Conditions: COVID-19 Pharmacokinetics Safety
Keywords: Intranasal spray Prophylaxis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 50
Healthy volunteers: yes

Brief summary:
This is a phase I randomized, placebo-controlled, single site to assess the local and systemic safety of intranasal Q-Griffithsin (Q-GRFT) after 14 doses in approximately 45 adult participants. Participants will be randomized 2:1 (Q-GRFT nasal spray: placebo nasal spray) resulting in 30 participants enrolled into the Q-GRFT arm and 15 participants enrolled into the placebo arm. A clinician will apply two metered doses of Q-GRFT in each nostril (400μl total) of the participant on the day of enrollment. Participants will be monitored in the clinic for 1 hour after administration and return for a 24-hour post dose visit. If safe and acceptable, a second period of daily administration by the participant for 13 days will commence. Safety assessments will be performed at day 7, day 14, and day 28 visits after the initiation of the second period. The expected duration of study participation for each participant will be approximately 6-8 weeks. The primary endpoint is the proportion of participants who experience a related Grade 2 or higher adverse event. Secondary and exploratory endpoints include persistence and systemic absorption of Q-GRFT, acceptability and the impact of Q-GRFT nasal spray on smell.

Detailed description:
This is a phase 1 study for intranasal application of Q-Griffithsin (Q-GRFT) spray as a prophylactic for severe acute respiratory syndrome-CoV-2. This randomized, placebo-controlled, single site will assess the local and systemic safety of intranasal Q-GRFT after 14 doses in approximately 45 adult participants. Participants will be randomized 2:1 (Q-GRFT nasal spray: placebo nasal spray) resulting in 30 participants enrolled into the Q-GRFT arm and 15 participants enrolled into the placebo arm. Accrual of approximately 45 evaluable participants is expected to take 6 months. The expected duration of study participation for each participant will be approximately 6-8 weeks. A clinician will apply two metered doses of Q-GRFT in each nostril (400μl total) of the participant on the day of enrollment. Participants will be monitored in the clinic for 1 hour after administration and return for a 24-hour post dose visit. If safe and acceptable, a second period of daily administration by the participant for 13 days will commence after a 5-49 day washout period. Safety assessments will be performed at day 7, day 14, and day 28 visits after the initiation of the second period. Additional safety assessments will be done by contacting participants between the 24-hour and 7-day visits and 7- and 14-day visits. The expected duration of study participation for each participant will be approximately 6-8 weeks. The primary endpoint is the proportion of participants who experience a related Grade 2 or higher adverse event. Secondary and exploratory endpoints include persistence and systemic absorption of Q-GRFT, acceptability and the impact of Q-GRFT nasal spray on smell.

Arms:
arm 1: Q-Griffithsin (Q-GRFT) nasal spray (7.5mg/mL). Two metered doses of 100μL into each nostril, total of 3mg Q-GRFT per administration, administered once daily for 14 consecutive days. arm 2: Placebo Nasal Spray. Two metered doses of 100μL into each nostril, administered once daily for 14 consecutive days.

Interventions: intervention 1: Q-Griffithsin intervention 2: Placebo
Intervention descriptions: intervention 1: Q-Griffithsin is derived from Griffithsin (GRFT) which is a non-glycosylated protein consisting of 121 amino acids. Q-GRFT contains a single amino acid substitution, M78Q variant, resistant to oxidation yet maintains the parent molecule's pharmacological profile. intervention 2: A matched vehicle solution manufactured and dispensed in same applicators as the active comparator.

Protocol document:
Prot_SAP_000.pdf: 
 
Phase 1 Clinical Trial of a Q GRFT Nasal Spray 
 
NCT05180500 
 
Document/IRB Approval Date: July 18, 2022 


 
 
 
 
 
 
Phase 1 Clinical Trial of a Q GRFT Nasal Spray 
 
Funding Agency: 
National Cancer Institute 
 
Grant Number: 3P30CA047904-32S5 
pIND Number: 152657 
Protocol Chair: 
Katherine Bunge, MD 
University of Pittsburgh 
Pittsburgh, PA USA 
 
IND Holder: 
Sharon L. Hillier, PhD 
University of Pittsburgh 
Pittsburgh, PA USA 
 
 
 
Study Site: 
UPMC Magee-Womens Hospital 
University of Pittsburgh Medical Center 
Pittsburgh, PA 
Phone: 412-641-6435 
Fax: 412-641-1133 
 
 
Version 5.0 
July 7, 2022 


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Phase 1 Clinical Trial of a Q GRFT Nasal Spray 
 
