Clinical trial NCT04408183
Conditions: SARS-CoV 2 Infection
Keywords: COVID-19
Sponsor: GeneOne Life Science, Inc.
Start date: 2020-06-10; Completion date: 2023-01-10
Enrollment: 184 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This clinical trial will evaluate the safety, tolerability and effectiveness of topical GLS-1200 nasal spray to reduce the incidence of confirmed, symptomatic SARS-CoV-2 infection.

Detailed description:
This Phase II randomized, placebo-controlled, double-blind study will assess whether topical GLS-1200 applied via nasal spray atomizer is well-tolerated and can reduce the incidence of confirmed SARS-CoV-2 infection. Subjects will be randomized to either the GLS-1200 or placebo group in a 2:1 ratio with a target enrollment of 225 subjects. Subjects will self-administer study drug three times daily for 4 weeks.

Arms: arm 1: 1 mL of GLS-1200 per nostril, TID arm 2: 1 mL of 0.9% Saline per nostril, TID
Interventions: intervention 1: GLS-1200 intervention 2: Placebo
Intervention descriptions: intervention 1: GLS-1200 is given as a nasal spray using an atomizer intervention 2: Placebo is given as a nasal spray using an atomizer

Protocol documents:
Prot_000.pdf: 
 
 
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Brief protocol title 
T2R-002 
 
 
Formal protocol title 
Efficacy, Safety, and Tolerability of GLS-1200 Topical Nasal 
Spray in the Prevention of Incident Confirmed SARS-CoV-2 
Infection  
 
 
 
Principal Investigator 
Pablo Tebas, MD  
Division of Infectious Diseases 
 
Co Investigator 
Henry Barham, MD  
Otorhinolaryngology 
 
Sub Investigators 
William Short, MD 
Keith Hamilton, MD 
Kathleen Degnan, MD 
Peter Liu, MD 
 
Regulatory Sponsor: 
GeneOne Life Science Inc.  
535 Pennsylvania Ave, Suite 200 
Ft. Washington, PA 19034 
(610) 707-5671 
 
 
IND Protocol Number: 
149390 
 
 
Clinical Trials.gov #: 
NCT04408183 
 
 
 
Version Summary 
Initial version:  
Version 7.0 
26 February 2021 
Amendment:  
 
 
 
 


 
 
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CONFIDENTIAL 
The information in this document is considered privileged and confidential by GeneOne Life 
Science, Inc. and may not be disclosed to others except to the extent necessary to obtain 
Institutional Review Board/Ethics committee approval and informed consent, or as required by 
local regulatory authorities. Persons to whom this information is disclosed must be informed that 
this information is privileged and confidential and that it must not be further disclosed without the 
written permission of GeneOne Life Science, Inc. Any supplemental information added to this 
document is also confidential and proprietary information of GeneOne Life Science, Inc. and must 
be kept in confidence in the same manner as the contents of this document. 
 
 
 
  
 
 


 
 
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PROTOCOL ACKNOWLEDGEMENT 
 
 
I have read this Protocol and agree that it contains all necessary details for carrying out the study 
described. I understand that it must be reviewed by the Institutional Review Board or Independent 
Ethics Committee overseeing the conduct of the study and receive approval or a favorable opinion 
before implementation. 
 
The signature of the Principal Investigator and Sponsor below constitute their approval of this 
protocol and provide the necessary assurances that this study will be conducted according to the 
Declaration of Helsinki, GCP, ICH guidelines, local legal and regulatory regulations as well as to 
all stipulations of the protocol in both the clinical and administrative sections, including statements 
regarding confidentiality. 
 
 
 
 
_________________________________ 
 
 
_________________ 
Investigator’s printed name and signature 
 
 
Date 
 
 
 
 
26 February 2021 
_________________________________ 
 
 
_________________ 
Medical Monitor 
 
 
 
 
 
Date 
 
 
 
Protocol Number: T2R-002 
Version Number: 7.0 / Version Date: 26 February 2021 
 
 
 
  
 
 
 
 


 
 
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TABLE OF CONTENTS 
 
PROTOCOL ACKNOWLEDGEMENT ................................................................................................... 3 
TABLE OF CONTENTS ........................................................................................................................... 4 
CLINICAL PROTOCOL SYNOPSIS ....................................................................................................... 8 
1. 
INTRODUCTION .............................................................................................................................. 10 
1.1 
Background and Rationale .................................................................................................. 10 
1.1.1 
Pre-clinical experience with quinine ......................................................................... 12 
1.1.2 
Human experience with quinine ................................................................................. 14 
1.2 
Investigational Agent ............................................................................................................ 17 
1.3 
Dose and Regimen Rationale .............................................................................................. 18 
1.4 
Risk/Benefit Assessment ..................................................................................................... 18 
2. 
HYPOTHESIS AND STUDY OBJECTIVES ................................................................................ 19 
2.1 
Hypothesis ............................................................................................................................... 19 
2.2 
Primary Objectives and Outcome Variables ................................................................... 19 
2.3 
Secondary Objectives and Outcome Variables ............................................................. 19 
2.4 
Exploratory Objectives ......................................................................................................... 19 
3. 
STUDY DESIGN ............................................................................................................................... 19 
3.1 
Safety Monitoring ................................................................................................................... 19 
4. 
SELECTION AND ENROLLMENT OF PARTICIPANTS .......................................................... 19 
4.1 
Recruitment of Participants ................................................................................................ 19 
4.2 
Inclusion Criteria .................................................................................................................... 20 
4.3 
Exclusion Criteria ................................................................................................................... 20 
4.4 
Discontinuation/Withdrawal of Study Participants ....................................................... 20 
5. 
STUDY PRODUCT .......................................................................................................................... 20 
5.1 
Investigational Product ........................................................................................................ 20 
5.2 
Packaging and Labeling ....................................................................................................... 21 
5.3 
Handling of Study Drug ........................................................................................................ 21 
5.4 
Dispensing of Study Drug .................................................................................................... 22 
5.6 
Preparation of Investigational Product ............................................................................ 22 
5.7 
Record of Investigational Product Disposition at Site ................................................. 22 
5.8 
Return and Destruction of Investigational Product ...................................................... 22 


 
 
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5.9 
 Device Accountability .......................................................................................................... 22 
6. 
STUDY PROCEDURES AND TREATMENTS ............................................................................ 23 
6.1 
Procedures by Visit (also see Table S2) .......................................................................... 23 
6.1.1 
Day 0: Review Study and Eligibility Criteria; Obtain Informed Consent, 
Enrollment ........................................................................................................................................ 23 
6.1.2 
Week 2: intermediate visit ............................................................................................ 23 
6.1.3 
Week 4: end of treatment ............................................................................................. 23 
6.1.4 
Week 6: follow up visit .................................................................................................. 23 
6.2 
Timing and Evaluations ........................................................................................................ 24 
6.2.1 
Informed Consent (Day 0) ............................................................................................ 24 
6.2.2 
Enrollment (Day 0) ......................................................................................................... 24 
6.2.3 
Safety Assessments ...................................................................................................... 24 
6.3 
Assessment of Laboratory Abnormalities ....................................................................... 25 
6.4 
Assessment of Clinical Adverse Events .......................................................................... 25 
6.5 
Nasopharyngeal swab PCR for presence of SARS-CoV-2 virus ............................... 25 
6.6 
Serum for SARS-CoV-2 antibodies .................................................................................... 25 
6.7 
Definition of confirmed SARS-CoV-2 infection and SARS-CoV-2 symptom score
 
26 
6.8 
Exposures to SARS-CoV-2 .................................................................................................. 26 
6.9 
Saliva for TAS2R genotyping .............................................................................................. 26 
7. 
EVALUATION OF SAFTY AND MANAGEMENT OF TOXICITY ............................................ 26 
7.1 
Safety Parameters .................................................................................................................. 26 
7.1.1 
Adverse Events (AEs) ................................................................................................... 26 
7.1.2 
Serious Adverse Events (SAEs) ................................................................................. 27 
7.1.3 
Unexpected Adverse Drug Reactions ....................................................................... 28 
7.1.4 
Assessing Severity (Intensity) .................................................................................... 28 
7.1.5 
Causal Relationship of Investigational Product to Adverse Events ................ 28 
7.1.6 
Abnormal Laboratory Value ........................................................................................ 29 
7.1.7 
Pregnancy During Study .............................................................................................. 29 
7.1.8 
Post-study Reporting Requirements ........................................................................ 30 
7.2 
Methods and Timing for Collection and Recording of Safety Data .......................... 30 
7.3 
Safety and Toxicity Management ....................................................................................... 30 
7.3.1 
Events Requiring Expedited Reporting .................................................................... 30 


 
 
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7.3.2 
Stopping Rules ............................................................................................................... 31 
7.3.3 
Unblinding ........................................................................................................................ 31 
8. 
STATISTICAL METHODS and CONSIDERATIONS ................................................................ 31 
8.1 
Data Sets to be Analyzed ..................................................................................................... 31 
8.2 
Demographic and Other Baseline Characteristics ........................................................ 32 
8.3 
Safety Analysis ....................................................................................................................... 32 
8.3.1 
Adverse events ............................................................................................................... 32 
8.3.2 
Laboratory Data .............................................................................................................. 32 
8.4 
Efficacy Analysis .................................................................................................................... 32 
8.5 
Secondary Analysis ............................................................................................................... 33 
8.6 
Interim Analysis ...................................................................................................................... 33 
8.7 
Sample Size and Randomization ....................................................................................... 33 
8.8 
Missing Values ........................................................................................................................ 33 
9. 
DATA COLLECTION, MONITORING, AND AE REPORTING ................................................ 33 
9.1 
Confidentiality ......................................................................................................................... 33 
9.2 
Source Documents ................................................................................................................ 33 
9.3 
Data Collection ....................................................................................................................... 34 
9.4 
Record Retention ................................................................................................................... 34 
9.5 
Safety and Quality Monitoring and Record Availability ............................................... 34 
9.6 
Adverse event (AE) Reporting ............................................................................................ 34 
9.6.1 
Study Reporting Period of Adverse Events ............................................................ 34 
9.6.2 
Study Reporting Period for Serious Adverse Events ........................................... 34 
9.6.3 
Notification of Serious Adverse Events ................................................................... 36 
9.7 
Study Discontinuation .......................................................................................................... 36 
10. 
PUBLICATION OF RESEARCH FINDINGS ........................................................................... 36 
11. 
LIST OF ABBREVIATIONS ....................................................................................................... 36 
12. 
REFERENCES ............................................................................................................................. 38 
 
List of Figures 
Figure 1.1.1.1-1: Quinine stimulation of NO release in sinonasal cells ........................................... 13 
Figure 1.1.1.2-1: PCR transcripts of viral NP and IAV-M1 genes ..................................................... 13 
Figure 1.2-1: Structure of Quinine sulfate, dihydrate .......................................................................... 18 
 


 
 
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List of Tables 
Table 1.1.2-1 Clinical trials utilizing quinine as “placebo” (from published literature) .................... 15 
Table 1.1.2-2 Adverse events of quinine versus placebo for leg cramps (Cochrane analysis*) .. 17 
Table 5.2-1 Study drug kit labels ........................................................................................................... 21 
Table 8.7-1 Range of treatment rates detectable with at least 80% power .................................... 33 
 
 
 


 
 
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CLINICAL PROTOCOL SYNOPSIS 
Title of study: Efficacy, Safety, and Tolerability of GLS-1200 Topical Nasal Spray in the Prevention of 
Incident Confirmed SARS-CoV-2 Infection  
Number of study sites and Countries/Regions: 2, US 
Target Number of study participants: 225 
Study Phase: II 
Study Type: Randomized, placebo-controlled, double-blind 
Research Hypothesis: GLS-1200 topical nasal spray will be well tolerated and can reduce the 
incidence of confirmed SARS-CoV-2 infection  
Primary study objectives and outcome variables:  
• Evaluate the safety and tolerability of GLS-1200 topical nasal spray  
• Incidence of SARS-CoV-2 infection, confirmed by PCR relative to treatment group 
Secondary study objectives and outcome variables: 
• Documentation of symptoms consistent with SARS-CoV-2 infections relative to treatment group    
Exploratory study objectives and outcome variables: 
• Incidence of SARS-CoV-2 seroconversion relative to treatment group 
• Assess the relationship of taste receptor genetics to incidence of SARS-CoV-2 infection and 
relative to treatment group 
Table S1: Dosing arms and treatment regimen 
Group 
N 
Treatment 
assignment 
Study drug 
Diluent 
Spray 
volume  
Treatment 
schedule 
1 
150 
GLS-1200 
1 mg/mL 
quinine 
sulfate, 
dihydrate 
0.9%  
sterile 
saline 
1 mL/ 
nostril 
TID x 4 
weeks 
2 
75 
Placebo  
(0.9% sterile 
saline) 
0.9% 
sodium 
chloride 
solution 
N/A 
1 mL/ 
nostril 
TID x 4 
weeks 
Study design: This Phase II randomized, placebo-controlled, double-blind study will assess whether 
topical GLS-1200 applied via nasal spray atomizer is well-tolerated and can reduce the incidence of 
confirmed SARS-CoV-2 infection. Subjects will be randomized to either GLS-1200 or placebo group 
in a 2:1 ratio with a target enrollment of 225 subjects. Subjects will self-administer study drug three 
times daily (TID) for 4 weeks.  
Safety assessments: Participants will be monitored for adverse events. Laboratory and 
electrocardiographic (ECG) safety assessments will be performed at baseline and at the completion 
of 4 weeks of treatment. Subjects will complete a diary with daily entries to document clinical 
symptoms consistent with SARS-CoV-2 infection. 
Study population: 
Inclusion criteria: 
1. 
Age 18 years or older 
2. 
Able to provide informed consent  
3. 
Able and willing to comply with study procedures 
4. 
Able and willing to utilize an approved form of pregnancy prevention for women of child-bearing 
potential through to the end of treatment.  
Exclusion criteria: 
1. Known allergy to quinine or quinidine or mefloquine 
2. Confirmed prior positive test for SARS-CoV-2 


 
 
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3. Treatment within the past 2 weeks with chloroquine, hydroxychloroquine, or remdesivir 
4. Pregnancy or documentation of pregnancy by pre-treatment urine pregnancy test or breast 
feeding or plans to become pregnant during the course of the study  
 
Table S2: Schedule of Events 
Tests and Observations 
Day 0 
Week 2  
Week 4 
Week 6  
Unscheduled 
Permitted window (days) 
 
±3d 
±3d 
±3d 
N/A 
Clinical Evaluations 
 
 
 
 
 
Obtain Written Informed Consent 
X 
 
 
 
 
Confirm Eligibility Criteria 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History and Concomitant Medications 
X 
X 
X 
X 
 
Physical Exam, height, weight, and Vital Signs1 
X 
X 
X 
X 
X 
Safety Evaluations 
 
 
 
 
 
Record Adverse Events 
 
X 
X 
X 
X 
Provide participant diary 
X 
 
 
 
 
Collect and review participant diary 
 
X2 
X 
X 
 
Perform 12-lead ECG 
X 
 
X 
 
 
Pregnancy test3 
X 
X 
X 
 
 
Blood for Hematology: CBC with differential 
X 
 
X 
 
 
Blood for Chemistry: Sodium, potassium, 
bicarbonate, glucose, BUN, Cr 
X 
 
X 
 
 
Study Related Procedures 
 
 
 
 
 
Dispense study drug & device, provide training 
X 
 
 
 
 
Collect nasopharyngeal swabs for viral PCR 
X 
X 
X 
X 
X 
Collect serum for viral antibodies 
X 
X 
X 
X 
 
Collect plasma for measurement of quinine 
 
X 
 
 
 
Collect saliva for TAS2R genotyping 
X 
 
 
 
 
Estimated Blood Volume per Visit (mL) 
40 
25 
40 
20 
 
 
1 A targeted physical exam will be performed at Weeks 2, 4 and 6 and at unscheduled visits.  
2 The participant diary will only be reviewed at Weeks 2 and 4; it will be reviewed and collected at Week 6. 
3 A urine pregnancy test will be administered. 
 
 


 
 
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1. 
INTRODUCTION 
This study will examine whether GLS-1200 topical nasal spray is safe, well tolerated and can 
reduce the risk of incident infection from SARS-CoV-2 as confirmed by PCR. GLS-1200 is a 
formulation of quinine sulfate, dihydrate at 1 mg/mL in 0.9% saline. 
1.1 
Background and Rationale 
Quinine is a known agonist for multiple bitter taste receptors (TAS2Rs). TAS2Rs not only line the 
tongue, but are also expressed on the surface of ciliated nasal epithelial cells. These TAS2Rs are 
a component of the innate immune system and the functionality of specific TAS2Rs is genetically 
determined with almost equal prevalence of functional and non-functional genotypes in the 
population. Quinine stimulation of ciliated nasal epithelial cells induces release of nitric oxide (NO). 
Release of NO from epithelial cells has been shown to reduce the growth of pathogenic bacteria. 
NO is also able to inhibit viral replication of numerous viruses including the Severe Acute 
Respiratory Syndrome coronavirus (SARS-CoV). Since the nares are a likely primary portal of 
entry for the SARS-CoV-2 virus, a virus highly related to SARS-CoV, it is postulated that SARS-
CoV-2 infection via the nasal route may be suppressed by quinine-induced NO production from 
ciliated nasal epithelial cells, akin to NO suppression of SARS-CoV. Such viral suppression may 
then be protective and limit the incidence and severity of SARS-CoV-2 infection.  
Similarly, improvement of the innate immune response to prevent infection within the nasal cavity 
has potential to reduce the burden of chronic rhinosinusitis (CRS). It has been shown that 
stimulation of nasal epithelial cells with phenylthiocarbamate (PTC), another bitter taste receptor 
agonist, induces transmembrane calcium fluxes that correlate with NO release [1]. This stimulation 
is associated with reductions in bacterial growth when nasal epithelial cells are overlaid with 
Pseudomonas aeruginosa [1].  
Exposure to NO has been shown to inhibit replication for many DNA and RNA viruses including 
hantavirus [2] and the murine hepatitis coronavirus [3]. Inhaled NO has also been reported to 
improve human hantavirus infection in a single case report [4].  
With regard to whether NO may be helpful in the treatment of SARS-CoV-2 infection, two groups 
showed that SARS-CoV replication is inhibited by NO as supplied by the NO donor molecule S-
nitroso-N-acetylpenicillamine [5] [6]. NO also prevented maturation of the viral S protein through 
inhibition of palmitoylation that results in reduced binding and viral fusion such that virions have 
reduced capacity for viral entry into target cells [7].  
In humans, bitter and sweet taste perception is governed by G-protein coupled receptors originally 
identified in oral taste bud type II cells [8] [9]. Receptors belonging to Taste Receptor Family-1 
subtypes 2 and 3 (T1R2/T1R3) detect sweet compounds such as glucose and sucrose. Greater 
than 50 Taste Receptor Family-2 (T2Rs) have been characterized. T2Rs are primarily bitter taste 
receptors and respond to a variety of bitter compounds including caffeine, denatonium, strychnine 
and quinine [10]. One subset of T2Rs, when activated, stimulates the respiratory epithelium to 
generate NO, while a second subset of T2Rs expressed on solitary chemosensory cells (SCCs), 
can stimulate release of antimicrobial peptides. Both T2R-mediated pathways are considered 
integral to the upper airway innate immune defense system [1]  [11]  [12]. 


