments. This should 
include the following: 
a. Documentation of the standard of care 
b. The clinical rationale for initiation of mechanical ventilation, if necessary 
c. Documentation of supportive measures for ARDS (e.g., proning, paralytics, 
etc.) 
d. Care decisions that are based on limitations of resources at the clinical site 
4. 
Adverse events 
5. 
Dose study drug 
6. 
At the time of discharge from the hospital, patients should be advised to use refrain 
from prolonged exposure to the sun or use at least SPF 50 on all exposed skin and 
protective clothing during prolonged sun exposure until the Day 60 adverse event 
assessment. 
8.5 
Day 3, Day 9, and Day 15 
The following additional assessment will be conducted on Days 3, Day 9 and 15: 
1. Serum Chemistry – (Appendix A) 
2. Hematology – (Appendix A) 
3. Assessment of primary and secondary endpoints (Day 15 only) 
4. Physical examination (including weight) (Day 15 only) 
5. 12 lead ECG (single) (Day 15 only) 
6. Pregnancy test (Day 15 only) 


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7. Plasma samples for pharmacokinetic assessment will be taken at baseline (prior to dosing 
on Day 15) and at 4 hours (±2 hours), 12 hours (±2 hours) after dosing on Day 15, and at 
24 hours (±2 hours) after dosing on Day 15 (prior to dosing on Day 16). (Day 15 only) 
8.6 
Day 22 ± 3 days (these assessments will also be done at Early Termination or 
Discontinuation from the study) 
The following assessments will be performed on Day 22 (± 3 days): 
1. 
Vital Signs (temperature/pulse/supine blood pressure) 
2. 
SpO2 
3. 
Physical examination (including weight) 
4. 
12-lead ECG (single) 
5. 
Chest X-ray or CT scan 
6. 
Clinical Laboratory tests 
a. Hematology (Appendix A) 
b. Serum chemistry (Appendix A) 
c. Urinalysis 
7. 
Adverse events 
8. 
Record the usage of any concomitant medications and ongoing treatments. 
9. 
Assessment of primary and secondary endpoints 
8.7 
Day 29 ± 3 days 
The following assessments will be performed at approximately Day 29 (± 3 days): 
1. Vital Signs (temperature/pulse/supine blood pressure) 
2. SpO2 
3. 
Physical examination (including weight) 
4. 
12-lead ECG (single) 
5. 
Chest X-ray or CT scan 
6. 
Clinical Laboratory tests 
a. Hematology (Appendix A) 
b. Serum chemistry (Appendix A) 
c. Urinalysis 
7. 
Adverse events 
8. 
Record the usage of any concomitant medications and ongoing treatments. 
9. 
Assessment of primary and secondary endpoints 
10. Pregnancy test 
8.8 
Follow up visits at Day 45 (± 3 days) and Day 60 (± 3 days) (can be conducted via 
phone/teleconference) 
1. Adverse events 
2. Assessment of primary and secondary endpoints (observational assessment) 


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8.9 
Subject Stopping Rules 
If, in the opinion of the investigator, the participation in the study is or is becoming 
detrimental to the well-being of a particular subject, this issue should be discussed with the 
Medical Monitor for this study and dosing may be discontinued. 
Subjects that experience a Grade 4 or greater toxicity according to the Common Terminology 
Criteria for Adverse Events (CTCAE) version 4 
(https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf) 
that is deemed to be possible, probably or definitely related to study drug will be discontinued 
from the study. Prior to discontinuation from the study, the grading of the event and causal 
relationship should be discussed with the Medical Monitor for the study. 
Subjects will be discontinued from dosing if AST or ALT levels are >5 times the upper limit 
of normal, or if AST or ALT levels are >3 times the upper limit of normal along with a total 
bilirubin elevation of >2 times the upper limit of normal. 
Subjects will be discontinued from dosing if Grade 3 diarrhea is observed. 
Subjects will be discontinued from dosing if Grade 3 neutropenia is observed. 
8.10 Early Discontinuation of Study Treatment 
A subject will be considered to have completed the efficacy portion of the trial if they 
received at least 21 days of treatment with study drug or the subject has been discharged from 
the hospital, or the subject has expired or the study is terminated by the sponsor.  Subjects 
may prematurely discontinue study treatment for any of the following reasons: 
1. 
Consent Withdrawn (specify the reason).   
2. 
Significant and unacceptable adverse event – specify the adverse event leading to 
discontinuation 
3. 
Investigator decision (specify the reason), must be approved by the Medical Monitor 
4. 
Non-compliance by subject with protocol requirements, must be approved by the Medical 
Monitor 
5. 
Lost to follow-up (record the date of last contact) 
6. 
Death (specify the following information) 
a. Date of death 
b. Death due to primary disease? Yes or no 
c. Death due to study drug? Yes or no 
d. Death due to adverse event? Yes or no 
7. 
Study terminated by the Sponsor 
8. 
Other reason (specify the reason) should be approved by the Medical Monitor 