Table of Contents 
LIST OF ABBREVIATIONS AND ACRONYMS .......................................................................... 5 
PROTOCOL SUMMARY ............................................................................................................ 7 
1 
KEY ROLES ....................................................................................................................... 9 
1.1 
Protocol Identification .................................................................................................. 9 
1.2 
Funding ....................................................................................................................... 9 
1.3 
Protocol Chair .............................................................................................................. 9 
1.4 
Laboratory ................................................................................................................... 9 
1.5 
IND .............................................................................................................................. 9 
2 
INTRODUCTION ............................................................................................................... 10 
2.1 
COVID-19 .................................................................................................................. 10 
2.2 
Q-GRFT ..................................................................................................................... 10 
2.3 
Rationale ................................................................................................................... 10 
2.4 
Safety Data: Q-GRFT ............................................................................................... 10 
2.5 
PK Data: Q-GRFT ..................................................................................................... 13 
2.6 
Summary ................................................................................................................... 14 
3 
OBJECTIVES ................................................................................................................... 15 
3.1 
Primary Objective: ..................................................................................................... 15 
3.2 
Primary Endpoint ....................................................................................................... 15 
3.3 
Secondary Objectives ................................................................................................ 15 
3.4 
Secondary Endpoints ................................................................................................. 15 
3.5 
Exploratory Objectives: .............................................................................................. 15 
3.6 
Exploratory Endpoints: ............................................................................................... 15 
4 
STUDY DESIGN ............................................................................................................... 15 
4.1 
Identification of Study Design..................................................................................... 15 
4.2 
Summary of Major Endpoints ..................................................................................... 15 
4.3 
Description of Study Population ................................................................................. 16 
4.4 
Time to Complete Accrual .......................................................................................... 16 
4.5 
Study Groups............................................................................................................. 16 
4.6 
Expected Duration of Participation ............................................................................. 16 
4.7 
Site ............................................................................................................................ 16 
5 
STUDY POPULATION ...................................................................................................... 16 
5.1 
Selection of the Study Population .............................................................................. 16 
5.2 
Recruitment ............................................................................................................... 16 
5.3 
Retention ................................................................................................................... 16 
5.4 
Inclusion Criteria ........................................................................................................ 16 
5.5 
Exclusion Criteria ....................................................................................................... 17 
6 
STUDY PRODUCTS ......................................................................................................... 18 
6.1 
Regimen .................................................................................................................... 18 
6.2 
Administration ............................................................................................................ 18 
6.3 
Study Product Formulation ........................................................................................ 18 
6.4 
Study Product Supply and Accountability ................................................................... 18 
6.5 
Study Product Provision ............................................................................................. 18 
6.6 
Concomitant Medications .......................................................................................... 18 
7 
STUDY PROCEDURES .................................................................................................... 19 
7.1 
Pre-Screening............................................................................................................ 19 
7.2 
Visit 1: Screening Visit ............................................................................................... 19 
7.3 
Visit 2: Enrollment ...................................................................................................... 19 
7.4 
Visit 3 Follow-Up Visit ................................................................................................ 21 
7.5 
Visit 4 [Extended Dosing; 1st week of study product provision] ................................... 21 
7.6 
Visit 5 [Extended dosing; second week of product provision) ..................................... 22 
7.7 
Visit 6 ........................................................................................................................ 22 