 
 
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Stimulation of T2Rs activates the canonical taste signaling cascade involving phospholipase C 
β2 (PLCβ2) and transient receptor potential cation channel subfamily M member 5 [1]. More 
recently, bitter and sweet receptors have been discovered in a variety of extra-oral tissues 
including the brain, thyroid, pancreas, testes and throughout the respiratory and gastrointestinal 
tracts [13] [14] [15].  
In the airway, taste receptors are present on a variety of cell types and have been shown to 
mediate several complementary components of innate immune defense. For example, ciliated 
sinonasal epithelial cells express T2R38 and respond to PTC and acyl-homoserine lactones, bitter 
compounds released by gram-negative bacteria such as Pseudomonas aeruginosa. Activation of 
T2R38 triggers an increase in intracellular calcium (Ca2+) yielding stimulation of NO synthase with 
resultant production of intracellular NO [16]. The NO, through cyclic GMP, increases ciliary beat 
frequency (CBF) and diffuses into the mucus layer where it has direct bactericidal activity [16] [17] 
[18]. Similarly, SCCs, rare epithelial cells that express both T1R2/3 and T2R receptors [19], also 
respond to bitter compounds secreted by bacteria in the upper airway. Stimulation of T2Rs on the 
surface of human SCCs by the bitter agonist denatonium elicits a calcium response that spreads 
via gap junctions to neighboring epithelial cells, triggering a release of pre-formed stores of 
antimicrobial peptides [1]  [20]. At the present time, it is thought that the repertoire of T2Rs expressed 
on ciliated cells and the repertoire of T2Rs expressed on SCCs are mutually exclusive. Recent 
work demonstrates that the NO-producing T2R response is exclusively found in ciliated cells, 
while production of antimicrobial peptides is driven only by T2R’s on SCCs [16] [1] [21]. 
The genes encoding the TAS2Rs localize primarily to chromosomes 7 and 12, each with 
functional and non-functional polymorphisms [22] [23]. The correlation between taste receptor 
genetics and function and its potential role in sinusitis presentation and outcome was first 
characterized for the bitter taste receptor T2R38. The gene for this bitter receptor, TAS2R38, has 
two prevalent allele polymorphisms that correlate with taste receptor function. Functional alleles 
are characterized by a position 49 proline, position 262 alanine, and position 296 valine (known 
as a PAV genotype) versus alanine, valine, and isoleucine at the respective positions (AVI 
genotype) for the non-functional allele [11]. Individuals who possess two functional alleles are 
considered as super tasters who are able to perceive bitter compounds such as propylthiouracil. 
Those with two AVI alleles are considered non-tasters and those with a single allele have 
heterogeneous taste perception [11]  [24]. Importantly, TAS2R38 allelic makeup directly correlates 
with ability to generate NO in response to TAS2R38 stimulation and clear Ps. aeruginosa of 
explanted sinonasal ciliated cells [16].  
Genetic variations in taste receptor functionality cause differential responsiveness in cells isolated 
from different individuals, and corresponding taste receptor function correlates with disease 
severity in CRS [1] [16] [25] [26] [27]. This has been best characterized for patients who are homozygous 
for the non-functional variant of T2R38. They are more likely to require surgical intervention for 
CRS, and more likely to develop a Gram-negative infection. Recent work has shown that 
phenotypic taste tests with denatonium, a broad T2R agonist, and sucrose, a T1R2/3 agonist, can 
reflect clinical disease status in CRS and partially stratify control subjects and CRS patients [28]. It 
is thought that patients with CRS possess hypo-responsive bitter taste receptors, rating 
denatonium as less bitter than controls, while also possessing hypersensitive sweet taste 
receptors, which compounds the reduced antimicrobial response to sinonasal pathogens.  
Quinine is derived from the bark of the cinchona tree. It is a centuries-old treatment for malaria, 
an ingredient in tonic water, and is also an agonist for multiple bitter taste receptors. Activation of 


 
 
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quinine-responsive bitter taste receptors, as discussed below and reviewed elsewhere [16] [17] [29] 
[30], stimulates the respiratory epithelium to generate NO that, in turn, increases mucociliary 
clearance and diffuses into the mucus where it is bactericidal. Quinine stimulates multiple bitter 
taste receptors including TAS2R4, TAS2R14, TAS2R31, TAS2R40, TAS2R43, and TAS2R46 as 
well as others. Whether one or more is important in the innate immune response is not known, 
nor has genetic background been correlated with clinical outcome as yet. A topical therapy to 
activate these taste receptors may help the sinuses clear infections through this natural innate 
defense mechanism, especially with a lower bacterial or viral burden.  
This study will explore the potential role of topical GLS-1200 to prevent confirmed infection from 
SARS-CoV-2. Individuals are to be recruited and assigned to either GLS-1200 or placebo 
treatment in a 2:1 ratio to be self-administered for 4 weeks. The primary outcome measures are 
the safety and tolerability of GLS-1200 nasal spray use and the incidence of SARS-CoV-2 
infection, as confirmed by PCR, relative to treatment group. 
1.1.1 Pre-clinical experience with quinine 
There is extensive literature regarding the ability of quinine to stimulate bitter taste receptors. In 
this section, we address the physiologic and functional changes that occur following quinine 
stimulation and the role that the bitter taste receptors have in innate immunity. The role of the 
bitter taste receptors is already established in the treatment of acute and chronic rhinosinusitis [31]. 
Quinine is a bitter agonist and alkaloid derivative isolated from the bark of the cinchona tree. It is 
known to stimulate nine T2Rs with varying efficacy [32]. Quinine-sensitive T2Rs, including T2R4 
[21] and T2R14 [33], are expressed in ciliated epithelial cells. As shown below, quinine stimulates a 
NO antimicrobial response in the airway, and that individuals in a CRS cohort are less sensitive 
to quinine in a phenotypic taste test. Additional preliminary work has also demonstrated that 
quinine stimulation of ciliated nasal epithelial cells appears to reduce viral replication of H1N1 
influenza.  
1.1.1.1. Quinine stimulation increases NO production in primary human sinonasal cells 
NO production was measured in response to quinine stimulation in ciliated sinonasal cells using 
the fluorescent probe 4-amino-5-methylamino-2’,7’-difluorescein (DAF-FM). DAF-FM reacts with 
NO-derived nitrogen species to form a fluorescent benzotriazole [16]. Using confocal imaging, NO 
production increases were calculated based on changes in fluorescence intensity. It is important 
to note that changes in intensity are noted in “DAF-FM units,” which can only be utilized in 
comparison to a control condition or an alternate condition, as absolute DAF-FM unit values may 
differ between experiments. Successive stimulation of cells with 0.01% and 0.1% quinine in 
ethanol (arrows) caused a dose-dependent increase in NO production over the course of 15 
minutes relative to the ethanol control (Figure 1.1.1.1-1 panel A and panel B, n=6 cultures). 
Average DAF-FM fluorescence increase was 913.4 ± 125.9 units for quinine-stimulated cultures, 
compared to a 125.9 ± 6.4 unit increase for cultures stimulated with 0.1% EtOH vehicle (n=3 
cultures, p<0.01). To demonstrate that increases in DAF-FM were due to the presence of NO and 
not a different reactive O2 or nitrogen species, cell cultures were stimulated in the presence of the 
nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME). Induction of NO related 
DAF-FM fluorescence in response to quinine was completely blocked by L-NAME (Figure 1.1.1.1-
1 panel C, n=3 cultures).  


 
 
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Figure 1.1.1.1-1: Quinine stimulation of NO release in sinonasal cells 
 
1.1.1.2. Quinine stimulation of human ciliated nasal epithelial cells inhibits viral replication 
of H1N1 influenza A  
The ability of quinine to inhibit viral replication was assessed in a human sinonasal air-liquid-
interface (ALI) model. ALI derived from two separate patients (A and B) were established. The 
ALI culture for subject B was more mature and had a higher density of cilia on the apical surface. 
Both ALI cultures were infected with human H1N1 influenza A strain PR8 at either a multiplicity 
of infection (MOI) of 1 or 10. One hour post-infection, the cells were stimulated with 0.1% quinine 
sulfate. The cells were maintained and fed daily for 72 hours with quinine treatment each day. 
After 72 hours, viral RNA was collected from the cell lysates. PCR of the influenza virus NP, IAV-
M1, and M1 genes was performed. As shown in Figure 1.1.1.2-1, there was a marked relative 
reduction in transcripts for both the NP (panel 1) and IAV-M1 (panel 2) genes in the more mature 
cells from ALI of subject B and a lesser relative reduction of transcripts in the ALI cells of subject 
A at a MOI of 1. Both viral RNA and cellular reference gene expression was lower and relative 
differences were less at the MOI of 10, suggestive of viral destruction of cells. Results for the viral 
M1 gene were similar (data not shown). 
 
Figure 1.1.1.2-1: PCR transcripts of viral NP and IAV-M1 genes 


 
 
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These data provide evidence of a possible anti-viral effect of quinine via stimulation of NO to 
inhibit viral replication. This effect may be less with high multiplicity of infection.  
1.1.1.4. Relevant studies of other investigators  
Several investigations have examined the effect of quinine on the lower airway, particularly in 
inflammatory modulation and bronchoconstriction. In mouse asthma models, pretreatment of 
animals with quinine reduces infiltration of inflammatory cells and also attenuates excessive 
mucus accumulation [34]. Specifically, a dose-dependent reduction of neutrophil and other immune 
cell recruitment was observed in a chemotactic gradient with quinine administration. Other studies 
have demonstrated a reduction in bronchoconstriction and airway remodeling with quinine, 
particularly due to smooth muscle relaxation [35]. The immunomodulatory effects of quinine 
responsive T2Rs throughout the airway are still being fully elucidated but utilizing quinine as an 
agonist to stimulate innate immune defenses may have therapeutic potential in CRS and other 
respiratory diseases. 
Common genetic variants in a cluster of bitter taste receptor genes on chromosome 12 appear to 
have a robust contribution to perception of quinine taste intensity [23]. Quinine taste sensitivity also 
appears to have been selected independently in some world populations, particularly for low 
concentrations of quinine [36]. A recent investigation demonstrated that patients with chronic 
rhinosinusitis with nasal polyps are significantly less sensitive to the bitter taste of quinine. This 
complements previous data showing that patients with the other CRS phenotype without nasal 
polyps are significantly less sensitive to denatonium, a broad T2R agonist [28]. However, 
denatonium is detected by T2Rs located on SCCs, and the SCC downstream response of T2R 
stimulation is an increase in antimicrobial peptide secretion, while NO release is more 
characteristic of a ciliated cell T2R response. These two bitter products, denatonium and quinine, 
elicit different physiologic responses and may each demonstrate unique T2R contributions to the 
two broad types of CRS (with and without polyps). Previous work also shows that patients with 
CRS irrespective of phenotype are more sensitive to sucrose, which is a T1R (sweet taste 
receptor) agonist. As T1R stimulation opposes the action of T2R stimulation in SCCs, these 
patients are thought to inhibit T2R function at lower airway glucose concentrations, such as during 
an early airway infection, due to this high affinity. Taste testing that aggregates differences in 
multiple bitter and sweet taste products that stimulate different receptors may prove useful in 
achieving improved patient stratification. Further work is necessary to optimize compound 
concentrations that most accurately reflect taste receptor affinities in the sinonasal tract.  
Quinine is a broad T2R agonist that stimulates NO responses with resultant bactericidal activity 
and increases in mucociliary clearance. The ability of quinine and other bitter tastants to harness 
innate immune defense mechanisms may have therapeutic potential as topical therapies for 
sinonasal diseases. Beyond this, inexpensive phenotypic taste tests for quinine and other bitter 
and sweet compounds can potentially predict airway taste receptor variation and associated 
predisposition to infectious or inflammatory disorders. Preclinical work has shown both 
antibacterial and possible antiviral activity.  
1.1.2 Human experience with quinine 
Quinine has been used in humans for hundreds of years for the treatment of malaria and, more 
recently, as a treatment for nocturnal leg cramps and other conditions. For the treatment of 
malaria, a typical oral dose of quinine is 600 mg three times daily and for leg cramps either 200 


 
 
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or 300 mg given at bed time. Quinine is also an additive to tonic water, a form of carbonated water 
made popular long ago by the British among those living in tropical regions, at a concentration of 
83 mg/L – or approximately 30 mg per 8 oz. drink.  
There is a large body of experience on the safety and tolerability of quinine given either nasally 
as a topical irrigation [37] or as an inhaled aerosol [38] [39] [40] [41] [42] [43] (Table 1.1.2-1). The first 
reported use of quinine delivered nasally was of “1 or 2 grains of quinine [sulphate powder, 65 or 
130 mg] …  to be fed into the nostrils as one would take tobacco snuff, in cases of facial neuralgia, 
tic douloureux, and hemicrania” published in the Indian Medical Gazette in 1869 [44]. Quinine has 
been utilized as a bitter compound to prevent unblinding of participants by masking the taste of 
the placebo in instances where study drugs were bitter tasting in 7 studies, totaling 652 persons. 
In these studies, quinine exposures ranged between 2.5 and 90 mg/day (Table 1.1.2-1). The 
duration of treatment ranged from 14 days to as long as 336 days (48 weeks). While most studies 
were of outpatients, one studied hospitalized patients admitted with exacerbations of cystic 
fibrosis (CF) [39]. Quinine exposure in this study was likely 3 mg/day as dosing appears to be the 
same as the two studies referenced in the methods [41] [43]. Although systemic exposure to quinine 
was not specifically measured in any study, it is likely that quinine given as inhaled treatment was 
completely (or near completely) absorbed, whereas quinine given as part of topical nasal irrigation 
[37] was only fractionally absorbed. Documentation of treatment in some studies was done through 
qualitative detection of quinine in the urine.   
Table 1.1.2-1 Clinical trials utilizing quinine as “placebo” (from published literature) 
Disease 
Route 
# given 
quinine  
Days of 
quinine 
Quinine 
dose 
(mg/ml) 
# times 
per day 
Vol 
(ml) 
Quinine 
exposure 
(mg/day) 
Comparator drug 
Ref 
CRS 
Nasal 
10 
28 
1 
3 
4 
12 
Tobramycin 
[37] 
CF 
Inh 
71 
84 
1 
3 
30 
90 
Tobramycin 
[42] 
CF 
Inh 
262 
84 
0.25  
2 
5 
2.5 
Tobramycin 
[43] 
CF 
Inh 
9 
14 
30 µg/kg 
2 
3.75 
~4.2 
Glutathione 
[38] 
CF 
Inh 
4 
14 
0.25 
4 
5 
6 
Amiloride 
[40] 
CF 
Inh 
164 
336 
0.25 
3 
4 
3 
0.9% v 9% saline 
with quinine 
[41] 
CF 
Inh 
132 
12.5* 
NS 
3 
4 
unk 
0.12% v 7% saline 
with quinine 
[39] 
CRS, chronic rhinosinusitis. CF, Cystic Fibrosis. NS – not stated; * length of stay was 13 for the 0.12% saline group, 
12 for the 7% saline group. * Days of treatment represent an average length of stay through hospitalization as 
reported.  
There were no reported safety issues attributable to quinine usage in the 7 clinical studies. More 
specifically, there were no reported electrocardiographic or hematologic adverse events reported 
in the studies. Adverse events documented for comparators such as tinnitus and voice changes 
for tobramycin [43] were not reported for the “placebo” arms (saline mixed with quinine) of the 
studies. Thus, quinine appears to be safe at doses similar to or far greater than that used in this 
protocol and for duration of treatment similar to or longer than proposed for this study.  
Quinine also appeared to have a modest effect on CF, there was an early decrease in the density 
of Ps. aeruginosa in expectorated sputum for patients in both the tobramycin arm and the saline 
mixed with quinine placebo arm albeit with less of a decrease in the quinine arm of the study [43]. 


 
 
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Notably, the difference of Ps. aeruginosa colonization density disappeared between the placebo 
(i.e., quinine) and tobramycin groups at 24 weeks of follow-up. Notably, there was an increase in 
antibiotic resistance of Pseudomonas isolates in the tobramycin arm that was not observed for 
the placebo (i.e., quinine) arm [43]. A similar effect on colonization of Ps. aeruginosa and S. aureus 
was observed in a study of hospitalized CF patients with a small decrease in bacterial density 
between admission and day 7 of treatment for both the treatment and control groups [39]. A long 
term study of normal saline vs hypertonic saline similarly showed no difference in Ps. aeruginosa 
density between baseline and either week 24 or 48 values [41]. 
One study compared topical nebulized tobramycin to placebo in patients with CRS. The study 
enrolled 21 patients who were refractory to medical and surgical treatment [37]. Quinine at a 
concentration of 1 mg/ml was added to saline for the placebo group and the tobramycin (active 
drug product) was also diluted in saline. Both treatments were well-tolerated.  Quality of life (QOL) 
measurement demonstrated a slower decline in the tobramycin group, with a difference that was 
statistically higher at baseline, week 2, and week 4, but not at the end of the observation period. 
The higher QOL score at weeks 2 and 4 for the tobramycin group was not qualitatively different 
from the baseline difference with the placebo, leading one to question whether tobramycin was 
more effective at any time period. Symptomatic scores for mucosal edema, post-nasal drip, and 
congestion were lower for the placebo saline/quinine group. Additionally, nasal congestion 
actually increased during tobramycin treatment whereas congestion decreased at all time-points 
in the placebo saline/quinine group. Thus, saline/quinine may have been superior to tobramycin 
nebulized topical treatment for refractory CRS.  
Studies of quinine use for leg cramps provides the clearest assessment of potential adverse 
effects. A 2015 Cochran review of 23 studies comprising 1586 participants provides the most 
comprehensive analysis [45]. Of note, 5 studies comprising 58% of participants were unpublished 
reports of drug studies filed with the FDA. Except for the unpublished reports, study quality was 
generally poor with randomization and blinding methods unclear. Dosing was either 200 or 300 
mg/day with treatment lengths ranging between 5 and 28 days, though most gave 14 days of 
treatment. Quinine-induced adverse effects were grouped into hypersensitivity events and dose-
related events [45]. Hypersensitivity events are idiosyncratic and include thrombocytopenia, 
angioedema, disseminated intravascular coagulation, pancytopenia, and hemolytic uremic 
syndrome. Dose dependent events and toxicities, such as cardiac abnormalities, gastrointestinal 
complaints, abdominal pain, tinnitus, vertigo, quinine-induced hypoglycemia, and renal 
insufficiency, typically did not occur until plasma concentrations of 10 mg/mL or more were 
achieved. Chronic use of higher doses of quinine can result in cinchonism: a syndrome comprised 
of tinnitus, dizziness, nausea, and headache. Frequencies of adverse reactions in the Cochrane 
review are shown in the table below. Minor adverse events were reported in 16 studies and major 
adverse events were reported as part of 18 studies (Table 1.1.2-2). Withdrawals attributed to 
transient study drug-associated events were reported for 12 quinine recipients versus 11 placebo 
recipients. Only one person developed a severe adverse event (SAE) leukopenia, 
thrombocytopenia, rash, myalgia, and nausea that resolved with stopping of quinine [45].  
In summary, quinine administered at doses of 200-300 mg for leg cramps was generally well 
tolerated. One SAE for hematologic abnormalities was reported out of approximately 806 quinine 
recipients. Similar findings were reported for an earlier meta-analysis by Man-Son-Hing et al. of 
a subset of 659 subjects from studies included in the Cochrane Review [46]. 


 
 
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Table 1.1.2-2 Adverse events of quinine versus placebo for leg cramps (Cochrane analysis*) 
Adverse event 
Quinine 
Placebo 
Relative risk  
(95% CI) 
Minor adverse events 
 
 
 
     No. of individuals (16 studies) 
725 
722 
 
Any minor event 
93 (12.8%) 
68 (9.4%) 
3% (0-6%) 
Gastrointestinal symptoms 
39 (5.4%) 
16 (2.2%) 
3% (1-5%) 
Headache 
36 (5.0%) 
33 (4.6%) 
NS 
Tinnitus 
10 (1.4%) 
1 (0.1%) 
NS 
Pruritus, scaly rash 
9 (1.2%) 
3 (0.4%) 
NS 
Dizziness, drowsiness 
8 (1.1%) 
8 (1.1%) 
NS 
Myalgia, paresthesia 
7 (1.0%) 
10 (1.4%) 
NS 
Visual disturbance 
4 (0.6%) 
2 (0.3%) 
NS 
Fever  
3 (0.4%) 
1 (0.1%) 
NS 
Major adverse events 
 
 
 
            No. of individuals (18 studies) 
806 
807 
 
Major event causing study stoppage 
12 (1.5%) 
11 (1.4%) 
NS 
Gastrointestinal symptoms 
7 (0.9%) 
1 (0.1%) 
NS 
Headache 
2 (0.2%) 
2 (0.2%) 
NS 
Tinnitus 
1 (0.1%) 
0 (0%) 
NS 
Pruritus, scaly rash 
2 (0.2%) 
0 (0%) 
NS 
Dizziness, drowsiness 
3 (0.4%) 
2 (0.2%) 
NS 
Myalgia, paresthesia 
1 (0.1%) 
0 (0%) 
NS 
Visual disturbance 
0 (0%) 
1 (0.2%) 
NS 
Fever  
1 (0.1%) 
0 (0%) 
NS 
*  Adapted from El-Tawil et al. [45]; NS – not significant.  
This study will assess the safety of topical nasal quinine sulfate, dihydrate (6 mg daily) delivered 
via nasal atomizer and its ability to decrease the incident rate of confirmed SARS-CoV-2 infection. 
Sterile 0.9% saline will be provided as the placebo control.  
1.2 
Investigational Agent 
GLS-1200 is used as the therapeutic agent in this study. GLS-1200 is formulated as a solution of 
quinine sulfate, dihydrate (Figure 1.2-1) USP dissolved into sterile normal saline (0.9% sodium 
chloride) at a concentration of 1 mg/ml and then filter sterilized. Quinine sulfate, dihydrate has a 
molecular weight of 782.94 g/mol.  
Sterile normal saline (0.9% sodium chloride) will be used as the placebo solution in this study.                             
 
 
   


 
 
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Figure 1.2-1: Structure of Quinine sulfate, dihydrate 
 
1.3 
Dose and Regimen Rationale  
The dose of quinine sulfate, dihydrate used in this protocol (1 mg/ml) given three times per day 
via nasal atomizer is similar to that used by Desrosiers et al. [37] (Table 1.1.2-1). Subjects will 
continue three times daily quinine sulfate, dihydrate usage for 4 weeks. This length of time for 
quinine exposure is the same as that used by Desrosier et al. (Table 1.1.2-1). The quinine sulfate, 
dihydrate treatment regime in this protocol is similar to that used in another protocol (IND 
BB128711) that was reviewed and approved by the University of Pennsylvania IRB (Protocol # 
821731).  
1.4 
Risk/Benefit Assessment 
In accordance with the International Conference on Harmonization (ICH), this study has been 
designed to minimize the risk to study participants. Quinine treatment in this study does not 
replace or change everyday precautions taken by the study participants in preventing SARS-CoV-
2 infection. 
Quinine sulfate, dihydrate exposure in this study is 6 mg/day (1 ml of a 1 mg/ml solution used to 
irrigate each nostril, for total exposure of 2 mg per application, three times daily) and is similar to 
that used by Desrosiers et al. to study tobramycin vs saline placebo (where the placebo contained 
1 mg/ml of quinine to mask taste) [37]. Doses ranging from 2.5 to 90 mg/day have been used as 
part of various studies for CF (Table 1.1.2-1). As reviewed above, the amount of quinine in an 8 
oz. glass of tonic water is greater than 25 mg, while typical doses of quinine prescribed for leg 
cramps is 200-300 mg/day and for malaria is 1800 mg/day (600 mg three times daily).  
The adverse effects of topical quinine are unknown. The adverse effects of orally prescribed 
quinine include hematologic changes (thrombocytopenia as most common and less commonly 
anemia) and electrocardiographic effects (particularly prolongation of the QTc). As reviewed, prior 
clinical studies of nasal or aerosol administered quinine in approximately 750 persons (Table 
1.1.2-1) showed no quinine-associated adverse events.  
The atomizer provided as part of this study is designed to provide a fine spray into the nose. There 
is the possibility that the atomizer will not function properly and will cause discomfort when used. 
Should this occur, study participants are asked to notify the study staff before their next dose. The 
study staff will discuss continued usage of the atomizer with the participant.  
If the GLS-1200 or saline are accidentally sprayed into the eyes, ears or mouth, irritation may 
occur that could require evaluation. If the syringe and atomizer are not fully connected, the study 
participant may only receive a partial amount of study drug. If the atomizer or syringe packaging 


 
 
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is found to be open prior to use, it is possible that either component could be contaminated and 
thus there is a risk for infection. Devices with damaged packaging should not be used.  
2. 
HYPOTHESIS AND STUDY OBJECTIVES 
2.1 
Hypothesis 
GLS-1200 topical nasal spray administered Day 0 through Week 4 will be safe, well tolerated and 
reduce the incidence of confirmed SARS-CoV-2 infection. 
2.2 
Primary Objectives and Outcome Variables 
• 
Evaluate the safety and tolerability of GLS-1200 topical nasal spray   
• 
Incidence of SARS-CoV-2 infection, confirmed by PCR relative to treatment group 
2.3 
Secondary Objectives and Outcome Variables 
• 
Symptom score of documented SARS-CoV-2 infection relative to treatment group 
2.4 
Exploratory Objectives 
• 
Incidence of SARS-CoV-2 seroconversion relative to treatment group 
• 
Assess the relationship of taste receptor genetics to incidence of SARS-CoV-2 infection 
and relative to treatment group 
3. 
STUDY DESIGN 
This is a Phase II, placebo-controlled, double-blind study of GLS-1200 topical nasal spray to 
assess the safety, tolerability, and ability to reduce the incidence of confirmed SARS-CoV-2 
infection. Following recruitment and informed consent, those meeting enrollment criteria will be 
randomized 2:1 (GLS-1200:placebo). Participants will initiate topical nasal spray applications 
immediately after randomization and will continue for 4 weeks. Participants will self-administer 
drug three times daily. The primary outcome measurements are safety, tolerability, and reduction 
in the diagnosis of PCR-confirmed SARS-CoV-2 infection. Follow-up will continue through 6 
weeks since some cases of SARS-CoV-2 infection may not be apparent until after the primary 
treatment period has concluded. Secondary measures will assess the incidence of symptoms 
between each visit, by treatment group.  In addition the average number of days subjects 
experience each symptom will be summarized by treatment group. Exploratory measures will 
assess the incidence of seroconversion in serum and the relationship of taste receptor genetics 
to incidence of SARS-CoV-2 infection both relative to treatment group.  
3.1 
Safety Monitoring 
Subjects will be randomized in a blinded fashion to one of two study treatments (quinine or 
placebo) at fixed doses. Clinical adverse events (AEs) will be reviewed at each visit up to end of 
the study. Subjects will be requested to maintain a daily symptom diary to monitor for viral related 
symptoms and to assess any other potential adverse effects through 2 weeks of follow-up. Safety 
monitoring will also include laboratory assessment of hematology, chemistry and ECG performed 
at baseline (pre-treatment) and at Week 4 (end of treatment).  
4. 
SELECTION AND ENROLLMENT OF PARTICIPANTS 
4.1 
Recruitment of Participants 
Adult volunteers will be recruited for the current study.  


