Conditions: COVID-19
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 217
Healthy volunteers: no

Brief summary:
Subjects who have documented exposure to SARS-CoV-2 (COVID-19) will receive 4 doses of PUL-042 Inhalation Solution or 4 doses of a placebo solution by inhalation over 10 days. Subjects will be followed for the incidence and severity of COVID-19 over 28 days. Subjects will be tested for infection with SARS-CoV-2 at the beginning, middle and end of the study.

Detailed description:

Arms:
arm 1: PUL-042 Inhalation Solution given by nebulization on Study Days 1, 3, 6, and 10 arm 2: Sterile saline for inhalation given by nebulization on Study Days 1, 3, 6, and 10

Interventions: intervention 1: PUL-042 Inhalation Solution intervention 2: Placebo
Intervention descriptions: intervention 1: 20.3 µg Pam2 : 29.8 µg ODN/mL (50 µg PUL-042) PUL-042 Inhalation Solution intervention 2: Sterile saline for inhalation

Protocol document:
Prot_ICF_000.pdf: 
Pulmotect, Inc. 
 
Protocol v. 1.60 
PUL-042-501 
 
 29 January 2021 
 
1 
 
 
 
CLINICAL STUDY PROTOCOL 
 
Title: A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of 
PUL-042 Inhalation Solution in Reducing the Infection Rate and Progression 
to COVID-19 in Adults Exposed to SARS-CoV-2 
 
Protocol Number:  
PUL-042-501 
 
IND Number/Version: 
148628/v.1.60 (29 January 2021) 
 
Investigational Product: 
PUL-042 Inhalation Solution 
 
 
IND Applicant and Sponsor: 
Pulmotect, Inc. 
3900 Essex Lane, Suite 575 
Houston, TX 77027 USA 
 
 
Medical Monitor: 
Anoshie Ratnayake, MD, MPH 
Pulmotect, Inc. 
3900 Essex Lane, Suite 575 
Houston, TX 77027 USA 
 
 
Investigational Site:   
Multicenter 
 
 
 
 
 
 Principal Monitor: 
 
 
 
 
 
 
 
Colin Broom, MD 
Pulmotect, Inc. 
3900 Essex Lane, Suite 575 
Houston, TX 77027 
 
 
____________________          ____________ 
Signature                                   Date 
 
Confidentiality Statement 
 
The confidential information in this document is provided to you as an investigator or consultant for review by you, your staff, and 
the applicable Institutional Review Board or Ethics Committee. Your acceptance of this document constitutes agreement that you 
will not disclose the information contained herein to others without written authorization from the sponsor. 
 
 


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INVESTIGATOR’S SIGNATURE 
 
I agree to abide by all the provisions set forth in this attached protocol. I also understand that these materials 
contain confidential information belonging to Pulmotect, Inc. Except as may be otherwise agreed to in 
writing, I agree to hold such information in confidence and not to disclose it to others (except where required 
by applicable law) nor use it for unauthorized purposes. In the event of actual or suspected breach of this 
obligation, Pulmotect, Inc. should be promptly notified. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 


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PROCEDURES IN CASE OF EMERGENCY 
 
Emergency Contact Information 
Role in Study 
Name 
Address and Telephone Number 
Sponsor Contact 
Brenton Scott, PhD 
Pulmotect, Inc. 
3900 Essex Lane, Suite 575 
Houston, TX 77027 USA 
(713) 579-9226 
bscott@pulmotect.com  
Principal Monitor 
Colin Broom, MD 
Pulmotect, Inc. 
3900 Essex Lane, Suite 575 
Houston, TX 77027 USA 
(832) 315-4807 
cbroom@pulmotect.com  
Medical Monitor 
Anoshie Ratnayake, MD, MPH 
 
 
Pulmotect, Inc. 
3900 Essex Lane, Suite 575 
Houston, TX 77027 USA 
(949) 629-8686 
anoshie@pulmotect.com 


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1. 
TABLE OF CONTENTS  
1. 
TABLE OF CONTENTS .............................................................................................4 
2. 
LIST OF TABLES ........................................................................................................7 
3. 
LIST OF FIGURES ......................................................................................................7 
4. 
LIST OF ABBREVIATIONS .......................................................................................8 
5. 
BACKGROUND ..........................................................................................................9 
5.1. 
Introduction ...................................................................................................................9 
5.2. 
Chemical Name and Structure ....................................................................................10 
5.3. 
Nonclinical Studies .....................................................................................................11 
5.4. 
Clinical Studies ...........................................................................................................11 
5.5. 
Dosing .........................................................................................................................13 
6. 
STUDY OBJECTIVES ..............................................................................................14 
6.1. 
Primary Objective .......................................................................................................14 
6.2. 
Secondary Objective ...................................................................................................14 
7. 
INVESTIGATIONAL PLAN .....................................................................................15 
7.1. 
Overall Study Design ..................................................................................................15 
7.2. 
Subject Selection ........................................................................................................15 
7.2.1. 
Inclusion Criteria ........................................................................................................15 
7.2.2. 
Exclusion Criteria .......................................................................................................16 
7.3. 
Study Integrity ............................................................................................................16 
7.4. 
Number of Subjects ....................................................................................................16 
7.5. 
Number of Study Sites ................................................................................................16 
7.6. 
Duration of Subject Participation ...............................................................................16 
7.7. 
Schedule of Study Activities ......................................................................................16 
7.8. 
Subject Participation ...................................................................................................18 
7.9. 
Study Day -2 to Day 1 (Screening) .............................................................................18 
7.10. 
Study Day 1 ................................................................................................................18 
7.10.1. 
Day 1 (Pre-dose) .........................................................................................................18 
7.10.2. 
Day 1 (Study Drug Administration) ...........................................................................19 
7.10.3. 
Day 1 (T0 +30 minutes [±15 minutes]) .......................................................................19 
7.11. 
Study Days 3, 6, and 10 (Study Drug Administration) ...............................................20 
7.11.1. 
Pre-dose ......................................................................................................................20 


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7.11.2. 
Days 3, 6, and 10 (Study Drug Administration) .........................................................20 
7.11.3. 
Days 3, 6, and 10 (T0 +30 minutes [±15 minutes]) ....................................................21 
7.12. 
Study Day 15 (Follow-up) ..........................................................................................21 
7.13. 
Early Discontinuation from Dosing and Study Withdrawal .......................................21 
7.14. 
Study Completion Day 29 ..........................................................................................22 
8. 
CLINICAL EVALUATIONS AND PROCEDURES ................................................23 
8.1. 
Medical History ..........................................................................................................23 
8.2. 
SARS-CoV-2 Infection Assessment ...........................................................................23 
8.3. 
Physical Examination and Vital Signs ........................................................................24 
8.4. 
SARS-CoV-2 Testing .................................................................................................24 
8.5. 
Spirometry ..................................................................................................................24 
9. 
DESCRIPTION OF STUDY TREATMENT .............................................................25 
9.1. 
Placebo ........................................................................................................................25 
9.2. 
PUL-042 Inhalation Solution ......................................................................................25 
9.2.1. 
PUL-042 .....................................................................................................................25 
9.3. 
Packaging and Labeling ..............................................................................................25 
9.4. 
Shipment and Storage .................................................................................................25 
9.5. 
Preparation and Administration ..................................................................................25 
10. 
CONCOMITANT MEDICATIONS, TREATMENTS, AND 
PROCEDURES ..........................................................................................................26 
11. 
STUDY WITHDRAWAL ..........................................................................................27 
11.1. 
Study Termination ......................................................................................................27 
11.2. 
Subject Withdrawal/Lost to Follow-up ......................................................................27 
12. 
ADVERSE EVENTS ..................................................................................................28 
12.1. 
Definitions ..................................................................................................................28 
12.2. 
Adverse Event Reporting Period ................................................................................29 
12.3. 
Treatment Emergent Adverse Events .........................................................................30 
12.4. 
Recording of AEs .......................................................................................................30 
12.5. 
Assessing Relationships of AE to Study Drug ...........................................................31 
12.6. 
Reporting Serious or Unexpected AEs .......................................................................31 
12.7. 
Follow-up of Adverse Events .....................................................................................32 
13. 
STATISTICAL METHODS .......................................................................................33 


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13.1. 
Sample Size Determination ........................................................................................33 
13.2. 
Subject Populations ....................................................................................................33 
13.3. 
Primary Objective .......................................................................................................33 
13.4. 
Secondary Objectives .................................................................................................34 
13.5. 
Safety Analysis ...........................................................................................................35 
14. 
ADMINISTRATION OF THE STUDY ....................................................................36 
14.1. 
Regulatory Considerations ..........................................................................................36 
14.2. 
Institutional Review Board (IRB)/Ethics Committee .................................................36 
14.3. 
Subject Information and Informed Consent ...............................................................36 
14.4. 
Data Safety Monitoring Board ....................................................................................37 
14.5. 
Adherence to the Protocol ..........................................................................................38 
14.6. 
Protocol Modifications ...............................................................................................38 
14.7. 
Data Collection ...........................................................................................................39 
14.8. 
Maintaining Records ...................................................................................................39 
14.9. 
Monitoring, Auditing, and Inspecting ........................................................................40 
14.10. 
Confidentiality ............................................................................................................41 
15. 
SAMPLE INFORMED CONSENT ...........................................................................42 
16. 
REFERENCES ...........................................................................................................54 
 


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2. 
LIST OF TABLES 
Table 1: 
Schedule of Events .....................................................................................................17 
Table 2: 
SARS-CoV-2 Infection Symptom Score ....................................................................23 
Table 3: 
Relationship of Adverse Event to the Administration of the Study Drug ..................31 
Table 4: 
Ordinal Scale for Clinical Improvement (Derived from draft WHO scale) ...............34 
3. 
LIST OF FIGURES 
 
Figure 1: 
Pretreatment with PUL-042 has been demonstrated to protect mice against 
Influenza A and B .......................................................................................................10 
Figure 2: 
Pretreatment with PUL-042 has been demonstrated to protect mice against 
SARS-CoV and MERS-CoV ......................................................................................10 
Figure 3: 
Structure and Nucleotide Sequence of PUL-042 Components Pam2 and 
ODN ............................................................................................................................11 
Figure 4 
Study Design ...............................................................................................................15 
 
 
 


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4. 
LIST OF ABBREVIATIONS 
The following abbreviations are used in this study protocol. 
Abbreviation or specialist term 
Explanation 
AE 
adverse event 
ANC 
absolute neutrophil count 
CFR 
Code of Federal Regulations 
COVID-19 
Disease caused by infection with SARS-CoV-2 
DSMB 
Data and Safety Monitoring Board 
eCRF 
electronic case report form 
EDC 
electronic data capture 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume in 1 second 
FVC 
Forced Vital Capacity 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation of Technical 
Requirements for Registration of Pharmaceuticals for Human Use 
IRB 
Institutional Review Board 
MERS 
Disease caused by infection with MERS-CoV 
ODN 
ODN M362 
OHRP 
Office for Human Research Protections 
Pam2 
Pam2CSK4 
PUL-042 
drug product consisting of a 4:1 molar ratio of Pam2:ODN; 
Inhalation Solution 
Pulmotect 
Pulmotect, Inc. 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS 
Disease caused by infection with SARS-CoV 
SARS-CoV-2 
Coronavirus causing COVID-19 
SWFI 
sterile water for injection 
TLR 
Toll-like receptor 
USP 
United States Pharmacopeia 
WHO 
World Health Organization 
 
 


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5. 
BACKGROUND 
This protocol is being conducted under a COVID-19 specific IND filed with the Division of Pulmonary, 
Allergy and Critical Care of the FDA and is intended to provide preliminary data on the efficacy and safety 
of PUL-042 in reducing the infection rate and progression to COVID-19 in adult subjects exposed to SARS-
CoV-2.  Evaluation of these data will determine the feasibility of advancing to Phase 3 clinical development 
to pursue an NDA filing and the potential for Emergency Use Authorization.   
This section includes a brief summary of the rationale for clinical investigation of PUL-042 and a summary 
of the nonclinical data available on PUL-042. More detailed information can be found in the Investigator’s 
Brochure. 
5.1. 
Introduction 
Respiratory infection can be caused by a variety of pathogenic organisms including bacteria, fungi, and 
viruses and is one of the leading causes of death worldwide1. Even in developed countries, respiratory 
infection continues to be the leading cause of death from infection and a serious complication for patients 
being treated for other diseases. The threat of respiratory infections is elevated when there is a decreased 
level of host resistance such as in immunosuppressed individuals and when there is an increased level of 
pathogen exposure such as in the case of bioterror attacks and biowarfare or epidemics and pandemics such 
as the current COVID-19 pandemic. 
Pulmotect, Inc. (Pulmotect) has developed a novel therapeutic to stimulate innate immunity in the lungs 
that may provide protection against lower respiratory tract infection. The technology platform is a direct 
result of basic research conducted by Pulmotect’s founders on the mechanisms of microbial resistance in 
the lung epithelium2,3,4,5,6. PUL-042 is a combination of two synthetic molecules, a lipopeptide (Pam2CSK4 
acetate [Pam2]) and a phosphorothioate oligodeoxynucleotide (ODN M362 sodium [ODN]) that act 
synergistically as agonists of Toll-like receptors (TLR)2/6 and TLR9, respectively. The response is 
primarily localized and specific to the site of administration. In animal studies, inhalation treatment with 
PUL-042 results in increased survival rates after respiratory exposure to a broad spectrum of pathogens 
including Gram-positive and Gram-negative bacteria (including three Class A bioterror agents), the fungus 
Aspergillus fumigatus, and viral pathogens.  
The activity of PUL-042 has been evaluated in animal models against a range of viruses as a single agent7 
and in combination with existing anti-viral drugs, including oseltamivir against influenza H3N2 for 
successful treatment at more advanced stages of infection8. 


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Figure 1: 
Pretreatment with PUL-042 has been demonstrated to protect mice against 
Influenza A and B 
 
 
Antiviral activity has also been demonstrated against coronavirus strains. In unpublished experiments 
conducted at the University of Texas Medical Branch at Galveston (UTMB) a single inhaled dose of PUL-
042 was shown to protect mice from SARS-CoV, and significantly reduced the amount of virus in the lungs 
after infection with MERS-CoV virus (Figure 2). The antiviral activity of PUL-042 therefore has the 
potential for the prevention of infection with the SARS-CoV-2 virus.  
Figure 2: 
Pretreatment with PUL-042 has been demonstrated to protect mice against 
SARS-CoV and MERS-CoV 
5.2. 
Chemical Name and Structure 
The investigational product, PUL-042 Inhalation Solution, is a combination of Pam2 and ODN. Pam2 is a 
synthetic 6-amino acid lipopeptide as an acetate salt, and ODN is a synthetic 25-base, single-stranded 
oligonucleotide that contains unmethylated CpG dinucleotides with a phosphorothioate backbone as a 
sodium salt. The structure of Pam2 and nucleotide sequence of ODN are shown in Figure 3. 


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Figure 3: 
Structure and Nucleotide Sequence of PUL-042 Components Pam2 and ODN 
Pam2 
 
C = carbon; H = hydrogen; O = oxygen; S = sulfur; Ser = serine, Lys = lysine; MW = molecular weight 
ODN 
5´–TCG TCG TCG TTC GAA CGA CGT TGA T–3´ 
M.W.: 8,049.5 
(single-stranded, nuclease-resistant phosphorothioate oligodeoxynucleotides) 
5.3. 
Nonclinical Studies 
The nonclinical pharmacology, pharmacokinetics, and toxicology of PUL-042 are described in detail in the 
Investigator’s Brochure.  
5.4. 
Clinical Studies 
The initial phase 1 study of PUL-042 Inhalation Solution (PUL-042-001) “A Randomized, Double-Blind, 
Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and 
Pharmacodynamics of PUL-042 Inhalation Solution in Healthy Subjects” has been completed. Subjects 
were administered a single dose of PUL-042 Inhalation Solution by nebulization. A total of 4 mL of a 
solution of PUL-042 at increasing concentrations was administered using sterile water for injection (SWFI) 
as the diluent.  
Review of the data from the PUL-042-001 study indicated that there was a potential pharmacodynamic 
effect indicated by a rise in the absolute neutrophil count (ANC) as measured at 4 hours post dose in subjects 
treated with PUL-042 Inhalation Solution compared to placebo. The ANC was at or near baseline levels 
when measured again at 24 hours post dose. All values were within the normal range at the 24-hour time 
point. The neutrophil response was confirmed in sheep and mice, and furthermore was shown to be dose 
dependent in mice. The time course of that response has been further explored in subjects in the study 
PUL-042-003 “A Randomized, Open-label, Crossover Study to Assess the Safety, Tolerability and 
Pharmacodynamics of PUL-042 Inhalation Solution in Healthy Subjects and the Effect of Pretreatment with 
Cromolyn Sodium or Albuterol Sulfate”. 