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The reason for discontinuation of study treatment will be documented for each subject. 
Subjects who discontinue prematurely will not be replaced. If a subject is discontinued from 
the study, he will be asked to complete all End of Study visit assessments and return all study 
materials (study medication and electronic device). At the time of discontinuation, please fill 
out the End of Study case report forms (eCRFs) and subject disposition eCRF pages. 
8.11 Adverse Events 
An adverse event (AE) is any unfavorable or unintended change in body structure (signs) or 
body function (symptoms), abnormal laboratory result that is associated with symptoms or 
requires treatment or worsening of a pre-existing condition. This includes all such events 
regardless of the presumed relationship between the event and the study medication(s). 
Any AE that occurs after the informed consent is signed but prior to dosing on Day 1 will be 
captured as part of the medical history and will be documented on the appropriate eCRF. This 
would include AEs resulting from concurrent illnesses, reactions to concomitant medications 
or progressive disease states. These AEs will be captured as part of the medical history. 
Each subject will be assessed for the development of any adverse events. Adverse events 
should be assessed at each visit to the clinic. This information should be obtained in the form 
of non-leading questions (e.g., "How are you feeling?") and from signs and symptoms 
detected during each examination, observations of the study personnel or spontaneous reports 
from the subjects. 
Any AEs such as complaints, signs, or symptoms that occur during the course of the study or 
designated follow-up periods will be recorded on the subject's case report form (eCRF). This 
would include AEs resulting from concurrent illnesses, reactions to concomitant medications, 
or progressive disease states. 
Whenever possible, the AE will be described on the case report form using standard medical 
terminology consistent with Common Terminology Criteria for Adverse Events (CTCAE) 
version 4 in order to avoid the use of vague, ambiguous or colloquial expressions. The 
investigator will evaluate all adverse events as to their intensity, relation to test medication, 
outcome and action taken. 
Each AE will be evaluated for duration, intensity, and relationship to (or association with) the 
study treatment (or other causes). Additionally, the actions taken (e.g., reduction of dosage, 
discontinuation of study medication, administration of treatment, etc.) and the resulting 
outcome of the AE will be indicated on the case report form. 
Any subject who is withdrawn from the study due to an adverse event will be followed until 
the outcome of the event is determined, and the investigator will prepare a written summary 
of the event and document the available follow-up information on the case report form. 


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8.11.1 
Intensity of Adverse Events 
The intensity of the AEs will be graded according to CTCAE version 4. For any adverse event 
that is not specifically covered in CTCAE version 4, the following criteria should be used: 
Grade 
Description 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
2 
Moderate; minimal, local or noninvasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living 
3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living 
4 
Life-threatening consequences: urgent intervention indicated. 
5 
Death related to AE 
If the intensity (Grade) changes within a day, the maximum intensity (Grade) should be 
recorded. If the intensity (Grade) changes over a longer period of time, the changes should be 
recorded as separate events (having separate onset and stop dates for each grade). 
8.11.2 
Test Medication Causality 
The relationship (or association) of each AE to the test medication will be assessed by the 
investigator according to the following definitions: 
Unrelated: 
There is no chance that the study medication caused the AE; other conditions, 
including concurrent illnesses, progression or expression of the disease state, or a reaction to a 
concomitant medication best explain the event. 
Unlikely: 
There is little chance that the study medication caused the AE; other 
conditions, including concurrent illnesses, progression or expression of the disease state, or a 
reaction to a concomitant medication best explain the event. 
Possible: 
The association of the AE with the study medication is unknown; however, the 
AE is not clearly due to another condition. 
Probable: 
A reasonable temporal association exists between the AE and treatment 
administration and, based on the investigator's clinical experience, the association of the AE 
with the study treatment seems likely. 
Definite: 
The association of the AE with the study medication has a direct relationship. 


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For the purpose of safety analyses, all AEs which are classified as "Possible," "Probable" or 
“Definite” will be considered treatment-related events. 
8.11.3 
Serious Adverse Events 
A serious adverse event (SAE) is defined as any experience that suggests a significant 
clinical hazard, contraindication, side effect, or precaution. This includes any event which: 
• Results in death. 
• Is life-threatening. 
• Requires inpatient hospitalization or causes prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity. 
• Results in congenital abnormality/birth defect. 
• Requires intervention to prevent permanent impairment or damage 
 
An SAE also may include other events, based on medical judgment, which jeopardize the 
subject and require medical or surgical intervention to prevent one of the outcomes listed 
above. 
Any SAE, including death due to any cause, which occurs during the study or within 60 days 
following initiation of dosing on study medication, whether or not related to the study 
medication, must be reported immediately via telephone (within 24 hours) to Veru Inc. Drug 
Safety. 
In addition, the investigator must immediately complete a Serious Adverse Event eCRF report 
form and electronically submit the form. The investigator will promptly notify the 
Institutional Review Board (IRB). 
If additional information regarding a previously submitted SAE is obtained, a follow-up SAE 
eCRF report should be completed and submitted as indicated above. Supporting source 
documentation should be provided to Worldwide Clinical Trials Drug Safety at the contact 
information below. 
 Worldwide Clinical Drug Safety Contact Information: 
Fax number: 1-866-387-5539 
 
 
E-mail: drugsafety@worldwide.com 
 
 
Worldwide Clinical Trials Medical Monitor: 
 
Noor Khaskhely, MD, PhD Sr. Medical Director, Medical Affairs Worldwide 
Clinical Trials 
Office +1 610 632 8151Mobile +1 919 324 4351 


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 noor.khaskhely@worldwide.com 
 