 
 
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4.2 
Inclusion Criteria 
1. Age 18 years or older 
2. Able to provide informed consent  
3. Able and willing to comply with study procedures 
4. Able and willing to utilize an approved form of pregnancy prevention for women of child-
bearing potential through to the end of treatment 
4.3 
Exclusion Criteria 
1. Known allergy to quinine, quinidine or mefloquine 
2. Confirmed prior positive test for SARS-CoV-2 
3. Treatment within the past 2 weeks with chloroquine, hydroxychloroquine, or remdesivir 
4. Pregnancy or documentation of pregnancy by pre-treatment urine pregnancy test or breast 
feeding or plans to become pregnant during the course of the study 
 
4.4 
Discontinuation/Withdrawal of Study Participants 
Participants will be considered to have completed the study when he/she completes all scheduled 
study treatments and follow-up visits. If a participant discontinues the study at any time after 
enrollment, but prior to the final scheduled study visit, the investigator will make every effort to 
have the participant complete all assessments. At a minimum, study participants will be 
encouraged to complete all procedures included in the final study visit should they elect to 
terminate early. All data collected up to the time of early termination will be used for final analyses 
except as noted below. Categories of early termination are defined below: 
• 
Voluntary withdrawal from the study: the participant verbalizes or states in writing their 
desire to withdraw from the study. Data already collected remains as part of the study.  
• 
Lost to follow-up: the participant terminates, does/will not return to complete study visits 
and cannot be located, or does not respond to written or telephonic contact.  
• 
Withdrawal of consent: the participant provides verbal or written request to withdraw from 
the study and also withdraws consent for use of study data. The investigator is encouraged 
to discuss withdrawal of consent to ensure that data collected up to the time of study 
withdrawal can be used for analysis.  
• 
Protocol violation: the participant failed to adhere to protocol requirements. Such events 
will be discussed between the Medical Monitor and the site PI to determine whether these 
events constitute a deviation that requires removal of the participant from the study and/or 
non-use of study data.  
• 
Adverse event (Adverse Reaction): clinical or laboratory events that in the medical 
judgement of the investigator are grounds for discontinuation for the best interest of the 
participant. This includes serious and non-serious adverse events regardless of relation 
to study drug.  
• 
Death: the participant died. 
5. 
STUDY PRODUCT 
5.1 
Investigational Product 
GLS-1200, containing quinine sulfate, dihydrate, USP, the investigational product used in this 
study, is a small molecule with a chemical structure as shown in Figure 1.2-1. Quinine sulfate, 
dihydrate, USP will be formulated in 0.9% sterile saline at 1 mg/ml, filter sterilized and provided 


 
 
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to participants in vials with 7.0 ml recoverable volume for daily use. Quinine has been shown to 
be stable in neutral, weak and strong acid solutions, and weak base solutions, without light 
exposure for up to 285 days [47]. In contrast, when ultraviolet exposure occurs, the solution’s pH 
influences the rate of decrease in the concentration of quinine: rapid loss in 0.0005N NaOH; much 
slower decreases in water or strong acids; and the slowest loss in weak solutions of 0.03N HCl 
[47]. The quinine solution is approximately pH 6 for this study. 
Sterile, 0.9% sodium chloride (normal saline), will be used as the placebo solution. Sterile saline 
will be provided in vials with 7.0 ml recoverable volume for daily use. 
5.2 
Packaging and Labeling  
Study product will be supplied in kits labeled only with a randomly generated Treatment Kit #. 
Each kit will contain 28 vials of study drug (sufficient for 28 days of treatment) with each vial 
containing 7 mL of study drug. Study product will be stored at the University of Pennsylvania 
Investigational Drug Service. Vials of drug will be provided packaged in a cardboard box and 
inside amber plastic bags to reduce UV exposure.  
Drug product labels are shown below in Table 5.2-1. Labels are generated in tandem as shown: 
one side to be affixed to each Drug Product kit and the second side as detachable for pharmacy 
logs. As participants present for randomization, treatment assignments will follow the 
randomization schema in successive order. The study pharmacist will write the Subject ID# and 
dispensing date on the two labels at the time of study drug dispensation. The side that had been 
affixed to the Drug Product Kit will remain, while the other half is detached and affixed into the 
Pharmacy Log form. As noted, the detachable side for Pharmacy is designated as to whether the 
vials in the kit contain active drug (GLS-1200) or placebo (0.9% saline).  
The randomized Treatment Kit # and the designation as Active or Placebo serve as independent 
confirmatory checks on treatment assignment.  
Table 5.2-1 Study drug kit labels 
Affixed to Drug Product Kit 
For Pharmacy Log 
Subject ID# _______________________     Date __________ 
T2R-002 Study                            TREATMENT KIT#: XXXX 
GLS-1200 / Placebo 7 ml (#28 vials)  
Site #101  Uinversity of Pennsylvania 
Pablo Tebas, MD 
Store between 2-25ºC (Refrigerated or Room Temp) 
Expiration Date: MM YYYY 
Packaged at the University of Pennsylvania, Philadelphia, PA 
For Investigational Use Only 
 
 
Subject ID# _______________________     Date __________ 
T2R-002 Study                            TREATMENT KIT#: XXXX 
GLS-1200 / Placebo 7 ml (#28 vials)  
Site #101  Uinversity of Pennsylvania 
Pablo Tebas, MD 
Store between 2-25ºC (Refrigerated or Room Temp) 
Exipration Date: MM YYYY 
Packaged at the University of Pennsylvania, Philadelphia, PA 
For Investigational Use Only 
 
ACTIVE / PLACEBO  
 
5.3 
Handling of Study Drug 
Study drug will be stored between 2°C and 25°C in the University of Pennsylvania Investigational 
Drug Service. Investigational product must be stored in a secure area according to local 
regulations.  


 
 
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5.4 
Dispensing of Study Drug 
It is the responsibility of the Investigators that study drug is dispensed only to study participants. 
Authorized personnel are the only ones to dispense product according to local regulation.  
At enrollment, study participants will be provided one kit containing 28 vials of study drug, 28 
nasal atomizers, and 84 syringes. Each vial and atomizer will be used for single-day drug 
administration and then discarded, while a new syringe will be used at each of the three daily 
administrations and then discarded.  
The study pharmacist or study coordinator will demonstrate to participants how to remove drug 
from the vial into syringes and to self-administer product. Coordinator will also review proper 
handling and storage conditions for the materials provided. A link will be provided to an 
instructional video on study drug handling and administration. 
5.5 
Precautions with Investigational Medicinal Product 
Participants will be instructed to keep all unused study drug either refrigerated or at room 
temperature. Participants will be instructed to keep in-use vials refrigerated at 2-8°C. 
5.6 
Preparation of Investigational Product 
Study product will be supplied in “ready to use” daily-use vials. Sufficient atomizers, vial adapters 
and syringes will be provided.  
5.7 
Record of Investigational Product Disposition at Site 
It is the responsibility of the Investigator to ensure that a current record of investigational product 
disposition is maintained at each study site where investigational product is inventoried and 
disposed. Records or logs must comply with applicable regulations and guidelines, and should 
include: 
• 
Amount received and placed in storage area; 
• 
Amount currently in storage area; 
• 
Label ID number or batch number and use date or expiry date; 
• 
Dates and initials of person responsible for each investigational product inventory 
entry/movement; 
• 
Amount dispensed to each participant, including unique participant identifiers; 
• 
Amount transferred to another area/site for dispensing or storage; 
• 
Amount destroyed, if applicable 
 
5.8 
Return and Destruction of Investigational Product 
Subjects will discard that day’s study drug vial after the third daily dose.  
5.9 
 Device Accountability  
The pharmacy will maintain a log to track the lot numbers and distribution of the atomizer used in 
the study, LMA® MAD NASAL™ Intranasal Mucosal Atomization Device. Participants can discard 
syringes after dosing both nostrils at each time point and can discard the atomizer after the third 
daily dose. Unused devices (if applicable) can be discarded at completion of study treatment 
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6. 
STUDY PROCEDURES AND TREATMENTS 
6.1 
Procedures by Visit (also see Table S2) 
6.1.1 Day 0: Review Study and Eligibility Criteria; Obtain Informed Consent, Enrollment  
Subjects will be recruited and provided the informed consent for review. Study staff will review 
the protocol with the prospective participant and obtain written informed consent. One copy of the 
informed consent will be maintained at the site, and the other given to the participant.  
Study procedures that will be completed include:  
• 
Review medical history, demographics  
• 
Review concomitant medications 
• 
Perform physical exam, height, weight, vital signs 
• 
Perform study ECG, provide order for baseline safety labs (CBC and Basic Metabolic 
Profile) 
• 
Perform baseline nasopharyngeal swab for viral PCR 
• 
Collect serum for viral antibodies 
• 
Collect saliva for TAS2R genotyping (collection of saliva for genetic testing is optional) 
• 
Provide instruction on self-administration of study drug and device 
• 
Provide study diary 
6.1.2 Week 2: intermediate visit  
Two weeks into the study participants will return to the study site to complete the following study 
procedures: 
• 
Review study drug self-administration 
• 
Review new concomitant medications 
• 
Review adverse effects, any new diagnosis of SARS-CoV-2 infection 
• 
Review study diary 
• 
Perform targeted physical exam 
• 
Perform nasopharyngeal swab for viral PCR  
• 
Collect serum for viral antibodies 
• 
Collect plasma for quinine measurement 
6.1.3 Week 4: end of treatment 
Study procedures that will be completed include:  
• 
Review new concomitant medications 
• 
Review adverse effects, any new diagnosis of SARS-CoV-2 infection  
• 
Perform targeted Physical exam 
• 
Review study diary 
• 
Perform nasopharyngeal swab for viral PCR 
• 
Perform ECG 
• 
Perform repeat safety labs (CBC and Basic Metabolic Profile) 
• 
Collect serum for viral antibodies 
6.1.4 Week 6: follow up visit 
Study procedures that will be completed include:  
• 
Review new concomitant medications 
• 
Review adverse effects, any new diagnosis of SARS-CoV-2 infection  


 
 
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• 
Review and collect study diary 
• 
Perform targeted physical exam 
• 
Perform nasopharyngeal swab for viral PCR 
• 
Collect serum for viral antibodies 
• 
Collect and review diary 
 
6.2 
Timing and Evaluations 
6.2.1 Informed Consent (Day 0) 
Study personnel will meet with prospective study participants, explain the study, and provide them 
with an informed consent form (ICF) that describes the eligibility criteria for entering the study, 
study treatments and follow-up procedures. An informed consent must be signed prior to any 
study related procedures being performed. A copy of the signed and dated consent form will be 
given to the participant.  
6.2.2 Enrollment (Day 0) 
Participants who consent to be in the study will be assigned a unique participant identification 
designation number (PID#). Once assigned, PID numbers cannot be reused for any reason. 
Information regarding participant’s PID# and screen date will also be documented on a screening 
log. See section 8.7 for allocation schedule and process.  
Medical History 
Investigators should document all significant illnesses that the participant has experienced as 
Medical History in the last 6 months. Illnesses’ first occurring or detected during the study and/or 
worsening of an existing illness that occurs after the first administration of study drug are 
documented as AEs on the electronic case report form (eCRF).  
Prior and Concomitant medications 
Prior treatments, defined as administered up to 8 weeks prior to the time of informed consent, will 
be recorded in the eCRF as prior medications. Concomitant treatments, defined as continuing or 
new treatments taken at or after the signing of the informed consent, will be recorded in the eCRF 
as concomitant medications. 
Review of study drug self-administration 
Study staff will review with the participant the procedures for self-administration and provide a link 
for an instructional video.  
Provide study drug and diary 
Study staff will provide participants with a kit containing study drug, syringes, and atomizers for 
28 days of treatment. A study diary will be provided and instructions on how to complete the diary 
will be reviewed.   
6.2.3 Safety Assessments 
6.2.3.1  
Adverse effects 
Adverse effects will be queried at the Week 2, 4, and 6 visits.  


 
 
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6.2.3.2  
Physical Assessments and Targeted Physical Assessment 
A physical examination will be performed at study enrollment and a targeted physical examination 
will be performed at the Week 2, 4 and 6 visits and any unscheduled visit.  
6.2.3.3  
Vital Signs 
Participant vital signs will be performed at all study visits.  
6.2.3.4  
Weight and Height 
Participant height and weight will be assessed and recorded at enrollment.  
6.2.3.5  
12-lead ECG 
A 12-lead ECG will be performed at enrollment and at the Week 4 visit.  
6.2.3.6  
Safety Laboratory Evaluations 
Blood draws for a complete blood count with differential and a basic metabolic panel (consisting 
of sodium, chloride, potassium, bicarbonate (CO2), blood urea nitrogen (BUN), creatinine, and 
glucose) will be performed at baseline and at the Week 4 visit.   
6.3 
Assessment of Laboratory Abnormalities 
Serum chemistries (basic metabolic panel) and complete blood count with differential blood count 
will be graded as noted in Section 7.1.  
6.4 
Assessment of Clinical Adverse Events 
Participants will also be queried regarding the occurrence of any adverse events, concomitant 
medications and new onset disease during their clinic visits. Participants will be reminded to 
contact study personnel and immediately report any event that may happen for the duration of 
the study up to and including the final study visit. Events will be recorded in eCRF.  
The Investigator will grade clinical AEs (based on discussions with study participants) using the 
NCI Common Terminology Criteria for Adverse Events v5.0. Laboratory abnormalities of grade 2 
or higher will be captured. 
6.5 
Nasopharyngeal swab PCR for presence of SARS-CoV-2 virus 
Nasopharyngeal swabs will be performed at baseline and Weeks 2, 4 and 6 to perform PCR to 
document the presence of SARS-CoV-2 virus RNA, which may be done by research use only 
(RUO) assays.  
Results of the Nasopharyngeal Swab 
Results of the nasopharyngeal swab may be received as soon as one day after testing.  
If the PCR results are positive for SARS-CoV-2 infection at enrollment, the participant will be 
asked to remain in the study, administer study drug as per protocol, comply with all required 
testing for safety, and complete the remaining visits. If the participant does not want to administer 
study drug or complete testing, they will be asked to consent to telephone contact for the 
remaining visits. 
6.6 
Serum for SARS-CoV-2 antibodies 
Serum will be collected at baseline and Weeks 2, 4 and 6 to measure SARS-CoV-2 antibodies 
using RUO assays.  


 
 
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6.7 
Definition of confirmed SARS-CoV-2 infection and SARS-CoV-2 symptom 
score 
Participants will be queried as to any new diagnosis of SARS-CoV-2 infection, defined as a 
positive PCR test for SARS-CoV-2. This definition is consistent with the current protocol for viral 
PCR testing. All deaths will be considered as treatment failures. 
Participants will also be instructed to maintain a symptom diary that includes those symptoms 
considered common for SARS-CoV-2. The diary is inclusive of symptoms identified by the World 
Health Organization for a diagnosis of SARS-CoV-2 as well as more recently identified symptoms 
such as conjunctivitis, diarrhea, and loss of taste or smell. Each symptom will score scored as 
present (score of 1) or absent (score of 0) for each two week interval and the incidence of each 
symptom will be summarized by treatment group.  In addition, the average number of days 
subjects had each symptom throughout the study period (6 weeks) will be summarized by 
treatment group.  
6.8 
Exposures to SARS-CoV-2 
Exposure history to patients known to have SARS-CoV-2 will be included as part of the participant 
diary.  
6.9 
Saliva for TAS2R genotyping 
Samples of saliva will be collected for genotype analysis of the bitter taste receptors (T2R) using 
chip technology that includes known common TAS2R single nucleotide polymorphisms (SNPs). 
Dense genotyping, after purification and quantification of genomic DNA, will interrogate and 
genotype 96 of the T2R SNPs with high minor allele frequency (mostly missense). The results of 
genotype analysis of T2Rs that are stimulated by quinine will serve as an exploratory co-variate 
of treatment outcome and be presented as a descriptive analysis. This data is for study purposes 
only and will not be entered into the participants’ clinical record.  
7. 
EVALUATION OF SAFTY AND MANAGEMENT OF TOXICITY 
7.1 
Safety Parameters 
7.1.1 Adverse Events (AEs) 
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, 
function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated 
with the use of a product whether or not considered related to the use of the product. In this study, 
such changes will be monitored, classified, and summarized, as Clinical or Laboratory AEs. 
Medical conditions/diseases present before starting the investigational drug will be considered 
adverse events only if they worsen after starting study treatment.  
An unexpected AE is:  
• 
Not identified in the Investigator’s Brochure (IB) or otherwise not expected from the 
characteristics of the clinical material 
• 
Not listed at the specificity or severity that has been previously observed 
 
Study related AEs include the following: 
• 
Pre- or post-treatment complications that occur as a result of protocol mandated procedure  


 
 
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• 
Any pre-existing condition that increases in severity, or changes in nature during or as a 
consequence of the study drug phase of a human clinical trial, will also be considered an AE 
• 
Complications and termination of pregnancy; see Section 7.1.8 for additional information.  
• 
All AEs that occur after enrollment and throughout the duration of the study will be recorded. 
Study related AEs do not include the following: 
• 
Elective medical or surgical procedures 
• 
Non-elective medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, 
transfusion) performed; the condition that leads to the procedure is an AE 
• 
Pre-existing diseases or conditions or laboratory abnormalities present or detected before 
study enrollment that do not worsen 
• 
Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social and/or convenience admissions). 
• 
Overdose without clinical sequelae  
• 
Any medical condition or clinically significant laboratory abnormality with an onset date before 
the first dosing and not related to a protocol associated procedure is not an AE. It is considered 
to be pre-existing and will be documented on the medical history eCRF 
• 
Any laboratory abnormality that is considered as non-significant or considered as related to 
another non-study related condition  
• 
Uncomplicated pregnancy 
• 
An induced elective abortion to terminate a pregnancy without medical reason 
7.1.2 Serious Adverse Events (SAEs) 
A serious adverse event (SAE) is any AE that meets one of the following conditions: 
• 
Death during the period of surveillance defined by the protocol; 
• 
Is immediately life-threatening (e.g., participant was, in the view of the Investigator, at 
immediate risk of death from the event as it occurred). This does not include an AE that, had 
it occurred in a more serious form, might have caused death; 
• 
An event requiring inpatient hospitalization or prolongation of existing hospitalization during 
the period of protocol defined surveillance (including any overnight stay in the hospital, 
regardless of the length of stay, even if the hospitalization is only a precautionary measure 
to allow continued observation. However, hospitalization (including hospitalization for an 
elective procedure) for continued treatment or assessment of a pre-existing condition that 
has not worsened, does not constitute an SAE. NOTE: Evaluation in a physician’s office, or 
at a hospital or other urgent care setting in an observational, non-admitted status regardless 
of the time period of observation, does not constitute an SAE; 
• 
Results in congenital anomaly or birth defect; 
• 
Results in persistent or significant disability/incapacity or substantial disruption of the ability 
to conduct normal life functions; 
• 
Is an important medical event that may not result in death, be life threatening, or require 
hospitalization, but based upon appropriate medical judgment, may jeopardize the participant 
and may require medical or surgical intervention to prevent one of the outcomes listed above. 
Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not 
result in inpatient hospitalization; 
• 
Is medically significant or requires intervention to prevent one or other of the outcomes listed 
above. 