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A similar potential pharmacodynamic effect was seen in the spirometry data (specifically the forced 
expiratory volume in 1 second [FEV1]) from PUL-042-001, likely due to the effect of PUL-042 on the 
bronchial airways. A dose-dependent decrease in FEV1 was seen with a nadir at approximately 30 minutes 
post-dose in subjects treated with PUL-042 Inhalation Solution. There was no comparable decline observed 
with placebo. These measurements were largely within the 12% change from baseline accepted as normal 
variability. This was followed by a recovery to near baseline levels at 24 hours post dose. Over the course 
of 7 days, the mean FEV1 was within 0-5% of the baseline value, with the subjects who received higher 
doses of PUL-042 showing a larger mean decrease in FEV1. None of the decreases in FEV1 were 
accompanied by signs of respiratory distress or a drop in oxygen saturation. None of the FEV1 results in 
the PUL-042 inhalation treated groups were statistically different from placebo after the 30-minute time 
point. The MTD delivered as a single dose was established as 40.6 µg Pam2 : 59.5 µg ODN in 
PUL-042-001. 
A second phase 1 study (PUL-042-003) has been completed. PUL-042-003 was a randomized, open-label, 
cross-over study to determine the safety and tolerability of PUL-042 Inhalation Solution and to explore the 
effect of pretreatment with either cromolyn sodium or albuterol sulfate. The primary objective of this study 
was to determine the safety and tolerability in healthy normal subjects of single or repeated doses of PUL-
042 in SWFI. Exploratory objectives include determining whether ANC was an indicator of biological 
activity and to determine 1) the duration of local biological activity in the bronchial airways by serial FEV1 
measurements, 2) whether the administration of cromolyn sodium prior to the administration of PUL-042 
had an effect on the FEV1 response, and 3) whether the administration of albuterol prior to the 
administration of PUL-042 had an effect on the FEV1 response.  
In protocol PUL-042-003, the first cohort of 8 subjects (cohort 1) received a dose of 20.3 µg Pam2 : 29.8 µg 
ODN (1/2 the single-dose MTD of PUL-042) with or without pretreatment with cromolyn sodium (4 each). 
Subjects were then crossed over to the alternative treatment after a 2-week follow-up period and an 
additional 2-week washout period. 
A similar design was used for the second cohort (8 subjects) with PUL-042 +/- albuterol sulfate. The second 
cohort of subjects received a total dose of 40.6 µg Pam2 : 59.5 µg ODN as two doses over 3 days (1 dose 
on Day 1 and 1 dose on Day 3) and a total dose of 81.2 µg Pam2 : 119 µg ODN as four doses over 32 days 
(1 dose each on Day 1, Day 3, Day 29 and Day 32).  
Results from PUL-042-003 showed no clinically significant abnormalities or changes from baseline for 
vital signs, electrocardiography, pulse oximetry, physical examination, or safety laboratory assessments.  
In general, FEV1 results were consistent with those seen in PUL-042-001 with an early onset decrease in 
FEV1 in some subjects that spontaneously reversed to near baseline levels over several minutes to hours. 
In the PUL-042-001 study, a small decrease in average FEV1 was also observed 7 days post-treatment (the 
last observation in that study) compared to the pre-dose baseline. A similar pattern was observed through 7 
days post-treatment in PUL-042-003. Observations at later time points showed sporadic decreases in FEV1 
values, but longer-term follow-up measurements of FEV1 gave results comparable to the initial pre-dose 
baseline values. As in study PUL-042-001, none of the decreases in FEV1 were accompanied by signs of 
respiratory distress or a drop in oxygen saturation. Pre-treatment with cromolyn sodium or albuterol sulfate 
had no significant effect on the short lasting FEV1 decreases observed following administration of PUL-
042.  


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Currently there is an ongoing Phase 2 study, PUL-042-402 (A Phase 2, Single-Center, Double-Blind, 
Placebo-Controlled Study of PUL-042 Inhalation Solution in Rhinovirus-induced Symptoms in Current 
Smokers with GOLD Stage 0 COPD), that is evaluating the effects of PUL-042 on peak lower respiratory 
symptoms and safety in subjects with an experimentally induced rhinovirus infection with laboratory human 
rhinovirus strain HRV A16. 
Subjects are dosed with PUL-042 (20.3 µg Pam2 : 29.8 µg ODN [50 µg PUL-042] ) or placebo 24 hours 
prior to viral inoculation and again 48 hours post inoculation. The subjects are then followed for 6 weeks. 
To date, 19 of the planned 24 subjects have completed the study and data from 18 subjects reviewed by the 
Data Safety Monitoring Board (DSMB). The DSMB approved enrolling 6 additional subjects based on the 
data from these subjects. The study has been suspended due to the COVID-19 pandemic but, is anticipated 
to re-start in Q4 2020. The study remains blinded to treatment related efficacy and safety. There have been 
no Serious Adverse Events reported and no apparent safety concerns with PUL-042 administration 
following a respiratory viral infection.  
5.5. 
Dosing 
The dose selected is based on the results of PUL-042-001, a single ascending dose study to determine the 
maximum tolerated dose of PUL-042 in healthy volunteers, PUL-042-003, an open-label crossover study 
to investigate the effects of pretreatment with cromolyn sodium or albuterol sulfate on the safety, 
tolerability, and pharmacodynamics of PUL-042 administered to healthy volunteers, and PUL-042-402 an 
ongoing double-blind study of PUL-042 in a COPD rhinovirus challenge model.  
Based on the results of these studies, the dose level of PUL-042 Inhalation Solution in the current study 
will be 20.3 µg Pam2 : 29.8 µg ODN/mL (50 µg PUL-042 [this is the same dose level currently used in the 
ongoing viral challenge study]). A total of up to 4 doses will be administered over a 10 day period for a 
total dose of 81.2 µg Pam2 : 119.2 µg ODN.  
Doses of PUL-042 or placebo will be prepared by an unblinded pharmacist and administered to the subject 
within 4 hours of preparation. Further details will be supplied in a pharmacy manual. 
Doses will be administered via nebulization to deliver 4 mL using a PARI Sprint nebulizer equipped with 
a filter valve to prevent aerosol generation. The nebulizer will be operated until all drug is delivered. Each 
nebulizer will be dedicated to each subject during participation in the study. A new filter pad will be used 
in the filter valve for each administration of PUL-042. A nose clip will be used during the nebulization 
procedure.  
Despite the use of the above nebulization equipment health care professionals should wear appropriate 
personal protective equipment and observe the procedure from a distance of at least six feet or preferably 
from another room until after nebulization has been completed.  


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6. 
STUDY OBJECTIVES 
6.1. 
Primary Objective  
To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-
CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with SARS-
CoV-2 infection, and 2) are asymptomatic at enrollment.     
The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the 
baseline value in the Ordinal Scale for Clinical Improvement within 28 days from the start of experimental 
therapy. 
 
6.2. 
Secondary Objective 
To determine the difference in incidence of SARS-CoV-2 infection 28 days from the start of experimental 
therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit 
To determine the difference in incidence of SARS-CoV-2 infection 14 days from the start of experimental 
therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit 
To compare the severity of COVID-19 within 14 days from the start of experimental therapy 
To compare the severity of COVID-19 within 28 days from the start of experimental therapy 
To assess the requirement for ICU admission within 28 days from the start of experimental therapy  
To assess the requirement for mechanical ventilation within 28 days from the start of experimental therapy 
To assess mortality within 28 days from the start of experimental therapy   
To determine the tolerability of PUL-042 Inhalation Solution in this population 
 
 


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Overall Study Design 
This will be a double-blind trial. A total of 200 subjects randomized 1:1 (PUL-042 Inhalation Solution: 
placebo) will be enrolled in the trial.  
Doses will be administered via nebulization with a PARI sprint nebulizer. All subjects will receive up to 4 
doses of PUL-042 Inhalation Solution or placebo over 10 days (Days 1, 3, 6, and 10).   
Note: There is no Day 0 in this study. 
An overview of the study design is presented in Figure 4. 
Figure 4 
Study Design 
 
 
 
7.2. 
Subject Selection 
7.2.1. 
Inclusion Criteria 
Subjects aged 18 years or older must fulfill all of the following inclusion criteria to be eligible for the study: 
 Subjects must have recent exposure to SARS-CoV-2 (such as repeated or extensive exposure to an 
infected individual(s) or cohabiting with a SARS-CoV-2  positive individual).   
 Subjects must be 50 years or older if the exposure is due to cohabitation.  
 Subjects must be free of clinical signs or symptoms of a potential COVID-19 diagnosis (Ordinal 
Scale for Clinical Improvement score of 0) with a SARS-CoV-2 infection symptom score (fever, 
cough, shortness of breath, and fatigue) of 0 in each category. 
  Spirometry (forced expiratory volume in one second FEV1 and forced vital capacity [FVC]) ≥70% 
of predicted value. 
 If female, the subject must be surgically sterile or  ≥ 1 year postmenopausal. If of child-bearing 
potential (including being < 1years postmenopausal) and, if participating in sexual activity that may 


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lead to pregnancy, the subject agrees to use an effective dual method of birth control (acceptable 
methods include intrauterine device, spermicide, barrier, male partner surgical sterilization, and 
hormonal contraception) during the study and through 30 days after completion of the study.  
 If female, must not be pregnant, plan to become pregnant, or nurse a child during the study and 
through 30 days after completion of the study. A pregnancy test must be negative at the Screening 
Visit, prior to dosing on Day 1. 
 If male, must be surgically sterile or, if not surgically sterile and if participating in sexual activities 
that may lead to pregnancy, be willing to practice two effective methods of birth control (acceptable 
methods include barrier, spermicide, or female partner surgical sterilization) during the study and 
through 30 days after completion of the study.  
 Ability to understand and give informed consent. 
7.2.2. 
Exclusion Criteria  
Subjects will be excluded if they fulfill any of the following exclusion criteria: 
1. Previous infection with SARS-CoV-2. 
2. Receipt of any vaccine for the prevention of COVID-19 (single or multiple doses). 
3. A SARS-CoV-2 infection symptom score greater than 0 in any of the 4 catergories (fever, cough, 
shortness of breath or fatigue) at the time of screening (Ordinal Scale for Clinical Improvement 
score of  0). 
4. Known history of chronic pulmonary disease (e.g., asthma [including atopic asthma, exercise-
induced asthma, or asthma triggered by respiratory infection], chronic pulmonary disease, 
pulmonary fibrosis, COPD), pulmonary hypertension, or heart failure. 
5. Any condition which, in the opinion of the Principal Investigator, would prevent full participation 
in this trial or would interfere with the evaluation of the trial endpoints. 
7.3. 
Study Integrity 
This will be a double-blind study randomized 1:1 PUL-042 Inhalation Solution: placebo.   
7.4. 
Number of Subjects 
Approximately 200 subjects (100 Pul-042 Inhalation Solution: 100 placebo) will be enrolled.  
7.5. 
Number of Study Sites 
There will be up to 20 study centers. 
7.6. 
Duration of Subject Participation 
Subjects will participate for approximately 28 days.  
7.7. 
Schedule of Study Activities  
The schedule of events is presented in Table 1. 


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Table 1: 
Schedule of Events  
Event 
Screening 
Dose 1a  
 
Dose 2, 3, 4 a  
Follow-up/Early 
Discontinuation from Study 
Study Completion 
V1 
V2  
V3, 4, 5 
V6 
V7 
Day -2 to Day 1 
Day 1b  
Days 3, 6, 10 
 
Day 15 
 
Day 29 
Informed consent 
X 
 
 
 
 
Medical history 
X 
 
 
 
 
Pregnancy testc 
X 
 
 
X 
X 
Physical exam 
X 
X 
X 
X 
 
Vital signsd 
X 
X 
X 
X 
 
Spirometrye 
X 
X 
X 
 
 
Symptom scoref 
X 
X 
X 
X 
X 
SARS-CoV-2 testg 
 
X 
 
X 
X 
Study drug administrationh 
 
X 
X 
 
 
Adverse events 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
Ordinal Scale for Clinical 
Improvement  
X 
X 
X 
X 
X 
Randomization  
X 
 
 
 
 
  
a Vital signs, adverse events, and concomitant medications will be assessed prior to administration of study medication and also at 30 minutes post-dose.  
b There is no Day 0 in this study 
c Urine pregnancy test or serum pregnancy test if women are of child-bearing potential. If urine pregnancy test is positive, a serum pregnancy test must be done. Pregnancy test is 
required for Early Discontinuation, not Day 15. 
d Vital signs will include body temperature, blood pressure measurements, heart rate, and respiratory rate.  
e Spirometry will be done at screening to document eligibility.  On days of dosing, spirometry will be done pre-dose and at 30 minutes (±15) minutes post-dose.  If the FEV1 is 
reduced > 10% compared to the pre-dose baseline the FEV1 should be repeated as clinically indicated 
f SARS-CoV-2 symptoms will be assessed at each visit according to the Symptom Score   
g SARS-CoV-2 testing will be performed pre-dose on Day 1 (Visit 2), Day 15 (Visit 6) and at Day  29 (Visit 7). Additional testing should be conducted at any point during the study 
when clinical symptoms are suggestive of potential COVID-19.  
h Study drug administration must be done by a health care professional 


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7.8. 
Subject Participation 
Subjects will be followed for the duration of the entire study (28 days) to assess the incidence of 
SARS-CoV-2 infection and progession to COVID-19.  The following are general guidelines for study 
conduct: 
• 
Subjects, including those in whom dosing is discontinued for any reason should complete all visits 
as outlined in the protocol. 
• 
Subjects who test positive for SARS-CoV-2 during the study, prior to the completion of the dosing 
regimen, may continue to receive additional doses of study drug up to Day 10 if treatment continues 
to be well tolerated at the discretion of the Principal Investigator. Subjects who withdraw from 
dosing should complete the Early Discontinuation Visit and complete the assessments on Day 29.    
7.9. 
Study Day -2 to Day 1 (Screening) 
The following assessments will be conducted prior to performing any study-specific procedures: 
• 
Informed consent: The subject will sign an informed consent form approved by the governing 
Institutional Review Board (IRB) or Ethics Committee. 
Once the informed consent is obtained, the following will be conducted as part of Screening to document 
subject eligibility for the study. 
• 
Medical history (including documentation of exposure to SARS-CoV-2) 
• 
Physical examination (including height and weight) 
• 
Vital signs  
• 
Spirometry 
• 
Serum pregnancy test or urine test (if urine test is positive, a serum test must be conducted)  
• 
SARS- CoV-2 infection symptom score 
• 
Concomitant medication assessment  
• 
Ordinal Scale for Clinical Improvement 
• 
Randomization to study treatment 
• 
Adverse event (AE) assessment (AE collection starts at the time the time of randomization to study 
treatment and is continuous throughout the study until 28 days after receiving study drug) 
7.10. 
Study Day 1 
7.10.1. 
Day 1 (Pre-dose) 
Assessments conducted during Screening do not have to be repeated if done on Day 1. 
The following should be obtained prior to dosing.  
• 
Physical examination  


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• 
Vital signs 
• 
Spirometry 
• 
Nasopharyngeal or oropharyngeal sample for SARS-CoV-2 testing 
• 
Adverse event assessment 
• 
Concomitant medication assessment 
• 
SARS- CoV-2 infection symptom score 
• 
Ordinal Scale for Clinical Improvement 
7.10.2. 
Day 1 (Study Drug Administration) 
Dosing 
PUL-042 administration must be supervised by a health care professional.  PUL-042 will be administered 
via a PARI Sprint nebulizer equipped with a filter valve to prevent aerosol generation. A nose clip will be 
used during the nebulization procedure. All doses will be administered as a constant volume (4 mL) via 
nebulization; the nebulizer will be operated until all drug has been delivered. All of the following time 
points are defined relative to the completion of dosing (T0). 
Post-Dose Guidelines 
In previous studies with healthy volunteers, some subjects have demonstrated a transient decrease in lung 
function, usually asymptomatic. To date, subjects have recovered to at or near baseline lung function values 
without the administration of rescue medication. However, if after administration of PUL-042 Inhalation 
Solution there are clinical symptoms (increased respiratory rate, cough, shortness of breath) of decreased 
lung function, albuterol (salbtuamol) can be administered. 
Following dosing, if a reduction of FEV1 >10% relative to pre-treatment is recorded, the subject 
should have the FEV1 measurement repeated as clinically indicated. If a reduction of FEV1 >12% 
relative to pre-treatment is recorded at 4 hours, the subject must be reviewed by the Principal 
Investigator prior to further dosing. If a reduction of FEV1 >12% relative to pre-treatment persists 
for up to 4 hours and is associated with clinical symptoms over this period, no further investigational 
treatment should be administered. Albuterol (salbutamol) may be given to symptomatic subjects at 
the discretion of the investigator. 
If a reduction of FEV1 >20% relative to pre-treatment is recorded, no further investigational 
treatment should be administered to that subject.   
7.10.3. 
Day 1 (T0 +30 minutes [±15 minutes]) 
• 
Vital signs 
• 
Spirometry  
• 
Adverse event assessment 
• 
Concomitant medication assessment 


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7.11. 
Study Days 3, 6, and 10 (Study Drug Administration) 
All procedures should occur ±1 day from the scheduled Study Day.  
7.11.1. 
Pre-dose 
On Days 3, 6, and 10 the following dosing guideline should be observed prior to dose administration:  
• 
At Investigator discretion, dosing can be HELD or STOPPED at any time for safety reasons. 
The following should be obtained prior to dosing.  
• 
Physical examination  
• 
Vital signs 
• 
Spirometry 
• 
Adverse event assessment 
• 
Concomitant medication assessment 
• 
SARS- CoV-2 infection symptom score 
• 
Ordinal Scale for Clinical Improvement 
7.11.2. 
Days 3, 6, and 10 (Study Drug Administration) 
Dosing  
PUL-042 administration must be supervised by a health care professional.  PUL-042 will be administered 
via a PARI Sprint nebulizer equipped with a filter valve to prevent aerosol generation. A nose clip will be 
used during the nebulization procedure. All doses will be administered as a constant volume (4 mL) via 
nebulization; the nebulizer will be operated until all drug has been delivered. All of the following time 
points are defined relative to the completion of dosing (T0). 
Note: Missed doses should not be replaced 
Post-Dose Guidelines 
In previous studies with healthy volunteers, some subjects have demonstrated a transient decrease in lung 
function, usually asymptomatic. To date, subjects have recovered to at or near baseline lung function values 
without the administration of rescue medication. However, if after administration of PUL-042 Inhalation 
Solution there are clinical symptoms (increased respiratory rate, cough, shortness of breath) of decreased 
lung function, albuterol (salbutamol) can be administered. 
Following dosing, if a reduction of FEV1 >10% relative to pre-treatment is recorded, the subject 
should have the FEV1 measurement repeated as clinically indicated. If a reduction of FEV1 >12% 
relative to pre-treatment is recorded at 4 hours, the subject must be reviewed by the Principal 
Investigator prior to further dosing. If a reduction of FEV1 >12% relative to pre-treatment persists 
for up to 4 hours  and is associated with clinical symptoms over this period, no further investigational 
treatment should be administered. Albuterol (salbutamol) may be given to symptomatic subjects at 
the discretion of the investigator.  