8.11.4 
Initial Reports 
SAEs will be collected from the time of first study drug administration through 60 days after 
first study drug administration.  SAEs and events of clinical interest must be reported to the 
Sponsor (or designee) within 24 hours of the knowledge of the occurrence.  
In the event an SAE is observed or reported, the SAE report will be completed as thoroughly 
as possible including all available details about the event and the signature of the Investigator. 
If the Investigator does not have all information about an SAE, the Investigator will not wait 
to receive additional information before notifying the Sponsor of the event and completing the 
form. The form will be updated when additional information is received.  
8.11.5 
Precautions 
Adverse events should be treated in accordance with standard medical practice. During the 
course of the study, the overall safety, and tolerability of all study treatments will be reviewed 
by the sponsor and the investigator. 
8.11.6 
Reporting of Adverse Events Associated with Study Drug Overdose, Misuse, 
Abuse or Medication Error 
AEs associated with study drug overdose, misuse, abuse, and medication error refer to AEs 
associated with uses of the study drug outside of that specified by the protocol. Overdose, 
misuse, abuse, and medication error are defined as follows: 
Overdose: Accidental or intentional use of the study drug in an amount higher than the 
protocol-defined dose 
Misuse:  Intentional and inappropriate use of study drug not in accordance with the protocol 
Abuse: Sporadic or persistent intentional excessive use of study drug accompanied by harmful 
physical or psychological effects 
Medication error: Any unintentional event that causes or leads to inappropriate study drug use 
or subject harm while the study drug is in the control of site personnel or the subject. 
All AEs associated with overdose, misuse, abuse, or medication error should be captured on 
the Adverse Event eCRF and also reported using the procedures detailed in Reporting of 
SAEs even if the AEs do not meet serious criteria. Abuse is always to be captured as an AE. If 
the AE associated with an overdose, misuse, abuse, or medication error does not meet serious 
criteria, it must still be reported using the SAE form and in an expedited manner but should be 
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8.12 Concomitant Medications and Concomitant Therapies 
Any medication (including OTC medications) taken by a subject within 30 days prior to the 
Screening Visit and during the course of the study and the reason for use of the medication 
will be recorded on the eCRF. Upon entering the study, each subject will be instructed to 
report the use of any medication (including OTC medications) to the investigator. 
Any radiation therapy (linear beam or seeds) taken by the subject within 30 days prior to the 
Screening Visit and during the course of the study, including type of treatment, and duration 
of the treatment will be recorded on the eCRF. 
8.13 Prohibited Medications 
The following medications are prohibited with the appropriate washout period, if any, for 
each prohibited medication: 
• Retroviral/antiretroviral medications, except for remdesivir  
• Any experimental drug/clinical trial, except for remdesivir and convalescent plasma 
 
8.14 Withdrawal of Subjects 
All subjects reserve the right to withdraw from the study at any time. The investigator will 
encourage all subjects who decide to withdraw from the study to complete all evaluations 
which may be necessary to assure that the subject is free of untoward effects and to seek 
appropriate follow-up for any continuing problems. 
 
a. 
Any subject who withdrawals consent will be withdrawn from the study. 
e. 
Any subject who is lost-to-follow-up will be withdrawn from the study. 
The investigator will withdraw any subject from the study if, in the investigator's opinion, it is 
not in the subject's best interest to continue. 
The date the subject is withdrawn from the study and the reason for discontinuation will be 
recorded on the case report form. When a subject fails to return for scheduled study visits, the 
investigator will make a reasonable effort to contact the subject and determine why the 
subject failed to return. This information will be documented on the study records. When a 
subject is withdrawn from the study (regardless of the reason), all evaluations required at the 
final study visit should be performed. 
9.0 
STATISTICAL ANALYSIS 
9.1 
Sample Size Calculation 
In the Phase 2, there are no power calculations done to determine the sample size. The Phase 
2 study is intended as a proof-of-concept study only.  