 
 
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Clarification of Serious Adverse Events 
• 
Death is an outcome of an AE, and not an adverse event in itself 
• 
The participant may not have been on investigational medicinal product at the occurrence of 
the event.  
• 
“Life-threatening” means that the participant was at immediate risk of death from the event 
as it occurred. This does not include an event that might have led to death if it had occurred 
with greater severity 
• 
Complications that occur during hospitalizations are AEs. If a complication prolongs the 
hospitalization, it is an SAE 
• 
Inpatient hospitalization means that the participant has been formally admitted to a hospital 
for medical reasons, for any length of time. This may or may not be overnight. Observation 
status or evaluation in an emergency department, urgent care setting, or outpatient office 
does not constitute an SAE.  
• 
The investigator will attempt to establish a diagnosis of the event on the basis of signs, 
symptoms, and/or other clinical information. In such cases, the diagnosis will be documented 
as the AE and/or SAE and not the individual signs/symptoms. 
Serious adverse events that are ongoing should be followed until resolution. The reporting period 
for SAEs is described in Section 9.6.2. 
7.1.3 Unexpected Adverse Drug Reactions 
An unexpected adverse drug reaction is a reaction for which the nature or severity is not 
consistent with the applicable product information (see Investigator’s Brochure). Until product 
information is amended, expedited reporting is required for additional occurrences of the reaction. 
Reports that add significant information on specificity or severity of a known, already documented 
SAE constitute unexpected events. 
7.1.4 Assessing Severity (Intensity) 
The Investigator will grade laboratory AEs and clinical AEs (based on discussions with study 
participants) using the NCI Common Terminology Criteria for Adverse Events v5.0: 
• 
Mild (Grade 1) 
• 
Moderate (Grade 2) 
• 
Severe (Grade 3) 
• 
Life-threatening consequences (Grade 4) 
• 
Death related to AE (Grade 5) 
Adverse events will be recorded on the eCRF at the severity reported by the investigator. 
If an ongoing AE worsens or increases in its severity or its relationship to the study drug changes, 
a new AE entry for the event should be entered on the eCRF. 
The following is a link to the grading scale: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Referenc
e_5x7.pdf 
7.1.5 Causal Relationship of Investigational Product to Adverse Events 
A causally related AE is one judged to have a suspected relationship to the administration of the 
investigational agent. Conversely, an AE may also be assessed as not related to the 
investigational product. The Investigator is responsible for reporting adverse events and judging 


 
 
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the relationship between the administration of the investigational product and an AE because the 
investigator is knowledgeable about the participant (e.g., medical history, concomitant 
medications), administers the investigational product, and monitors the participant’s response to 
the investigational product. The Sponsor will assess the overall safety of the investigational 
product and determine whether expedited reporting to regulatory agencies is indicated. 
Investigators should use their knowledge of the Study Participant, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether or not an 
adverse event is considered to be related to the study drug by the following criteria: 
• 
Related – the investigator considers that there is a causal relationship between the event and 
study drug; 
• 
Probably related – the Investigator considers that there is a probability of a causal relationship 
of the event to the study drug 
• 
Possibly related – the investigator considers that there is a possible causal relationship of the 
event to the study drug 
• 
Not related – the investigator considers that the event has no relationship to administration of 
the study drug  
The following guidance should also be taken into consideration: 
• 
Temporal relationship of event to initiation of study drug; 
• 
Course of the event, discontinuation of study drug, or reintroduction of study drug (when 
applicable); 
• 
Known association of the event with the study drug or with similar treatments; 
• 
Known association of the event with the disease under study; 
• 
Presence of risk factors in the Study Participant or use of concomitant medications known to 
increase the occurrence of the event 
7.1.6 Abnormal Laboratory Value 
Grade 2 and higher laboratory abnormalities (e.g., serum chemistry, CBC) are to be recorded.  
Any laboratory abnormality that is new in onset or worsened in severity or frequency from the 
baseline condition and meets one of the following criteria will be recorded as an AE: 
• 
Requires therapeutic intervention or diagnostic tests 
• 
Leads to discontinuation of study treatment 
• 
Has accompanying or inducing symptoms or signs 
• 
Is judged by the investigator as clinically significant 
7.1.7 Pregnancy During Study 
Pregnancy is an exclusion criterion for participation in this study. Women of childbearing potential 
should either be unable to conceive or use a form of birth control such as a diaphragm, birth 
control pills, IUD, or regular use of male or female condom. If a participant becomes pregnant 
during the time of the study, they will be asked to contact study staff after the end of the study to 
report on the outcome of pregnancy.  


 
 
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7.1.8 Post-study Reporting Requirements 
All AEs and SAEs including deaths, regardless of cause or relationship, must be reported for 
participants on study (including any protocol-required post-treatment follow-up). 
Investigators are not obligated to actively seek AEs or SAEs beyond the follow up period for 
participants. However, if the Investigator learns of an AE or SAE that occurs after the completion 
or termination visit and the event is deemed by the Investigator to be probably or possibly related 
to the study treatment, he/she should promptly document and report the event to the study team 
and medical monitor. 
7.2 
Methods and Timing for Collection and Recording of Safety Data 
At the time of each study visit, participants will be queried as to adverse events that have occurred 
in the interim period and the current status of any AE that was reported at a prior visit that has not 
yet resolved. As delineated above, both solicited and non-solicited events will be sought. 
Additionally, labs and ECGs will be reviewed for safety.   
All AEs, regardless of severity, seriousness, or presumed relationship to study treatment, must 
be recorded using medical terminology in source documents and on the eCRF. Whenever 
possible, a diagnosis will be documented, in lieu of symptoms. The source document and the 
eCRF must contain the Investigator’s opinion concerning the relationship of the AE to study 
treatment. 
AEs should be described with the following attributes: 
• 
Duration (start and end dates) 
• 
Seriousness 
• 
Severity 
• 
Causality 
• 
Action(s) taken 
• 
Outcome 
7.3 
Safety and Toxicity Management 
The Medical Monitor will be responsible for the overall safety monitoring of the study. The site 
Investigator will be responsible locally for safety.  
Safety assessments include the following: 
• 
Incidence of all adverse events classified by system organ class, preferred term, severity, and 
relationship to study treatment 
• 
Changes in safety laboratory parameters  
7.3.1 Events Requiring Expedited Reporting 
Events requiring expedited reporting (ERER) are defined as any Adverse Events including: 
• 
Grade 3 or greater fever; 
• 
Grade 3 or greater systemic symptoms;  
• 
Grade 3 or greater laboratory abnormalities 
The most severe grade for that particular event is to be documented in the eCRFs. 
Sites will inform the Sponsor of any ERER within 24 hours to discuss whether dosing to the 
participant should continue. 


 
 
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7.3.2 Stopping Rules 
If any of the following situations occur, then further enrollment and Study Treatments will be halted 
immediately until a thorough investigation has been conducted by the Medical Monitor and 
Principal Investigator and the IRB (if applicable): 
• 
Three (3) or more participants experience an ERER assessed as related to Study Treatment;  
• 
Any participant experiences a potentially life threatening AE, Grade 4 AE or death assessed 
as related to Study Treatment; 
• 
Five (5) or more participants across both treatment arms experience the same or similar grade 
3 or 4 adverse event, assessed as related to Study Treatment; 
• 
Any report of anaphylaxis of Grade 3 or greater assessed as related to Study Treatment. 
Upon conclusion, the sponsor or designee will notify all investigators and the IRB/REC (if required) 
regarding the outcome of any investigation.  
Any SAE or death assessed as related to Study Treatment will lead to an immediate halt of study 
enrollment and Study Treatments, until the event has been investigated and Sponsor has 
consulted with FDA. 
Study restart will occur following approval of the IRB/REC and/or FDA as applicable.  
Guidelines for assessing relatedness are detailed in Section 7.1.5. 
7.3.3 Unblinding 
This is a double-blind study. 
Emergency unblinding for AEs may be performed. This option may be used ONLY if the 
patient’s well-being requires knowledge of the patient’s treatment assignment. Unblinding 
should only be considered for the safety of the patient. If unblinding is deemed necessary 
by the Investigator, the Investigator can unblind the patient’s treatment allocation after 
discussion and approval by Sponsor Medical Monitor. The Investigator must note the 
date, time, and reason for unblinding. The Investigator should inform the Sponsor that the 
patient was unblinded, however they are not required to reveal to the Sponsor the 
patient’s treatment allocation. 
Unblinded information will only be accessible to those who need to be involved in the 
safety reporting to Health Authorities, Ethics Committees, and/or IRBs. 
Investigators will receive only blinded information unless unblinded information is judged 
necessary for safety reasons. 
8. 
STATISTICAL METHODS and CONSIDERATIONS 
Prior to the analysis of the final study data, a detailed Statistical Analysis Plan (SAP) will be written 
describing all analyses that will be performed. The SAP will contain any modifications to the 
analysis plan described below. 
8.1 
Data Sets to be Analyzed 
Any participant who is randomized to a treatment allocation will be considered part of the intention-
to-treat (ITT) population. The ITT population will be used for the summary of all demographic and 
baseline characteristics and for analysis of the primary outcome. Subjects lost to follow-up, 
requiring rescue therapy, those who discontinue study prior to completion of the primary treatment 


 
 
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end point (Week 4) and those who test positive for SARS-CoV-2 infection at Weeks 2 or 4 will be 
considered as treatment failures. Separate analysis will examine treatment failures in the period 
between the cessation of study treatment (Week 4) and the end of study (Week 6). All deaths will 
be considered as treatment failures. All subjects will be grouped in analyses and summaries 
based on their randomization allocation. The following analysis populations will be defined from 
the ITT population: 
• 
The safety analysis set includes all randomized participants and is synonymous with the ITT 
set except that patients will be grouped based on treatment actually received.  
• 
Per-protocol (PP) analysis set includes all participants who complete the trial and who receive 
≥90% Study Treatments through to either diagnosis of SARS-CoV-2 infection (study end point) 
or to end of study for those without a SARS-CoV-2 diagnosis, based on subject completed 
accountability logs, and have no significant protocol violations. Participants in this sample will 
be grouped to treatment arms they actually received. This set will be used as a sensitivity 
analysis to summarize the primary and secondary efficacy outcomes. 
8.2 
Demographic and Other Baseline Characteristics 
Demographic and baseline data, vital signs, medical history, concomitant illnesses, and current 
medications/treatments will be summarized by means of descriptive statistics: continuous 
variables as mean, median, standard deviation, and interquartile ranges and categorical variables 
as frequencies and percentages, stratified by treatment arm based on the ITT population. 
8.3 
Safety Analysis 
All safety and tolerability summaries will be performed on the safety analysis population.  
8.3.1 Adverse events 
Treatment emergent AEs will be summarized by frequencies and will be presented by system 
organ class and preferred term with the number and percentage of participants affected. 
Frequencies will be presented with respect to maximum severity and to strongest relationship to 
Study Treatment. Multiple occurrences of the same AE will be counted only once following a 
worst-case approach with respect to severity and relationship to Study Treatment.  
The proportion of participants experiencing any AEs (Grade 1-4) following treatment with study 
drug will be presented as part of the safety analysis set. The precision with which this sample 
result estimates the rate of similar AEs in the population represented by the study sample will be 
reported in terms of 95% confidence intervals (CI) around the sample proportions. This will 
provide 95% confidence that the rate of severe adverse effects is not greater than the upper limit 
of the CI around the proportion of participants with grade 3+ events in the study sample. 
8.3.2 Laboratory Data 
Continuous response variables per time point and changes from baseline will be summarized with 
mean, median, minimum, and maximum values. Categorical response variables will be 
summarized per time point with percentages.  
8.4 
Efficacy Analysis 
The primary efficacy analysis is the difference between groups of confirmed SARS-CoV-2 
infection as based on the ITT analysis population. 


 
 
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8.5 
Secondary Analysis 
Secondary outcomes will be summarized as to the incidence of each symptom by treatment group 
and the average number of days each symptom was present over the course of the study (6 
weeks).  Summaries will be presented, noncumulatively by visit and well as cumulatively over 4 
weeks of treatment. 
8.6 
Interim Analysis 
No interim analysis is planned. 
8.7 
Sample Size and Randomization 
The sample size for this study is based on an infection rate in the placebo group of 10%. A 2:1 
randomization of 225 subjects would have a power of 80.8% to detect a difference of 9% between 
groups at alpha = 0.05 assuming 1% of individuals in the treatment group was confirmed to be 
infected with SARS-CoV-2. Table 8.7-1 below provides a range of treatment rates that could be 
detected with at least 80% power using this sample size.  
Table 8.7-1 Range of treatment rates detectable with at least 80% power 
Treated 
Infection Rate 
(N=150) 
Placebo 
Infection Rate 
(N= 75) 
Difference 
Treated - Placebo 
Actual 
Power 
0 
7.3% 
-7.3% 
80.3% 
1% 
10% 
-9% 
80.8% 
2.5% 
13.5% 
-11% 
80.3% 
5% 
18.1% 
-13.1% 
80.4% 
7.5% 
22.1% 
-14.6% 
80.3% 
10% 
25.7% 
-15.7% 
80.0% 
 
8.8 
Missing Values 
If a subject is lost to follow-up, or for some reason fails to provide an assessment of the primary 
endpoint, the subject will be considered a treatment failure per the ITT population.  
9. 
DATA COLLECTION, MONITORING, AND AE REPORTING 
9.1 
Confidentiality 
Information about study participants will be kept confidential to the best of the study site’s ability. 
In the event that a participant revokes authorization to collect or use personal health information 
(PHI), the sponsor retains the ability to use all information collected prior to the revocation of 
participant authorization. For participants that have revoked authorization to collect or use PHI, 
attempts should be made to obtain permission to collect at least vital status (i.e., that the 
participant is alive) at the end of their scheduled study period. 
9.2 
Source Documents 
Source data is all information, original records or clinical findings, observations, or other activities 
in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are 
contained in original source documents. Examples of these original documents, and data records 
include (as applicable): hospital records, clinical and office charts, laboratory notes, memoranda, 


 
 
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participant’s diaries or evaluation checklists, pharmacy dispensing records, recorded data from 
automated instruments, copies or transcriptions certified after verification as being accurate and 
complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, participant 
files, pharmacy records, laboratory records, medical records (including electronic records) relative 
to the clinical trial.  
9.3 
Data Collection 
Data will be collected using Electronic Data Capture (EDC). Participants will be identified by PID#. 
Initial data collection may utilize a paper form of the EDC. Any such records will be maintained as 
source data.  
9.4 
Record Retention 
It is the Investigator’s responsibility to retain study essential documents as per country regulations: 
in the US for at least 2 years after the last approval of a marketing application in their country and 
until there are no pending or contemplated marketing applications in their country or at least 2 
years have elapsed since the formal discontinuation of clinical development of the investigational 
product. The sponsor will inform the investigator/institution as to when these documents are no 
longer needed to be retained. 
9.5 
Safety and Quality Monitoring and Record Availability 
Monitoring 
Monitoring of the clinical trial will be performed by experienced monitors, who will report to the 
Sponsor as outlined in the Monitoring Plan. 
Record availability and auditing 
The investigator will make study documents (e.g., ICFs, drug accountability forms) and pertinent 
hospital or clinic records readily available for inspection by the local IRB, the site monitors, 
regulatory agencies, GeneOne Life Science, Inc. or its designee for confirmation of the study data. 
Participation as an investigator in this study implies acceptance of potential inspection by 
regulatory authorities and applicable compliance and quality assurance offices. 
9.6 
Adverse event (AE) Reporting 
To assure the safety of the participants, information about all AEs, whether volunteered by the 
participant, discovered by investigator or study staff questioning, or detected through physical 
examination, laboratory test or other means, will be collected and recorded in the participant’s 
source documents and followed as appropriate. 
A summary of the study’s overall progress will be forwarded to regulatory agencies according to 
the local requirements.  
9.6.1 Study Reporting Period of Adverse Events 
Solicited and unsolicited AEs will be collected throughout the study and recorded.  
9.6.2 Study Reporting Period for Serious Adverse Events  
SAEs occurring from the time of consent through to the end of the study are to be reported without 
regard to causality. SAE’s should be reported to GeneOne Life Science within 24 hours of 
discovery. Investigators should also report SAEs to their local IRB/REC as required.  


 
 
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Expedited reporting of SAEs will be determined by GeneOne Life Science using reference safety 
information specified in the Investigator’s Brochure. An event may qualify for expedited reporting 
to regulatory authorities if it is an SAE, unexpected per reference safety information and 
considered related following the guidelines in Section 7.1.4 (Suspected Unexpected Serious 
Adverse Reaction, SUSAR) in line with relevant legislation. All investigators will receive a safety 
letter notifying them of relevant SUSAR reports. The Investigator should notify the Ethics 
Committee as soon as is practical, of serious events in writing where this is required by local 
regulatory authorities, and in accordance with the local institutional policy.  
At any time after completion of the SAE reporting period, if an Investigator becomes aware of an 
SAE that is suspected by the Investigator to be related to the study drug, the event will be reported 
to the Sponsor or its designee. 
If the Investigator becomes aware of an SAE after the last scheduled follow-up contact, and 
considers the event related to prior Study Treatment, the Investigator will report it to GeneOne 
Life Science. 
SAE TELEPHONE AND CONTACT INFORMATION: 
MEDICAL MONITOR: 
Joel Maslow, MD PhD MBA 
 
MAILING ADDRESS: 
PHONE: 
(484) 965-9147p; (610) 331-7844 c 
 
GeneOne Life Science, Inc. 
MEDICAL LIAISON: 
Celine Remigio, RN DPT 
 
1040 DeKalb Pike 
CELL: 
(914) 606-1199 
 
Suite 200 
EMAIL: 
cremigio@geneonels-us.com 
 
Blue Bell, PA 19422 
24 hr Answering Service (215) 703-5843 
 
 
GeneOne FACSIMILE: 
(484) 965-9146 
 
 
GeneOne Safety Email 
GeneOneSafety@geneonels-us.com 
 
 
 
The report should contain as much clinical safety information as possible, but at minimum, the 
initial report must include the following information: 
• 
Participant number and Study name 
• 
Date of Onset and Date of Resolution (if applicable) 
• 
Detailed description of event 
• 
Investigational product (if known) 
• 
Causal relationship of event to investigational product 
• 
Reporter name and contact information 
Follow-up reports will be sent as soon as more information becomes available. Events for which 
the study participant seeks medical care, the study site will attempt to obtain relevant medical 
records to include as source documents. These include but are not limited to discharge summary, 
results of relevant laboratory tests, and reports of relevant radiographic studies. In the case of 
death, the investigator will attempt to procure relevant reports (such as autopsy reports, medical 
examiner report, discharge summary).  
Each SAE must be followed by the investigator until resolution, stabilization, or return to baseline, 
even if this extends beyond the end of the study, with follow-up report filed to provide a summary 
of the event through resolution.  


 
 
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Clinical Protocol 
 
 
 
-36- 
 
 
The original SAE form must be kept at the study site. Copies (or electronic copy) will be provided 
to GeneOne Life Science or its representative, who will be responsible for reporting to regulatory 
authorities as indicated, and copy will be forwarded to the study sites IRB/REC.  
9.6.3 Notification of Serious Adverse Events 
In accordance with local regulations, the Sponsor shall notify the appropriate regulatory 
authorities, and all participating investigators in a written safety report of any adverse experience 
associated with the use of the product that is both serious and unexpected (e.g., FDA Form 3500A 
in the US). Reports of SAEs shall be made as soon as possible and in no event later than 15 
calendar days after the Sponsor’s initial receipt of the information. Written notification may be 
submitted on the form described above or equivalent or in a narrative format and shall bear 
prominent identification of its contents. Each written notification to regulatory agencies shall be 
transmitted to the division that has responsibility for review. In each written safety report, the 
Sponsor shall identify all safety reports previously filed concerning a similar adverse experience, 
and shall analyze the significance of the adverse experience in light of the previous, similar reports. 
The Sponsor shall also notify the relevant regulatory authorities by telephone, facsimile, or email 
transmission of all deaths and any unexpected fatal or life-threatening experience, regardless of 
causality, as soon as possible but in no event later than 7 calendar days after the Sponsor’s initial 
receipt of the information. Each telephone call or facsimile transmission to regulatory agencies 
shall be transmitted to the division that has responsibility for review.  
Follow up information to a safety report shall be submitted as soon as the relevant information is 
available. If the results of a Sponsor’s event investigation show that an adverse drug experience 
not initially determined to be reportable is, in fact, reportable, the Sponsor shall report such 
experience in a written safety report as soon as possible, but in no event later than 15 calendar 
days after the determination is made. Results of investigations of other safety information shall 
be submitted, as appropriate, in an information amendment or annual report. In the event of death, 
if an autopsy is performed, a copy of the report, redacted for PHI but labeled with the PID#, should 
be sent to GeneOne Life Science, Inc. 
9.7 
Study Discontinuation 
GeneOne Life Science reserves the right to discontinue the study for safety or administrative 
reasons, including lack of enrollment, at any time. Investigational product must be returned to 
GeneOne, unless instructed otherwise. Document retention will follow local regulation.   
10. 
PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be allowed. Any proposed presentation, abstract and/or 
manuscript must be made available to GeneOne at least 60 days prior to submission. GeneOne 
shall have fifteen (15) days for review. If GeneOne considers that material would reveal 
protectable intellectual property, GeneOne may request a delay in submission for a maximum of 
three (3) months from the date of receipt in order for patent application(s) to be filed with the 
United States Patent and Trademark Office and/or foreign patent office(s). 
11. 
LIST OF ABBREVIATIONS 
AE 
Adverse event 
ALI 
Air-liquid-interface 


 
 
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Clinical Protocol 
 
 
 
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AVI 
Alanine-valine-isoleucine, non-functional TAAS2R38 allele 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
CBF 
Ciliary beat frequency 
CF 
Cystic fibrosis 
CI 
Confidence interval 
CRS 
Chronic rhinosinusitis 
DAF-FM 
4-amino-5-methylamino-2’,7’-difluorescein 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
ERER 
Event requiring expedited reporting 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
IRB 
Investigation review board 
ITT 
Intention-to-treat 
L-NAME 
L-NG-nitroarginine methyl ester 
MOI 
Multiplicity of infection 
NO 
Nitric oxide 
NS 
Not stated 
PAV 
Proline-alanine-valine, functional TAS2R38 allele 
PHI 
Personal health information 
PID# 
Participant identification designation number 
PP 
Per-protocol 
PTC 
Phenylthiocarbamide 
QOL 
Quality of Life 
RUO 
Research Use Only laboratory assay 
SAE  
Serious adverse event 
SAP 
Statistical analysis plan 
SCC 
Solitary chemosensory cells  
SNP 
Single nucleotide polymorphism 
SUSAR 
Suspected unexpected serious adverse reaction 
TAS2R 
Type 2 taste receptor, bitter taste receptor 
TID 
Thrice daily 
USP 
United States pharmacopeia 
 


 
 
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Clinical Protocol 
 
 
 
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12. 
REFERENCES 
1. Lee RJ, Kofonow JM, Rosen PL, Siebert AP, Chen B, Doghramji L, et al. Bitter and sweet taste 
receptors regulate human upper respiratory innate immunity. J Clin Invest 2014 124(3):1393-1405. 
2. Klingström J, Akerström S, Hardestam J, Stoltz M, Simon M, Falk KI, et al. Nitric oxide and 
peroxynitrite have different antiviral effects against hantavirus replication and free mature virions. 
Eur J Immunol 2006 36(10):2649-2657. 
3. Pope M, Marsden PA, Cole E, Sloan S, Fung LS, Ning Q, et al. Resistance to murine hepatitis virus 
strain 3 is dependent on production of nitric oxide. J Virol 1998 72(9):7084-7090. 
4. Rosenberg RB, Waagner DC, Romano MJ, Kanase HN, Young RB. Hantavirus pulmonary syndrome 
treated with inhaled nitric oxide. Pediatr Infect Dis J 1998 17(8):749-752. 
5. Akerström S, Mousavi-Jazi M, Klingström J, Leijon M, Lundkvist A, Mirazimi A. Nitric oxide inhibits the 
replication cycle of severe acute respiratory syndrome coronavirus. J Virol 2005 79(3):1966-1969. 
6. Keyaerts E, Li S, Vijgen L, Rysman E, Verbeeck J, Van Ranst M, et al. Antiviral activity of chloroquine 
against human coronavirus OC43 infection in newborn mice. Antimicrob Agents Chemother 2009 
53(8):3416-3421. 
7. Akerström S, Gunalan V, Keng CT, Tan YJ, Mirazimi A. Dual effect of nitric oxide on SARS-CoV 
replication: viral RNA production and palmitoylation of the S protein are affected. Virology 2009 
395(1):1-9. 
8. Iwata S, Yoshida R, Ninomiya Y. Taste transductions in taste receptor cells: basic tastes and 
moreover. Curr Pharm Des 2014; 20(16):2684-2692. 
9. Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, et al. Coding of sweet, bitter, and 
umami tastes: different receptor cells sharing similar signaling pathways. Cell 2003 112(3):293-301. 
10. Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, et al. The molecular receptive 
ranges of human TAS2R bitter taste receptors. Chem Senses 2010; 35(2):157-170. 
11. Lee RJ, Cohen NA. Taste receptors in innate immunity. Cell Mol Life Sci 2015; 72(2):217-236. 
12. Lee RJ, Cohen NA. Role of the bitter taste receptor T2R38 in upper respiratory infection and chronic 
rhinosinusitis. Curr Opin Allergy Clin Immunol 2015; 15(1):14-20. 
13. Clark AA, Liggett SB, Munger SD. Extraoral bitter taste receptors as mediators of off-target drug 
effects. FASEB J 2012 26(12):4827-4831. 
14. Depoortere I. Taste receptors of the gut: emerging roles in health and disease. Gut 2014 63(1):179-
190. 
15. Laffitte A, Neiers F, Briand L. Functional roles of the sweet taste receptor in oral and extraoral 
tissues. Curr Opin Clin Nutr Metab Care 2014 17(4):379-385. 
16. Lee RJ, Xiong G, Kofonow JM, Chen B, Lysenko A, Jiang P, et al. T2R38 taste receptor polymorphisms 
underlie susceptibility to upper respiratory infection. J Clin Invest 2012; 122(11):4145-4159. 
17. Lee RJ, Cohen NA. The emerging role of the bitter taste receptor T2R38 in upper respiratory 
infection and chronic rhinosinusitis. Am J Rhinol Allergy 2013; 27:283-286. 
18. Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ. Motile cilia of human airway epithelia are 
chemosensory. Science 2009 325(5944):1131-1134. 
19. Tizzano M, Cristofoletti M, Sbarbati A, Finger TE. Expression of taste receptors in solitary 
chemosensory cells of rodent airways. BMC Pulm Med 2011 11:3. 
20. Carey RM, Workman AD, Hatten KM, Siebert AP, Brooks SG, Chen B, et al. Denatonium-induced 
sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes. Int Forum Allergy Rhinol 
2017; 7(7):699-704. 