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7.8 
Visit 7 ........................................................................................................................ 23 
7.9 
Visit Window Periods ................................................................................................. 23 
7.10 
Participants Who Become Pregnant .......................................................................... 24 
7.11 
Interim Visits .............................................................................................................. 24 
7.12 
Clinical Evaluations and Procedures .......................................................................... 24 
7.13 
Laboratory Evaluations .............................................................................................. 25 
7.14 
Specimen Collection and Processing ......................................................................... 25 
7.15 
Biohazard Containment ............................................................................................. 25 
8 
ASSESSMENT OF SAFETY AND CLINICAL MANAGEMENT ........................................ 26 
8.1 
Safety Monitoring ....................................................................................................... 26 
8.2 
Clinical Data Safety Review ....................................................................................... 26 
8.3 
Adverse Events Definitions ........................................................................................ 26 
8.4 
Clinical Management of Adverse Events .................................................................... 27 
8.5 
Product Removal ....................................................................................................... 28 
8.6 
Criteria for Early Termination of Study Participation ................................................... 28 
9 
STATISTICAL CONSIDERATIONS .................................................................................. 29 
9.1 
Review of Study Design ............................................................................................. 29 
9.2 
Sample Size and Accrual ........................................................................................... 29 
9.3 
Study Endpoints ........................................................................................................ 30 
9.3.1 Primary Endpoint ...................................................................................................... 30 
9.3.2 Secondary Endpoints ............................................................................................... 30 
9.3.3 Exploratory Endpoints .............................................................................................. 30 
9.4 
Blinding and Unblinding ............................................................................................. 30 
9.5 
Randomization........................................................................................................... 30 
9.6 
Data Monitoring and Analysis .................................................................................... 30 
9.6.1 Data Monitoring ........................................................................................................ 30 
9.6.2 Statistical Analysis .................................................................................................... 31 
9.6.3 Analysis Cohort ........................................................................................................ 31 
10 HUMAN SUBJECTS CONSIDERATIONS ........................................................................ 32 
10.1 
Special Populations ................................................................................................... 32 
Women and Minorities ....................................................................................................... 32 
10.2 
Informed Consent Process ........................................................................................ 32 
10.3 
Incentives .................................................................................................................. 34 
10.4 
Participant Confidentiality .......................................................................................... 34 
10.5 
Communicable Disease Reporting ............................................................................. 34 
10.6 
Study Discontinuation ................................................................................................ 34 
11 LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT ................................. 35 
11.1 
Laboratory Specimens ............................................................................................... 35 
11.1.1 Urine Samples ........................................................................................................ 35 
11.1.2 Respiratory Samples .............................................................................................. 35 
11.1.3 Blood ...................................................................................................................... 35 
11.2 
Biohazard Containment ............................................................................................. 36 
12 ADMINISTRATIVE PROCEDURES .................................................................................. 36 
12.1 
Protocol Registration ................................................................................................. 36 
12.2 
Data Coordination ...................................................................................................... 36 
12.3 
Study Monitoring ........................................................................................................ 36 
12.4 
Protocol Compliance .................................................................................................. 36 
12.5 
Investigator’s Records ............................................................................................... 36 
APPENDIX 1 SCHEDULE OF STUDY VISITS AND PROCEDURES ....................................... 37 
REFERENCES ......................................................................................................................... 38 


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Table 1:  Visit 1 Procedures ...................................................................................................... 19 
Table 2:  Visit 2 Procedures ...................................................................................................... 20 
Table 3:  Visit 3 Follow-up Visit Procedures .............................................................................. 21 
Table 4:  Visit 4 Follow-up Visit Procedures .............................................................................. 21 
Table 5:  Visit 5 Follow-up Visit Procedures .............................................................................. 22 
Table 6:  Visit 6 Follow-up Visit Procedures .............................................................................. 22 
Table 7:  Visit 7 Follow-up Visit Procedures .............................................................................. 23 
Table 8:  DAIDS toxicity table .................................................................................................... 27 
Table 9: 95% confidence intervals for the true rate at all possible observed Grade 2 or higher 
adverse event rates ................................................................................................................... 29 
Table 10:  Laboratory Test Methods .......................................................................................... 35 


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Phase 1 Clinical Trial of a Q GRFT Nasal Spray 
PREVENT COVID 101 
 
LIST OF ABBREVIATIONS AND ACRONYMS 
 
ADA 
Anti-drug Antibody 
AE 
Adverse Event 
ALT 
Alanine Transaminase 
AST 
Aspartate Aminotransferase 
CBC 
Complete Blood Count 
CDC 
Centers for Disease Control and Prevention 
API 
Active Pharmaceutical Ingredient 
BID 
Twice daily 
BSIT 
Brief Smell Identification Test 
FIH 
First in Human 
GRFT 
Griffithsin 
IV 
Intravenous 
IRB 
Institutional Review Board 
MERS 
Middle Eastern Respiratory Syndrome 
MTD 
Maximum Tolerated Dose 
NIH 
National Institutes of Health 
NOAEL 
No Observed Adverse Effect Level 
PBS 
Phosphate-buffered Saline 
PCR 
Polymerase chain reaction 
SARS 
Severe Acute Respiratory Syndrome 
SID 
Once daily 
SOP 
Standard operating procedure(s) 


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Phase 1 Clinical Trial of a Q GRFT Nasal Spray 
Team Roster 
 
 
Katherine Bunge, MD MPH 
Protocol Chair 
Department of Obstetrics, 
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-6967 
Email: kbunge@mail.magee.edu 
 
Catherine Chappell, MD MSc 
Co-investigator 
Department of Obstetrics, 
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
300 Halket Street 
Pittsburgh, PA 15213 USA 
Phone: 412-641-1403 
Email: chappellca@upmc.edu 
 
Leslie Meyn, PhD 
Biostatistician/Epidemiologist 
Department of Obstetrics, 
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone: 412-641-4233 
Email: meynla@mwri.magee.edu 
 