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9.2 
Populations 
Intent-to-Treat (ITT) population: All enrolled subjects who have taken at least one dose of 
study drug. The ITT population will be used as the safety population. 
Modified Intent-to-treat (MITT) population: All enrolled subjects who have taken at least 
7 doses of study drug. 
9.3 
Efficacy Analyses 
A statistical analysis plan will be written for this Phase 2 clinical study. A detailed description 
of the analyses that will be conducted will be included in that document. 
9.3.1 Primary Endpoint 
The primary endpoint for the study will be the proportion of subjects that are alive without 
respiratory failure at Day 29. Respiratory failure is defined endotracheal intubation and 
mechanical ventilation, extracorporeal membrane oxygenation, high-flow nasal cannula 
oxygen delivery, noninvasive positive pressure ventilation, clinical diagnosis of respiratory 
failure with initiation of none of these measures only when clinical decision making is driven 
solely by resource limitation. 
This analysis will compare the percentage of subjects that are alive without respiratory failure 
on Day 22 (responder). The percentage of subjects that meet these criteria in each of the two 
treatment groups will be summarized and compared observationally and statistically. 
The number and percentage of responders will be summarized by treatment group. 
Responders will be analyzed using a logistic regression model. This model will include 
treatment as a factor and study site and WHO Ordinal Scale for Clinical Improvement at 
baseline as a covariates. Odds ratios, standard errors, 95% confidence intervals and p-values 
for the treatment difference will be presented. 
The primary analysis will be performed on the ITT population. Subjects for whom respiratory 
failure and/or vital status at Day 29 cannot be established will be excluded from the analysis, 
noting that the number of such subjects is expected to be minimal. A sensitivity analysis will 
be performed treating these subjects as non-responders. A further sensitivity analysis also be 
performed on the mITT population. 
9.4 
Secondary Analyses 
Full details for the handling of missing data, and consideration of subjects that die during the 
study for those endpoints that do not directly incorporate death, will be included in the 
Statistical Analysis Plan. 
9.4.1 Secondary Endpoints 
9.4.1.1 Mean change from baseline in WHO Ordinal Scale for Clinical Improvement at 
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The mean change in WHO Ordinal Scale for Clinical Improvement from baseline to Day 22 
and from baseline to Day 29 will be assessed.  
The worst category recorded on Day -1 will be baseline and the worst category recorded on 
Day 22 and Day 29 of the study will be used in this analysis.  
Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) will be 
summarized for absolute values, and change from baseline by treatment group and visit.  
Change from baseline will be analyzed using mixed model for repeated measures (MMRM) 
including treatment, visit and treatment-by-visit interaction as fixed effects and study site and 
WHO Ordinal Scale for Clinical Improvement at baseline as covariate. The resulting F-tests 
will be based on Kenward-Roger’s adjusted degrees of freedom. Least squares means, 
standard errors, 95% confidence intervals and p-values for treatments and treatment 
differences at each visit will be presented. 
9.4.1.2 Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for 
Clinical Improvement at Day 15, Day 22, and Day 29 
Proportion of subjects that are Grade 5, 6, 7, or 8 on the WHO Ordinal Scale for Clinical 
Improvement at Day 15, Day 22, and Day 29 will be assessed. This analysis will compare the 
percentage of subjects that have NOT progressed to a WHO Ordinal Scale for Clinical 
Improvement score of 5, 6, 7, or 8 (responder) on Day 15, Day 22 or Day 29. The worst 
category on each day of the study will be used in this analysis. The percentage of subjects that 
meet these criteria in each of the two treatment groups will be summarized and compared 
observationally and statistically.  
This endpoint will be analyzed using the same methodology as for the primary endpoint.   
9.4.1.3 Proportion of subjects with normalization of fever and oxygen saturation 
through Day 15, Day 22, and Day 29.  
The percentage of subjects with normalization of fever and oxygen saturation through Day 15, 
Day 22 and Day 29 (inclusive) will be summarized. A subject will be considered as a 
treatment success if fever normalization maintained for at least 24 hours AND peripheral 
capillary oxygen saturation (SpO2) >94% sustained for 24 hours is observed. 
This analysis will compare the percentage of subjects that meet the composite endpoint of 
fever normalization maintained for at least 24 hours AND peripheral capillary oxygen 
saturation (SpO2) >94% sustained for 24 hours is observed (responder) at Day 15, Day 22, 
and Day 29. The percentage of subjects that meet these criteria in each of the two treatment 
groups will be summarized and compared observationally and statistically. 
This endpoint will be analyzed using the same methodology as for the primary endpoint. 
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Days on mechanical ventilation will be summarized using descriptive statistics (n, mean, 
standard deviation, median, minimum and maximum) by treatment group. Treatment 
comparison will be based on analysis of covariance (ANCOVA) model including treatment as 
a factor and study site and WHO Ordinal Scale for Clinical Improvement at baseline as 
covariates. Treatment difference, standard error, 95% confidence interval and p-value will be 
presented. 
9.4.1.5 All-cause mortality at Day 15, Day 22, and Day 29 
The number and percentage for all-cause mortality will be summarized by treatment group 
and timepoint. 
This endpoint will be analyzed using the same methodology as for the primary endpoint. 
All-cause mortality will be analyzed by comparing the survivor functions between treatment 
arms using Kaplan-Meier methodology. Proportion of mortality and 95% confidence intervals 
at Day 15, Day 22 and Day 29 will be reported. Log-rank test will be performed to test the 
homogeneity of survival curves between the treatment groups. Cox’s proportional hazards 
model will be fitted to assess the significance of the differences between treatment arms. 
Model will include term for treatment and WHO Ordinal Scale for Clinical Improvement at 
baseline as covariate. 
9.4.1.6 Proportion of patients alive and free of respiratory failure at Day 15, and Day 22 
The percentage of subjects alive and free of respiratory failure through Day 15, and Day 22 
(inclusive) will be summarized. 
This analysis will compare the percentage of subjects that are alive and free of respiratory 
failure (responder) at Day 15, and Day 22. The percentage of subjects that meet these criteria 
in each of the three treatment groups will be summarized and compared observationally and 
statistically. 
This endpoint will be analyzed using the same methodology as for the primary endpoint. 
9.4.1.7 Proportion of patients alive and discharged from the ICU at Day 15, Day 22, and 
Day 29 
The percentage of subjects alive and discharged from the ICU through Day 15, Day 22 and 
Day 29 (inclusive) will be summarized. 
This analysis will compare the percentage of subjects that are alive and discharged from the 
ICU (responder) at Day 15, Day 22, and Day 29. The percentage of subjects that meet these 
criteria in each of the two treatment groups will be summarized and compared observationally 
and statistically. 
This endpoint will be analyzed using the same methodology as for the primary endpoint. 