 
 
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Clinical Protocol 
 
 
 
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21. Yan CH, Hahn S, McMahon D, Bonislawski D, Kennedy DW, Adappa ND, et al. Nitric oxide production 
is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity. Am J Rhinol 
Allergy 2017; 31(2):85-92. 
22. Knaapila A, Hwang LD, Lysenko A, Duke FF, Fesi B, Khoshnevisan A, et al. Genetic analysis of 
chemosensory traits in human twins. Chem Senses 2012; 37(9):869-881. 
23. Reed DR, Zhu G, Breslin PA, Duke FF, Henders AK, Campbell MJ, et al. The perception of quinine 
taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 
12. Hum Mol Genet 2010; 19(21):4278-4285. 
24. Fischer ME, Cruickshanks KJ, Pankow JS, Pankratz N, Schubert CR, Huang GH, et al. The associations 
between 6-n-propylthiouracil (PROP) intensity and taste intensities differ by TAS2R38 haplotype. J 
Nutrigenet Nutrigenomics 2014; 7(3):143-152. 
25. Adappa ND, Farquhar D, Palmer JN, Kennedy DW, Doghramji L, Morris SA, et al. TAS2R38 genotype 
predicts surgical outcome in nonpolypoid chronic rhinosinusitis. Int Forum Allergy Rhinol 2016; 6(1):25-
33. 
26. Adappa ND, Truesdale CM, Workman AD, Doghramji L, Mansfield C, Kennedy DW, et al. Correlation 
of T2R38 taste phenotype and in vitro biofilm formation from nonpolypoid chronic rhinosinusitis 
patients. Int Forum Allergy Rhinol 2016 6(8):783-791. 
27. Adappa ND, Zhang Z, Palmer JN, Kennedy DW, Doghramji L, Lysenko A, et al. The bitter taste 
receptor T2R38 is an independent risk factor for chronic rhinosinusitis requiring sinus surgery. Int 
Forum Allergy Rhinol 2014; 4(1):3-7. 
28. Workman AD, Brooks SG, Kohanski MA, Blasetti MT, Cowart BJ, Mansfield C, et al. Bitter and sweet 
taste tests are reflective of disease status in chronic rhinosinusitis. J Allergy Clin Immunol Pract 2017; 
pii: S2213-2198(17)30739-0. doi: 10.1016/j.jaip.2017.09.014. [Epub ahead of print]  
29. Lee RJ, Chen B, Redding KM, Margolskee RF, Cohen NA. Mouse nasal epithelial innate immune 
responses to Pseudomonas aeruginosa quorum-sensing molecules require taste signaling 
components. Innate Immun 2014; 20(6):606-617. 
30. Lee RJ, Cohen NA. Bitter and sweet taste receptors in the respiratory epithelium in health and 
disease. J Mol Med (Berl) 2014; 92(12):1235-1244. 
31. Workman AD, Maina IW, Brooks SG, Kohanski MA, Cowart BJ, Mansfield C, et al. The role of quinine-
responsive taste receptor family 2 in airway immune defense and chronic rhinosinusitis. Front 
Immunol 2018 9:624. doi: 10.3389/fimmu.2018.00624. 
32. Upadhyaya JD, Chakraborty R, Shaik FA, Jaggupilli A, Bhullar RP, Chelikani P. The 
pharmacochaperone activity of quinine on bitter taste receptors. PLoS One 2016; 11(5):e0156347. doi: 
10.1371/journal.pone.0156347. 
33. Hariri BM, McMahon DB, Chen B, Freund JR, Mansfield CJ, Doghramji LJ, et al. Flavones modulate 
respiratory epithelial innate immunity: Anti-inflammatory effects and activation of the T2R14 
receptor. J Biol Chem 2017; 292(20):8484-8497. 
34. Sharma P, Yi R, Nayak AP, Wang N, Tang F, Knight MJ, et al. Bitter taste receptor agonists mitigate 
features of allergic asthma in mice. Sci Rep 2017 7:46166. 
35. Pan S, Sharma P, Shah SD, Deshpande DA. Bitter taste receptor agonists alter mitochondrial 
function and induce autophagy in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2017 
313(1):L154-L165. 
36. Ledda M, Kutalik Z, Souza Destito MC, Souza MM, Cirillo CA, Zamboni A, et al. GWAS of human bitter 
taste perception identifies new loci and reveals additional complexity of bitter taste genetics. Hum 
Mol Genet 2014; 23(1):259-267. 


 
 
T2R-002 
GeneOne Life Science, Inc. 
 
Clinical Protocol 
 
 
 
-40- 
 
 
37. Desrosiers MY, Salas-Prato M. Treatment of chronic rhinosinusitis refractory to other treatments 
with topical antibiotic therapy delivered by means of a large-particle nebulizer: Results of a controlled 
trial. Otolaryngol Head Neck Surg 2001; 125:265-269. 
38. Bishop C, Hudson VM, Hilton SC, Wilde C. A pilot study of the effect of inhaled buffered reduced 
glutathione on the clinical status of patients with cystic fibrosis. Chest 2005; 127(1):308-317. 
39. Dentice RL, Elkins MR, Middleton PG, Bishop JR, Wark PA, Dorahy DJ, et al. A randomised trial of 
hypertonic saline during hospitalisation for exacerbation of cystic fibrosis. Thorax 2016; 71(12):141-
147. 
40. Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance and 
lung function in cystic fibrosis with hypertonic saline N Engl J Med 2006; 354:241-250. 
41. Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, et al. A controlled trial of long-
term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med 2006; 354(3):229-240. 
42. Ramsey BW, Dorkin HL, Eisenberg JD, Gibson RL, Harwood IR, Kravitz RM, et al. Efficacy of 
aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med 1993 328(24):1740-1746. 
43. Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, Williams-Warren J, et al. Intermittent 
administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999; 340(1):23-30. 
44. Durant JJ. On the nasal administration of sulphate of quinine. Indian Medical Gazette 1869; 1 
February:42. 
45. El-Tawil S, Al Musa T, Valli H, Lunn MP, Brassington R, El-Tawil T, et al. Quinine for muscle cramps. 
Cochrane Database Syst Rev 2015; 5(4):CD005044. 
46. Man-Son-Hing M, Wells G, Lau A. Quinine for nocturnal leg cramps: a meta-analysis including 
unpublished data. J Gen Intern Med 1998; 13(9):600-606. 
47. Kyker GC, Cornatzer WE, McEwen MM. The ultraviolet irradiation of quinine. J Biol Chem 1946; 
162:353-361. 
 
 

SAP_001.pdf: 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
 
Study Title: 
Efficacy, Safety, and Tolerability of GLS-1200 Topical 
Nasal Spray in the Prevention of Incident Confirmed SARS-
CoV-2 Infection 
Name of Test Drug: 
GLS-1200 
 
Study Number: 
 
T2R-002 
 
 
Protocol Version: 
7.0 
 
 
Protocol Date: 
26 February 2021 
 
 
Analysis Plan Version: 
2.0 
 
 
Analysis Plan Date: 
21 January 2022 
 
 
Analysis Plan Author: 
Catalyst Clinical Research, LLC 
 
 
 
CONFIDENTIAL AND PROPRIETARY INFORMATION 
 


 
CONFIDENTIAL 
Page 2 
21JAN2022 
SIGNATURE PAGE 
 
 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
Dr. Joel Maslow 
Chief Medical Officer 
GeneOne Life Science Inc. 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
Susan E. Spruill, MS, PStat® 
Statisticial Consultant 
Applied Statistics and Consulting 
 
 
 
 
Signature 
 
 
 
 
 
 
 
 
Date 
Ahmed Tariq, MS 
Biostatistician 
Catalyst Clinical Research, LLC 
 
21-Jan-2022
21-Jan-2022
21-Jan-2022


GeneOne Life Science Inc. 
Statistical Analysis Plan 
T2R-002 
                    Version 2.0  
 
 
CONFIDENTIAL 
Page 3 
21JAN2022 
LIST OF ABBREVIATIONS ................................................................................................................................. 5 
1. 
INTRODUCTION ......................................................................................................................................... 6 
2. 
STUDY OBJECTIVES .................................................................................................................................. 6 
2.1. 
Primary Objectives ............................................................................................................................ 6 
2.2. 
Secondary Objective ......................................................................................................................... 6 
2.3. 
Exploratory Objective ....................................................................................................................... 6 
3. 
STUDY DESIGN AND PLAN ...................................................................................................................... 6 
4. 
DETERMINATION OF SAMPLE SIZE ...................................................................................................... 9 
5. 
GENERAL ANALYSIS CONSIDERATIONS ............................................................................................. 9 
6. 
ANALYSIS POPULATIONS ........................................................................................................................ 9 
6.1. 
Intent-to-treat (ITT) Population ........................................................................................................ 9 
6.2. 
Safety Population .............................................................................................................................. 9 
6.3. 
Per-protocol (PP) Population ............................................................................................................ 9 
7. 
STUDY POPULATION ................................................................................................................................ 9 
7.1. 
Subject Disposition ........................................................................................................................... 9 
7.2. 
Protocol Deviations ........................................................................................................................... 9 
7.3. 
Demographics and Baseline Characteristics ................................................................................... 10 
7.4. 
Medical History ............................................................................................................................... 10 
7.5. 
Prior and Concomitant Medications ................................................................................................ 10 
7.6. 
Drug Exposure ................................................................................................................................ 10 
7.7. 
Treatment Compliance .................................................................................................................... 10 
8. 
EFFICACY ANALYSES ............................................................................................................................ 11 
8.1. 
Definition of the Primary Efficacy Endpoint .................................................................................. 11 
8.2. 
Analysis of the Primary Efficacy Endpoint ..................................................................................... 11 
8.3. 
Definition of the Secondary Efficacy Endpoint .............................................................................. 11 
8.4. 
Analysis of the Secondary Efficacy Endpoint ................................................................................. 11 
8.5. 
Definition of the Exploratory Efficacy Endpoint ............................................................................ 12 
8.6. 
Analysis of the Exploratory Efficacy Endpoint ............................................................................... 11 
9. 
SAFETY ANALYSES ................................................................................................................................. 12 
9.1. 
Adverse Events................................................................................................................................ 12 
9.1.1. 
Severity ......................................................................................................................... 12 
9.1.2. 
Relationship ................................................................................................................... 12 
9.1.3. 
Serious Adverse Events ................................................................................................. 13 
9.1.4. 
Treatment-Emergent Adverse Events (TEAEs) ............................................................ 13 
9.1.4.1. 
Definition of Treatment-Emergent ........................................................... 13 
9.1.4.2. 
Incomplete Dates...................................................................................... 14 
9.1.5. 
Summaries of Adverse Events....................................................................................... 14 
9.2. 
Clinical Laboratory Evaluations ...................................................................................................... 14 
9.3. 
Vital Signs ....................................................................................................................................... 14 
9.4. 
ECG Results .................................................................................................................................... 15 
9.5. 
Physical Exam ................................................................................................................................. 15 


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Statistical Analysis Plan 
T2R-002 
                    Version 2.0  
 
 
CONFIDENTIAL 
Page 4 
21JAN2022 
APPENDIX A: PRESENTATION OF DATA AND PROGRAMMING SPECIFICATIONS ........................... 16 
APPENDIX B: TABLE OF CONTENTS FOR STATISTICAL TABLES AND LISTINGS ............................. 19 
APPENDIX C: TABLE LAYOUTS .................................................................................................................... 23 
APPENDIX D:  FIGURE LAYOUTS.................................................................................................................. 47 
APPENDIX E:  LISTING LAYOUTS ................................................................................................................. 50 
 


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Statistical Analysis Plan 
T2R-002 
                    Version 2.0  
 
 
CONFIDENTIAL 
Page 5 
21JAN2022 
LIST OF ABBREVIATIONS 
 
 
AE  
adverse event  
ATC 
Anatomical Therapeutic Chemical 
BMI 
body mass index 
bpm 
beats per minute  
CRF  
case report form  
CSR  
Clinical Study Report 
DBP  
diastolic blood pressure  
ECG  
electrocardiogram  
ET 
early termination 
FDA 
Food and Drug Administration 
GI 
gastrointestinal 
HBsAg  
hepatitis B surface antigen  
HCV  
hepatitis C virus  
ICH  
International Conference on Harmonisation  
IP 
Investigational Product 
ITT 
Intent-to-Treat 
MedDRA Medical Dictionary for Regulatory Activities 
OTC 
over-the-counter 
PT 
preferred term 
SAE  
serious adverse event  
SBP  
systolic blood pressure  
SD  
standard deviation  
SOC  
system organ class 
TFLs 
tables, figures, and listings 
ULN 
upper limit of normal 
WHO 
World Health Organization 


GeneOne Life Science Inc. 
Statistical Analysis Plan 
T2R-002 
                    Version 2.0  
 
 
CONFIDENTIAL 
Page 6 
21JAN2022 
1. 
INTRODUCTION 
This document outlines the statistical methods to be implemented during the analyses of data 
collected within the scope of GeneOne Life Science Inc.’s Protocol T2R-002 [Efficacy, Safety, 
and Tolerability of GLS-1200 Topical Nasal Spray in the Prevention of Incident Confirmed 
SARS-CoV-2 Infection]. The purpose of this plan is to provide specific guidelines from which 
the statistical analyses will proceed. Any deviations from this plan will be documented in the 
clinical study report (CSR). 
The reader is referred to the following complementary documents: 
 Protocol T2R-002, version 7.0, dated 26Feb2021 
 Case Report Form (CRF), version 1.017, dated 04Jun2020 
 Symptom Diary, version 2, dated 16Apr2020 
 Treatment Diary, version 1, dated 28 Mar2020 
 DMP, version 1.0, dated 19Jun2020 
2. 
STUDY OBJECTIVES 
2.1. 
Primary Objectives 
The primary objectives of the study are to evaluate the safety and tolerability of GLS-1200 
topical nasal spray as well as the incidence in the diagnosis of PCR-confirmed SARS-CoV-2 
infection by treatment group. 
2.2. 
Secondary Objective 
The secondary objective is to assess the documentation of symptoms consistent with SARS-
CoV-2 infections relative to treatment group. 
2.3. 
Exploratory Objective 
The exploratory objective of the study is to assess the incidence of seroconversion in serum and 
the relationship of taste receptor genetics to incidence of SARS-CoV-2 infection relative to 
treatment group. 
3. 
STUDY DESIGN AND PLAN 
This is a Phase II, placebo-controlled, double-blind study of GLS-1200 topical nasal spray to 
assess the safety, tolerability, and ability to reduce the incidence of confirmed SARS-CoV-2 
infection. Following recruitment and informed consent, those meeting enrollment criteria will be 
randomized 2:1 (GLS-1200:Placebo). Participants will initiate topical nasal spray applications 
immediately after randomization and will continue for 4 weeks. Participants will self-administer 
drug three times daily. Follow-up will continue through 6 weeks since some cases of SARS-
CoV-2 infection may not be apparent until after the primary treatment period has concluded. The 
primary outcome measurements are safety, tolerability, and reduction in the diagnosis of PCR-
confirmed SARS-CoV-2 infection. Secondary measures will assess the incidence of symptoms 


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Statistical Analysis Plan 
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                    Version 2.0  
 
 
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21JAN2022 
between each visit, by treatment group.  In addition the average number of days subjects 
experience each symptom will be summarized by treatment group. Exploratory measures will 
assess the incidence of seroconversion in serum and the relationship of taste receptor genetics to 
incidence of SARS-CoV-2 infection both relative to treatment group.


GeneOne Life Science Inc.  
Statistical Analysis Plan 
T2R-002 
                    Version 2.0  
 
 
CONFIDENTIAL 
Page 8 
21JAN2022 
Table 1: Schedule of Assessments 
Tests and Observations 
Day 0 
Week 2  
Week 4 
Week 6  
Unscheduled 
Permitted window (days) 
 
±3d 
±3d 
±3d 
N/A 
Clinical Evaluations 
 
 
 
 
 
Obtain Written Informed Consent 
X 
 
 
 
 
Confirm Eligibility Criteria 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Medical History and Concomitant Medications 
X 
X 
X 
X 
 
Physical Exam, height, weight, and Vital Signs1 
X 
X 
X 
X 
X 
Safety Evaluations 
 
 
 
 
 
Record Adverse Events 
 
X 
X 
X 
X 
Provide participant diary 
X 
 
 
 
 
Collect and review participant diary 
 
X2 
X 
X 
 
Perform 12-lead ECG 
X 
 
X 
 
 
Pregnancy test3 
X 
X 
X 
 
 
Blood for Hematology: CBC with differential 
X 
 
X 
 
 
Blood for Chemistry: Sodium, potassium, bicarbonate, 
glucose, BUN, Cr 
X 
 
X 
 
 
Study Related Procedures 
 
 
 
 
 
Dispense study drug & device, provide training 
X 
 
 
 
 
Collect nasopharyngeal swabs for viral PCR 
X 
X 
X 
X 
X 
Collect serum for viral antibodies 
X 
X 
X 
X 
 
Collect plasma for measurement of quinine 
 
X 
 
 
 
Collect saliva for TAS2R genotyping 
X 
 
 
 
 
Estimated Blood Volume per Visit (mL) 
40 
25 
40 
20 
 
1 A targeted physical exam will be performed at Weeks 2, 4 and 6 and at unscheduled visits.  
2 The participant diary will only be reviewed at Weeks 2 and 4; it will be reviewed and collected at Week 6. 
3 A urine pregnancy test will be administered. 


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                   Version 2.0 
 
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4. 
DETERMINATION OF SAMPLE SIZE 
The sample size for this study assumes an infection rate in the placebo group of 10%. A 2:1 
randomization of 225 subjects would have a power of 80.8% to detect a difference of 9% 
between groups at alpha = 0.05 assuming 1% of individuals in the treatment group are confirmed 
to be infected with SARS-CoV-2.  
5. 
GENERAL ANALYSIS CONSIDERATIONS 
The statistical analysis results will be reported using tables, listings, and figures (TLFs). 
Summaries of continuous variables will display means, standard deviations (SDs), medians, 
minimums, maximums and the number of observations. Summaries of categorical variables will 
display frequency counts and percentages. 
All analyses will be performed using SAS Version 9.4 or higher. 
6. 
ANALYSIS POPULATIONS 
6.1. 
Intent-to-treat (ITT) Population 
The ITT Population will include all randomized to treatment allocation. 
6.2. 
Safety Population 
The Safety Population will include all subjects who received at least one dose of study treatment. 
6.3. 
Per-protocol (PP) Population 
The PP Population will include all subjects who complete the trial and who receive ≥ 90% of the 
study treatments through to either diagnosis of SARS-CoV-2 infection (study end point) or to 
end of study (4 weeks), based on subject’s completed doses on the treatment diary form, and who 
have no significant protocol deviations. 
7. 
STUDY POPULATION 
7.1. 
Subject Disposition 
The number and percentage of subjects in each analysis population, who completed the study 
and who discontinued prior to study completion will be presented by treatment (GLS-1200 and 
placebo) and overall. Disposition will also by summarized by site.  Subjects who discontinued 
prior to completing the study will also be summarized by reason for discontinuation.  
Subject disposition will also be listed. 
7.2. 
Protocol Deviations 
Protocol deviations with significance will be listed. 