Henry Nabeta, PhD 
University of Louisville 
Owensboro Cancer Research Program 
1020 Breckenridge Street, Suite 201 
Owensboro, KY 42303 
Phone: 502-852-841 
Email: henry.nabeta@louisville.edu 
 
Nobuyuki Matoba, PhD 
Co-Investigator 
Dept of Pharmacology and Toxicology 
University of Louisville School of Medicine 
Phone: 502-852-8412 
Email: n.matoba@louisville.edu 
 
Kenneth Palmer, PhD 
Co-Investigator 
University of Louisville 
Owensboro Cancer Research Program 
1020 Breckenridge Street, Suite 201 
Owensboro, KY 42303 
Phone: 270-691-5960 
Email: Kenneth.Palmer@louisville.edu 
 
Sharon Hillier, PhD 
IND Holder 
Department of Obstetrics, 
Gynecology and Reproductive Sciences 
University of Pittsburgh School of Medicine 
204 Craft Avenue 
Pittsburgh, PA 15213 USA 
Phone: 412-641-8933 
Email: hillsl@upmc.edu 
 
Sravan Patel, PhD 
Co-Investigator 
Department of Pharmaceutical Science 
University of Pittsburgh 
204 Craft Ave 
Pittsburgh, PA 15213 
Phone: 412-624-4087 
Email: srp75@pitt.edu 
 
Lisa Rohan, PhD 
Co-investigator 
Department of Pharmaceutical Sciences 
University of Pittsburgh School of Pharmacy 
204 Craft Avenue 
Pittsburgh, PA 15213 
Phone: 412-641-6108 
Email: rohanlc@upmc.edu 


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Phase 1 Clinical Trial of a Q GRFT Nasal Spray 
PREVENT COVID 101 
 
PROTOCOL SUMMARY 
 
Short Title: 
PREVENT COVID 101 
Protocol Chair: 
Katherine Bunge, MD 
Sample Size: 
45 evaluable participants. 
Study Population: 
SARS CoV-2 vaccinated, healthy, 18 – 55 years old 
 
Study Sites: 
UPMC Magee-Womens Hospital, Pittsburgh, PA 
 
Study Design: 
A phase I randomized, placebo-controlled, single site safety study 
 
Study Duration:     Accrual of approximately 45 evaluable participants is expected to take 6 
months. The expected duration of study participation for each participant 
will be approximately 6-8 weeks. This includes the screening period. 
 
 
Study Products: 
Q-GRFT Nasal Spray (7.5mg/mL) and Placebo Nasal Spray. 2 sprays of 
100µL each nostril, total of 3mg Q-GRFT per administration 
 
Study Regimen: 
All participants will apply two metered doses of Q-GRFT in each nostril 
(400µl total). The spray will be administered by a clinician on the day of 
enrollment. Participants will be monitored in the clinic for 1 hour after 
administration and return for a 24-hour post dose visit. If safe and 
acceptable, a second period of daily administration for 13 days will 
commence. Safety assessments will be performed at day 7, day 14, and 
day 28 visits after the initiation of the second period.  Additional safety 
assessments will be done by contacting participants between visit 4 – 5 
and visit 5 –6.   
Study Schema: 
 
Note:  the window between V1 and V2 has been increased to 60 days


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Primary Objectives: 
• 
To assess the local and systemic safety of intranasal Q-GRFT after 14 doses 
Endpoints: 
• 
The proportion of participants who experience a related Grade 2 or higher adverse event 
Secondary Objectives: 
• 
Persistence: To determine the persistence of Q-GRFT in the respiratory tract after a single 
dose and after 13 days of daily use as assessed by nasopharyngeal swab 
• 
Pharmacokinetics: To determine the systemic absorption of Q-GRFT after administration 
of a single dose and after 13 days of daily use 
• 
Acceptability: To assess the acceptability of a Q-GRFT nasal spray 
Secondary Endpoint: 
• 
Persistence: Q-GRFT concentrations from nasopharyngeal swabs collected 24 hours after 
a single dose and 24 hours after 13 consecutive daily doses 
• 
Pharmacokinetics: Q-GRFT concentrations in plasma 24 hours after the first dose and 24 
hours after the 13th consecutive daily dose 
• 
Acceptability: Self-reported assessment of qualities of the experience with the nasal spray 
through a Likert scoring of acceptability questions 
Exploratory Objective: 
• 
To assess the impact of Q-GRFT nasal spray on smell 
• 
Persistence: Q-GRFT concentrations from oropharyngeal and nares swabs collected 24 
hours after a single dose and 24 hours after 13 consecutive daily doses 
• 
Presence of Q-GRFT in the gastrointestinal tract after 13 days of consecutive use 
• 
To determine the potential of the Q-GRFT study drug product to induce an immune response 
by measuring the generation of anti-drug antibodies (ADAs) in plasma/blood samples after 
multiple Q-GRFT intranasal spray treatments 
Exploratory Endpoint: 
• 
Change in Brief Smell Identification Test (BSIT) score after 13 days of consecutive daily 
doses compared to baseline 
• 
Persistence: Q-GRFT concentrations from oropharyngeal and nares swabs collected 24 
hours after first dose and 24 hours after the 13th consecutive daily dose 
• 
Presence: Q-GRFT concentrations from rectal swab collected 24 hours after the 13th 
consecutive daily dose 
• 
Immunogenicity of Q-GRFT study product delivered by an intranasal spray system 
• 
Humoral antibody responses to Q-GRFT in plasma/blood by ELISA 