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If a reduction of FEV1 >20% relative to pre-treatment is recorded, no further investigational 
treatment should be administered to that subject.   
 
7.11.3. 
Days 3, 6, and 10 (T0 +30 minutes [±15 minutes]) 
• 
Vital signs 
• 
Spirometry  
• 
Adverse event assessment 
• 
Concomitant medication assessment 
7.12. 
Study Day 15 (Follow-up) 
Assessments should occur within +1 day of target Study Day. 
The following assessments will be conducted: 
• 
Physical examination  
• 
Vital signs 
• 
Nasaopharyngeal or oropharyngeal sample for SARS-CoV-2 testing 
• 
Adverse event assessment 
• 
Concomitant medication assessment 
• 
SARS- CoV-2 infection symptom score 
• 
Ordinal Scale for Clinical Improvement 
7.13. 
Early Discontinuation from Dosing and Study Withdrawal 
Subjects who have received at least one dose of investigational treatment and are discontinued from 
dosing should continue to the final assessment at Day 29 according to the schedule of events specified 
for pre-dose assessments. There will be no post-dose assessments for these subjects.   
Should the subject’s study participation end prior to the completion of Study Day 15, the following 
assessments will be conducted as soon as possible after the decision to withdraw from the study is made. 
• 
Physical examination  
• 
Vital signs 
• 
Serum pregnancy test or urine test (if urine test is positive, a serum test must be conducted) 
• 
Nasaopharyngeal or oropharyngeal sample for SARS-CoV-2 testing   
• 
Adverse event assessment 
• 
Concomitant medication assessment 


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• 
SARS- CoV-2 infection symptom score 
• 
Ordinal Scale for Clinical Improvement 
7.14. 
Study Completion Day 29 
Assessments should occur within +2 days of target Study Day. 
• 
Serum pregnancy test or urine test (if urine test is positive, a serum test must be conducted) 
• 
SARS- CoV-2 Symptom Score 
• 
Adverse event assessment 
• 
Concomitant medication assessment 
• 
Ordinal Scale for Clincal Improvement 
• 
Nasaopharyngeal or oropharyngeal sample for SARS-CoV-2 testing     
 
 


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8. 
CLINICAL EVALUATIONS AND PROCEDURES 
8.1. 
Medical History 
Medical history will include significant medical conditions, surgical history, and all medications, both 
prescription and nonprescription, taken within 14 days prior to screening. Exposure to SARS-CoV-2 
infected individuals or patients with COVID-19 will be documented. 
8.2. 
SARS-CoV-2 Infection Assessment  
Ordinal Scale for Clinical Improvement: A nine point scale will be used to assess the severity of 
COVID-19 which has been derived from the draft scale proposed by WHO.9 
The following table will be used to assess symptoms due to SARS-CoV-2 infection:  
Table 2: 
SARS-CoV-2 Infection Symptom Score 
Symptom 
Score (0-3) 
Cough 
 
Shortness of breath or difficulty breathing  
 
Muscle aches or fatigue  
 
 
Score (0-4) 
Fever  
 
Symptom Scores (Cough, Shortness of breath or difficulty breathing, Muscle aches or fatigue) 
0- None 
1- Mild (occasional or not bothersome) 
2- Moderate (frequent or bothersome) 
3- Severe (interferes with daily activities) 
Note: Fever will be scored based on temperature recorded as part of vital signs and graded 
according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials: 
• 
0   
 
 
 
 
No Fever 
 
 
 
 
• 
1- Mild  
 
 
 
38.0-38.4oC/100.4-101.1oF 
• 
2-Moderate  
 
 
38.5-38.9oC/101.2-102.0oF 
• 
3-Severe 
 
 
 
39.0-40.0oC/102.1-104.0oF 
• 
4-Life Threatening  
 > 40.0oC/>104.0oF 
 


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8.3. 
Physical Examination and Vital Signs 
A qualified medical person will perform a physical examination at all indicated visits. 
• 
Physical examination: general appearance, head, eyes, ears, nose, throat, neck, cardiovascular, 
lungs, abdomen, lymph nodes, extremities, neurological, skin, musculoskeletal, and other.  
• 
Vital signs will include body temperature, blood pressure, heart rate, and respiratory rate. 
8.4. 
SARS-CoV-2 Testing 
All  testing associated with the conduct of the study will be conducted at a central laboratory designated by 
the Sponsor. At every sampling time point, a nasopharyngeal swab or an oropharyngeal swab will be taken.  
Directions for specimen collection, handling and transport will be provided in the Laboratory Manual. 
8.5. 
Spirometry  
American Thoracic Society or British Thoracic Society guidelines should be followed in the conduct of 
spirometry assessments performed at screening.  
 
 
 


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9. 
DESCRIPTION OF STUDY TREATMENT 
9.1. 
Placebo 
Sterile saline for inhalation will be used as the placebo. 
9.2. 
PUL-042 Inhalation Solution 
Additional information concerning PUL-042 including receipt, storage, preparation, and time windows for 
preparation and subject administration will be provided in the Pharmacy Manual. 
The teratogenic effects of PUL-042 are unknown. 
9.2.1. 
PUL-042 
The investigational product, PUL-042 Inhalation Solution, is a combination of Pam2CSK4 acetate and 
ODN M362 sodium (4:1 molar ratio [Pam2:ODN]). PUL-042 is formulated as a solution in SWFI, USP, 
with no other excipients, at a pH of 5 to 8. Pam2 is a synthetic 6-amino acid lipopeptide, and ODN is a 
synthetic 25-base, single-stranded phosphorothioate oligodeoxynucleotide. The structure of Pam2 and the 
nucleotide sequence of ODN are shown in Section 5.2 (Figure 3). 
The investigational product components (Pam2CSK4 and ODN M362 sodium) are manufactured by: 
Albany Molecular Research (Glasgow) Ltd. Todd Campus, West of Scotland Science Park, Acre Road, 
Glasgow G20 0XA, UK. 
9.3. 
Packaging and Labeling 
PUL-042 will be packaged as separate component solutions of Pam2 and ODN in 5-mL Type I sterile glass 
vials or 2-mL Type I sterile glass vials, sealed with a rubber injection stopper and an aluminum tear-off 
overseal. PUL-042 components will be manufactured, labeled, and packaged under Good Manufacturing 
Practice guidelines. Sterile saline for inhalation will be supplied by the investigative site. 
9.4. 
Shipment and Storage 
Individual components of PUL-042, Pam2 Solution and ODN Solution, are stored frozen (-20 ±5°C) at the 
drug distribution center and will be shipped to the site on dry ice.  
Cartons containing 5-mL or 2-mL glass vials of individual PUL-042 components (Pam2 and ODN) will be 
sent to the clinical study site pharmacy. The study drug components will be stored frozen (-20 ±5°C) at the 
study site until ready for use.   
9.5. 
Preparation and Administration 
The pharmacist at the clinical site will be responsible for the preparation of the appropriate concentration 
of PUL-042 by dilution of the components of PUL-042 in SWFI. Specific instructions will be provided for 
the preparation of PUL-042 Inhalation Solution in the Pharmacy Manual.  PUL-042 Inhalation Solution 
must be administered within 4 hours of preparation.   


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10. 
CONCOMITANT 
MEDICATIONS, 
TREATMENTS, 
AND 
PROCEDURES 
All concomitant medications, including prescription and nonprescription over-the-counter drugs, vitamins, 
or nutritional supplements, taken during the 14 days prior to screening or while a participant is on study 
will be recorded in the electronic case report form (eCRF). Documentation will include start and stop dates 
and reasons for use. 
Any diagnostic, therapeutic, or surgical procedures performed during the study period will be documented. 


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11. 
STUDY WITHDRAWAL 
11.1. 
Study Termination 
The entire study may be terminated at any point based on the evaluation of the study or development 
program by Pulmotect. A Data Safety Monitoring Board (DSMB) will review unblinded data on the first 
40 subjects then again at 80 subjects and 120 subjects with additional ad hoc reviews at the request of the 
DSMB. The DSMB can also request that study enrollment be paused at any time should enrollment be 
faster than anticpated such that adequate safety review is not able to occur between the specified review 
meetings.  
11.2. 
Subject Withdrawal/Lost to Follow-up 
Subjects who are discontinued from dosing during the study and have received at least one dose of 
investigational treatment must be followed to Day 29 according to the schedule of events specified above 
for pre-dose assessments. There will be no post-dose assessments for these subjects.   
Subjects will be free to withdraw from the study at any time without giving a reason. Subjects will be 
considered withdrawn from the study in the event of any of the following reasons: 
• 
Withdrawal of the subject’s consent for any reason. 
• 
Subject lost to follow-up prior to the Study Day 29 assessments. 
In the event a subject withdraws from the study for any reason, the Investigator must notify Pulmotect as 
soon as possible and complete the applicable eCRF pages. An effort should be made to capture the reason(s) 
for withdrawal.  
Subjects that withdraw should complete the Early Discontinuation assessments as soon as possible. 
A subject is considered lost to follow-up after 3 documented attempts to contact the subject without success. 
Subjects who withdraw after the start of study drug administration will not be replaced.  


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12. 
ADVERSE EVENTS 
Adverse events will be described and graded according to the Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. 
Symptoms and events  associated with SARS-CoV-2 infection will be scored as per the SARS-CoV-2 
infection symptom score (Table 2) and the Ordinal Scale for Clinical Improvement (Table 4).  These 
findings should not be reported as Adverse Events. 
12.1. 
Definitions 
Adverse Event (AE) 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not 
considered drug related. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, 
for example), symptom, or disease temporally associated with the use of a medicinal (investigational) 
product, whether or not related to the medicinal (investigational) product.  
An abnormal laboratory value will be considered an AE if it qualifies as such based on the Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. 
Throughout the course of the study, every effort should be made to remain alert to possible AEs. Subjects 
should be encouraged to report AEs spontaneously or in response to general, nondirected questioning. 
With the occurrence of an AE, the primary concern is the safety of the subject. Appropriate management 
of the AE should always be the first priority. 
Suspected Adverse Reaction 
Defined as any adverse event for which there is a reasonable possibility that the drug caused the adverse 
event. For the purposes of IND safety reporting “reasonable possibility” means there is evidence to suggest 
a causal relationship between the drug and the adverse event. Suspected adverse reaction implies a lesser 
degree of certainty about causality than adverse reaction, which means any adverse event caused by the 
drug. 
Life-Threating Adverse Event or Life-Threatening Suspected Adverse Reaction 
An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the 
investigator or sponsor, its occurrence places the patient or subject at immediate risk of death. It does not 
include an adverse event or suspected adverse reaction that, had it occurred in a more severe form might 
have caused death. 
Serious Adverse Event (SAE) or Serious Suspected Adverse Reaction 
The terms “serious” and “severe” are not synonymous. Adverse events classified as “serious” have defined 
regulatory requirements. Those classified as “severe” do not have defined regulatory requirements unless 
they are also classified as “serious”.  


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The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate, or severe 
myocardial infarction); the event itself, however, may be of relatively minor medical significance (such as 
severe headache).  
An AE is classified as “serious” based on the criteria outlined below. Seriousness (not severity) defines the 
regulatory reporting obligations. 
An adverse event or suspected adverse reaction is considered “serious” if in the view of either the 
investigator or sponsor, it results in any of the following outcomes:  
• 
Death 
• 
A life-threatening adverse event  
• 
In-patient hospitalization or prolongation of existing hospitalization 
• 
Persistent or significant incapacity or substantial disruption to conduct normal life functions 
• 
A congenital anomaly/birth defect 
• 
Intervention to prevent any one of the other outcomes listed above (based on medical judgment) 
Important medical events that may not result in death, be life-threatening, or require hospitalization may be 
considered serious when, based on appropriate medical judgment, they may jeopardize the subject and may 
require medical or surgical intervention to prevent one of the outcomes listed above. Examples of such 
medical events are allergic bronchospasm requiring intensive treatment in the emergency room or at home, 
blood dyscrasias, convulsions that do not result in in-patient hospitalization, or the development of drug 
dependency or drug abuse. 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the Investigator’s 
Brochure or is not listed in the Investigator’s Brochure at the specificity and severity observed. 
Serious and Unexpected Adverse Event or Suspected Adverse Reaction 
Any AE or suspected adverse reaction that occurs during the subject’s participation in the study that meets 
the criteria for both serious and unexpected as defined above is considered a serious and unexpected AE or 
suspected adverse reaction. 
12.2. 
Adverse Event Reporting Period 
The AE reporting period for this study is continuous and begins at the time of randomization to study 
treatment and ends on Study Day 29. 
In addition, any known untoward event that occurs subsequent to the AE reporting period that the 
Investigator assesses as related to the investigational medication should also be reported as an AE. 
All AEs (both serious and nonserious) must be followed until resolution or until a stable clinical endpoint 
is reached. All measures required for AE management and the ultimate outcome of the AE must be recorded 
in the source documentation and in the eCRF.  


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12.3. 
Treatment Emergent Adverse Events 
Treatment-emergent AEs are defined as those that begin or worsen after the start of study drug 
administration. 
12.4. 
Recording of AEs 
All AEs will be documented in the appropriate section of the eCRF.  
NOTE: Symptoms and events associated with SARS-CoV-2 infection will be scored as per the SARS-
CoV-2 infection symptom score (Table 2) and the Ordinal Scale for Clinical Improvement (Table 4).  
These findings should not be reported as Adverse Events. 
In the event that the electronic data capture (EDC) system cannot be accessed and a SAE or serious 
suspected adverse reaction has occurred, a paper SAE report form will be available to be completed and 
faxed or emailed to the Sponsor or their designee. 
The following will be recorded for each AE in the eCRF: 
• 
A description of the AE in medical terms. Whenever possible, a diagnosis should be given when 
signs and symptoms are due to common etiology (e.g., cough, runny nose, sneezing, sore throat, 
and head congestion should be reported as “upper respiratory infection”)  
• 
Start date 
• 
Stop date 
• 
The severity (i.e., grade) as assessed by the Investigator according to the definitions in the 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Trials. If the AE is not specifically listed in the reference above, the following 
grades should be used:  
o Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
o Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL (Activities of Daily Living) 
o Grade 3 Severe or medically significant but not immediately life threatening; hospitalizaton 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL 
o Grade 4 Life-threatening consequences; urgent intervention indicated 
o Grade 5 Death related to AE 
• 
The causal relationship to study drug as assessed by the Investigator; the decisive factor in the 
documentation is the temporal relation between the AE and the study drug. 
• 
Action(s) taken (e.g., study drug administration interrupted, study drug not administered, none, 
unknown). 
• 
The outcome (e.g., recovered/resolved, not recovered/not resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown). 