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9.4.1.8 Proportion of patients alive and discharged from hospital at Day 15, Day 22, and 
Day 29 
The percentage of subjects alive and discharged from the hospital through Day 15, Day 22 
and Day 29 (inclusive) will be summarized. 
This analysis will compare the percentage of subjects that are alive and discharged from the 
hospital (responder) at Day 15, Day 22, and Day 29. The percentage of subjects that meet 
these criteria in each of the two treatment groups will be summarized and compared 
observationally and statistically. 
This endpoint will be analyzed using the same methodology as for the primary endpoint. 
9.4.1.9 Days in ICU 
Days in ICU will be summarized using descriptive statistics (n, mean, standard deviation, 
median, minimum and maximum) by treatment group.  
Days in ICU will be analyzed using the same methodology as for Days on Mechanical 
Ventilation (section 9.4.1.4). 
9.4.1.10 Days in hospital 
Days in hospital will be summarized using descriptive statistics (n, mean, standard deviation, 
median, minimum and maximum) by treatment group.  
Days in hospital will be analyzed using the same methodology as for Days on Mechanical 
Ventilation (section 9.4.1.4). 
9.4.1.11 Proportion of subjects on mechanical ventilation at Day 15, Day 22, and Day 29 
The percentage of subjects on mechanical ventilation through Day 15, Day 22 and Day 29 
(inclusive) will be summarized. 
This analysis will compare the percentage of subjects that are NOT on mechanical ventilation 
(responder) at Day 15, Day 22, and Day 29. The percentage of subjects that meet these criteria 
in each of the two treatment groups will be summarized and compared observationally and 
statistically. 
This endpoint will be analyzed using the same methodology as for the primary endpoint.  
9.4.1.12 Mean change from baseline in C-reactive protein at Day 9 
The mean change in C-reactive protein from baseline to Day 9 will be assessed.  
Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) will be 
summarized for absolute values, and change from baseline by treatment group.  


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Change from baseline will be analyzed using mixed model for repeated measures (MMRM) 
including treatment, visit and treatment-by-visit interaction as fixed effects and study site and 
C-reactive protein level at baseline as covariate. The resulting F-tests will be based on 
Kenward-Roger’s adjusted degrees of freedom. Least squares means, standard errors, 95% 
confidence intervals and p-values for treatments and treatment differences at each visit will be 
presented. 
9.5 
Interim Analysis 
Due to the unexpectedly slow enrollment into this study, Veru is conducting a limited interim 
analysis after 24 subjects have been treated for 15 days or have discontinued from the study. 
The interim analysis will focus on the following endpoints: 
1. Proportion of subjects alive without respiratory failure at Day 15 
This will analyzed similar to the outline in Section 9.4.1.6. 
2. Days in ICU up to Day 15 
This will be analyzed similar to the outline in Section 9.4.1.9. However, only to Day 
15. The highest possible number of days in the ICU is 15 days. 
3. Days in hospital up to Day 15 
This will be analyzed similar to the outline in Section 9.4.1.10. However, only to Day 
15. The highest possible number of days in the hospital is 15 days. 
4. Exogenous oxygen use (shift table from baseline to Day 3, 9 and 15) 
This will be three shift tables (increase, decrease, no change) from baseline to Day 3, 
baseline to Day 9, and baseline to Day 15. 
9.6 
Pharmacokinetic Analysis 
The pharmacokinetics of VERU-111 will be assessed on Day 15. Plasma samples for 
pharmacokinetic assessment will be taken at baseline (prior to dosing on Day 15) and at 4 
hours (±2 hours), 12 hours (±2 hours) after dosing on Day 15, and at 24 hours (±2 hours) after 
dosing on Day 15 (prior to dosing on Day 16). 
AUC0-t, Cmax, Tmax, kel, Cl/F, T½, and Vd/F will be estimated through standard methodology 
with this limited sampling schedule.  
The limited sampling schedule is used due to limitations on study personnel entering the 
patient’s room during the day. If the sample is missed due to restrictions in entering the room, 
then this sample will be listed as missing. 
The blood sample should be collected in a 6 mL K2EDTA blood collection tube at each 
collection time.  
Immediately after collection, the tube will be gently inverted several times to mix the 
anticoagulant with the blood sample. The blood sample should be kept at room temperature 
until processed. The blood samples should be processed within 20 minutes after collection. 
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minutes at 1,500 x g (at room temperature). The plasma fraction will be withdrawn by pipette 
and divided into two polypropylene freezing tubes (with each tube receiving approximately 
equal aliquots). All plasma samples will be placed into a freezer at -20oC (or below) within 1 
hour after collection. (NOTE: A flash freezing in dry ice or liquid nitrogen is NOT required 
under this protocol but may be used.) 
9.6.1 Plasma Sample Labels 
The plasma freezing tube labels will contain the following information: 
• Subject Number 
• Study Number 
• Site Number 
• Dosing time (hour and minute) 
• Sample time (hour and minute) 
• Aliquot Number: Aliquot A or B 
• Species and Matrix: Human Plasma 
• Sample Sequence Number 
• Barcode Number 
Labels will be fixed to freezing tubes in a manner that will prevent the label from becoming 
detached after freezing.  
All plasma samples will be stored frozen (-20°C or below). Details of the method validation 
and sample analysis will be included with the final report. 
9.7 
Safety Analysis 
The frequency of adverse events (AEs) will be tabulated by MedDRA term and system organ 
class. The incidence of AEs and the maximum intensity and frequency of AEs will be 
summarized. A new onset AE is defined as an AE that was not present prior to treatment with 
study medication but appeared following treatment or was present at treatment initiation but 
worsened during treatment. An AE that was present at treatment initiation but resolved and 
then reappeared while the subject was on treatment is a new-onset AE (regardless of the 
intensity of the AE when the treatment was initiated). 
All laboratory results, vital sign measurements, and other safety variables will be summarized 
using appropriate descriptive statistics. Changes from baseline will be computed and will be 
summarized using appropriate descriptive statistics. 
9.7.1 Data Safety Monitoring Board 
A Data Safety Monitoring Board will review the unblinded safety data from this Phase 2 
study, including all SAEs, every 2 weeks, or more often if the safety observations. 