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                   Version 2.0 
 
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7.3. 
Demographics and Baseline Characteristics 
Demographics, baseline data, vital signs, medical history, prior and concomitant medications and 
treatments will be summarized by means of descriptive statistics: continuous variables as mean, 
median, SD, minimum/maximum ranges and categorical variables as frequencies and 
percentages, stratified by treatment arms and overall, based on the ITT population. These 
summaries will also by provided by site.  Demographic and baseline characteristics will be listed.  
7.4. 
Medical History 
Medical history verbatim terms collected from the CRF will be mapped to system organ classes 
(SOCs) and preferred terms (PTs) using the Medical Dictionary for Regulatory Activities 
(MedDRA) (version 23.0).  
Summaries (number and percentage of subjects) of medical history by SOC and PT will be 
provided by treatment and overall.  
A listing of medical history will be provided. 
7.5. 
Prior and Concomitant Medications 
Medication verbatim names collected from the CRF will be mapped to Anatomical Therapeutic 
Chemical (ATC) Classes and Preferred Names using the World Health Organization's 
WHODrug Global March 2020 version. Preferred Names will consist of only the base 
compounds and not the salts (e.g., Naproxen Sodium will be listed only as Naproxen). 
Concomitant medications will be summarized for each treatment by ATC class and preferred 
name. Prior and concomitant medications will be listed. 
A prior medication is defined as a medication that was administered up to 8 weeks prior to first 
dose of study treatment. All other medications will be considered concomitant.  
7.6. 
Drug Exposure 
Exposure summaries of duration of exposure, total number of doses taken, and total number of 
doses missed, will be provided by treatment. Duration of exposure is defined as the date of last 
dose minus the date of first dose, regardless if any doses were missed in between. 
Dosing data collected from treatment diaries will be listed along with any treatment side effects 
or device issues, and the number of known or suspected exposures to SARS-CoV-2. 
7.7. 
Treatment Compliance 
Treatment compliance is defined as the total number of administered doses, as recorded in the 
treatment diary, divided by the total number of planned doses. Each recorded dose will be 
considered to be a complete dose of study drug. Descriptive statistics of treatment compliance as 
well as the proportion of subjects falling into different  treatment compliance categories (<50%, 
50%-80%, and >80%) will be summarized by treatment group.  
 


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Unless differences are observed between sites in the baseline characteristics and demographics 
that would confound interpretation of efficacy and safety results, all efficacy and safety will be 
summarized over both sites.  If there are concerns for confounded results due to site differences 
in demographic or baseline characteristics, then all efficacy and safety results will be subset by 
sites as well as overall.  However, no treatment comparisons within sites will be made since the 
study is not powered to assess treatment effect within sites. 
 
8. 
EFFICACY ANALYSES  
8.1. 
Definition of the Primary Efficacy Endpoint 
The primary efficacy endpoint is the incidence of SARS-CoV-2 infection, confirmed by PCR at 
any time within four weeks of treatment initiation. Participants will be queried as to any new 
diagnosis of SARS-CoV-2 infection, defined as a positive PCR test for SARS-CoV-2. Subjects 
who test negative for SARS-CoV-2 infection at Weeks 2 and 4 will be considered treatment 
successes. Subjects who are lost to follow-up, require rescue therapy, discontinue the study prior 
to completion of Week 4, or test positive for SARS-CoV-2 infection at at any point within four 
weeks of treatment initiation will be considered treatment failures. All deaths will be considered 
as treatment failures. 
8.2. 
Analysis of the Primary Efficacy Endpoint 
The number and percentage of treatment failures as well as treatment successes will be presented 
by treatment and compared using Fisher’s exact test.  Additionally, the number and percentage of 
subjects who test positive as well as those who test negative for SARS-CoV-2 infection will be 
provided by treatment at each visit (Weeks 2, 4 and 6). This summary and analysis will be 
performed for both the ITT and PP populations. 
8.3. 
Definition of the Secondary Efficacy Endpoint 
The secondary efficacy endpoint is the documentation of symptoms consistent with SARS-CoV-
2 infections.  Subjects will be instructed to maintain a symptom diary that includes those 
symptoms considered common for SARS-CoV-2. The diary is inclusive of symptoms identified 
by the World Health Organization for a diagnosis of SARS-CoV-2 as well as more recently 
identified symptoms such as conjunctivitis, diarrhea, and loss of taste or smell. Each symptom 
will be scored as present (score of 1) or absent (score of 0) and will be recorded in the symptom 
diary on a daily basis.   
8.4. 
Analysis of the Secondary Efficacy Endpoint 
The incidence of each symptom will be summarized by treatment group for each two week 
interval.  In addition, the average number of days subjects had each symptom throughout the 
study period (6 weeks) will be summarized by treatment group. Summaries will be presented 
noncumulatively by visit as well as cumulatively over 4 weeks of treatment. The secondary 
analysis will be performed for the ITT population. 


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8.5. 
Definition of the Exploratory Efficacy Endpoint 
The exploratory efficacy endpoint is the incidence of SARS-CoV-2 seroconversion.   
8.6. 
Analysis of the Exploratory Efficacy Endpoint 
The cumulative number and percentage of subjects who seroconvert at each post-baseline visit 
will be presented by treatment for the ITT population. The relationship of taste receptor genetics 
to incidence of SARS-CoV-2 infection relative to treatment group will be examined on an adhoc 
basis and is outside the scope of this document. 
9. 
SAFETY ANALYSES 
All safety analyses will be based on the Safety Population. 
 
9.1. 
Adverse Events 
An adverse event (AE) is defined as any unfavorable and unintended change in the structure, 
function, or chemistry of the body, or worsening of a pre-existing condition, temporally 
associated with the use of a product whether or not considered related to the use of the product. 
In this study, such changes will be monitored, classified, and summarized, as Clinical or 
Laboratory AEs. Medical conditions/diseases present before starting the investigational drug will 
be considered adverse events only if they worsen after starting study treatment. Verbatim terms 
on CRFs will be mapped to preferred terms (PTs) and system organ classes (SOCs) using the 
Medical Dictionary for Regulatory Activities (MedDRA) (version 23.0).  
 
9.1.1. 
Severity 
AEs are graded by the investigator as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), 
Grade 4 (potentially life threatening) or Grade 5 (death) according to the NCI Common 
Terminology Criteria for Adverse Events version 5.0. 
9.1.2. 
Relationship  
Based on the criteria described below, AEs will be classified according to one of the following 
categories:  
•     Related – the investigator considers that there is a causal relationship between the event 
and study drug  
•     Probably related – the investigator considers that there is a probability of a causal 
relationship of the event to the study drug  
•     Possibly related – the investigator considers that there is a possible causal relationship of 
the event to the study drug 
•     Unlikely related – the investigator considers that there is an unlikely causal relationship 
of the event to the study drug 
•     Not related – the investigator considers that the event has no relationship to 
administration of the study drug  
 


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For the purpose of analysis, related AEs are those reported as “Related,” “Probably related,” 
“Possibly related” and unrelated AEs are those reported as "Unlikely related" or “Not related.” 
Events for which the investigator did not record relationship will be considered related for 
analysis. Data listings will show relationship as missing. 
9.1.3. 
Serious Adverse Events 
An SAE is any adverse drug experience occurring at any dose that results in any of the following 
outcomes:  
 
• 
Death during the period of surveillance defined by the protocol; 
• 
Is immediately life-threatening (e.g., participant was, in the view of the Investigator, at 
immediate risk of death from the event as it occurred). This does not include an AE that, 
had it occurred in a more serious form, might have caused death; 
• 
An event requiring inpatient hospitalization or prolongation of existing hospitalization 
during the period of protocol defined surveillance (including any overnight stay in the 
hospital, regardless of the length of stay, even if the hospitalization is only a 
precautionary measure to allow continued observation. However, hospitalization 
(including hospitalization for an elective procedure) for continued treatment or 
assessment of a pre-existing condition that has not worsened, does not constitute an SAE. 
NOTE: Evaluation in a physician’s office, or at a hospital or other urgent care setting in 
an observational, non-admitted status regardless of the time period of observation, does 
not constitute an SAE; 
• 
Results in congenital anomaly or birth defect; 
• 
Results in persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions; 
• 
Is an important medical event that may not result in death, be life threatening, or require 
hospitalization, but based upon appropriate medical judgment, may jeopardize the 
participant and may require medical or surgical intervention to prevent one of the 
outcomes listed above. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization; 
• 
Is medically significant or requires intervention to prevent one or other of the outcomes 
listed above. 
 
9.1.4. 
Treatment-Emergent Adverse Events (TEAEs) 
9.1.4.1. Definition of Treatment-Emergent 
TEAEs are events that either: 
a)  began on or after the date and time of first dose or 


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b) had no recorded start date and the stop date is not before the date and time of first dose. 
 
9.1.4.2. Incomplete Dates 
If the date of onset is incomplete, then the month and year (or year alone if month is not 
recorded) of onset determine treatment emergence as follows. The event is treatment emergent if 
the month and year of onset (or year of onset) of the event is the same as or after the month and 
year (or year) of date of first dose. 
9.1.5. 
Summaries of Adverse Events 
An overall summary of AEs will display, by treatment, the number and percentage (with 95% 
exact binomial confidence interval) of subjects who had any TEAE, whose strongest TEAE 
relationship to study drug is related or not related, whose maximum TEAE severity is mild, 
moderate, or severe, who had any SAE, any Serious TEAE, any TEAE leading to study 
discontinuation, and any TEAE leading to death.  
The following summaries (number and percentage of subjects) of AEs (by SOC and PT) will be 
provided by treatment: 
• 
All TEAEs 
• 
All TEAEs by strongest relationship 
• 
All TEAEs by maximum severity grade 
• 
All Serious AEs 
• 
All Serious TEAEs 
• 
All TEAEs leading to study discontinuation 
• 
All TEAEs leading to death 
 
These summaries will present the number and percentage of subjects with at least one qualifying 
AE. Subjects may have more than one AE per SOC and PT. Each summary will be ordered by 
descending order of incidence of SOC and PT within each SOC.  
In addition to the by-treatment summaries, data listings will be provided for the following: 
• 
All AEs (with a flag indicating whether the event is treatment emergent) 
• 
SAEs 
• 
AEs leading to study discontinuation 
• 
Deaths 
9.2. 
Clinical Laboratory Evaluations 
Shift  from baseline in laboratory parameter results (indicated as Low, Normal, or High) will be 
summarized for each post-baseline visit. Mean (+/- SD) laboratory parameter values will be 
graphically presented over time by treatment. All laboratory parameters will be listed and include 
indicators for low/high and clinical significance as determined by the investigator. 
 


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9.3. 
Vital Signs  
Vital signs (temperature, heart rate, systolic blood pressure (SBP), diastolic blood pressure 
(DBP)) will be summarized using descriptive statistics (sample size, mean, SD, median, 
minimum, and maximum) at baseline and at each post-baseline time point by treatment. Change 
from baseline will also be summarized at each post-baseline time point. Mean (+/- SD) Vital 
Sign values will be graphically presented over time by treatment. All vital signs results will be 
listed. 
9.4. 
ECG Results 
Shift from baseline in 12-Lead ECG overall interpretion (results are Normal, Abnormal Not 
Clinically Significant (NCS), or Abnormal Clinically Significant (CS)) will be summarized at 
each post-baseline visit by treatment. Mean (+/- SD) continuous ECG parameter values will be 
graphically presented over time by treatment. 
 
Additionally, the number and percentage of subjects will be summarized for the following QTcF 
Interval result categories at baseline and each post-baseline visit by treatment: 
 
 <=450 msec (males) or <=470 msec (females) 
 >450 msec (males) or >470 msec (females) 
 Change from baseline <=60 msec (only applies to Week 4) 
 Change from baseline >60 msec (only applies to Week 4) 
 
A listing of ECG results will present the interpretations of abnormalities and whether these are 
considered clinically significant by the investigator.  
 
9.5. 
Physical Exam 
Physical exam findings will be listed.


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APPENDIX A: PRESENTATION OF DATA AND PROGRAMMING SPECIFICATIONS 
 
Tables 
• 
Formal organization of tabulations may be changed during programming if appropriate, 
e.g., tables for the different variables may be combined into a single table, or tables with 
more than one variable may be split into several tables. 
• 
Means, medians, and quartiles will be presented to one more decimal place than the raw 
data. SDs will be presented to two more decimal places than the raw data. Minimums and 
maximums will be reported with the same number of decimal places as the raw data.  
• 
Percentages will be presented to the tenths place. 
• 
For frequency counts of categorical variables, categories whose counts are zero will be 
displayed for the sake of completeness. For example, if none of the subjects discontinue 
due to “lost to follow-up,” this reason will be included in the table with a count of 0. 
Categories with zero counts will not have zero percentages displayed. 
• 
The last footnote will be “Reference: xxx”, where xxx indicates the source listing 
number(s).   
 
Listings 
• 
Formal organization of the listing may be changed during programming if appropriate, 
e.g., additional variables may be included, change in the column order, or the listing may 
be split into multiple parts due to space constraints, etc. 
• 
If not otherwise specified, all data listings will be sorted by treatment, subject number, 
visit, and date/time as appropriate.   
• 
All date values will be presented in a ISO 8601 date (e.g., 2001-08-29) format.  
• 
All observed time values will be presented using a 24-hour clock HH:MM:SS format 
(e.g., 01:35:45 or 11:26). Seconds will only be reported if they were measured as part of 
the study. 
 
Missing or incomplete dates, i.e., AEs and concomitant medications 
The most conservative approach will be systematically considered. If the AE onset date is 
missing or incomplete, it is assumed to have occurred during the study treatment phase (i.e., 
considered a TEAE) except if the partial onset date or other data such as the stop date, indicates 
differently. Similarly, a medication with partial start and stop dates could be considered as a 
concomitant treatment. 
 
The following algorithms will be applied to missing and incomplete start and stop dates: 
 
Start Dates 
• 
If the day portion of the start date is missing, then the start date will be estimated to be 
equal to the date of IP administration, provided the start month and year are the same as 
IP administration and the stop date is either after IP administration or completely missing. 
Otherwise, the missing day portion will be estimated as ‘01’. 
• 
If both the day and month portions of the start date are missing, then the start date will be 
estimated to be equal to the date of IP administration, provided the start year is the same 
as IP administration and the stop date is either after IP administration or completely 


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missing. Otherwise, the event will be assumed to start on the first day of the given year, 
e.g., 2013-??-?? is estimated as 2013-01-01. 
• 
If the start date is completely missing and the stop date is either after IP administration or 
completely missing, the start date will be estimated to be the day of IP administration. 
Otherwise, the start date will be estimated to be the first day of the same year as the stop 
date. All other non-AE and non-concomitant medication day calculations where only 
partial dates are available will be handled as follows: the first day of the month will be 
used in the calculations if the day part of a start date is missing while January 1 will be 
employed if both the month and day parts of a start date are missing. 
 
• 
For treatment start dates, if patients are randomized and have non-missing visit data for 
Week 4 as well as non-missing treatment diary data, then start date is set to earliest 
treatment diary date. If patient’s treatment diary data is missing or Week 4 visit is 
missing, then treatment start date is set to earliest recorded exposure date. Drug 
dispensation date is used as treatment start date if no other data is available. 
 
Stop Dates 
• 
If only the day of resolution is unknown, the day will be assumed to be the last of the 
month, e.g., 2013-01-?? will be treated as 2013-01-31.  
• 
If both the day and month of resolution are unknown, the event will be assumed to have 
ceased on the last day of the year, e.g., 2013-??-?? will be treated as 2013-12-31.  
• 
If the stop date is completely missing or the event is continuing, the event will be 
assumed to be after IP administration and will be left as missing. 
 
• 
For treatment stop dates, if patient has non-missing treatment diary data but has data gaps 
of more than 3 days, then treatment stop date is set to start date + 28 days. If treatment 
diary data is non-missing and there are no data gaps of 3 days or more then treatment stop 
date is set to last treatment diary date. If treatment diary data is missing but patient is 
recorded to have completed study, then treatment stop date is set to start date + 28 days. 
Finally, if treatment diary data is missing and patient has not completed the study, then 
treatment stop date is set to study withdrawal date. 
 
Standard Calculations 
Variables requiring calculation will be derived using the following formulas: 
 
• 
Study Day – The day in relation to the first dose date (Day 0), calculated as date – first 
dose date. 
• 
Days – A duration expressed in days between two dates (start date and end date)  is 
calculated using the formulas noted below: 
• 
duration in days = end date  – start date + 1, where end date ≥ start date 
• 
duration in days = end date  – start date, where end date < start date 


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• 
Months – A duration expressed in months is calculated as the number days divided by 
365.25/12 (~30.4).  
• 
Years – A duration expressed in years between one date (date1) and another later date 
(date2) is calculated using the formula: duration in years = (date2-date1+1)/365.25  
• 
Height – Height entries made in inches (in) are converted to centimeters (cm) using the 
following formula: height (cm) = height (in) × 2.54 
• 
Weight – Weight entries made in pounds (lb.) are converted to kilograms (kg) using the 
following formula: weight (kg) = weight (lb.) / 2.2046 
• 
Temperature – Temperature entries in degrees Fahrenheit are converted to degrees 
centigrade using the following formula: temp (degrees centigrade) = 5/9 × [temp (degrees 
Fahrenheit) - 32] 
• 
Change from baseline – Change from baseline will be calculated as: Change = post 
baseline value – baseline value 
• 
Percent change from baseline – Change from baseline will be calculated as: percent 
change from baseline = [(post baseline value – baseline value) / baseline value] 
× 100 


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APPENDIX B: TABLE OF CONTENTS FOR STATISTICAL TABLES AND LISTINGS 
 
The following TL numbering is completed according to ICH guidelines.  The ICH heading 
number and description are in bold. Minor changes from this planned index do not need to be 
amended in the SAP. Formal organization of tabulations may be changed during programming if 
appropriate, e.g., tables for the different variables may be combined into a single table, or tables 
with more than one variable may be split into several tables. 
 
List of Tables 
 
ICH 
Heading 
Table 
Number 
 
Table Description 
14.1 
 
DEMOGRAPHIC/BASELINE DATA 
 
14.1.1.1 
Subject Disposition (All Subjects) 
 
14.1.1.2 
Reason For Screen Failure (All Screen Failure Subjects) 
 
14.1.2 
Demographic and Baseline Characteristics (Safety Population) 
 
14.1.3 
Medical History (Safety Population) 
 
14.1.4 
Concomitant Medications (Safety Population) 
 
14.1.5 
Exposure and Treatment Compliance (Safety Population) 
14.2 
 
EFFICACY DATA 
 
14.2.1.1 
Incidence of SARS-CoV-2 Infection by Visit (ITT Population) 
 
14.2.1.2 
Incidence of SARS-CoV-2 Infection by Visit (PP Population) 
 
14.2.2 
Incidence of Individual Symptoms and Average Number of Days 
with Symptoms by Visit Interval (ITT Population) 
 
14.2.3 
Cumulative Incidence of SARS-CoV-2 Seroconversion by Visit 
(ITT Population) 
14.3 
 
SAFETY DATA 
14.3.1 
 
Displays of Adverse Events 
 
14.3.1.1 
Overall Summary of Adverse Events (Safety Population) 
 
14.3.1.2 
Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term (Safety Population) 
 
14.3.1.3 
Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term, and Strongest Relationship to Study Drug (Safety 
Population) 
 
14.3.1.4 
Treatment-Emergent Adverse Events by System Organ Class, 
Preferred Term, and Maximum Severity Grade (Safety Population) 
 
14.3.1.5 
Related Treatment-Emergent Adverse Events by System Organ 
Class, Preferred Term, and Maximum Severity Grade (Safety 
Population) 
14.3.2 
 
Serious and Significant Adverse Events 
 
14.3.2.1 
Serious Adverse Events by System Organ Class and Preferred 
Term (Safety Population) 
 
14.3.2.2 
Serious Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term (Safety Population) 


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ICH 
Heading 
Table 
Number 
 
Table Description 
 
14.3.2.3 
Treatment-Emergent Adverse Events Leading to Study 
Discontinuation by System Organ Class and Preferred Term 
(Safety Population) 
 
14.3.2.4 
Treatment-Emergent Adverse Events Leading to Death by System 
Organ Class and Preferred Term (Safety Population) 
14.3.4 
 
Laboratory 
 
14.3.4.1 
Shift from Baseline in Hematology Results by Test and Visit 
(Safety Population) 
 
14.3.4.2 
Shift from Baseline in Chemistry Results by Test and Visit (Safety 
Population) 
 
14.3.4.3 
Observed and Change from Baseline in Vital Sign Results by Test 
and Visit (Safety Population) 
 
14.3.4.4.1 
Shift from Baseline in 12-Lead ECG Overall Interpretation by Visit 
(Safety Population) 
 
14.3.4.4.2 
Summary of QTcF Interval (msec) by Visit and Result Category 
(Safety Population) 
 
 
 


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List of Figures 
 
ICH 
Heading 
Figure 
Number 
 
Figure Description 
14.3.4 
 
Laboratory 
 
14.3.4.1 
Line Plots of Mean (+/- SD) Hematology Results vs. Time by Test 
(Safety Population) 
 
14.3.4.2 
Line Plots of Mean (+/- SD) Chemistry Results vs. Time by Test 
(Safety Population) 
 
14.3.4.3 
Line Plots of Mean (+/- SD) Vital Sign Results vs. Time by Test 
(Safety Population) 
 
14.3.4.4 
Line Plots of Mean (+/- SD) 12-Lead ECG Results vs. Time by 
Test (Safety Population) 


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List of Data Listings 
ICH Heading 
Listing 
Number 
 
Listing Description 
16.2 
 
SUBJECT DATA LISTINGS 
16.2.1 
 
Discontinued Subjects 
 
16.2.1 
Subject Disposition 
16.2.2 
 
Protocol Deviations 
 
16.2.2 
Protocol Deviations  
16.2.3 
 
Subjects Excluded from the Safety Analysis 
 
16.2.3 
Inclusion/Exclusion Criteria 
16.2.4 
 
Demographic and Baseline Data 
 
16.2.4.1 
Demographic and Baseline Characteristics 
 
16.2.4.2 
Medical History 
 
16.2.4.3 
Prior and Concomitant Medications 
16.2.5 
 
Compliance and/or Drug Concentration Data  
 
16.2.5.1 
Exposure and Treatment Compliance 
 
16.2.5.2 
Treatment Diary 
 
16.2.5.3 
Plasma Collection for Measurement of Quinine 
16.2.6 
 
Individual Efficacy Response Data  
 
16.2.6.1 
PCR Results 
 
16.2.6.2 
Symptom Scores 
 
16.2.6.3 
Seroconversion 
16.2.7 
 
Adverse Events listings 
 
16.2.7.1 
Adverse Events 
 
16.2.7.2 
Serious Adverse Events 
 
16.2.7.3 
Adverse Events Leading to Study Discontinuation 
 
16.2.7.4 
Deaths 
16.2.8 
 
Laboratory and Other Data 
 
16.2.8.1 
Hematology 
 
16.2.8.2 
Chemistry 
 
16.2.8.3 
Vital Signs 
 
16.2.8.4 
12-Lead Electrocardiogram 
 
16.2.8.5 
Physical Examination 
 
16.2.8.6 
Pregnancy Test 


 
 
APPENDIX C: TABLE LAYOUTS 
 


 
 
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Table 14.1.1.1 
Subject Disposition 
(All Subjects) 
 
Study Site 
   Subject Status 
 
GLS-1200 
Placebo 
 
Overall 
Overall 
 
 
 
 
 
Screened  
 
 
 
 
xx 
Screen Failures  
xx 
ITT Population [1] 
 
xx 
xx 
 
xx 
Safety Population [2] 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
PP Population [3] 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
 
 
 
 
 
Completed the study [4] 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Discontinued the study 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Reason for discontinuation 
 
 
 
 
 
<Reason #1> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
<Reason #2> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
<Reason #3> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Site 101 
. 
. 
. 
Site 108 
. 
. 
. 
 