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• 
Whether it caused the subject to discontinue the study. 
If in any 1 subject the same AE occurs on several occasions (unless the AE is continuous and of stable 
grade), the AE in question will be documented and assessed at each occurrence. 
Should a pregnancy of a female participant or a partner of a male participant occur, it must be reported and 
recorded in the eCRF. Pregnancy in itself is not regarded as an AE unless there is suspicion that an 
investigational product may have interfered with the effectiveness of a contraceptive medication. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or congenital 
abnormality) must be followed up and documented even if the subject was discontinued from the study. 
All reports of congenital abnormalities/birth defects are SAEs. Spontaneous miscarriages should also be 
reported and handled as SAEs. Elective abortions without complications should not be handled as AEs. 
12.5. 
Assessing Relationships of AE to Study Drug 
The Investigator must record his/her opinion concerning the relationship of the AE to study therapy on the 
AE eCRF. Table 3 provides guidance for assigning relationship to the study drug. 
Table 3: 
Relationship of Adverse Event to the Administration of the Study Drug  
Unrelated 
There is not a temporal relationship to study drug or there is a reasonable causal 
relationship between another drug, concurrent disease, or circumstance and the 
AE. The AE is clearly not related to study drug. 
Unlikely  
There is a temporal relationship to study drug, but there is not a reasonable 
causal relationship between the study drug and the AE. The AE is doubtfully 
related to study drug. 
Possibly 
There is a reasonable causal relationship between the study drug and the AE. 
The AE may be related to study drug. 
Probably 
There is a reasonable causal relationship between the study drug and the AE. 
The AE is likely related to the study drug. 
Definitely 
There is a causal relationship between the study drug and the AE. The AE is 
clearly related to the study drug. 
12.6. 
Reporting Serious or Unexpected AEs 
Any SAE or serious suspected adverse reaction that occurs during the course of the study will be reported 
within 24 hours after the site becomes aware of the event. 
All SAE reporting will adhere to the United States Code of Federal Regulations (CFR), specifically 21 CFR 
312.32 for Investigational New Drugs, and applicable local regulations. The Investigator will notify the 
governing IRB or Ethics Committee of any SAEs and safety reports per IRB or Ethics Committee reporting 
requirements. 


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12.7. 
Follow-up of Adverse Events 
All AEs (both serious and non-serious) should be followed until resolution or until a stable clinical endpoint 
is reached. All measures required for AE management and the ultimate outcome of the AE must be recorded 
in the source document and the eCRF. 
Any SAE or serious suspected adverse reaction follow-up information requested should be provided in a 
timely manner. The additional information may include copies of hospital reports, autopsy reports, or other 
relevant documents. 


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13. 
STATISTICAL METHODS  
13.1. 
Sample Size Determination 
The trial size of 200 subjects (100 PUL-042 inhalation solution: 100 placebo) was chosen based on clinical 
considerations. The rates of infection to adequately estimate a sample size for a statistically significant 
result are unknown.    
Enrolled subjects will be randomized with equal probability to receive blinded treatment consisting of either 
PUL-042 or placebo. 
13.2. 
Subject Populations 
Intent to Treat Population (ITT) 
The ITT population will include all randomized subjects who receive at least one dose of experimental 
treatment (i.e., PUL-042 or Placebo) 
The ITT population will be the primary data source used to address the primary study efficacy objectives 
Modified Intention to Treat (MITT) 
The MITT population will include all randomized subjects who receive at least one dose of experimental 
treatment (i.e., PUL-042 or Placebo) and are negative for SARS-CoV-2 infection at the time of 
administration of the first dose. 
Safety Population 
The Safety population is the ITT population defined as all randomized subjects who have received at least 
one dose of experimental treatment. The Safety population will be the data source used to evaluate the 
safety and tolerability of experimental treatment for this study. 
13.3. 
Primary Objective  
To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-
CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with  
SARS-COV-2 infection and 2) who are asymptomatic at enrollment.  
The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the 
baseline value in the Ordinal Scale for Clinical Improvement within 28 days from the start of experimental 
therapy. The Ordinal Scale for Clinical Improvement is a 9-point scale that measures disease severity at a 
given point in time.  Notably, a score of 0 indicates that an individual is infection-free. The difference in 
scores obtained at different times provides a quantitative assessment of the incidence of infection and 
change in disease severity over that time interval.  The change in severity between the placebo- and actively-
treated groups will be analyzed by a linear statistical model adjusting for the main effect of randomized 
treatment and other relevant covariates (e.g., age, baseline OSCI Score, and presence of comorbidities).  
Because the statistical properties of these score differences might not conform to the theoretical 
requirements of this procedure, a Wilcoxon Rank-Sum (nonparametric) test may also be used to analyze 
the main effect of treatment.   Full details of the planned analysis will be included in the Statistical Analysis 
Plan that will be developed for this study.    


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The Ordinal Scale for Clinical Improvement to be used in this study is derived from a draft scale proposed 
by the World Health Organization9 for clinical improvement as presented below in Table 4: 
Table 4: 
Ordinal Scale for Clinical Improvement (Derived from draft WHO scale) 
Descriptor 
Score 
No clinical or virological evidence of infection 
0 
Infected but no limitation of activities 
Limitation of activities 
1 
2 
Hospitalized not requiring  oxygen therapy (SpO2 > 93% on room 
air)  
Oxygen by mask or nasal prongs 
3 
 
4 
Non-invasive ventilation or high-flow oxygen 
Intubation and mechanical ventilation 
Ventilation + additional organ support- pressors, RRT, ECMO 
5 
6 
7 
Death 
8 
It is possible that medically justified treatment and or procedures cannot be implemented due to the 
unavailability of equipment (e.g., scarcity of ventilators).  In such cases, the data recorded in the eCRF 
should reflect the prescribed circumstances rather than the reality.  For example, if clinical evaluation of a 
patient indicates the need for mechanical ventilation when no ventilator is available, that patient should be 
scored as 6 – “Intubation and mechanical ventilation” not as a lower score on the Ordinal Scale for Clinical  
Improvement.   
13.4. 
Secondary Objectives 
To determine the difference in incidence of SARS-CoV-2 infection 28 days from the start of experimental 
therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit 
To determine the difference in incidence of SARS-CoV-2 infection 14 days from the start of experimental 
therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit (MITT) 
To compare the severity of COVID-19 within 14 days from the start of experimental therapy (ITT) 
To compare the severity of COVID-19 within 28 days from the start of experimental therapy (ITT) 
To assess the requirement for ICU admission within 28 days from the start of experimental therapy (ITT)  
To assess the requirement for mechanical ventilation within 28 days from the start of experimental therapy 
(ITT) 
To assess mortality within 28 days from the start of experimental therapy (ITT) 
To determine the tolerability of PUL-042 Inhalation Solution in this population (ITT population) 


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13.5. 
Safety Analysis 
A comprehensive statistical analysis plan (SAP) will be finalized prior to unblinding of the study results. 
The SAP may modify the plans outlined in the protocol; however, any major modifications of planned 
analyses will be reflected in a protocol amendment. Safety data will be presented in tabular and/or graphical 
format and summarized descriptively, if appropriate. 
Adverse events will be described and graded according to the Toxicity Grading Scale for Healthy Adult 
and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. 
Treatment-emergent AEs, vital signs, physical examinations, clinical laboratory data, lung function tests, 
and noncompliance will be reviewed on an ongoing basis during the study to evaluate the safety of the 
subjects.  


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14. 
ADMINISTRATION OF THE STUDY 
14.1. 
Regulatory Considerations 
This study will be conducted in compliance with the protocol, International Conference on Harmonisation 
(ICH) Good Clinical Practice (GCP) Guidelines, and the applicable local regulatory requirements. This 
study will be conducted in accordance with the ethical principles that originate in the Declaration of 
Helsinki and ICH Guidelines for GCP. 
Study protocols and informed consent forms will be approved by the appropriate IRB or Ethics Committee 
prior to initiation of the study. All subjects will sign an informed consent form prior to any study-specific 
procedures. The study will be monitored for regulatory and protocol compliance by a study monitor selected 
by Pulmotect. 
14.2. 
Institutional Review Board (IRB)/Ethics Committee 
The Investigator must submit the final protocol and proposed informed consent document to an IRB/ethics 
committee that complies with the ICH GCP. The IRB/ethics committee will provide the Investigator with 
a written decision regarding the conduct of the study and a copy of the document will be forwarded to the 
Sponsor. The study will not be initiated and subjects will not be enrolled until the appropriate 
documentation of IRB/ethics committee approval of the study protocol and the informed consent form has 
been received. 
Substantive modifications to the protocol must be submitted to the IRB/ethics committee for approval. 
Administrative changes to the protocol, such as revisions for clarification that do not affect the conduct of 
the study or increase the risk to the subject, should be submitted to the IRB/ethics committee for 
informational purposes; formal approval is not required. 
The Investigator must also submit any written information that will be given to the study subjects, as well 
any subject recruitment material, to the IRB/ethics committee for approval prior to use. 
The Investigator will make appropriate and timely reports to the IRB/ethics committee as required by 
applicable government regulations and IRB/ethics committee policy. In addition to progress reports, all 
known information regarding SAEs will be reported per IRB/ethics committee requirements. 
It is the Investigator's obligation to provide the Sponsor with copies of all study-related correspondence 
with the IRB/ethics committee in a timely fashion and to retain the originals as part of the Site Regulatory 
File. The Site Regulatory File will be made available as requested for monitoring or quality assurance 
review during site audits and to governmental regulatory representatives as required. 
14.3. 
Subject Information and Informed Consent 
Written informed consent must be obtained from each subject in accordance with the ICH GCP. Informed 
consent must be obtained prior to performing any study-specific procedures. The consent form that is used 
must be approved by both the reviewing IRB/ethics committee and Pulmotect. 
The subject and the individual explaining the study will sign the current IRB/ethics committee-approved 
version of the consent form. A copy of the signed consent form will be given to the subject. The date that 
consent was obtained will be recorded on the eCRF as well as in the subject's source documents. 


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A copy of each version of the informed consent form that has been approved by the IRB/ethics committee 
will be provided to the Sponsor. Care should be taken that the current approved version of the consent form 
is provided to the subject for review and signature. It is possible that in some cases an updated consent form 
will contain significant information that will require a previously enrolled subject to sign the updated 
consent form. Original signed consent forms must be in the Site Regulatory File and be available for review 
by authorized individuals. 
A sample consent form is provided in Section 15. 
14.4. 
Data Safety Monitoring Board 
An external DSMB will be used to evaluate safety of the study in an ongoing manner. There will be three 
voting members. None of the voting members will have any affiliation with Pulmotect, Inc. A full 
description of the membership, role, and responsibilities of the DSMB will be finalized prior to the start of 
the study, and will be provided in the DSMB charter. The DSMB will evaluate safety at regular intervals 
including early in the trial.  
The DSMB chair has the ability to pause study enrollment at any point during the study for any reason 
including rapid enrollment which could hinder the DSMB’s ability to review the safety of PUL-042 
Inhalation Solution in a timely manner relative to overall enrollment.  The first evaluation will be done after 
40 subjects have completed dosing. Unless the DSMB recommends to the contrary, enrollment will be 
allowed to continue until 80 patients have completed dosing. Enrollment beyond 80 subjects will require 
formal DSMB review of the data from the first 40 subjects to have been completed with explicit approval 
to continue enrollment beyond 80 subjects. Subsequent evaluations will occur at 120 patients with further 
ad hoc meetings at the discretion of the DSMB.  
One potential recommendation of the DSMB is to stop the study due to safety concerns.  Any imbalance in 
the incidence of AEs between placebo and active treatment is to be further reviewed by the DSMB taking 
into account the totality of evidence in order to render a recommendation to the sponsor regarding study 
continuation. As specified in the DSMB charter the formal review of data will take place at each meeting 
of the DSMB after 40, 80 and 120 subjects have completed dosing. Ad hoc meetings can also be called.  
As a further effort to ensure the safety of PUL-042, a stopping rule that is based only on mortality will be 
employed.  This rule will be implemented if there is a high probability of excess mortality risk among 
patients randomized to PUL-042.  The following hierarchical analysis of mortality will be performed after 
50% of subjects have been enrolled (50/group) and followed up for 28 days from the start of investigational 
therapy: 
1) Based on blinded data, if no more than 3 deaths have occurred during the study this analysis will 
not be conducted due to the lack of evidence of increased mortality risk attributable to PUL-042.   
If more than 3 deaths occur: 
2) The Unblinded statistician will evaluate unblinded mortality data to determine the treatment 
specific death rate (i.e., DTx = DeathsTx / NTx; Tx = Active or Placebo).   
3) If the difference, Δ,  in treatment-specific death rates (i.e., Δ = DActive – DPlacebo) is greater than 7.5%, 
the DSMB will further review the totality of evidence and render a recommendation to the sponsor 
regarding study continuation. 


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Characteristics of this rule are as follows: 
Assuming that the true underlying control arm mortality rate is 5% and using a normal approximation when 
comparing proportions, the probability of stopping is approximately:  
• 
90% if the true underlying mortality rate attributable to PUL-042 is 25%. 
• 
62% if the true underlying mortality rate attributable to PUL-042 is 15%. 
• 
only 11% if the true underlying mortality rate attributable to PUL-042 is 5% (equal to the 
assumed true underlying control arm mortality rate) 
14.5. 
Adherence to the Protocol 
The study shall be conducted as described in this protocol except for an emergency situation in which proper 
care of the subject requires immediate alternative intervention. This protocol refers to the protocol as 
provided by Pulmotect and approved by both the IRB/ethics committee and submitted to the FDA as part 
of the Investigational New Drug Application that is in effect. While FDA regulations permit the protocol 
to be amended, this must be done in accordance with the provisions agreed upon in Section 14.6.  
Any material deviation from study procedures (identified by site personnel or monitor) will be documented. 
Major subject-level deviations will be captured on the protocol deviation form in the eCRF. A list of 
protocol deviations will be compiled and reviewed by the Principal Investigator and Sponsor to identify 
major and minor deviations periodically using the following criteria: 
Major – A serious breach of protocol and GCP compliance, which may also impact subject safety or study 
endpoints. Examples include (but are not limited to):  
• 
Violation of inclusion/exclusion criteria  
• 
Dose calculation error  
• 
Failure to collect primary endpoint data  
Minor – An administrative breach of protocol procedure that has minimal impact on regulatory compliance, 
subject safety, or study endpoints. Examples include (but are not limited to):  
• 
Visits conducted out of established timeframes  
• 
Dose timing out of established timeframes  
• 
Missing selected laboratory panel parameters  
14.6. 
Protocol Modifications 
The Investigator will not modify this protocol without obtaining the concurrence of Pulmotect. All protocol 
amendments will be issued by Pulmotect, and must be signed and dated by the Investigator prior to 
implementation of the amendment. Pulmotect will submit protocol modifications to regulatory agencies as 
required by 21 CFR 312.30. The Investigator is responsible for notifying the IRB/ethics committee of 
changes. Any changes that potentially affect subject safety or significantly alter the conduct of the study 
(e.g., changes to inclusion or exclusion criteria, study drug dosage, study procedures, etc.) must have written 
approval prior to implementation.  


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Note: The IRB/ethics committee may require the informed consent form be revised to reflect the study 
revisions.  
In situations requiring a departure from the protocol for a subject that has been enrolled appropriately, the 
Investigator or other physician in attendance will contact Pulmotect by telephone. If possible, this contact 
will occur before implementing any departure from the protocol. In all cases, contact must be made as soon 
as possible in order to discuss the situation and agree on an appropriate course of action. The source 
documents must reflect any departure from the protocol and be transcribed into the eCRF. The investigator 
is responsible for notifying the IRB/ethics committee of any departures from the protocol. 
No requests for a waiver from the specified inclusion/exclusion criteria will be granted. 
14.7. 
Data Collection 
Study data will be entered into an EDC system (eCRFs). Subject screening information will be recorded by 
the study site. The following will be the minimum captured: initials, subject personal identification number, 
date of screening, and enrollment status. 
Data collected through the completion of experimental procedures required by this protocol will be recorded 
in the subject's source documentation. These data will then be transcribed into the eCRF. 
All required study data will be entered into the eCRFs provided by Pulmotect. All study data should be 
entered into the eCRF as soon as possible after collection. All information in the eCRFs must be supported 
by original data in the subject’s medical records. All medical records, laboratory printouts, notes made by 
the physician, and other materials such as x-rays will be considered source data and must be available for 
inspection by Pulmotect, its designees, or regulatory authorities. 
Appropriate training of the study site will be conducted prior to study initiation to assist with making entries 
and corrections to data entered into an eCRF. The Investigator remains responsible for the accuracy and 
adequacy of all data entered into the eCRFs (EDC system).  
Data will be monitored as described in Section 14.9. Data entered into eCRFs will be reviewed and 
compared with source documents by monitors that are adequately trained using the EDC system.  
Upon further data processing, queries may be generated and sent electronically to the Investigator for 
clarification or correction. The Investigator or designee will address any queries and provide resolution 
within the EDC system. 
The eCRF will be signed (electronically) by the Investigator after review (date and time will be captured in 
the eCRF audit trail). After completion of the study, completed eCRFs will be electronically transferred to 
Pulmotect and/or designee and stored in the archives according to the data management plan. Once the 
eCRFs are signed by the Investigator, the data manager will lock the eCRFs for data analysis. 
14.8. 
Maintaining Records 
A Site Regulatory Binder must be maintained at the investigative site and will contain the documents 
identified in the list of Essential Documents according to ICH GCP, including a signed Investigator 
Agreement. Pulmotect, or its designee, will provide a Site Regulatory Binder to the site. 