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The recruitment of this Phase 2 study is expected to be completed within 4 weeks of first 
patient, first dose. Therefore, from first patient, first dose, to last patient, last dose is expected 
to be <50 days. 
10.0 
ADMINISTRATION PROCEDURES 
10.1 Study Conduct and Compliance 
The study will be conducted in accordance with the Code of Federal Regulations (21 CFR 
parts 50, 54, 56, 312, and 314), which originates from the ethical principles laid down in the 
Declaration of Helsinki. Good Clinical Practices (GCPs) and the policies and procedures of 
the Sponsor and/or its authorized representative will also be followed. This clinical trial will 
be overseen and managed by a contract research organization (CRO) and the Sponsor. The 
CRO will be responsible for data management, data handling, statistical analysis, quality 
assurance and the final study report. The Sponsor will be responsible for project management 
of the CRO and clinical monitoring. 
Sponsor Emergency Contact Info: 
K. Gary Barnette, Ph.D. 
Chief Scientific Officer 
Veru Inc. 
Cell: 919-426-3611 
 
Before initiating a trial, the Investigator/Institution should have written and dated 
approval/favorable opinion from the Independent Ethics Committee (IEC)/IRB for the trial 
protocol/amendment(s), written informed consent form, any consent form updates, subject 
recruitment procedures (e.g., advertisements), any written information to be provided to 
subjects and a statement from the IEC/IRB that they comply with GCP requirements. The 
IEC/IRB approval must identify the protocol version as well as the documents reviewed. 
After IEC/IRB approval, changes will require a formal amendment. Once the study has 
started, amendments should be made only in exceptional circumstances. Changes that do not 
affect subject safety or data integrity are classified as administrative changes and generally do 
not require ethical approval. If ethically relevant aspects are concerned, the IEC/IRB must be 
informed and, if necessary, approval sought prior to implementation. Ethical approval on 
administrative changes will be obtained if required by local/site IEC/IRB. 
10.2 Informed Consent 
Prior to study entry, the Investigator, or a person designated by the Investigator, will explain 
the nature, purpose, benefits and risks of participation in the study to each subject, subject’s 
legally acceptable representative or impartial witness. Written informed consent must be 
obtained prior to the subject entering the study (before initiation of any study-related 
procedure and administration of the investigational medicinal product (IMP). Sufficient time 
will be allowed to discuss any questions raised by the subject. 


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The Sponsor will provide a sample informed consent form. The final version-controlled form 
must be agreed to by the Sponsor and the IEC/IRB and must contain all elements included in 
the sample form, in language readily understood by the subject. Each subject’s original 
consent form, personally signed and dated by the subject or by the subject’s legally acceptable 
representative, and by the person who conducted the informed consent discussion, will be 
retained by the Investigator. The Investigator will supply all enrolled subjects with a copy of 
their signed informed consent. 
The consent form may need to be revised during the trial should important new information 
become available that may be relevant to the safety of the subject or as a result of protocol 
amendments. In this instance approval should always be given by the IEC/IRB. It is the 
Investigator’s responsibility to ensure that all subjects subsequently entered into the study and 
those currently in the study sign the amended form. This is documented in the same way as 
previously described. Subjects who have completed the study should be informed of any new 
information that may impact on their welfare/wellbeing. 
The Investigator should, with the consent of the subject, inform the subject’s primary 
physician about their participation in the clinical trial. 
10.3 Protocol Amendments 
In the event that an amendment to this protocol is required, it will be classified into one of the 
following three categories: 
• 
Non-Substantial Amendments are those that are not considered ‘substantial’ (e.g., 
administrative changes) and as such only need to be notified to the IECs/IRBs or 
Competent Authorities (CA) for information purposes. 
• 
Substantial Amendments are those considered ‘substantial’ to the conduct of the clinical 
trial where they are likely to have a significant impact on: 
- the safety or physical or mental integrity of the subjects; 
- the scientific value of the trial; 
- the conduct or management of the trial; or 
- the quality or safety of the IMP used in the trial. 
Substantial amendments must be notified to the IECs/IRBs and CA. Prior to 
implementation, documented approval must be received from the IECs/IRBs. In the case 
of the CA in the EU member states, approval or ‘favorable opinion’ can be assumed if the 
CA has raised no grounds for non-acceptance during an allocated time period (to be 
confirmed with the Sponsor’s Regulatory Affairs (RA) representative) following 
acknowledgment of receipt of a valid application to make a substantial amendment. 
• 
Urgent Amendments are those that require urgent safety measures to protect the trial 
subjects from immediate hazard and as such may be implemented immediately by the 
Sponsor with subsequent IECs/IRBs and CA notification, forthwith. 


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10.4 Protocol Deviations 
It is the responsibility of the Investigator and Sponsor to ensure compliance with the study 
protocol. When the protocol is not followed, it can put the safety of study subjects at risk as 
well as jeopardize the accuracy and reliability of the study results which could lead to a 
rejection of the data by regulatory authorities. 
All identified deviations from the protocol must be documented and reported to the Sponsor 
using the appropriate electronic form to be supplied by the Sponsor. Deviations will be 
categorized into minor deviations or major deviations; definitions and examples of deviations 
will be provided by the Sponsor. The Sponsor will be reviewing all deviations on an ongoing 
basis. 
10.5 Data Handling and Recordkeeping 
10.5.1 Data Handling 
Data will be recorded at the site on the eCRF and reviewed by the clinical research associate 
(CRA) during monitoring visits. The CRA will verify data recorded in the EDC system with 
source documents. All corrections or changes made to any study data must be appropriately 
tracked in an audit trail in the EDC system. An eCRF will be considered complete when all 
missing, incorrect, and/or inconsistent data has been accounted for and electronically signed 
by the Investigator or assignee. 
Data will be processed using a validated computer system conforming to regulatory 
requirements. 
10.5.2 Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel 
must log into the system using their secure username and password in order to enter, review, 
or correct study data. These procedures must comply with Title 21 of the Code of Federal 
Regulations (21 CFR Part 11) and other appropriate international regulations. All passwords 
will be strictly confidential. 
10.5.3 Medical Information Coding 
For medical information, the following thesauri will be used: 
• Latest version of MedDRA (version 18.1 or higher) for medical history and AEs, and 
• World Health Organization Drug Dictionary Enhanced (Sept. 2015 or later) for prior and 
concomitant medications. 
10.5.4 Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the data, will be applied to the data in order to ensure accurate, 
consistent, and reliable data. Data identified as erroneous, or data that are missing, will be 
referred to the site for resolution through data queries. 