 
 
 
 
Percentages are based on the ITT Population.  
[1] The Intent-to-treat (ITT) Population includes all randomized to treatment allocation. 
[2] The Safety Population includes all subjects who received at least one dose of study treatment. 
[3] The Per-protocol (PP) Population includes all subjects who completed the trial, received >=90% of the study treatments, and have no significant protocol deviations. Trial completion is defined as either completing 
Week 4 or meeting the study endpoint of PCR confirmed SARS-CoV-2 infection. 
[4] Study completion is defined as completing all visits regardless of drug compliance. 
Reference: Listing 16.2.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming note: Sort discontinuation reasons by descending overall frequency. List all reasons per CRF page. 
 
 


 
 
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Table 14.1.1.2 
Reason for Screen Failure 
(All Screen Failure Subjects) 
Study Site    Reason 
 
 
Overall 
(xx) 
Overall 
 
 
 
<Reason #1>   
 
 
x (xx.x%) 
<Reason #2>   
 
 
x (xx.x%) 
<Reason #3>   
 
 
x (xx.x%) 
 
 
 
Site 101 
 
 
 
 
 
 
<Reason #1>   
 
 
x (xx.x%) 
<Reason #2>   
 
 
x (xx.x%) 
<Reason #3>   
 
 
x (xx.x%) 
 
 
 
Site 108 
 
 
 
 
 
 
<Reason #1>   
 
 
x (xx.x%) 
<Reason #2>   
 
 
x (xx.x%) 
<Reason #3>   
 
 
x (xx.x%) 
 
 
 
Reference: Listing 16.2.3 and Listing 16.2.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming note: Sort screen failure reasons by descending overall frequency. List all reasons per CRF page. 
 


 
 
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Table 14.1.2 
Demographic and Baseline Characteristics 
(Safety Population) 
 
 
Study Site 
    Characteristic 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
Overall 
(N=XX) 
 
 
 
 
Overall 
 
 
 
 
 
 
 
 
Age (years) 
 
 
 
 
n 
xx 
xx 
 
xx 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
xx.x (xx.xx) 
Median 
xx.x 
xx.x 
 
xx.x 
Min, Max 
xx, xx 
xx, xx 
 
xx, xx 
 
 
 
 
 
<65 years 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
>=65 years 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
 
 
 
 
Sex 
 
 
 
 
Male 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Female 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
 
 
 
 
Race 
 
 
 
 
American Indian or Alaskan Native 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Asian  
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Black or African American 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Native Hawaiian or Other Pacific Islander 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
White 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Other 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
 
 
 
 
 
Ethnicity 
 
 
 
 
Hispanic or Latino 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
Not Hispanic or Latino 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
 
 
 
 
Baseline is the last non-missing value prior to first dose of study treatment. 
Reference: Listing 16.2.4.1 and Listing 16.2.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
 


 
 
GeneOne Life Science Inc. 
Page 2 of 2 
Protocol: T2R-002 
 
 
Table 14.1.2 
Demographic and Baseline Characteristics 
(Safety Population) 
 
Characteristic 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
Overall 
(N=XX) 
 
 
 
 
Height (cm) 
 
 
 
 
n 
xx 
xx 
 
xx 
Mean (SD) 
xx.x (x.xx) 
xx.x (x.xx) 
 
xx.x (x.xx) 
Median 
xx.x 
xx.x 
 
xx.x 
Min, Max 
xx, xx 
xx, xx 
 
xx, xx 
 
 
 
 
Weight (kg) 
 
 
 
 
n 
xx 
xx 
 
xx 
Mean (SD) 
xx.x (x.xx) 
xx.x (x.xx) 
 
xx.x (x.xx) 
Median 
xx.x 
xx.x 
 
xx.x 
Min, Max 
xx, xx 
xx, xx 
 
xx, xx 
 
 
 
 
BMI (kg/m^2) 
 
 
 
 
n 
xx 
xx 
 
xx 
Mean (SD) 
xx.x (x.xx) 
xx.x (x.xx) 
 
xx.x (x.xx) 
Median 
xx.x 
xx.x 
 
xx.x 
Min, Max 
xx, xx 
xx, xx 
 
xx, xx 
Site 101 
. 
. 
. 
Site 108 
. 
. 
. 
 
 
 
 
 
 
 
 
Baseline is the last non-missing value prior to first dose of study treatment. 
Reference: Listing 16.2.4.1 and Listing 16.2.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.1.3 
Medical History 
(Safety Population) 
 
Study Site 
System Organ Class  
   Preferred Term 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
Overall 
(N=XX) 
Overall 
 
 
 
 
 
Subjects with at least one medical history  
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #1> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #2> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
 . 
 
 
 
 
 
 . 
Site 101 
. 
. 
. 
Site 108 
. 
. 
. 
 
 
 
 
 
 
 
 
 
 
MedDRA = Medical Dictionary for Regulatory Activities; SOC = System Organ Class; PT = Preferred Term. 
Medical history terms are coded using MedDRA version 23.0 and ordered by descending order of overall incidence of SOC and overall incidence of PT within each SOC. At each level of summation (overall, SOC, PT), subjects 
reporting more than one medical history term are counted only once. 
Reference: Listing 16.2.4.2 and Listing 16.2.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.1.4 
Concomitant Medications 
(Safety Population) 
 
Study Site 
ATC Class 
 Preferred Name 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
Overall 
 
 
 
 
Subjects who received any concomitant  
medications 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
<ATC Class # 1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Name #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Name #2> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Name #3> 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
<ATC Class # 2> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Name #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Name #2> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Name #3> 
 
x (xx.x%) 
x (xx.x%) 
 
 . 
 
 
 
 
 . 
 
 
 
 
Site 101 
. 
. 
. 
Site 108 
. 
. 
. 
 
 
 
 
A concomitant medication is any medication that was ongoing or started on or after the date of first dose. 
Medications are coded using WHODrug Global (March 2020) and ordered by descending order of overall incidence of ATC class and overall incidence of preferred name within each class. At each level of summation 
(overall, ATC class, preferred name), subjects reporting more than one medication are counted only once. 
Reference: Listing 16.2.4.3 and Listing 16.2.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Sort table by descending overall count of ATC class and descending overall count of preferred name within each class. 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of 2 
Protocol: T2R-002 
 
Table 14.1.5 
Exposure and Treatment Compliance 
(Safety Population) 
 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
Overall 
 
 
 
Duration of exposure (days) [1] 
 
 
 
n 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
Total number of doses taken 
 
 
 
n 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
Total number of doses missed 
 
 
 
n 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
Treatment compliance [2] 
 
 
 
n 
xx 
xx 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
 
 
 
 
 
<50% 
x (xx.x%) 
x (xx.x%) 
 
50%-80% 
x (xx.x%) 
x (xx.x%) 
 
>80% 
x (xx.x%) 
x (xx.x%) 
 
Site 101 
. 
. 
Site 108 
. 
. 
 
 
 
[1] Duration of exposure is defined as the date of last dose minus the date of first dose + 1. 
[2] Treatment compliance is defined as the total number of doses taken divided by the total number of planned doses times 100. 
Reference: Listing 16.2.5.1 and Listing 16.2.1 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
Table 14.2.1.1 
Incidence of SARS-CoV-2 Infection by Visit 
(ITT Population) 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
p-value [1] 
 
 
 
Treatment Success [2] 
x (xx.x%) 
x (xx.x%) 
x.xxx 
Treatment Failure [3] 
x (xx.x%) 
x (xx.x%) 
 
Lost to follow-up   
x (xx.x%) 
x (xx.x%) 
 
Required recue therapy  
x (xx.x%) 
x (xx.x%) 
 
Discontinued study prior to completion of Week 4  
x (xx.x%) 
x (xx.x%) 
 
Tested positive for SARS-CoV-2 infection at any time up to Week 4  
x (xx.x%) 
x (xx.x%) 
 
Had missing PCR result at any visit up to Week 4  
x (xx.x%) 
x (xx.x%) 
 
Died  
x (xx.x%) 
x (xx.x%) 
 
 
 
 
Week 0 PCR Result  
 
 
 
n 
x 
x 
 
Negative   
x (xx.x%) 
x (xx.x%) 
 
Positive 
x (xx.x%) 
x (xx.x%) 
 
 Missing   
x (xx.x%) 
x (xx.x%) 
 
 
 
 
Week 2 PCR Result  
 
 
 
n 
x 
x 
 
Negative   
x (xx.x%) 
x (xx.x%) 
 
Positive 
x (xx.x%) 
x (xx.x%) 
 
 Missing 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
... 
 
 
 
 
 
 
[1] The p-value is calculated using a Fisher’s exact test.  
[2] Subjects who test negative for SARS-CoV-2 infection at Weeks 2 and 4 are considered treatment successes.  
[3] Subjects who met any of the reasons listed are considered treatment failures. Subjects who fail treatment for multiple reasons are counted once for each reason. 
Reference: Listing 16.2.6.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming note: Continue for remaining visits. Repeat for Table 14.2.1.2 Incidence of SARS-CoV-2 Infection (PP Population). 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
Table 14.2.2 
Incidence of Individual Symptoms and Average Number of Days with Symptoms by Visit Interval 
(ITT Population) 
 
Symptom 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
 
Subjects who reported Body Aches at least once from Day 1 to Week 2 
x (xx.x%) 
x (xx.x%) 
Subjects who reported Body Aches at least once from Week 2 to Week 4 
x (xx.x%) 
x (xx.x%) 
Subjects who reported Body Aches at least once from Week 4 to Week 6 
x (xx.x%) 
x (xx.x%) 
Subjects who reported Body Aches at least once during the overall treatment phase [1] 
x (xx.x%) 
x (xx.x%) 
 
 
 
Number of days subjects reported Body Aches from Day 1 to Week 2 
 
 
 
n 
x 
x 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
 
 
 
 
Number of days subjects reported Body Aches from Week 2 to Week 4 
 
 
 
n 
x 
x 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
 
 
 
 
Number of days subjects reported Body Aches from Week 4 to Week 6 
 
 
 
n 
x 
x 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
 
 
 
 
Number of days subjects reported Body Aches during the overall treatment phase [1] 
 
 
 
n 
x 
x 
 
Mean (SD) 
xx.x (xx.xx) 
xx.x (xx.xx) 
 
Median 
xx.x 
xx.x 
 
Min, Max 
xx, xx 
xx, xx 
 
 
 
Percentages are based on the ITT Population. 
Number of days summaries include subjects who experienced no symptoms, reported as 0 days. 
[1] Includes the time from Day 1 to Week 4. 
Reference: Listing 16.2.6.2.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Continue for each individual symptom. 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
Table 14.2.3 
Cumulative Incidence of SARS-CoV-2 Seroconversion by Visit 
(ITT Population) 
 
Visit 
Seroconverted 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
 
Week 2 
 
 
n 
x 
x 
Yes 
x (xx.x%) 
x (xx.x%) 
No 
x (xx.x%) 
x (xx.x%) 
 
 
Week 4 
 
 
n 
x 
x 
Yes 
x (xx.x%) 
x (xx.x%) 
No 
x (xx.x%) 
x (xx.x%) 
 
 
Week 6 
 
 
n 
x 
x 
Yes 
x (xx.x%) 
x (xx.x%) 
No 
x (xx.x%) 
x (xx.x%) 
 
 
The incidence of seroconversion is summarized based on results obtained at or prior to the visit. 
Reference: Listing 16.2.6.3 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.3.1.1 
Overall Summary of Adverse Events 
(Safety Population) 
 
 
 
GLS-1200 
(N=XX) 
n (%) [95% CI] 
Placebo 
(N=XX) 
n (%) [95% CI] 
 
 
 
 
 
Subjects with any TEAE  
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects whose strongest TEAE relationship to study drug is related [1] 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects whose strongest TEAE relationship to study drug is not related [2] 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects whose maximum TEAE severity grade is Mild [3] 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects whose maximum TEAE severity grade is Moderate [3] 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects whose maximum TEAE severity grade is Severe [3] 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects with any SAE 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects with any serious TEAE 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects with any TEAE leading to study discontinuation 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
Subjects with any TEAE leading to death 
 
x (xx.x%) [xx.x% - xx.x%] 
x (xx.x%) [xx.x% - xx.x%] 
 
 
 
 
 
AE = adverse event; SAE = Serious Adverse Event; TEAE = Treatment-Emergent Adverse Event; CI = Confidence Interval 
The 95% CIs for the subject percentages are calculated using an exact binomial distribution. 
[1] Related TEAEs are those with a relationship of related, possibly related, or probably related. If the relationship is missing, it is considered related. 
[2] Not related TEAEs are those with a relationship of unlikely related or not related. 
[3] Severity grades are determined according to the NCI Common Terminology Criteria for Adverse Events version 5.0. 
Reference: Listing 16.2.7.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.3.1.2 
Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
(Safety Population) 
 
System Organ Class  
   Preferred Term 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
 
 
 
 
Subjects with at least one TEAE 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #2> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 . 
 
 
 
 
 . 
 
 
 
 
 
 
 
 
AE=adverse event; TEAE = Treatment-Emergent Adverse Event; MedDRA = Medical Dictionary for Regulatory Activities. 
AEs are coded using MedDRA version 23.0 and ordered by descending order of overall incidence of SOC and overall incidence of PT within each SOC. At each level of summation (overall, SOC, PT), subjects reporting more 
than one TEAE are counted only once. 
Reference: Listing 16.2.7.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.3.1.3 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, and Strongest Relationship to Study Drug 
(Safety Population) 
 
System Organ Class  
   Preferred Term 
 
GLS-1200 
(N=XX) 
Placebo 
 (N=XX) 
 
 
Related 
Not Related 
Related 
Not Related 
 
 
 
 
 
 
 
Subjects with at least one TEAE 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
<System Organ Class #1> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
<System Organ Class #2> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 . 
 
 
 
 
 
 
 . 
 
 
 
 
 
 
 
 
 
 
 
 
AE=adverse event; TEAE = Treatment-Emergent Adverse Event; MedDRA = Medical Dictionary for Regulatory Activities. 
AEs are coded using MedDRA version 23.0 and ordered by descending order of overall incidence of SOC and overall incidence of PT within each SOC. At each level of summation (overall, SOC, PT), subjects reporting more 
than one TEAE are counted only once using the strongest relationship. 
Related TEAEs are those with a relationship of related, possibly related, or probably related. If the relationship is missing, it is considered related. Not Related TEAEs are those with a relationship of unlikely related or not 
related. 
Reference: Listing 16.2.7.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.3.1.4 
Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Severity Grade 
(Safety Population) 
 
System Organ Class  
   Preferred Term 
 
 
GLS-1200 
(N=XX) 
 
 
 
Placebo 
(N=XX) 
 
 
Mild 
Moderate 
Severe 
 
Mild 
Moderate 
Severe 
 
 
 
 
 
 
 
 
Subjects with at least one TEAE 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
<System Organ Class #1> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
 
 
 
<System Organ Class #2> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 
x (xx.x%) 
x (xx.x%) 
x (xx.x%) 
 . 
 
 
 
 
 
 
 
 
 . 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE=adverse event; TEAE = Treatment-Emergent Adverse Event; MedDRA = Medical Dictionary for Regulatory Activities 
AEs are coded using MedDRA version 23.0 and ordered by descending order of overall incidence of SOC and overall incidence of PT within each SOC. At each level of summation (overall, SOC, PT), subjects reporting more 
than one TEAE are counted only once using the highest grade. 
Severity grades are determined according to the NCI Common Terminology Criteria for Adverse Events version 5.0. 
Reference: Listing 16.2.7.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
Repeat Table 14.3.1.4 layout for: 
Table 14.3.1.5 
Related Treatment-Emergent Adverse Events by System Organ Class, Preferred Term, and Maximum Severity Grade 
(Safety Population) 


 
 
GeneOne Life Science Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
   Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.3.2.1 
Serious Adverse Events by System Organ Class and Preferred Term 
(Safety Population) 
 
System Organ Class  
   Preferred Term 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
 
 
 
 
Subjects with at least one SAE 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #2> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 . 
 
 
 
 
 . 
 
 
 
 
 
 
 
 
SAE=serious adverse event; MedDRA = Medical Dictionary for Regulatory Activities. 
AEs are coded using MedDRA version 23.0 and ordered by descending order of overall incidence of SOC and overall incidence of PT within each SOC. At each level of summation (overall, SOC, PT), subjects reporting more 
than one AE are counted only once. 
Reference: Listing 16.2.7.2 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 


 
 
GeneOne Life Science Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
   Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.3.2.2 
Serious Treatment-Emergent Adverse Events by System Organ Class and Preferred Term 
(Safety Population) 
 
System Organ Class  
   Preferred Term 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
 
 
 
 
Subjects with at least one serious TEAE 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #2> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 . 
 
 
 
 
 . 
 
 
 
 
 
 
 
 
AE=adverse event; TEAE = Treatment-Emergent Adverse Event; MedDRA = Medical Dictionary for Regulatory Activities. 
AEs are coded using MedDRA version 23.0 and ordered by descending order of overall incidence of SOC and overall incidence of PT within each SOC. At each level of summation (overall, SOC, PT), subjects reporting more 
than one TEAE are counted only once. 
Reference: Listing 16.2.7.2 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
 
Table 14.3.2.3 
Treatment-Emergent Adverse Events Leading to Study Discontinuation by System Organ Class and Preferred Term 
(Safety Population) 
 
System Organ Class  
   Preferred Term 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
 
 
 
 
Subjects with at least one TEAE leading to study discontinuation 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #2> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 . 
 
 
 
 
 . 
 
 
 
 
 
 
 
 
AE=adverse event; TEAE = Treatment-Emergent Adverse Event; MedDRA = Medical Dictionary for Regulatory Activities 
AEs are coded using MedDRA version 23.0 and ordered by descending order of overall incidence of SOC and overall incidence of PT within each SOC. At each level of summation (overall, SOC, PT), subjects reporting more 
than one TEAE are counted only once. 
Reference: Listing 16.2.7.3 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
 


 
 
Table 14.3.2.4 
Treatment-Emergent Adverse Events Leading to Death by System Organ Class and Preferred Term 
(Safety Population) 
 
System Organ Class  
   Preferred Term 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
 
 
 
 
Subjects with at least one TEAE leading to death 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 
 
 
 
 
<System Organ Class #2> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #1> 
 
x (xx.x%) 
x (xx.x%) 
 
<Preferred Term #2> 
 
x (xx.x%) 
x (xx.x%) 
 
 . 
 
 
 
 
 . 
 
 
 
 
 
 
 
 
AE=adverse event; TEAE = Treatment-Emergent Adverse Event; MedDRA = Medical Dictionary for Regulatory Activities 
AEs are coded using MedDRA version 23.0 and ordered by descending order of overall incidence of SOC and overall incidence of PT within each SOC. At each level of summation (overall, SOC, PT), subjects reporting more 
than one TEAE are counted only once. 
Reference: Listing 16.2.7.4 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Table 14.3.4.1 
Shift from Baseline in Hematology Results by Test and Visit 
(Safety Population) 
 
Test 
Visit 
GLS-1200 
(N=XX) 
Baseline 
Placebo 
(N=XX) 
Baseline 
Low 
Normal 
High 
Low  
Normal 
High 
 
 
 
 
 
 
<Test #1> (units) 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
n 
 
x 
 
 
x 
 
  Low 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  High 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
Baseline is the last non-missing value prior to first dose of study treatment. 
Percentages are based on n, the number of subjects with both a baseline and post-baseline result at the visit. 
Shifts are based on local labs from each site. 
Reference: Listing 16.2.8.1 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Continue for all hematology tests. 
 