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According to the United States Federal Regulations (21 CFR 312.57[c]), all records and reports related to 
this clinical study must be retained by the Investigator for at least 2 years after approval of a marketing 
application and until there are no pending or contemplated marketing applications or until at least 2 years 
have elapsed since the formal discontinuation of clinical development of the investigational product. 
Pulmotect will inform the Investigator as to when these documents no longer need to be retained. These 
documents must be stored in a secure archive and be available in the event of a regulatory audit. 
Study records that must be retained in the Site Regulatory Binder (or the Pharmacy Manual, if appropriate) 
may include, but are not necessarily limited to: study personnel identification, designation and signature 
list, subject screening records, subject roster (names omitted), protocol and any amendments or 
administrative changes, product disposition records, essential documents identified in ICH GCP guidelines, 
correspondence, laboratory accreditations, and normal laboratory ranges. The site must keep the binder 
current and available along with relevant subject charts and study reports for review by the Sponsor, 
IRB/Ethics Commitee, FDA, and/or local regulatory authorities.  
14.9. 
Monitoring, Auditing, and Inspecting 
Pulmotect or its designee will monitor all aspects of the study with respect to current GCP and standard 
operating procedures for compliance with applicable regulations and to ensure that the rights of subjects 
are protected. Pulmotect or a designee (e.g., clinical research organization) will assure the accuracy of the 
data and the selection of a qualified Investigator and appropriate study center. The protocol procedures will 
be reviewed with the Investigator and associated personnel prior to study initiation and during periodic 
monitoring visits. Pulmotect or a designee will review eCRFs for accuracy and completeness during on-
site monitoring visits. Discrepancies will be resolved with the Investigator or designee as appropriate. 
Remote monitoring may be conducted as required to identify trends and issues, evaluate enrollment status, 
query status, data quality, AEs, etc. 
Pulmotect or its designees will monitor the study using the following methods: 
• 
Frequent telephone contacts 
• 
Periodic site visits 
• 
Review of original subject records, eCRFs, drug accountability and storage, and general study 
documentation 
To ensure the study can be adequately monitored, the Investigator will cooperate in providing Pulmotect, 
or Pulmotect’s designee, with direct access to all study source documents (e.g., subject charts and study 
files) and responding to inquiries that may arise as a result of the document review. 
Review of these documents will usually occur during a routine monitoring visit but may also be required 
during a visit by a quality assurance auditor. The Investigator will also provide direct access to these records 
to regulatory representatives if and when requested. Pulmotect reserves the right to terminate the study if 
access to source documentation of work performed in this study is denied to the Pulmotect, its designee, or 
regulatory representatives. 


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14.10. 
Confidentiality 
The anonymity of subjects participating in this study must be maintained. Subjects will be identified by 
their assigned number and their initials in all written communications between the Investigator and 
Pulmotect, or Pulmotect’s designee. Documents that are not submitted to Pulmotect and that identify the 
subject (e.g., signed informed consent, source documents/charts) will be made available to Pulmotect or 
regulatory authorities for inspections, but will be maintained in confidence. 
All study-related information provided by Pulmotect to the Investigator and not previously published, 
including but not limited to the active study agent identity, the Investigator's Brochure, the study protocol, 
verbal and written communication, eCRFs, assay methods, and scientific data, will be considered 
confidential. In addition, all information developed during the conduct of the clinical investigation of the 
study agent is also considered confidential. Neither the Investigator nor any of his/her employees or agents 
shall disclose or use this information for any purpose other than the performance of the clinical study. Such 
information shall remain the confidential and proprietary property of Pulmotect, and disclosure to others 
will be limited to other physicians who are conducting studies with the same active study agent, the 
IRB/ethics committee, and the applicable regulatory authorities, except by prior written permission of 
Pulmotect or its agents. At such time that information becomes widely and publicly available through no 
fault of the Investigator, the obligation of nondisclosure toward that particular information will cease. 


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15. 
SAMPLE INFORMED CONSENT 
 
INFORMED CONSENT/AUTHORIZATION FOR PARTICIPATION IN RESEARCH 
 
Study Title: A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of PUL-042 
Inhalation Solution in Reducing the Infection Rate and Progession to COVID-19 in Adults 
Exposed to SARS-CoV-2 
 
RESEARCH CONSENT SUMMARY 
You are being asked for your consent to take part in a research study. This document provides a 
concise summary of this research. It describes the key information that we believe most people 
need to decide whether to take part in this research. Later sections of this document will provide 
all relevant details. 
 
WHAT SHOULD I KNOW ABOUT THIS RESEARCH? 
 
• Someone will explain this research to you. 
• Taking part in this research is voluntary. Whether you take part is up to you. 
• If you do not take part, it will not be held against you. 
• You can take part now and later drop out, and it will not be held against you 
• If you do not understand, ask questions. 
• Ask all the questions you want before you decide. 
HOW LONG WILL I BE IN THIS RESEARCH? 
 
We expect that your taking part in this research will last for approximately 28 days.  Your study 
doctor will inform you of how long you will be in the study and when study visits are required. 
 
WHY IS THIS RESEARCH BEING DONE? 
 
The purpose of this research is try to see whether an experimental drug, PUL-042 Inhalation 
Solution (PUL-042), is effective in preventing infection with the COVID-19 virus (SARS-CoV-2) 
and reducing the severity of  COVID-19 illness in particpants who become infected.  
 
WHAT HAPPENS TO ME IF I AGREE TO TAKE PART IN THIS RESEARCH? 
 
If you decide to take part in this research study, you will take the experimental drug, PUL-042 
Inhalation Solution (PUL-042) or a placebo 4 times over a 10 day period. The study visits may 
involve collection of mouth/nasal swabs in addition to completion of physical examination, vital 
signs and lung function tests.  Urine samples or blood samples will be required for females of child 
bearing potential.  
 
 


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COULD BEING IN THIS RESEARCH HURT ME? 
 
The most important risks or discomforts that you may expect from taking part in this research may 
include irritation of the airways resulting in symptoms such as cough and tightness of the chest. 
WILL BEING IN THIS RESEARCH BENEFIT ME? 
 
There is no guarantee that you will receive personal benefit from participating in this study. The 
information gathered during this study could help develop treatments to prevent or reduce illness 
from  SARS-CoV-2  virus infection in other patients. 
 
WHAT OTHER CHOICES DO I HAVE BESIDES TAKING PART IN THIS 
RESEARCH? 
You may choose not to take part in this study without any penalty or loss of benefits to which you 
are otherwise entitled. The treatment being tested in this study is intended to be given in addition 
to any standard treatment needed, not as a replacement or alternative. If you choose not to take 
part, you will still receive the standard treatment that you would normally receive. 
You are being asked to take part in this study because you have have had docoumented exposure 
to the SARS-CoV-2 virus.  
 
DESCRIPTION OF RESEARCH 
 
1. 
PURPOSE OF STUDY 
 
This study will try to see whether an experimental drug, PUL-042 Inhalation Solution (PUL-042), 
is effective in preventing COVID-19 infection or reducing the severity of COVID-19 illness in 
participants who have been exposed to SARS-CoV-2, but have no documented infection of the 
virus at the time of enrollment.    
 
2. 
DESCRIPTION OF STUDY 
 
This is an investigational study. PUL-042 has not yet been approved by the U.S. Food and Drug 
Administration (FDA) or other Regulatory Authority to treat any medical condition and is not 
available for sale to the public or to be prescribed by a doctor. PUL-042 is a combination of two 
molecules (called Pam2 and ODN for short) mixed in sterile water. Previous studies in animals 
have shown that PUL-042 may help tissues in the lungs to resist infections better.  
 
PUL-042 will be given through a nebulizer. This is a machine that uses a small motor to turn liquid 
into a mist, like a humidifier, so that you can breathe the drug into your lungs. You breathe in the 
mist through a plastic tube or facemask. Using a nebulizer is not painful or uncomfortable and is 
a common method of giving drugs during asthma attacks. It will take around 10 minutes to breathe 
in all of the study drug. 
 
A total of up to approximately 200 participants will be enrolled in this study, all at up to 20 centers.  
Participants in the study will receive either PUL-042 or a placebo (an inactive agent that appears 


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identical to PUL-042). There is a 50% chance you will receive PUL-042 (like flipping a coin).  
Neither you or your doctor will know if you receive PUL-042 or placebo. However, your study 
doctor can find out which study group you are in if there is an emergency. All study procedures 
will be provided free of charge. If you decide to participate in this study, you will have assessments 
done over the course of approximately 28 days. The assessments performed at each Study Day are 
described below. 
 
Study Day -2 to Study Day 1 
• You will read this informed consent document and discuss any questions you have 
with the study staff. No other parts of this study will be performed until all your 
questions have been answered and you have signed this form, indicating that you 
want to take part in the study. 
• The study doctor will collect information about your overall health and medical 
history, including documenting your exposure to SARS-CoV-2. You will be asked 
by study staff whether you have been diagnosed with COVID-19 illness. 
• A physical examination will be performed. 
• Your vital signs (blood pressure, pulse, temperature, and breathing rate) will be 
measured 
• Your lung function will be measured by having you blow into a tube 
• Women who can become pregnant will take a serum or urine pregnancy test. If a 
urine test is positive, the results will be confirmed with a blood pregnancy test. If 
you are pregnant, you will not be allowed to participate in the study. 
• You will be asked about any recent health issues and medications you are taking. 
 
Study Day 1 
• A physical examination will be performed. 
• Your vital signs (blood pressure, pulse, temperature, and breathing rate) will be 
measured 
• Your lung function will be measured by having you blow into a tube  
• A specimen will be taken by inserting a swab into your nasal passage or from the 
back of your mouth in order to test for the SARS-CoV-2 virus  
• You will be asked about any recent health issues and medications you have taken. 
• You will be given the study treatment (PUL-042 or placebo) through the 
nebulizer. 
• Your vital signs (blood pressure, pulse, temperature, and breathing rate) and your 
lung function (by having you blow into a tube) will be measured at 30 minutes after 
you finish taking taking PUL-042.  
 
If you are confirmed to have a SARS-CoV-2 infection at any time during the course of the 
study, you may continue to recieve further doses of PUL-042 if treatment has been well 
tolerated and at the discretion of the Principal Investigator. 
 


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Study Day 3  
• A physical examination will be performed. 
• Your vital signs (blood pressure, pulse, temperature, and breathing rate) will be 
measured. 
• Your lung function will be measured by having you blow into a tube 
• You will be asked about any recent health issues and medications you have taken 
since the assessment. 
• You will be given the study treatment (PUL-042 or placebo) through the 
nebulizer. 
• Your vital signs (blood pressure, pulse, temperature, and breathing rate) and your 
lung function (by having you blow into a tube) will be measured at 30 minutes after 
you finish taking PUL-042.  
Study Day 6 
Study Day 6 will have the same procedures as Study Day 3  
 
Study Day 10 
Study Day 10 will have the same procedures as Study Day 3.  
 
Study Day 15 
• A physical examination will be performed. 
• Your vital signs (blood pressure, pulse, temperature, and breathing rate) will be 
measured. 
•  A specimen will be taken by inserting a swab into your nasal passage or from the 
back of your mouth in order to test for the SARS-CoV-2 virus.You will be asked 
about any recent health issues and medications you are taking. 
Study Day 29 
• You will be asked about any recent health issues and medications you are taking. 
• A specimen will be taken by inserting a swab into your nasal passage or from the 
back of your mouth in order to test for the SARS-CoV-2 virus A   
• Women who can become pregnant will take a urine pregnancy test. If the test is 
positive, the results will be confirmed with a blood pregnancy test.  
 
This visit will end your participation in the study. 
 
If dosing with experimental treatment is discontinued for any reason, you will be asked to complete 
all scheduled pre-treatment procedures but, will not receive further treatments or post-treatment 
measurements. It is still important that you complete all scheduled visits up to the Study Day 29 
assessment. 
 
If you withdraw from the study for any other reasons you will need to complete an Early 
Discontinuation Vist that will have the same procedures as Study Day 15 with the addition that 
women who can become pregnant will take a urine pregnancy test. If the test is positive, the results 
will be confirmed with a blood pregnancy test 
 
 


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3. 
RISKS, SIDE EFFECTS, AND DISCOMFORTS TO PARTICIPANTS 
 
Two previous studies in humans have been completed in which 49 people received PUL-042. The 
side effects noted in these 49 participants that were considered at least possibly related to PUL-042 
administration included: 
• a potential short term decrease in the ability of the lungs to transfer gas from inhaled 
air to red blood cells in 14 of 33 participants 
• a short term increase in the number of white blood cells in 12 participants 
• a short term decrease in the amount of air that can be forced out after a deep breath 
in 14 participants 
• increased mucus in the nose or throat in 2 participants 
• cough in 4 participants 
• productive cough in 1 participant 
• increased mucus in the lungs in 1 participant 
• phlegm production in 1 participant 
• aches in 1 participant 
• chills in 1 participant 
• viral symptoms in 1 participant 
• chest pain, chest tightness, chest heaviness in 1 participant 
 
Most of these side effects were mild and none were considered serious. As with any investigational 
study, the current study may involve unpredictable risks to the participants.  
 
Blood draws may cause pain, bleeding, and/or bruising. You may faint and/or develop an infection 
with redness and irritation of the vein at the site where blood is drawn.  
 
You may be asked questions about your medical history that are sensitive in nature. You may 
refuse to answer any question that makes you feel uncomfortable. If you have concerns about this, 
you are encouraged to contact your doctor or the study chairperson. 
 
Pregnancy-Related Risks  
Because taking part in this study can result in risks to an unborn or breastfeeding baby, you should 
not become pregnant, breastfeed a baby, or father a child while on this study. You must use birth 
control during the study if you are sexually active.  
 
Birth Control Specifications 
If you are female, you must either have gone through menopause (at least one year since your last 
period) or be surgically sterilized (had a hysterectomy or your tubes tied). If you are capable of 
becoming pregnant and, if participating in sexual activity that may lead to pregnancy, you agree 
to use an effective dual method of birth control (acceptable methods include intrauterine device, 
spermicide, barrier, male partner surgical sterilization, and hormonal contraception) during the 
study and through 30 days after completion of the study.  


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If male, you must be surgically sterile (vasectomy) or, if not surgically sterile and if participating 
in sexual activities that may lead to pregnancy, you must be willing to practice two effective 
methods of birth control (acceptable methods include barrier, spermicide, or female partner 
surgical sterilization) during the study and through 30 days after completion of the study.  
Females: If you are pregnant, you will not be enrolled on this study. If you become pregnant or 
suspect that you are pregnant, you must tell your doctor right away. Getting pregnant may result 
in your removal from this study.  
 
Males: Tell the doctor right away if your partner becomes pregnant or suspects pregnancy.  
 
If a pregnancy occurs during the study, you or your partner will be asked to report on the course 
of the pregnancy and birth of the child. 
 
 
4.         WHAT ARE MY RESPONSIBILITIES AS A RESEARCH PARTICIPANT 
If you decide to participate in this medical research study, these are your responsibilities:  
• 
Report all symptoms, side effects, injuries or medical treatments to your study doctor right 
away. Your safety depends on the prompt description of what you experience in the study. 
The quality of the safety information also depends on your prompt reporting. 
• 
Attend all study visits.   
• 
Report all medicines (including health supplements) taken. Safety and data quality depends 
telling your study doctor about everything you take. 
 
Follow your study doctor’s instructions about medicines and procedures you need to treat side 
effects. 
 
5. 
POTENTIAL BENEFITS 
 
There may be no medical benefits for you in this study. The information gathered during this study 
could help develop treatments to prevent or reduce the severity of COVID-19  illness in other 
patients. 
 
6. 
ALTERNATIVE PROCEDURES OR TREATMENTS 
 
You may choose not to take part in this study without any penalty or loss of benefits to which you 
are otherwise entitled. The treatment being tested in this study is intended to be given in addition 
to any standard treatment needed, not as a replacement or alternative. If you choose not to take 
part, you will still receive the standard treatment that you would normally receive. 
  
7.        WHAT ABOUT CONFIDENTIALITY? 
Your medical records will remain confidential. While you are part of the study, you may be asked 
that the investigators communicate with your other doctors. 
 


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For your protection and safety, your medical records may be reviewed by:  
• The sponsor of this trial, Pulmotect or their designees 
• The Institutional Review Board, or Ethics Committee (the agency that oversees human 
research at the Institution) 
• The US Food and Drug Administration (FDA) or other Regulatory Authority 
• Department of Health and Human Services (DHHS [US only]) 
• Department of Defense (US only) 
• The Office for Human Research Protections (OHRP), the agency that oversees human 
research in the US (US only).  
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by 
U.S. Law. This Website will not include information that can identify you. At most, the Website will 
include a summary of the results. You can search this Website at any time. 
 
Absolute confidentiality cannot be guaranteed because of the need to give information to these parties. 
The results of this research study may be presented at meetings or in publications. Your name or 
identity will not be used for publication or publicity purposes. 
 
Your name or the names of other participants will not be revealed in any data collected by the 
Sponsor.  The United States Food and Drug Administration (FDA), Research Ethics Boards 
(REB), Institutional Review Boards (IRB), the Sponsor, or designee, or agents, may inspect and 
copy your medical records (without disclosing your identity) relating to this study. The results of 
this study will be reported to the FDA, and to other regulatory agencies. Absolute confidentiality 
cannot be guaranteed because of the need to give information to these parties.  
 
You have the right to see and copy your personal health information related to the research study 
to request information, rectification, erasure, restriction of your personal data processing as long 
as the study doctor holds the information or research institution. However, for the scientific 
validity of the study, you will not be able to review some of the study information until after the 
study has been completed. 
 