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The eCRFs must be reviewed and electronically signed by the Investigator in order to be 
considered complete. 
10.5.5 Record Keeping 
Records of subjects, source documents, monitoring visit logs, eCRFs, inventory of study 
drugs, regulatory documents, and other Sponsor correspondence pertaining to the study must 
be kept in the appropriate study files at the site. Source data is defined as all information in 
original records and certified copies of original records of clinical findings, observations, or 
other activities in a clinical study necessary for the evaluation and reconstruction of the 
clinical study. Source data are contained in source documents (original records or certified 
copies). These records will be retained in a secure file for the period as set forth in the Clinical 
Study Agreement. Prior to transfer or destruction of these records, the Sponsor must be 
notified in writing and be given the opportunity to further store such records.  
10.6 Data Quality 
Monitored eCRFs transferred from the investigational site to the assigned Data Management 
group will be reviewed (secondary monitoring) for completeness, consistency, legibility and 
protocol compliance. 
Reasons should be given on the relevant eCRF for any missing data and other protocol 
deviations. Any electronic queries and items not adequately explained will require additional 
electronic manual queries to be raised to the Investigator by the monitor for 
clarification/correction. The Investigator must ensure that queries are dealt with promptly. All 
data changes and clarifications can be viewed in the audit trail function of the eCRF. 
Clinical site personnel must make themselves available for any potential audit by the Sponsor 
or Sponsor representative and regulatory authorities, such as, but not limited to, United States 
Food and Drug Administration. The clinical site personnel must be completely responsive and 
cooperative during these audits. 
10.7 Regulatory Approval 
As required by local regulations, the Sponsor’s Regulatory Affairs group will ensure all legal 
regulatory aspects are covered, and obtain approval of the appropriate regulatory bodies, prior 
to study initiation in regions where an approval is required. 
10.8 Publication Policy 
The Sponsor encourages acknowledgement of all individuals/organizations involved in the 
funding or conduct of the study, including medical writers or statisticians subject to the 
consent of each individual and entity concerned, including acknowledgement of the Sponsor. 
The results of this study may be published or communicated to scientific meetings by the 
Investigators involved in the study. For multicenter studies, a plan for scientific publication 
and presentation of the results may be agreed and implemented by the study Investigators or a 
Steering Committee. The Sponsor requires that reasonable opportunity be given to review the 


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content and conclusions of any abstract, presentation, or paper before the material is 
submitted for publication or communicated. This condition also applies to any amendments 
that are subsequently requested by referees or journal editors. The Sponsor will undertake to 
comment on the draft documents within the time period agreed in the contractual 
arrangements, including clinical trial agreements, governing the relationship between the 
Sponsor and authors (or the author’s institution). Requested amendments will be incorporated 
by the author, provided they do not alter the scientific value of the material. 
If patentability would be adversely affected by publication, this will be delayed until (i) a 
patent application is filed for the content of the publication in accordance with applicable 
provisions of the clinical trial agreement concerned, (ii) the Sponsor consents to the 
publication, or (iii) the time period as may be agreed in the contractual arrangements, 
including clinical trial agreements, governing the relationship between the Sponsor and 
authors (or authors’ institution) after receipt of the proposed publication by the Sponsor, 
whichever of (i), (ii) or (iii) occurs first. 
The author undertakes to reasonably consider the Sponsor's request for delay to the proposed 
publication should the Sponsor reasonably deem premature to publish the results obtained at 
the then stage of the study. 
10.9 Clinical Study Report 
A final clinical study report will be prepared according to the ICH guideline on structure and 
contents of clinical study reports. A final clinical study report will be prepared where any 
subject has signed informed consent, regardless of whether the trial is completed or 
prematurely terminated. Where appropriate an abbreviated report may be prepared. The CSR 
will be in compliance with any applicable regulatory requirements, national laws in force and 
will be in English. 
10.10 Contractual and Financial Details 
The Investigator (and/or, as appropriate, the hospital/institution authorized representative) and 
the Sponsor will sign a clinical study agreement prior to the start of the study, outlining 
overall Sponsor and Investigator responsibilities in relation to the study. Financial 
remuneration will cover the cost per included subject, based on the calculated costs of 
performing the study assessments and other activities in accordance with the protocol, and the 
specified terms of payment will be described in the contract. The contract should describe 
whether costs for pharmacy, laboratory and other protocol-required services are being paid 
directly or indirectly. 
10.11 Insurance and Indemnity 
The Sponsor will obtain Product Liability insurance providing coverage relating to the clinical 
study and subjects participating therein. 