Repeat Table 14.3.4.1 layout for: 
Table 14.3.4.2 
Shift from Baseline in Chemistry Results by Test and Visit 
(Safety Population) 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Table 14.3.4.3 
Observed and Change from Baseline in Vital Sign Results by Test and Visit 
(Safety Population) 
 
Test 
Visit 
GLS-1200 
(N=XX) 
 
Placebo 
(N=XX) 
 
Observed 
Change from Baseline 
 
Observed 
Change from Baseline 
 
 
 
 
 
 
 
<Test #1> (units) 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
 
  n 
x 
 
 
x 
 
 
  Mean (SD) 
xx.xx (xx.xxx) 
 
 
xx.xx (xx.xxx) 
 
 
  Median 
x.xx 
 
 
x.xx 
 
 
  Min, Max 
xx.x, xx.x 
 
 
xx.x, xx.x 
 
 
 
 
 
 
 
 
 
Week 2 
 
 
 
 
 
 
  n 
x 
x 
 
x 
x 
 
  Mean (SD) 
xx.xx (xx.xxx) 
xx.xx (xx.xxx) 
 
xx.xx (xx.xxx) 
xx.xx (xx.xxx) 
 
  Median 
x.xx 
x.xx 
 
x.xx 
x.xx 
 
  Min, Max 
xx.x, xx.x 
xx.x, xx.x 
 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
  n 
x 
x 
 
x 
x 
 
  Mean (SD) 
xx.xx (xx.xxx) 
xx.xx (xx.xxx) 
 
xx.xx (xx.xxx) 
xx.xx (xx.xxx) 
 
  Median 
x.xx 
x.xx 
 
x.xx 
x.xx 
 
  Min, Max 
xx.x, xx.x 
xx.x, xx.x 
 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
Week 6 
 
 
 
 
 
 
  n 
x 
x 
 
x 
x 
 
  Mean (SD) 
xx.xx (xx.xxx) 
xx.xx (xx.xxx) 
 
xx.xx (xx.xxx) 
xx.xx (xx.xxx) 
 
  Median 
x.xx 
x.xx 
 
x.xx 
x.xx 
 
  Min, Max 
xx.x, xx.x 
xx.x, xx.x 
 
xx.x, xx.x 
xx.x, xx.x 
 
 
 
 
 
 
 
 
Baseline is the last non-missing value prior to first dose of study treatment. 
Reference: Listing 16.2.8.3 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Continue for all vital sign tests. 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Table 14.3.4.4.1 
Shift from Baseline in 12-Lead ECG Overall Interpretation by Visit 
(Safety Population) 
 
GLS-1200 
(N=XX) 
Baseline 
Placebo 
(N=XX) 
Baseline 
Normal 
Abnormal NCS 
Abnormal CS 
Normal 
Abnormal NCS 
Abnormal CS 
 
 
 
 
 
 
Week 4 
 
 
 
 
 
 
n 
 
x 
 
 
x 
 
  Normal 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Abnormal NCS 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Abnormal CS 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
 
(N)CS = (Not) Clinically Significant. 
Baseline is the last non-missing value prior to first dose of study treatment. 
Percentages are based on n, the number of subjects with both a baseline and post-baseline result at the visit. 
Reference: Listing 16.2.8.4 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Table 14.3.4.4.2 
Summary of QTcF Interval (msec) by Visit and Result Category 
(Safety Population) 
 
Visit 
Result Category 
 
GLS-1200 
(N=XX) 
Placebo 
(N=XX) 
 
 
 
Baseline 
 
 
n 
x 
x 
<=450 msec (males) or <=470 msec (females) 
xx (xx.x) 
xx (xx.x) 
>450 msec (males) or >470 msec (females) 
xx (xx.x) 
xx (xx.x) 
 
 
 
Week 4 
 
 
n 
x 
x 
<=450 msec (males) or <=470 msec (females) 
xx (xx.x) 
xx (xx.x) 
>450 msec (males) or >470 msec (females) 
xx (xx.x) 
xx (xx.x) 
Change from baseline <=60 msec 
xx (xx.x) 
xx (xx.x) 
Change from baseline >60 msec 
xx (xx.x) 
xx (xx.x) 
 
 
 
Baseline is the last non-missing value prior to first dose of study treatment. 
Percentages are based on n, the number of subjects with a baseline and post-baseline (for Week 4) result at the visit. 
Reference: Listing 16.2.8.4 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
 


 
 
APPENDIX D:  FIGURE LAYOUTS 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Figure 14.3.4.1 
Line Plots of Mean (+/-SD) Hematology Results vs. Time by Test 
(Safety Population) 
 
 
 
 
 
 
 
 
Reference: Listing 16.2.8.1 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Display each hematology test on a separate page. 
Repeat Figure 14.3.4.1 layout for: 
Figure 14.3.4.2 


 
 
Line Plots of Mean (+/-SD) Chemistry Results vs. Time by Test 
Safety Population 
 
Figure 14.3.4.3 
Line Plots of Mean (+/-SD) Vital Sign Results vs. Time by Test 
Safety Population 
 
Figure 14.3.4.4 
Line Plots of Mean (+/-SD) 12-Lead ECG Results vs. Time by Test 
Safety Population 
 


 
 
APPENDIX E:  LISTING LAYOUTS 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.1 
Subject Disposition 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Study Site 
Informed 
Consent 
Date 
Randomization 
Date 
ITT 
Population [1] 
Safety 
Population [2] 
PP 
Population [3] 
First Dose 
Date 
Study 
Completion 
Status 
Study Completion or 
Discontinuation 
Date 
(Study Day) 
xxxxx 
xxxxx 
yyyy-mm-dd  
yyyy-mm-dd  
Yes/No 
Yes/No 
Yes/No 
yyyy-mm-dd  
xxxxxxxxxx 
yyyy-mm-dd (xx) 
xxxxx 
xxxxx 
yyyy-mm-dd  
yyyy-mm-dd  
Yes/No 
Yes/No 
Yes/No 
yyyy-mm-dd  
xxxxxxxxxx 
yyyy-mm-dd (xx) 
xxxxx 
xxxxx 
yyyy-mm-dd  
yyyy-mm-dd  
Yes/No 
Yes/No 
Yes/No 
yyyy-mm-dd  
xxxxxxxxxx 
yyyy-mm-dd (xx) 
xxxxx 
xxxxx 
yyyy-mm-dd  
yyyy-mm-dd  
Yes/No 
Yes/No 
Yes/No 
yyyy-mm-dd  
xxxxxxxxxx 
yyyy-mm-dd (xx) 
xxxxx 
xxxxx 
yyyy-mm-dd  
yyyy-mm-dd  
Yes/No 
Yes/No 
Yes/No 
yyyy-mm-dd  
xxxxxxxxxx 
yyyy-mm-dd (xx) 
xxxxx 
xxxxx 
yyyy-mm-dd  
yyyy-mm-dd  
Yes/No 
Yes/No 
Yes/No 
yyyy-mm-dd  
xxxxxxxxxx 
yyyy-mm-dd (xx) 
xxxxx 
xxxxx 
yyyy-mm-dd  
yyyy-mm-dd  
Yes/No 
Yes/No 
Yes/No 
yyyy-mm-dd  
xxxxxxxxxx 
yyyy-mm-dd (xx) 
xxxxx 
xxxxx 
yyyy-mm-dd  
yyyy-mm-dd  
Yes/No 
Yes/No 
Yes/No 
yyyy-mm-dd  
xxxxxxxxxx 
yyyy-mm-dd (xx) 
[1] The Intent-to-treat (ITT) Population includes all randomized to treatment allocation. 
[2] The Safety Population includes all subjects who received at least one dose of study treatment. 
[3] The Per-protocol (PP) Population includes all subjects who completed the trial, received >=90% of the study treatments, and have no significant protocol deviations. Trial completion is defined as either completing 
Week 4 or meeting the study endpoint of PCR confirmed SARS-CoV-2 infection. 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.2 
Protocol Deviations 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Deviation Date 
(Study Day) 
Deviation Category 
Description 
xxxxxx 
yyyy-mm-dd (xx) 
Major/Minor 
xxxxxx 
xxxxxx 
yyyy-mm-dd (xx) 
Major/Minor 
xxxxxx 
xxxxxx 
yyyy-mm-dd (xx) 
Major/Minor 
xxxxxx 
xxxxxx 
yyyy-mm-dd (xx) 
Major/Minor 
xxxxxx 
xxxxxx 
yyyy-mm-dd (xx) 
Major/Minor 
xxxxxx 
xxxxxx 
yyyy-mm-dd (xx) 
Major/Minor 
xxxxxx 
xxxxxx 
yyyy-mm-dd (xx) 
Major/Minor 
xxxxxx 
xxxxxx 
yyyy-mm-dd (xx) 
Major/Minor 
xxxxxx 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.3 
Inclusion/Exclusion Criteria 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
All eligibility criteria met 
Criterion not met 
Criterion Description 
xxxxxx 
Yes/No 
Inclusion xx/Exclusion xx 
xxxxxxxx 
xxxxxx 
Yes/No 
Inclusion xx/Exclusion xx 
xxxxxxxx 
xxxxxx 
Yes/No 
Inclusion xx/Exclusion xx 
xxxxxxxx 
xxxxxx 
Yes/No 
Inclusion xx/Exclusion xx 
xxxxxxxx 
xxxxxx 
Yes/No 
Inclusion xx/Exclusion xx 
xxxxxxxx 
xxxxxx 
Yes/No 
Inclusion xx/Exclusion xx 
xxxxxxxx 
xxxxxx 
Yes/No 
Inclusion xx/Exclusion xx 
xxxxxxxx 
xxxxxx 
Yes/No 
Inclusion xx/Exclusion xx 
xxxxxxxx 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: If more than one criterion ID is selected for a subject, list each one on a separate line. 
  


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.4.1 
Demographic and Baseline Characteristics 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Age 
(years) 
Sex 
Race 
Ethnicity 
Height 
(cm) 
Weight 
(kg) 
BMI 
(kg/m^2) 
xxxxxx 
xx 
Male/Female 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xx.x 
xx.x 
xxxxxx 
xx 
Male/Female 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xx.x 
xx.x 
xxxxxx 
xx 
Male/Female 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xx.x 
xx.x 
xxxxxx 
xx 
Male/Female 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xx.x 
xx.x 
xxxxxx 
xx 
Male/Female 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xx.x 
xx.x 
xxxxxx 
xx 
Male/Female 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xx.x 
xx.x 
xxxxxx 
xx 
Male/Female 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xx.x 
xx.x 
xxxxxx 
xx 
Male/Female 
xxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xx.x 
xx.x 
Baseline is the last non-missing value prior to first dose of study treatment. 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.4.2 
Medical History 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Any medical history 
System Organ Class/ 
Preferred Term/ 
Verbatim Term 
Start Date 
Ongoing 
Stop Date 
xxxxxx 
Yes/No 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxxx 
yyyy-mm-dd 
Yes/No 
yyyy-mm-dd 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxx 
yyyy-mm-dd 
Yes/No 
yyyy-mm-dd 
xxxxxx 
Yes/No 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxxx 
yyyy-mm-dd 
Yes/No 
yyyy-mm-dd 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxx 
yyyy-mm-dd 
Yes/No 
yyyy-mm-dd 
xxxxxx 
Yes/No 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxxx 
yyyy-mm-dd 
Yes/No 
yyyy-mm-dd 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxx 
yyyy-mm-dd 
Yes/No 
yyyy-mm-dd 
MedDRA = Medical Dictionary for Regulatory Activities. 
Medical history terms are coded using MedDRA version 23.0. 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.4.3 
Prior and Concomitant Medications 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
ATC Class/ 
Preferred Name/ 
Verbatim Term 
Start Date 
(Study Day)/ 
End Date 
(Study Day) 
Dose 
Units 
Route 
Frequency 
Indication 
 
xxxxxx 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxxx 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxx 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxx 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxxx* 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxx 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxx 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxxx 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx/ 
xxxxxxxxx/ 
xxxxxxxx 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
 
 
 
 
Medications are coded using WHODrug Global (March 2020). 
Prior medications are denoted by *. 
A prior medication is defined as a medication that was administered up to 8 weeks prior to first dose of study treatment. A concomitant medication is any medication that is ongoing or started on or after the date of first 
dose. 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.5.1 
Exposure and Treatment Compliance 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Date of first dose 
Date of last dose 
Duration of Exposure 
(days) [1] 
Number of Days 
with At Least One Dose Taken 
Total Doses Taken 
Total Doses 
Missed 
Treatment Compliance [2] 
xxxxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx 
xx 
xx 
xx% 
xxxxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx 
xx 
xx 
xx% 
xxxxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx 
xx 
xx 
xx% 
xxxxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx 
xx 
xx 
xx% 
xxxxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx 
xx 
xx 
xx% 
xxxxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx 
xx 
xx 
xx% 
xxxxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx 
xx 
xx 
xx% 
xxxxxx 
yyyy-mm-dd 
yyyy-mm-dd 
xx 
xx 
xx 
xx 
xx% 
 
 
[1] Duration of exposure is defined as the date of last dose minus the date of first dose + 1. 
[2] Treatment compliance is defined as the total number of doses taken divided by the total number of planned doses times 100. 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.5.2 
Treatment Diary 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Day 
Date (Study Day) 
Dose 1 Taken 
Dose 2 Taken 
Dose 3 Taken 
Diary Comments 
SARS-CoV-2 Exposures: 
# Suspected 
SARS-CoV-2 Exposures: 
# Known 
 
 
 
xxxxxx 
xx 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Yes/No 
xxxxxxxx 
xx 
xx 
xx 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Yes/No 
xxxxxxxx 
xx 
xx 
xx 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Yes/No 
xxxxxxxx 
xx 
xx 
xx 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Yes/No 
xxxxxxxx 
xx 
xx 
xx 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Yes/No 
xxxxxxxx 
xx 
xx 
xx 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Yes/No 
xxxxxxxx 
xx 
xx 
xx 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Yes/No 
xxxxxxxx 
xx 
xx 
xx 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Yes/No 
xxxxxxxx 
xx 
xx 
 
 
 
 
 
 
 
 
 
 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.5.3 
Plasma Collection for Measurement of Quinine 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Visit 
Plasma Collected 
Collection Date/Time 
(Study Day) 
Date of Last Spray 
Administration 
(Study Day) 
Test Result 
(unit) 
xxxxxx 
Week 2 
Yes/No 
yyyy-mm-dd hh:mm 
(xx)  
yyyy-mm-dd 
(xx)  
xx.x 
xxxxxx 
Week 2 
Yes/No 
yyyy-mm-dd hh:mm 
(xx)  
yyyy-mm-dd 
(xx)  
xx.x 
xxxxxx 
Week 2 
Yes/No 
yyyy-mm-dd hh:mm 
(xx)  
yyyy-mm-dd 
(xx)  
xx.x 
xxxxxx 
Week 2 
Yes/No 
yyyy-mm-dd hh:mm 
(xx)  
yyyy-mm-dd 
(xx)  
xx.x 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.6.1 
PCR Results 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Visit 
Nasopharyngeal Swabs for Viral PCR 
Collected 
Collection Date 
(Study Day) 
Test Result 
xxxxxx 
Day 0 
Yes/No 
yyyy-mm-dd 
(xx)  
Negative/Positive 
Week 2 
Yes/No 
yyyy-mm-dd 
(xx)  
Negative/Positive 
Week 4 
Yes/No 
yyyy-mm-dd 
(xx)  
Negative/Positive 
Week 6 
Yes/No 
yyyy-mm-dd 
(xx)  
Negative/Positive 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 
 
 
 


 
 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.6.2 
Symptom Scores 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Day 
Date 
 
Fever 
Cough 
Sore 
Throat 
Headache 
Shortness 
of 
Breath 
Body 
Aches 
Fatigue 
GI 
Issues 
Runny 
Nose 
Sneezing 
Loss 
of 
Smell 
Loss 
of 
Taste 
Red 
Eyes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
xx 
yyyy-mm-dd 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
xx 
yyyy-mm-dd 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
xx 
yyyy-mm-dd 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
xx 
yyyy-mm-dd 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
xx 
yyyy-mm-dd 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
xx 
yyyy-mm-dd 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
xx 
yyyy-mm-dd 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
xx 
yyyy-mm-dd 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
0/1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0=No, 1=Yes 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.6.3 
Seroconversion 
 
Treatment: GLS-1200, Placebo 
 
Subject 
ID 
Visit 
Serum for Viral Antibodies 
Collected 
Collection Date 
(Study Day) 
Titer 
Seroconversion 
xxxxxx 
Day 0 
Yes/No 
yyyy-mm-dd 
(xx)  
xx 
Yes/No 
Week 2 
Yes/No 
yyyy-mm-dd 
(xx)  
xx 
Yes/No  
Week 4 
Yes/No 
yyyy-mm-dd 
(xx)  
xx 
Yes/No  
Week 6 
Yes/No 
yyyy-mm-dd 
(xx)  
xx 
Yes/No  
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
  
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.7.1 
Adverse Events 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
System Organ Class/ 
Preferred Term/ 
Verbatim Term 
Start Date 
(Study Day)/ 
End Date 
(Study Day) 
Severity 
Relationship 
Action Taken 
Serious 
Outcome 
Study Discontinuation 
Treatment Required 
 
xxxxxx 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxx 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
Grade x 
xxxxxxxxxx 
xxxxxxxxxx 
Yes/No 
xxxxxxxxxx 
Yes/No 
Yes/No 
 
xxxxxx 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxx 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
Grade x 
xxxxxxxxxx 
xxxxxxxxxx 
Yes/No 
xxxxxxxxxx 
Yes/No 
Yes/No 
 
xxxxxx 
xxxxxxxxxxxxxxx/ 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxx 
yyyy-mm-dd (xx)/ 
yyyy-mm-dd (xx) 
Grade x 
xxxxxxxxxx 
xxxxxxxxxx 
Yes/No 
xxxxxxxxxx 
Yes/No 
Yes/No 
 
Severity grades are determined according to the NCI Common Terminology Criteria for Adverse Events version 5.0. 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Sort by Treatment, Subject ID, AE start date and end date. 
 
Repeat Layout of Listing 16.2.7.1 for: 
 
Listing 16.2.7.3 Adverse Events Leading to Study Discontinuation 
 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.7.2 
Serious Adverse Events 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
System Organ Class/ 
Preferred Term/ 
Verbatim Term 
Start Date 
(Study Day) 
End Date 
(Study Day) 
Severity 
Relationship 
Action Taken 
SAE Criteria 
Outcome 
Study Discontinuation Treatment 
Required 
 
xxxxxx 
xxxxxxxxxxxxxxx/ 
yyyy-mm-dd (xx) yyyy-mm-dd (xx) Grade x 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
Yes/No 
Yes/No 
 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxx 
 
xxxxxx 
xxxxxxxxxxxxxxx/ 
yyyy-mm-dd (xx) yyyy-mm-dd (xx) Grade x 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
Yes/No 
Yes/No 
 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxx 
 
xxxxxx 
xxxxxxxxxxxxxxx/ 
yyyy-mm-dd (xx) yyyy-mm-dd (xx) Grade x 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
Yes/No 
Yes/No 
 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxx 
 
xxxxxx 
xxxxxxxxxxxxxxx/ 
yyyy-mm-dd (xx) yyyy-mm-dd (xx) Grade x 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
xxxxxxxxxx 
Yes/No 
Yes/No 
 
xxxxxxxxxxxxxx/ 
xxxxxxxxxxxxx 
 
 
SAE = Serious Adverse Event 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Sort by Treatment, Subject ID, AE start date and end date. 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.7.4 
Deaths 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Death Date 
(Study Day) 
If Death is Due to AE, 
AE Term/ Start Date (Study Day) 
xxxxxx 
yyyy-mm-dd (xx) 
xxxxxxxxxxxxx/ yyyy-mm-dd (xx) 
xxxxxx 
yyyy-mm-dd (xx) 
xxxxxxxxxxxxx/ yyyy-mm-dd (xx) 
xxxxxx 
yyyy-mm-dd (xx) 
xxxxxxxxxxxxx/ yyyy-mm-dd (xx) 
xxxxxx 
yyyy-mm-dd (xx) 
xxxxxxxxxxxxx/ yyyy-mm-dd (xx) 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Sort by Treatment, Subject ID. 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.8.1 
Hematology 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Visit 
Date/Time 
(Study Day) 
Lab Test 
Result 
Reference Range 
xxxxxx 
Day 0 
yyyy-mm-dd hh:mm (xx) 
xxxxxxxxxx 
xx.x L, CS 
xxxx - xxxx 
xxxxxxxxxx 
xx.x 
xxxx - xxxx 
xxxxxxxxxx 
xx.x 
xxxx - xxxx 
xxxxxxxxxx 
xx.x 
xxxx - xxxx 
xxxxxxxxxx 
xx.x H, NCS 
xxxx - xxxx 
xxxxxxxxxx 
xx.x 
xxxx - xxxx 
xxxxxxxxxx 
xx.x 
xxxx - xxxx 
xxxxxxxxxx 
xx.x 
xxxx - xxxx 
Visit 4 
yyyy-mm-dd hh:mm (xx) 
xxxxxxxxxx 
xx.x 
xxxx - xxxx 
xxxxxxxxxx 
xx.x 
xxxx - xxxx 
L=Low, H=High, (N)CS=(Not) Clinically Significant 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
Programming Note: Repeat for Listing 16.2.8.2 Chemistry 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.8.3 
Vital Signs 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Visit 
Date/Time 
(Study Day) 
Diastolic Blood 
Pressure 
(mmHg) 
Systolic Blood 
Pressure 
(mmHg) 
Heart Rate 
(beats/min) 
Temperature 
(C) 
Height 
(cm) 
Weight 
(kg) 
 
 
 
 
 
 
 
xxxxxx 
Day 0 
yyyy-mm-dd hh:mm (xx) 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
Week 2 
yyyy-mm-dd hh:mm (xx) 
xx.x 
xx.x 
xx.x 
xx.x 
Week 4 
yyyy-mm-dd hh:mm (xx) 
xx.x 
xx.x 
xx.x 
xx.x 
Week 6 
yyyy-mm-dd hh:mm (xx) 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.8.4 
12-Lead Electrocardiogram 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Visit 
ECG Date/Time 
(Study Day) 
Parameter 
Result 
Overall Interpretation 
Abnormal Findings 
xxxxxx 
Day 0 
yyyy-mm-dd hh:mm (xx) 
xxxxxxxxxxxx 
xx.x 
Normal/Abnormal NCS/Abnormal CS 
xxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
Week 4 
yyyy-mm-dd hh:mm (xx) 
xxxxxxxxxxxx 
xx.x 
Normal/Abnormal NCS/Abnormal CS 
xxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
xxxxxxxxxxxx 
xx.x 
N(CS)=(Not) Clinically Significant  
 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.8.5 
Physical Examination 
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Visit 
Date 
(Study Day) 
Exam 
Performed 
Clinically Significant Findings 
xxxxxx 
Day 0 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Week 2 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Week 4 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Week 6 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
xxxxxx 
Day 0 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Week 2 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Week 4 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Week 6 
yyyy-mm-dd (xx) 
Yes/No 
Yes/No 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 
 


 
 
GeneOne Life Science Inc. 
Page 1 of x 
Protocol: T2R-002 
 
Listing 16.2.8.6 
Pregnancy Test  
 
Treatment: GLS-1200, Placebo 
 
Subject ID 
Visit 
Date 
(Study Day) 
Test Performed 
Result 
xxxxxx 
Day 0 
yyyy-mm-dd (xx) 
Yes/No 
Negative/Positive 
Week 2 
yyyy-mm-dd (xx) 
Yes/No 
Negative/Positive 
Week 4 
yyyy-mm-dd (xx) 
Yes/No 
Negative/Positive 
xxxxxx 
Day 0 
yyyy-mm-dd (xx) 
Yes/No 
Negative/Positive 
Week 2 
yyyy-mm-dd (xx) 
Yes/No 
Negative/Positive 
Week 4 
yyyy-mm-dd (xx) 
Yes/No 
Negative/Positive 
Source: \\xx\xxx\xxx\xxx\xxxxxx\xxxxxxxxxxxxxxxx\xxxx\xxxxx.sas  
date 
 time 
 


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