8. 
REMOTE MONITORING 
We will keep your study records private and confidential. Certain people may need to see your 
study records. By law, anyone who looks at your records must keep them completely confidential.  
Due to the nature of this study, the sponsor of this study and affiliated contract research 
organization will not be able to review your study data while at your medical facility.  The 
reviewing of your data may be required to be performed from an outside location.   
If you sign and date this document, you give permission to the study’s Sponsor (Pulmotect) or 
their designee who have been contracted to help in the conduct the study and the review of your 
data to use or disclose (release) your health information electronically outside of the clinical study 
site in a manner that is intended to protect the confidentiality of your data.  In preparing copies of 
your medical records to be released electronically, the clinical study site staff will “de-identify” 


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the records, removing any directly identifiable data such as your name, initials, medical record 
number and full date of birth. The records will only be identifiable using the study number assigned 
to you by the study site.  The disclosure is specific to this clinical study.   
The only people who will be allowed to see these records are: 
• The research team, including the study doctors and research staff, research nurses, and all 
other research staff as well as other doctors involved in your care. 
• Certain government and university staff who need to know more about the study. For 
example, individuals who provide oversight on this study may need to look at your records. 
This is done to make sure that we are doing the study in the right way. They also need to 
make sure that we are protecting your rights and your safety. 
• Any agency of the country, state, provincial, or local government that regulates this 
research. This includes, Food and Drug Administration (FDA), State and Local Health 
Departments, the Department of Health and Human Services (DHHS), Department of 
Defense (DOD), and the Office for Human Research Protection (OHRP), European 
Medicines Agency (EMA) 
• Institutional Review Board (IRB) and its related staff who have oversight responsibilities 
for this study and other offices who oversee this research. 
• The sponsors of this study and any affiliated contract research organization. 
The health information that we may use or disclose (release) for this research study may include: 
• All information in a medical record 
• Results of physical examinations  
• Medical history  
• Lab tests 
• Health information related your Covid-19 infection 
 
9. 
ADDITIONAL INFORMATION 
 
You may ask the study chair any questions you have about this study. You may contact the study 
chair, Dr. XX, at XXX-XXXX. You may also contact the Chair of the Institutional Review Board or 
Ethics Committee (a committee that reviews research studies) at xxxxx with any questions that 
you have regarding this study and your rights as a study participant. 
 
Your participation in this research study is strictly voluntary. You may choose not to take part in 
this study without any penalty or loss of benefits to which you are otherwise entitled. You may 
also withdraw from participation in this study at any time without any penalty or loss of benefits. 
 
If you decide you want to stop taking part in the study, it is recommended for your safety that you 
first talk to your doctor. If you withdraw from this study, you can still choose to be treated. 
 


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The study doctor or the Sponsor may remove you from the study without your consent for any of 
the following reasons:  
 
• if it appears to be medically harmful to you, 
• if you fail to follow directions for participating in the study, 
• if it is discovered you do not meet the study requirements,  
• at the discretion of the study doctor,  
• if the study is canceled,  
• or if you become pregnant. 
 
If your participation in this study is stopped for any reason, you will be asked to complete the early 
discontinuation study procedures for your safety. An Early Discontinuation study visit, will be 
scheduled.  
  
You will be asked to complete the assessments at Study Day 29. 
 
If you agree to be in this study, you will be given a signed and dated copy of this consent form. 
 
This study or your participation in it may be changed or stopped at any time by the study chair, 
Pulmotect, Inc., the U.S. Food and Drug Administration (FDA) or other Regulatory Authority, the 
Office for Human Research Protections (OHRP - a regulatory agency that oversees research in 
humans), or the IRB/Ethic Committee. 
 
You will be informed of any new findings that might affect your willingness to continue taking 
part in the study. 
 
The institution conducting the study may benefit from your participation and/or what is learned in 
this study. 
 
This study is supported by Pulmotect, Inc. with funding from the Department of Defense. 
 
In a medical emergency, you may be cared for by someone who has a financial interest with the 
study sponsor(s). If you have any questions about this, you may call the IRB. 
 
10. 
STUDY COSTS AND COMPENSATION 
 
If you suffer injury as a direct result of taking part in this study, the institution’s health providers 
will provide medical care. Pulmotect may pay for the treatment of the injury or illness. The 
institution cannot determine at this time what you may be reimbursed for. A financial counselor 
will be made available to you after the injury or illness is reported. You may also contact the Chair 
of the IRB or Ethics Committee at XXX-XXXX with questions about study-related injuries. By 
signing this consent form, you are not giving up any of your legal rights. 
 
A new public health declaration, called the Public Readiness and Emergency Preparedness 
Declaration (PREP), was issued by the Department of Health and Human Services on March 10, 


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2020.  This declaration limits the legal rights of a subject participating in a COVID-19 clinical 
study that uses a drug, device or vaccine designed to treat, diagnose, cure or prevent COVID-19. 
This includes the study treatment, PUL-042 used in this study.  Participants using PUL-042 in 
this study will have limits on their right to sue the manufacturers, the study sponsor, healthcare 
providers and others for significant injuries and adverse reactions. 
 
Certain tests, procedures, and/or drugs that you may receive as part of this study may be without 
cost to you because they are for research purposes only. However, your insurance provider and/or 
you may be financially responsible for the cost of care and treatment of any complications resulting 
from the research tests, procedures, and/or drugs. Standard medical care that you receive under 
this research study will be billed to your insurance provider and/or you in the ordinary manner. 
Before taking part in this study, you may ask about which parts of the research-related care may 
be provided without charge, which costs your insurance provider may pay for, and which costs 
may be your responsibility. You may ask that a financial counselor be made available to you to 
talk about the costs of this study. 
 
There are no plans to compensate you for any patents or discoveries that may result from your 
participation in this research. 
 
11. 
AUTHORIZATION FOR USE AND DISCLOSURE OF PROTECTED HEALTH 
INFORMATION 
 
A. During the course of this study, the research team will be collecting and using your protected 
health information. This information may include personal identifying information about you 
(such as your name, race, date of birth, gender, city, and zip code), your medical history, study 
schedule, and the results of any of your tests, therapies, and/or procedures. The purpose of 
collecting and sharing this information is to learn about how the study procedures may affect the 
disease and any study-related side effects. Your doctor and the research team may share your study 
information with the parties named in Section D below. 
 
B. Signing this consent and authorization form is optional However, if you refuse to provide 
authorization to use and disclose your protected health information for this study, you will not be 
able to participate in this research study. 
 
C. The institution will take appropriate steps to keep your protected health information private 
when possible, and it will be protected according to state and federal law. However, there is no 
guarantee that your information will remain confidential, and it may be re-disclosed at some point. 
Federal agencies (such as the FDA, other Regulatory Agencies, Office for Human Research 
Protections (OHRP)), Pulmotect or its designee, and the IRB/Ethics Committee might view or 
receive your record in order to collect data and/or meet legal, ethical, research, and safety-related 
obligations.  
 
D. Your protected health information may be shared with the following parties: 
 
• Pulmotect, Inc. (and/or any future sponsors of the study) and its designees 


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• CTI Clinical Trial & Consulting, a company Pulmotect has hired to help run this study 
and analyze its results 
• Department of Defense (US) 
• Federal agencies that require reporting of clinical study data (such as the FDA and 
OHRP) 
• The governing IRB/Ethics Committee   
• Officials of the institution  
• Clinical study monitors who verify the accuracy of the information 
• Individuals with medical backgrounds who determine the effect that the study 
procedures may have on the disease 
• Individuals who put all the study information together in report form 
 
E. There is no expiration date for the use of your protected health information. In California and 
any other state that requires an expiration date, the Authorization will expire 50 years after you 
sign and date this authorization document.  You may withdraw your authorization to share your 
protected health information at any time in writing. Instructions on how to do this can be found in 
XXXXXXX. You may contact the IRB/Ethics Committee questions. If you withdraw your 
authorization, you will be removed from the study and the study chair and staff will no longer use 
or disclose your protected health information in connection with this study, unless the study chair 
or staff needs to use or disclose some of your research-related protected health information to 
preserve the scientific value of the study. Data collected about you up to the time you withdrew 
will be used and included in the data analysis. The parties listed in Section D above may use and 
disclose any study data that were collected before you canceled your authorization. 
 
 
 
 


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CONSENT/AUTHORIZATION 
(Adult Participants Only) 
 
I understand the information in this consent form. I have had a chance to read the consent form for 
this study or have had it read to me. I have had a chance to think about it, ask questions, and talk 
about it with others as needed. I give XXXX permission to enroll me on this study. By signing this 
consent form, I am not giving up any of my legal rights. I will be given a signed copy of this 
consent document. 
 
 
_______________________________________         ____________________ 
SIGNATURE OF PARTICIPANT                               DATE 
 
WITNESS TO CONSENT  
 
I was present during the explanation of the research to be performed under Protocol PUL-042-501. 
 
 
_______________________________________         ____________________ 
SIGNATURE OF WITNESS TO THE VERBAL        DATE  
CONSENT PRESENTATION (OTHER THAN  
PHYSICIAN)  
 
A witness signature is only required for vulnerable adult participants.  
 
 
 
 
 
 
PERSON OBTAINING CONSENT 
 
I have discussed this clinical research study with the participant and/or his or her authorized 
representative, using language that is understandable and appropriate. I believe that I have fully 
informed this participant of the nature of this study and its possible benefits and risks and that the 
participant understood this explanation. 
 
 
_______________________________________                        ____________________ 
SIGNATURE of Person Authorized to Obtain Consent                               DATE  
 


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16. 
REFERENCES 
 
1World Health Organization. "Fact Sheet: The top ten causes of death." Fact Sheet No 310, July 2013. Web. 
November 2013: http://who.int/mediacentre/factsheets/fs310/en/ 
2Evans SE, Tuvim MJ, Fox CJ, et al. Inhaled innate immune ligands to prevent pneumonia. Br J Pharmacol. 
2011; 163(1):195-206. 
3Evans SE, Xu Y, Tuvim MJ, Dickey BF. Inducible innate resistance of lung epithelium to infection. Annu 
Rev Physiol. 2010b; 72:413-435. 
4Clement CG, Evans SE, Evans CM, et al. Stimulation of lung innate immunity protects against lethal 
pneumococcal pneumonia in mice. Am J Respir Crit Care Med. 2008; 177(12):1322-1330. 
5Tuvim MJ, Evans SE, Clement CG, Dickey BF, Gilbert BE. Augmented lung inflammation protects 
against influenza A pneumonia. PLoS One. 2009; 4(1):e4176. 
6Evans SE, Scott BL, Clement CG, et al. Stimulated innate resistance of lung epithelium protects mice 
broadly against bacteria and fungi. Am J Respir Cell Mol Biol. 2010a; 42(1):40-50. 
7Tuvim MJ, Gilbert BE, Dickey BF, Evans SE. Synergistic TLR2/6 and TLR9 activation protects mice 
against lethal influenza pneumonia. PLoS One. 2012; 7(1):e30596. 
8Leiva-Juarez MM, Kirkpatrick CT, Gilbert BE, et al. Combined aerosolized Toll-like receptor ligands are 
an effective therapeutic agent against influenza pneumonia when co- administered with oseltamivir. Eur J 
Pharmacol. 2018 January 05; 818: 191–197. 
9World Health Organization. WHO-COVID-19: Treatment Trial Design Master Protocol Synopsis, Draft 
February 18, 2020.  
https://www.who.int/blueprint/priority-diseases/key-action/COVID-
19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf) 
https://www.who.int/blueprint/priority-diseases/key-action/multicenter-adaptive-RCT-of-investigational-
therapeutics-for-COVID-19.pdf?ua=1 
 
 

SAP_001.pdf: 
 
Pulmotect PUL-042-501 Statistical Analysis Plan v1.0 
 
CONFIDENTIAL  
 
Page 1 of 21 
 
 
 
 
 
 
 
 
 
 
 
A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of PUL-042 Inhalation 
Solution in Reducing the Infection Rate and Progression to COVID-19 in Adults Exposed to 
SARS-CoV-2 
 
Protocol Number: PUL-042-501 
Protocol Version: 1.60 
Protocol Date: 29 January 2021 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
Version 1.0 
 
 
 


 
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A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of PUL-042 Inhalation 
Solution in Reducing the Infection Rate and Progression to COVID-19 in Adults Exposed 
to SARS-CoV-2 
 
 
STATISTICAL ANALYSIS PLAN 
Version 1.0 
 
 
 
Author: 
 
Yuhui Qiu 
 
 
 
 
 
 
 
 
Principal Biostatistician, CTI  
 
 
 
 
 
CTI Biostatistics 
Reviewer: 
 
David McCollum 
 
 
 
 
 
 
 
Director, Global Biostatistics, CTI  
 
 
 
 
 
 
 
 
Sponsor Approval: Colin Broom  
   
                         
 
 
 
Chief Executive Officer  
 
 
 
Pulmotect, Inc. 
 
 
 
 
 
 


 
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Table of Contents 
LIST OF ABBREVIATIONS ..................................................................................................................................... 5 
1. 
INTRODUCTION .............................................................................................................................................. 6 
2. 
OBJECTIVES AND ENDPOINTS ................................................................................................................... 6 
2.1 
OBJECTIVES .................................................................................................................................................. 6 
2.1.1 
Primary Objective .................................................................................................................................... 6 
2.1.2 
Secondary Objectives ............................................................................................................................... 6 
2.2 
ENDPOINTS ................................................................................................................................................... 6 
2.2.1 
Primary Efficacy Endpoint ...................................................................................................................... 6 
2.2.2 
Secondary Efficacy Endpoints ................................................................................................................. 7 
2.2.3 
Safety and Tolerability Endpoints ............................................................................................................ 7 
3. 
INVESTIGATIONAL PLAN ............................................................................................................................ 7 
3.1 
STUDY DESIGN ............................................................................................................................................. 7 
3.2 
TREATMENT .................................................................................................................................................. 8 
3.2.1 
Randomization Scheme and Treatment Arm Assignment ......................................................................... 8 
3.2.2 
Blinding ................................................................................................................................................... 8 
3.2.3 
Dosing Schedule ...................................................................................................................................... 8 
3.2.4 
Subject Compliance ................................................................................................................................. 8 
4. 
GENERAL CONSIDERATIONS FOR DATA ANALYSIS ........................................................................... 8 
4.1 
DATA QUALITY ASSURANCE ........................................................................................................................ 9 
4.2 
ANALYSIS SETS ............................................................................................................................................. 9 
4.3 
ASSESSMENT WINDOWS ............................................................................................................................. 10 
4.4 
HANDLING OF DROPOUTS OR MISSING DATA ............................................................................................. 10 
4.5 
MULTIPLE COMPARISONS ........................................................................................................................... 10 
4.6 
DATA DERIVATIONS AND TRANSFORMATIONS ........................................................................................... 10 
5. 
STUDY SUBJECTS .......................................................................................................................................... 10 
5.1 
DISPOSITION OF SUBJECTS .......................................................................................................................... 10 
5.2 
PROTOCOL DEVIATIONS .............................................................................................................................. 11 
5.3 
DEMOGRAPHIC CHARACTERISTICS ............................................................................................................. 11 
5.4 
BASELINE CHARACTERISTICS ..................................................................................................................... 11 
5.5 
MEDICAL HISTORY ..................................................................................................................................... 11 
5.6 
CONCOMITANT MEDICATIONS AND PROCEDURES ....................................................................................... 11 
6. 
EFFICACY ANALYSES .................................................................................................................................. 12 
6.1 
PRIMARY EFFICACY ENDPOINT AND ANALYSIS .......................................................................................... 12 
6.2 
SECONDARY EFFICACY ENDPOINTS AND ANALYSES .................................................................................. 13 
Incidence of  SARS-CoV-2 infection through Day 29 ......................................................................................... 13 
Incidence of  SARS-CoV-2 infection through Day 15 ......................................................................................... 13 
Severity of COVID-19 through Day 15 ............................................................................................................... 13 
Ordinal Scale through Day 29 ............................................................................................................................ 14 
Symptom Score .................................................................................................................................................... 14 
Subjects requiring ICU admission ...................................................................................................................... 14 
Number of ICU Days .......................................................................................................................................... 15 
Subjects requiring mechanical ventilation .......................................................................................................... 15 


 
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Number of days on mechanical ventilation ......................................................................................................... 15 
Mortality Rate through Day 29 ........................................................................................................................... 16 
6.3 
SUBGROUP ANALYSES ................................................................................................................................ 16 
7. 
SAFETY AND TOLERABILITY ANALYSIS .............................................................................................. 16 
7.1 
EXTENT OF EXPOSURE AND COMPLIANCE .................................................................................................. 16 
7.2 
ADVERSE EVENTS ....................................................................................................................................... 17 
7.2.1 
Treatment-emergent Adverse Events ..................................................................................................... 17 
7.2.2 
Adverse Event Severity ........................................................................................................................... 17 
7.2.3 
Adverse Event Relationship to Study Drug ............................................................................................ 17 
7.2.4 
Serious Adverse Events .......................................................................................................................... 17 
7.2.5 
Adverse Event Summaries ...................................................................................................................... 18 
7.3 
PULMONARY FUNCTION TESTING ............................................................................................................... 19 
7.4 
VITAL SIGNS ............................................................................................................................................... 19 
7.5 
OTHER SAFETY MEASURES ......................................................................................................................... 19 
8. 
INTERIM ANALYSES .................................................................................................................................... 20 
9. 
SAMPLE SIZE AND POWER CALCULATIONS ....................................................................................... 20 
10. 
REFERENCES ............................................................................................................................................. 20 
11. 
APPENDIX ................................................................................................................................................... 21 
11.1 
APPENDIX A: SCHEDULE OF EVENTS .......................................................................................................... 21 