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11.0 
REFERENCES  
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Burkard C et al. Coronavirus cell entry occurs through the endo-/lysosomal pathway in a 
proteolysis-dependent manner. PLOS Pathogens 10:e1004502, 2014. 
Cascella M. et al. Features, evaluation, and treatment coronavirus (COVID-19) StatPearls 
2020  www.ncbi.nlm.nih.gov/books/NBK554776. 
Chen J et al. Discovery of novel 2-aryl-4-benzoyl-imidazole (ABI-III) analogues targeting 
tubulin polymerization as antiproliferative agents.  J Med Chem 55:7285-7289, 2012. 
Cooper GM. The Cell: A Molecular Approach.2nd edition. Sunderland(MA): Sinauer 
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Criglar JM et al. A novel form of rotavirus NSP2 and phosphorylation-dependent NSP2-
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processes requiring stabilized microtubules. PLoS One 7:e47947, 2012. 
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Li CM et al. Orally bioavailable tubulin antagonists for paclitaxel-refractory cancer. Pharm 
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12.0 
APPENDICES 
12.1 Appendix A: 
Clinical Laboratory Tests (local laboratory) 
Hematology: 
Serum Chemistry: 
Hemoglobin 
Sodium 
Hematocrit 
Potassium 
Red Blood Cell Count 
Chloride 
White Blood Cell Count 
Bicarbonate 
White Blood Cell Differential 
BUN 
Platelet Count 
Creatinine 
Reticulocyte Count 
Calcium 
Cardiac Troponin 
Phosphorus 
 
Total Protein 
Urinalysis: 
Albumin 
pH 
Total Bilirubin 
Specific Gravity 
SGOT (ALT) 
Protein 
SGPT (AST) 
Glucose 
Alkaline phosphatase 
Leucocytes 
LDH 
Nitrates 
GGT 
Ketones 
Glucose 
Blood 
Ferritin 
Microscopic Examination (only if urinalysis results are 
abnormal) 
D-dimer 
 
C-reactive protein 
 
 
 
 


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12.2 Appendix B: Schedule of Study Evaluations 
Day 
Screena 
Day 1 Days 2-21 Days 3, 9, & 15 Day 16 Days 22d and 29   Days 45 and 60 
Informed Consent and 
HIPAA 
X 
 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
 
Assessment of Eligibility 
X 
X 
 
 
 
 
 
Physical Exam 
X 
X 
 
Xf 
 
X 
 
Vital signs 
X 
X 
X 
 
 
X 
 
Pregnancy test (female 
subjects only) 
X 
 
Xf 
 
 
Xg 
 
12-lead ECG (single) 
X 
 
 
Xf 
 
X 
 
Chest X-ray or CT 
 
X 
 
 
 
X 
 
Clinical Laboratory Tests 
 
 
 
 
 
 
 
Hematology 
X 
X 
 
X 
 
X 
 
Urinalysis 
X 
X 
 
 
 
X 
 
Serum Chemistry 
X 
X 
 
X 
 
X 
 
Temperature/SpO2 
X 
X 
Xe 
 
 
X 
 
Dosingb,c 
 
X 
X 
 
 
 
 
Pharmacokinetic assessment 
 
 
 
Xh, f 
Xh 
 
 
Assessment of primary and 
secondary efficacy endpoints 
 
 
 
Xf 
 
X 
X 
Assessment of conmeds 
X 
X 
X 
 
 
X 
 
Assessment of AEs 
 
X 
X 
 
 
X 
X 
a Screening evaluations are to be conducted within 2 days prior to Day 1. 
b Subjects will be treated for 21 days OR until discharged from hospital 
c Subjects can be discontinued if they are not responding to therapy 
d Early termination assessments the same as Day 22 assessments 
e Temperature and SpO2 will be taken every 12 hours on these days 
f Day 15 only 
g Day 29 only 
h Plasma samples for pharmacokinetic assessment will be taken at baseline (prior to dosing on Day 15) and at 4 hours (±2 hours), 12 hours (±2 hours) after dosing on Day 15, and at 24 hours (±2 hours) after dosing on 
Day 15 (prior to dosing on Day 16). 


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PROTOCOL SIGNATURE PAGE 
 
Protocol Number: 
V0211901 
Protocol Date: 
FINAL Amendment 6 (Version 7)/ 25 September 2020 
 
 
Protocol Title: 
Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for 
the Treatment of Severe Acute Respiratory Syndrome Coronavirus 
2 (SARS-CoV-2) in Patients at High Risk for Acute Respiratory 
Distress Syndrome (ARDS). 
 
 
SIGNATURE: 
 
 
 
Sponsor 
 
Date 
. 
 
Name and Title of Sponsor Representative 
 
 
 
This signature of the Sponsor Representative constitutes approval of this protocol. 
 
 


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PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
Protocol Number: 
V0211901 
Protocol Title: 
Randomized, Placebo-Controlled, Phase 2 Study of VERU-111 for 
the Treatment of Severe Acute Respiratory Syndrome Coronavirus 
2 (SARS-CoV-2) in Patients at High Risk for Acute Respiratory 
Distress Syndrome (ARDS). 
Protocol Date: 
FINAL Amendment 6 (Version 7)/ 25 September 2020 
 
 
SIGNATURE: 
 
 
 
 
Principal Investigator: 
 
Date 
 
 
Name of Principal Investigator (Please Print) 
 
 
 
 
Address of Principal Investigator 
 
 
The signature of the Principal Investigator constitutes approval of this protocol and an 
assurance that this study will be conducted according to all requirements of this protocol 
and according to Good Clinical Practices (GCP).