 
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LIST OF ABBREVIATIONS  
Abbreviation 
Definition 
ADL 
Activities of Daily Living 
AE 
Adverse event 
ATC 
Anatomical, Therapeutic, and Chemical 
BMI 
Body mass index 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CTCAE 
Common Terminology Criteria for Adverse Events 
COVID-19 
Coronavirus Disease 2019 caused by the SARS-CoV-2 virus 
DSMB 
Data and Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
FEV1 
forced expiratory volume in 1 second 
ICU 
Intensive care unit 
ITT 
Intention to Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified Intention to Treat 
ODN 
ODN M362 
Pam2 
Pam2CSK4 
PI 
Principal Investigator 
PT 
Preferred term 
PUL-042 
drug product consisting of a 4:1 molar ratio of Pam2:ODN; 
Inhalation Solution 
SAE 
Serious adverse event 
SAF 
Safety 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Coronavirus causing COVID-19 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
WHO 
World Health Organization 
 
 


 
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1. INTRODUCTION 
This statistical analysis plan (SAP) is based on the Protocol # PUL-042-501 Version 1.60, dated 
19 January 2021, and titled “A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety 
of PUL-042 Inhalation Solution in Reducing the Infection Rate and Progression to COVID-19 in 
Adults Exposed to SARS-CoV-2.”  See the study protocol for full details.  
This document details the statistical methods planned to perform the analysis for Data Safety 
Monitoring Board (DSMB), as well as the final analysis of the study. 
2. OBJECTIVES AND ENDPOINTS 
2.1 
Objectives 
2.1.1 
Primary Objective 
To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with 
SARS-CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to 
individuals with SARS-CoV-2 infection, and 2) are asymptomatic at enrollment. 
2.1.2 
Secondary Objectives 
• To determine the difference in incidence of SARS-CoV-2 infection 28 days from the start 
of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment 
visit 
• To determine the difference in incidence of SARS-CoV-2 infection 14 days from the start 
of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment 
visit  
• To compare the severity of COVID-19 within 14 days from the start of experimental 
therapy 
• To compare the severity of COVID-19 within 28 days from the start of experimental 
therapy  
• To assess the requirement for ICU admission within 28 days from the start of experimental 
therapy  
• To assess the requirement for mechanical ventilation within 28 days from the start of 
experimental therapy  
• To assess mortality within 28 days from the start of experimental therapy  
• To determine the tolerability of PUL-042 Inhalation Solution in this population 
2.2 
Endpoints 
2.2.1 
Primary Efficacy Endpoint 
The primary endpoint is the severity of COVID-19 as measured by the maximum difference from 
the baseline value in the Ordinal Scale for Clinical Improvement within 28 days from the start of 
experimental therapy. 


 
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2.2.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints include the following: 
• Incidence of SARS-CoV-2 infection 28 days from the start of experimental therapy in 
subjects who test negative for SARS-CoV-2 at the pre-treatment visit 
• Incidence of SARS-CoV-2 infection 14 days from the start of experimental therapy in 
subjects who test negative for SARS-CoV-2 at the pre-treatment visit 
• Severity of COVID-19 as measured by the maximum difference from the baseline value in 
the Ordinal Scale for Clinical Improvement within 14 days from the start of experimental 
therapy. 
• Ordinal Scale for Clinical Improvement within 28 days from the start of experimental 
therapy 
• SARS-Cov-2 Symptom Score during the study 
• Proportion of subjects requiring ICU admission from Day 1 to Day 29 
• Number of ICU Days from Day 1 to Day 29 
• Proportion of subjects requiring mechanical ventilation from Day 1 to Day 29 
• Number of days on mechanical ventilation from Day 1 to Day 29 
• All-cause mortality rate through Day 29 
2.2.3 
Safety and Tolerability Endpoints 
• Reduction in forced expiratory volume in 1 second (FEV1) from Pre-dose to Post-dose 
• Treatment-emergent serious adverse events (SAEs) through Day 29 
• Treatment-emergent adverse events (TEAEs) and severity through Day 29 
• Vital signs 
3. INVESTIGATIONAL PLAN 
3.1 
Study Design 
This will be a double-blind trial. A total of approximately 200 subjects randomized 1:1 (PUL-042 
Inhalation Solution: placebo) will be enrolled in the trial.  
Doses will be administered via nebulization with a PARI Sprint nebulizer. All subjects will receive 
up to 4 doses of PUL-042 Inhalation Solution or placebo over 10 days (Days 1, 3, 6, and 10). 
Subjects will participate for approximately 28 days. See Appendix A for the Schedule of Events. 
An overview of the study design is presented below: 


 
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3.2 
Treatment 
3.2.1 
Randomization Scheme and Treatment Arm Assignment 
Subjects will be randomly assigned to receive PUL-042 Inhalation Solution or placebo in a 1:1 
ratio. A central randomization system, the Medication Assignment Center (MAC; CTI Clinical 
Trial and Consulting Services), will be used for this study. 
3.2.2 
Blinding 
The sponsor, subjects, Principal Investigator (PI), and site study staff (except for the unblinded 
study drug personnel) will not know the treatment (PUL-042 vs. placebo) a subject receives. The 
CRO staff dealing with blinded site study staff and the study statistician will also be blinded. The 
statistician who generates the production randomization code, MAC Operators who perform the 
randomization and the unblinded study team will be unblinded to the treatment a subject receives.  
All doses of study drug (i.e., both Active and Placebo) will be prepared at the site, so the site 
Pharmacists will also be unblinded.  
3.2.3 
Dosing Schedule 
The dose level of PUL-042 Inhalation Solution in this study will be 20.3 μg Pam2 : 29.8 μg 
ODN/mL (50 μg PUL-042). A total of up to 4 doses will be administered over a 10-day period for 
a total dose of 81.2 μg Pam2 : 119.2 μg ODN.  
Doses of PUL-042 or placebo will be prepared by an unblinded pharmacist and administered to 
the subject within 4 hours of preparation.  
Doses will be administered via nebulization to deliver 4 mL using a PARI Sprint nebulizer 
equipped with a filter valve to prevent aerosol generation. The nebulizer will be operated until all 
drug is delivered.   
3.2.4 
Subject Compliance 
Any material deviation from study procedures (identified by site personnel or monitor) will be 
documented. Major subject-level deviations will be captured on the protocol deviation form. A list 
of protocol deviations will be compiled and reviewed by the PI and Sponsor to identify major and 
minor deviations periodically using the criteria specified in the Protocol, Section 14.5.   
4. GENERAL CONSIDERATIONS FOR DATA ANALYSIS 
Unless otherwise specified, continuous variables will be summarized using descriptive statistics 
(n, mean, standard deviation, median, minimum, and maximum).  Categorical variables will be 
summarized showing the number and percentage of subjects within each category.   


 
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Summary results will be provided for each treatment group.  All tabulations will be based on 
pooled data across centers. 
Unscheduled visits will be excluded from the summaries but will be included in the data listings. 
All statistical tests will be two-sided and tested at the 10% level of significance.   
Analyses will be performed using SAS for Windows statistical software, version 9.4 or higher 
(SAS, Cary, NC), except where other software may be deemed more appropriate. 
CTI will perform all efficacy and safety analyses described in this SAP.   
Subject data will be listed, sorted by treatment group and subject number. When applicable, listings 
will be additionally sorted by visit and assessment date/time. 
4.1 
Data Quality Assurance 
Once all the source verification is complete, all queries are resolved, and the database has been 
updated appropriately, the database will be locked and made available to CTI Biostatistics for final 
analysis.  
Data may be pulled by CTI Biostatistics for DSMB analysis at a time when source verification and 
query resolution is ongoing. 
All SAS programs used to create analysis data sets, tables, and listings are double programmed. 
The SAS outputs will be compared and the programs will be updated until the outputs match. 
4.2 
Analysis Sets 
The following three analysis sets will be defined for this study: 
Intent to Treat (ITT) Set 
The ITT set is defined as all randomized subjects who receive at least one dose of experimental 
treatment (i.e., PUL-042 or Placebo). Randomized subjects are to be symptoms free and not known 
to be SARS-CoV-2 positive at baseline.  The primary analysis of the efficacy endpoints will be 
carried out using the ITT set based on the randomized treatment, except for the first two secondary 
efficacy endpoints listed in Section 2.2.2. 
Modified Intent to Treat (mITT) Set 
The mITT set will include all randomized subjects who receive at least one dose of experimental 
treatment (i.e., PUL-042 or Placebo) and are negative for SARS-CoV-2 infection at the time of 
administration of the first dose. 
The mITT set will be used for the analyses of the first two secondary efficacy endpoints listed in 
Section 2.2.2. 
Safety (SAF) Set 
The SAF set is also defined as all randomized subjects who receive at least one dose of 
experimental treatment (i.e., PUL-042 or Placebo), but subjects are categorized based on the 
treatment actually received rather than as randomized. All safety and tolerability analyses will be 
carried out using the SAF set. If, as is expected, the Safety analysis set is redundant (i.e., is identical 
to the ITT analysis set), the ITT set will be used for the assessments of safety and tolerability.    


 
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4.3 
Assessment Windows 
Data will be summarized by nominal study visit recorded in the database. 
4.4 
Handling of Dropouts or Missing Data 
Except for the time to event endpoint (Table 1), partial end dates of prior and concomitant 
medications (Section 5.6), and partial onset dates of AEs (Section 7.2.1), all other missing data  
will be treated as missing and no method for imputation is planned.  
Missing data on the time to event endpoint will have events coded as right censored per the 
following table: 
Table 1 Missing Data Coding for Time to Event Data Analysis 
Endpoint 
Right Censoring  
Subject Survival  
Subjects who are still alive as of the last known follow-up will be 
right censored as of the date of last subject contact when the subject 
was known to be alive. 
4.5 
Multiple Comparisons 
Because of the exploratory nature of this study, there will be no adjustment for multiple 
comparisons.     
4.6 
Data Derivations and Transformations 
The following derivations will be used in this study: 
Study Day (Note:  There is no day 0 in this study):  
• Date of assessment – date of 1st Study Drug administration + 1 for assessments done on or 
after date of 1st Study Drug administration 
• Date of assessment – date of 1st Study Drug administration for assessments done before 
date of 1st Study Drug administration 
Baseline Observation: the last non-missing value prior to 1st Study Drug administration.  
Duration:  
• Duration in days = end date – start date + 1 
• Duration in minutes = end time in minutes – start time in minutes  
5. STUDY SUBJECTS 
5.1 
Disposition of Subjects 
A table of frequency counts and percentages of all subjects who are randomized, and in each 
analysis set will be provided. Subject disposition including study completion status and reasons 
for early termination will be tabulated by treatment group and overall.  A by subject listing will be 
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5.2 
Protocol Deviations 
Distribution of the types of protocol deviations and the number of subjects that deviate from the 
protocol will be tabulated for the treatment groups in the ITT set. Protocol deviations will also be 
tabulated by severity (e.g., minor or major) if appropriate. A listing of all protocol deviations will 
be provided. 
5.3 
Demographic Characteristics 
Descriptive statistics will be used to summarize the demographic characteristics (age, gender, race, 
ethnicity, height, weight, and Body Mass Index [BMI]) for the ITT set.  A by subject listing will 
be provided. 
5.4 
Baseline Characteristics 
Baseline characteristics of ITT subjects including SARS-CoV-2 exposure and spirometry results 
at Screening will be listed and tabulated.   
5.5 
Medical History 
All medical conditions and surgical procedures will be classified by system organ class (SOC) and 
preferred term (PT) using the Medical Dictionary for Regulatory Activities (MedDRA). The 
number and percent of subjects with each medical condition and surgical procedure will be 
presented for each SOC and PT for the ITT set. 
5.6 
Concomitant Medications and Procedures 
All concomitant medications collected will be coded using the World Health Organization (WHO) 
Drug Dictionary.  The number and percent of ITT subjects using concomitant medications will be 
tabulated by Anatomical, Therapeutic, and Chemical (ATC) level 2 and by preferred name.  If the 
ATC level 2 is missing, the higher ATC level term will be used in the medication summary table 
and data listing. 
A listing of all medications will be provided. The listing will include flags for prior medications. 
Prior medications are defined as medications that ended prior to the date of first Study Drug 
administration. Concomitant medications are defined as medications that started at any time but 
ended on or after the date of first Study Drug administration, including those that are ongoing at 
study completion. In the case of a partial end date/time, in order to determine whether a medication 
is prior or concomitant, the following conservative imputation rule will be used: the unknown 
portions of a medication end date will be imputed to the latest possible. The imputed medication 
end date will then be compared with the date of first Study Drug administration to determine if the 
medication is prior or concomitant.  
Note the imputed end date will only be used to determine whether a medication is prior or 
concomitant. The actual date reported on the electronic case report forms (eCRFs) will be 
presented in the listing. 
Concomitant procedures will be collected via free text in the eCRF. These data will be presented 
in a listing. 


 
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6. EFFICACY ANALYSES 
Data on all efficacy endpoints will be listed and tabulated as appropriate. 
6.1 
Primary Efficacy Endpoint and Analysis 
The primary efficacy analysis will be carried out on the ITT set. 
The primary efficacy variable is the severity of COVID-19 as measured by the maximum 
difference from the baseline value in the Ordinal Scale for Clinical Improvement within 28 days 
from the start of experimental therapy. Randomized subjects are to be symptoms free and not 
known to be SARS-CoV-2 positive at baseline.  
The Ordinal Scale for Clinical Improvement is a 9-point scale that measures disease severity at a 
given point in time. Notably, a score of 0 indicates that an individual is infection-free. The 
difference in scores obtained at different times provides a quantitative assessment of the incidence 
of infection and change in disease severity over that time interval.  
The Ordinal Scale for Clinical Improvement to be used in this study is derived from a draft scale 
proposed by the World Health Organization[1] for clinical improvement as presented below: 
Table 2 
Ordinal Scale for Clinical Improvement (Derived from draft WHO scale)[1] 
Descriptor 
Score 
No clinical or virological evidence of infection 
0 
Infected but no limitation of activities 
Limitation of activities 
1 
2 
Hospitalized not requiring oxygen therapy (SpO2 > 93% on 
room air) 
Oxygen by mask or nasal prongs 
3 
4 
Non-invasive ventilation or high-flow oxygen  
Intubation and mechanical ventilation 
Ventilation + additional organ support- pressors, RRT, ECMO 
5 
6 
7 
Death 
8 
 
The null hypothesis is that there is no difference in mean maximum change in Ordinal scale from 
baseline through Day 29 between randomized treatment groups; H0: ∆t - ∆c = 0.  The alternative 
hypothesis is that the mean maximum change in Ordinal scale from baseline through Day 29 are 
different between the treatment groups; H1: ∆t - ∆c ≠ 0. 
The change in severity of COVID-19 between the placebo- and actively-treated groups will be 
compared using an analysis of covariance (ANCOVA) model, including the maximum change in 


 
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Ordinal scale from baseline through Day 29 as a dependent variable, treatment group as a fixed 
effect, and baseline characteristics such as age as a covariate.  
From this model, the least-squares (LS) means and 90% CIs for each treatment group, the treatment 
difference in the LS means, the 90% CI for the difference, and the associated p-value will be 
presented.   
If the data cannot support ANCOVA model assumption, a sensitivity analysis will be performed 
using proportional-odds cumulative logit model. The cumulative logits model will compare lower 
ordinal scales to higher ones, or equivalently, more favorable outcomes to less favorable ones. The 
model may be adjusted for baseline characteristics such as age, if appropriate. The estimated odds 
ratio and 95% CI will be presented.  
The proportional odds assumption will be tested using a score test at the two-sided alpha level of 
0.05. In the event that the proportional odds assumption is not satisfied, given the anti-conservative 
nature of the score test, the proportional odds model will still be used for the analysis, and the 
results will be presented along with the score test p-value to help put these results in context. If the 
proportion odds assumption is rejected or if the proportional odds model fails to converge, an 
alternative analysis using Cochran-Mantel-Haenszel (CMH) test will be performed to evaluate the 
association between the treatment groups and the maximum change in ordinal scale from baseline. 
The p-value for CMH row mean scores statistic will be reported. 
6.2 
Secondary Efficacy Endpoints and Analyses 
Incidence of  SARS-CoV-2 infection through Day 29 
The analysis of the proportion of subjects who had a positive result from the SARS-CoV-2 test 
within 28 days from the first dose of study drug will be performed using the mITT set.   
The null hypothesis is that there is no difference in proportions of subjects with SARS-CoV-2 
infection through Day 29 between randomized treatment groups; H0: πt - πc = 0.  The alternative 
hypothesis is that the proportions of subjects with SARS-CoV-2 infection through Day 29 are 
different between the treatment groups; H1: πt - πc ≠ 0. 
The proportion of mITT subjects with SARS-CoV-2 infection within each treatment group will be 
presented along with a two-sided exact (Clopper-Pearson) 90% confidence interval (CI). 
The observed difference in the proportion of subjects with SARS-CoV-2 infection between 
treatment groups along with the exact unconditional 90% CI for risk difference will be calculated. 
The null hypothesis will be tested using Fisher’s exact method and the p-value will be reported. 
Incidence of  SARS-CoV-2 infection through Day 15 
The analysis of the proportion of mITT subjects who had a positive result from SARS-CoV-2 test 
within 14 days from the first dose of study drug will be performed using the method described 
above for the analysis of incidence of SARS-CoV-2 infection through Day 29.   
Severity of COVID-19 through Day 15 
The change in severity of COVID-19 from baseline through Day 15 between the treatment groups 
will be compared using an ANCOVA model, including the maximum change in Ordinal scale from 
baseline through Day 15 as a dependent variable, treatment group as a fixed effect, and baseline 


 
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characteristics such as age as a covariate.  
From this model, the least-squares (LS) means and 90% CIs for each treatment group, the treatment 
difference in the LS means, the 90% CI for the difference, and the associated p-value will be 
presented. 
If the data cannot support ANCOVA model assumption, a sensitivity analysis will be performed 
using proportional-odds cumulative logit model as described above for the primary efficacy 
endpoint analysis. 
Ordinal Scale through Day 29 
The absolute value and change from baseline in the Ordinal scale from Day 1 through Day 29 will 
be summarized by treatment group and visit using descriptive statistics. 
The number and percentages of subjects in each severity category of the 9-point Ordinal Scale will 
be presented by visit and treatment group. 
Graphical illustrations of the Ordinal Scales through Day 29 will be presented using stacked bar 
chart for each treatment group. The X axis representing time points and Y axis representing the 
cumulative number of subjects for each Ordinal Scale. Each bar is divided into a number of sub-
bars stacked end to end corresponding to different Ordinal Scales. 
The changes in Ordinal Scales through Day 29 will be examined using box and whisker plots  for 
each treatment group. The X axis representing the post-baseline time points and the Y axis 
representing the change from baseline in Ordinal Scales at each post-baseline visit. 
Symptom Score 
The symptoms due to SARS-CoV-2 infection will be assessed and the symptom scores (Cough (0-
3), Shortness of breath or difficulty breathing (0-3), Muscle aches or fatigue (0-3), Fever (0-4)) 
will be recorded in the eCRF. 
The respiratory symptom score will be calculated by summing the symptom scores from Cough 
and Shortness of breath or difficulty breathing. The total symptom score will be calculated by 
summing all symptom scores.  
The scores from each symptom together with calculated respiratory symptom scores and total 
symptom scores will be summarized by presenting the number and percentage of ITT subjects for 
each category by visit and treatment group. 
Each symptom score (Cough, Shortness of breath or difficulty breathing, Fatigue, Fever, 
Respiratory, Total) from each post-baseline timepoint will be compared between treatment groups 
using non-parametric Wilcoxon Rank Sum test at 2-sided alpha level of 0.1. The p-value will be 
presented at each post-baseline visit.  
A radar plot will be created by presenting each symptom score in group mean at each time point 
by treatment group. 
Subjects requiring ICU admission  
Subject data pertaining to ICU admission will be recorded in the database.  
The proportion of ITT subjects who are admitted to the ICU from Day 1 to Day 29 within each 


 
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treatment group will be  presented along with a two-sided exact (Clopper-Pearson) 90% confidence 
interval (CI). 
The observed difference in the proportion of subjects requiring ICU admission between treatment 
groups along with the exact unconditional 90% CI for risk difference will be calculated. The null 
hypothesis will be tested using Fisher’s exact method and the p-value will be reported. 
Subjects who have died without ICU admission during the study will be counted as requiring ICU 
admission for the analysis. 
Number of ICU Days  
The number of ICU days from Day 1 to Day 29 will be calculated based on the ICU admission and 
discharge dates recorded in the eCRF. The calculated number of ICU days will be compared 
between treatment groups using 2-sided Student’s t-test. The 90% CI and p-value will be 
presented. 
If the Student’s t-test normality assumption is found to be clearly violated, a sensitivity analysis 
will be performed using a non-parametric Wilcoxon rank-sum test.  The p-value from the test will 
be presented. 
Subjects who died will be assigned as hospitalized in the ICU for the number of days remaining 
from the day of death to Day 29 for the analysis. Subjects who are alive and never admitted into 
the ICU will be included in the analysis with a value of zero ICU days. 
Subjects who were at ICU at study completion will be assigned an ICU end date equal to the date 
of completion for the purpose of deriving number of ICU days. 
Subjects requiring mechanical ventilation  
Subject data pertaining to mechanical ventilation use will be recorded in the database.  
The proportion of ITT subjects who were on mechanical ventilation from Day 1 to Day 29 within 
each treatment group will be analyzed and compared using the method described above for the 
analysis of subjects requiring ICU admission. 
Subjects who have died without mechanical ventilation during the study will be counted as 
requiring mechanical ventilation for the analysis. 
Number of days on mechanical ventilation  
The number of days on mechanical ventilation from Day 1 through Day 29 will be calculated based 
on the start/stop dates of mechanical ventilation recorded in the eCRF.  Number of days on 
mechanical ventilation will be compared between treatment groups using 2-sided Student’s t-test. 
The 90% CI and p-value will be presented. 
If the Student’s t-test normality assumption is found to be clearly violated, a sensitivity analysis 
will be performed using a non-parametric Wilcoxon rank-sum test.  The p-value from the test will 
be presented. 
Subjects who died will be assigned as being on mechanical ventilation for the number of days 
remaining to Day 29 for the analysis.  Subjects who had mechanical ventilation ongoing at study 
completion will be assigned a mechanical ventilation end date equal to the date of study completion 
for the purpose of deriving duration of mechanical ventilation. Subjects who are alive and never 


 
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placed on mechanical ventilation will be included in the analysis with a value of zero days on 
mechanical ventilation. 
Mortality Rate through Day 29 
Subject status (Alive/Death) will be recorded in the database. If the vital status of the subject is 
missing at the end of the study, then the subject will be excluded from the binomial analysis for 
the mortality rate.  The subject will be included in the Kaplan-Meier (KM) analysis with right 
censoring at the date the subject was last known to be alive.  
The mortality rate (proportion of ITT subjects who die) through Day 29 within each treatment 
group will be presented along with a two-sided exact (Clopper-Pearson) 90% confidence interval 
(CI). 
The observed difference in the mortality rate between treatment groups along with the exact 
unconditional 90% CI for risk difference will be calculated. The null hypothesis will be tested 
using Fisher’s exact method and the p-value will be reported. 
If deemed appropriate, an alternative analysis will be performed in which the survival rates will 
be estimated using the KM method. The KM estimates along with 90% CIs and survival curves 
will be provided. Based on the KM estimates, the survival probabilities and associated 90% CIs 
on Days 15 and 29 will be reported; in addition, the 25%, 50% (median), and 75% percentiles of 
the survival time with associated 90% CIs will be provided, as data permit. The survival rates 
between treatment groups will be compared using Log-rank test and the p-value from Log-rank 
test will be presented. 
6.3 
Subgroup Analyses 
Exploratory subgroup analyses of the primary efficacy endpoint by baseline characteristics, e.g. 
age group and gender, will be performed using the analysis method described in Section 6.1, if 
appropriate. 
Additional analyses may be performed to gain a better understanding but would not replace 
analyses planned for primary and secondary efficacy endpoints. 
7. SAFETY AND TOLERABILITY ANALYSIS 
Safety and tolerability assessments will include adverse events (AEs), vital signs, and pulmonary 
function tests. If there is a difference between the ITT set and SAF set, then all safety summaries 
(or analyses if applicable) will be conducted using the SAF set. Otherwise, the ITT set will be 
used. No formal hypothesis testing will be performed to compare differences between treatment 
groups. 
7.1 
Extent of Exposure and Compliance 
The number of doses received will be summarized by treatment group. The duration of study drug 
administration in minutes, the reason for study drug discontinuation, and whether 100% of study 
drug (4 mL) was delivered will be summarized for each dose by treatment group.   


 
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7.2 
Adverse Events 
The AE reporting period for this study is continuous and begins at the time of randomization to 
study treatment and ends on Day 29.  All AEs (both serious and nonserious) must be followed until 
resolution or until a stable clinical endpoint is reached. All measures required for AE management 
and the ultimate outcome of the AE must be recorded in the source documentation and in the 
eCRF.  
AEs will be classified by SOC and PT using the most recent version of MedDRA. 
7.2.1 
Treatment-emergent Adverse Events 
Treatment-emergent AEs are defined as those that begin or worsen after the start of study drug 
administration.  
For adverse events with incomplete start dates, the same imputation algorithm for partial date 
information as described in Section 5.6 will be used for the determination of an AE being treatment 
emergent or not. Briefly, the unknown portions of an AE onset date will be imputed to the latest 
possible before being compared to the date of first study drug administration. 
7.2.2 
Adverse Event Severity 
The severity (i.e., grade) of an AE will be assessed by the Investigator according to the definitions 
in the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. If the AE is not 
specifically listed in the reference above, the following grades should be used: 
• Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
• Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age- 
appropriate instrumental Activities of Daily Living (ADL) 
• Grade 3 Severe or medically significant but not immediately life threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL 
• Grade 4 Life-threatening consequences; urgent intervention indicated 
• Grade 5 Death related to AE 
7.2.3 
Adverse Event Relationship to Study Drug 
The Investigator must record his/her opinion concerning the relationship of the AE to study therapy 
(Unrelated, Unlikely, Possibly, Probably, Definitely) on the AE eCRF. See study protocol, Section 
12.5 for details.  
7.2.4 
Serious Adverse Events 
An AE or suspected adverse reaction is considered “serious” if in the view of either the investigator 
or sponsor, it results in any of the following outcomes: 
• Death 
• A life-threatening adverse event 
• In-patient hospitalization or prolongation of existing hospitalization 


 
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• Persistent or significant incapacity or substantial disruption to conduct normal life 
functions 
• A congenital anomaly/birth defect 
• Intervention to prevent any one of the other outcomes listed above (based on medical 
judgment) 
7.2.5 
Adverse Event Summaries 
All AEs (serious and non-serious) occurring after randomization and before the end of study, 
regardless of relationship to study drug, will be included and classified by SOC and PT using 
MedDRA.        
For TEAEs, the following will be summarized and presented: 
i. 
An overall summary of TEAEs, which includes:   
a. the number and percentage of subjects experiencing a TEAE 
b. the number and percentage of subjects experiencing a TEAE by strongest 
relationship to study drug 
c. the number and percentage of subjects experiencing a TEAE by greatest severity 
d. the number and percentage of subjects experiencing a treatment-emergent SAE 
e. the number and percentage of subjects experiencing a TEAE leading to death 
f. the number and percentage of subjects experiencing a TEAE leading to study 
withdrawal 
ii. 
the number and percentage of subjects experiencing a TEAE by SOC and PT. 
iii. 
the number and percentage of subjects experiencing a potentially related TEAE by SOC 
and PT, where a potentially related TEAE is defined as any TEAE with a causal 
relationship to study drug assessed as ‘Possibly Related’, ‘Probably Related’, or ‘Definitely 
Related’. 
iv. 
the number and percentage of subjects experiencing a TEAE by SOC, PT and the strongest 
relationship to study drug 
v. 
the number and percentage of subjects experiencing a TEAE by SOC, PT and the greatest 
severity 
vi. 
the number and percentage of subjects experiencing a treatment-emergent SAE by SOC 
and PT 
vii. 
the number and percentage of patients experiencing a TEAE leading to death by SOC and 
PT 
viii. 
the number and percentage of subjects experiencing a TEAE leading to study withdrawal 
by SOC and PT 
In the overall summary of TEAEs table (i), besides tabulating the number and percentage of 
subjects, the total number of TEAE episodes will also be provided. If a subject has repeated 
episodes of a particular TEAE, all episodes will be counted in the summary table.   


 
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In the remaining summary tables, the incidence of TEAEs will be calculated by dividing the 
number of subjects who have experienced the event by the total number of subjects.  Thus, the 
incidence of TEAEs is shown in terms of the total number of subjects and not in terms of the total 
number of episodes.  If a subject has repeated episodes of a particular TEAE, only the most severe 
episode, or the episode with the strongest causal relationship to study drug, will be counted in the 
summary tables.  
A subject with more than one type of TEAE in a particular SOC or PT will be counted only once 
in the total of subjects experiencing TEAEs in that particular SOC or PT.  
All occurrences of all AEs and SAEs will be listed for each subject, grouped by treatment group.  
The listing will contain the following information: treatment group, verbatim term, SOC, PT, 
severity and grade (1-Mild, 2-Moderate, 3-Severe, 4-Life threatening, 5-Death), relationship to 
study drug, date and day of onset, date and day of resolution or death, action taken with regard to 
study drug, the outcome, whether the event was an SAE, whether it led to study withdrawal, and 
whether it is a TEAE. Listings will be sorted by treatment group, subject identification number, 
onset date, SOC, and PT. If the onset date is completely missing, then these events will be 
presented first. If the onset date is missing a month or a day, then these events will be presented 
before any complete dates. 
7.3 
Pulmonary Function Testing 
Spirometry tests including FEV1 (L), % predicted FEV1, FVC (L), % predicted FVC and 
FEV1/FVC values will be collected at screening and FEV1 (L) will also be recorded at the time 
points presented in the Appendix A.  FEV1 results will be summarized by presenting descriptive 
statistics of raw data of FEV1 (L) and percent change from each Pre-dose value to Post-dose value 
on the dosing days.  
The proportion of subjects with percent decrease in FEV1 (L) from Pre-dose value to Post-dose 
value will be presented for each category: >10% and <=12% of reduction; >12% and <=20% of 
reduction; and >20% of reduction at each measurement time point (Day 1, Day 3, Day 6 and Day 
10).  
The percent change in FEV1 (L) from Pre-dose value to the protocol defined 30-min Post-dose 
values will be illustrated in a box/whisker graph on each dosing day by treatment group.  
Spirometry results from unscheduled visits will be excluded from table summaries but will be 
included in the data listing.     
7.4 
Vital Signs 
Descriptive summaries of pre and post treatment vital signs including systolic and diastolic blood 
pressure, pulse, respiratory rate, and body temperature will be prepared for each treatment group 
by visit.   
A listing of all vital sign assessments throughout the study will be provided. 
7.5 
Other Safety Measures 
Pregnancy test results, if applicable, will be presented in a listing. 


 
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8. INTERIM ANALYSES 
An external DSMB will be used to evaluate safety of the study in an ongoing manner. A full 
description of the membership, role, and responsibilities of the DSMB is provided in the DSMB 
charter. As specified  there, a formal review of data will take place at DSMB meetings scheduled 
to occur after 40, 80 and 120 subjects have completed dosing.  
As a further effort to ensure the safety of PUL-042, a stopping rule that is based only on mortality 
will be employed. A recommendation to stop the study would be made only if there is a high 
probability of excess mortality risk among subjects randomized to PUL-042. The following 
hierarchical analysis of mortality will be performed after 50% of subjects have been enrolled 
(50/group) and followed up for 28 days from the start of investigational therapy: 
1) Based on blinded data, if no more than 3 deaths have occurred during the study this analysis 
will not be conducted due to the lack of evidence of increased mortality risk attributable to 
PUL-042. 
If more than 3 deaths occur: 
2) The Unblinded statistician will evaluate unblinded mortality data to determine the 
treatment specific death rate (i.e., DTx = DeathsTx / NTx; Tx = Active or Placebo). 
3) If the difference, Δ, in treatment-specific death rates (i.e., Δ = DActive – DPlacebo) is greater 
than 7.5%, the DSMB will further review the totality of evidence and render a 
recommendation to the sponsor regarding study continuation. 
Characteristics of this rule are as follows: 
Assuming that the true underlying control arm mortality rate is 5% and using a normal 
approximation when comparing proportions, the probability of stopping is approximately: 
• 90% if the true underlying mortality rate attributable to PUL-042 is 25%. 
• 62% if the true underlying mortality rate attributable to PUL-042 is 15%. 
• only 11% if the true underlying mortality rate attributable to PUL-042 is 5% (equal to the 
assumed true underlying control arm mortality rate). 
9. SAMPLE SIZE AND POWER CALCULATIONS 
The trial size of 200 subjects (100 PUL-042 inhalation solution: 100 placebo) was chosen based 
on clinical considerations. The rates of infection to adequately estimate a sample size for a 
statistically significant result are unknown. 
Enrolled subjects will be randomized with equal probability to receive blinded treatment consisting 
of either PUL-042 or placebo.    
10. REFERENCES 
1. World Health Organization. WHO-COVID-19: Treatment Trial Design Master Protocol 
Synopsis, Draft February 18, 2020 


 
Pulmotect PUL-042-501 Statistical Analysis Plan v1.0 
 
CONFIDENTIAL  
 
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11. APPENDIX 
11.1 
Appendix A: Schedule of Events