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1 
KEY ROLES 
 
1.1 
Protocol Identification 
Protocol Title: 
Phase 1 Clinical Trial of a Q-GRFT Nasal Spray 
Short Title: 
PREVENT COVID 101 
 
1.2 
Funding 
Funding Agency: 
National Cancer Institute 
9609 Medical Center Drive 
Building 9609 MSC 9760 
Bethesda, MD 20892-9760 
Phone: 1-800-422-6237 
 
1.3 
Protocol Chair 
Protocol Chair: 
Katherine Bunge 
University of Pittsburgh School of Medicine 
Magee-Womens Hospital 
300 Halket Street 
Pittsburgh, PA 15213 
Phone: 412-641-6967 
Email: kbunge@mail.magee.edu 
 
 
1.4 
Laboratory 
Safety Labs: 
UPMC Presbyterian Shadyside CP PUH 
UPMC Clinical Laboratory Building 
3477 Euler Way 
Pittsburgh, PA 15213 
 
Pharmacology: 
Matoba Lab 
University of Louisville 
Owensboro Cancer Research Program 
1020 Breckenridge Street, Suite 201 
Owensboro, KY 42303 
Phone: 502-852-8412 
Email: n.matoba@louisville.edu 
1.5 
IND 
IND Holder: 
Sharon L. Hillier, PhD 
University of Pittsburgh School of Medicine 
Magee-Womens Hospital 
300 Halket Street 
Pittsburgh, PA 15213 
Phone: 412-641-6435 
Email: hillsl@upmc.edu 


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2 
INTRODUCTION 
 
2.1 
COVID-19 
The pandemic due to Coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 has led to 
more than 4.7 million deaths globally and 688,000 deaths in the US as of September 27, 20211. 
SARS-CoV-2 transmission occurs predominantly through oral and nasal routes leading to high 
viral replication in the oropharynx and nasopharynx. 
 
2.2 
Q-GRFT 
Q-GRFT is derived from Griffithsin (GRFT) which is a non-glycosylated protein consisting of 121 
amino acids. Q-GRFT contains a single amino acid substitution, M78Q variant, resistant to 
oxidation yet maintains the parent molecule’s pharmacological profile. 
 
Q-GRFT is obtained from Nicotiana benthamiana plants. It targets mannose residues on the 
surface of viral glycoproteins with nanomolar affinity and neutralizes a broad spectrum of 
coronaviruses. Studies in human bronchial airway epithelium cultures (EpiAirwayTM – AIR-100) 
confirm that Q-GRFT inhibits SARS-CoV-2 infection. Intranasal and inhalation griffithsin (GRFT) 
has shown protection against SARS and MERS respectively in animal models. Over the past 17 
years, three coronaviruses of the Betacoronavirus genus have emerged as serious human 
pathogens. Coronavirus envelope Spike proteins (S) are very heavily glycosylated, with each 
spike trimer displaying 66 N-linked glycans in SARS-CoV-2, 69 in SARS-CoV and 75 in MERS- 
CoV. GRFT and Q-GRFT inhibits viral entry of all coronaviruses tested, including SARS-CoV, 
MERS CoV and SARS-CoV-2. Moreover, delivery of GRFT to the upper respiratory tract provides 
significant protection from SARS-CoV, MERS-CoV and paramyxovirus Nipah virus in animal 
models. Q-GRFT is being investigated for prevention of SARS-CoV-2 infection and is 
administered intranasally for this indication. 
 
2.3 
Rationale 
This is a phase I randomized, placebo-controlled, single site safety study. This is a first in human 
multi-day dose clinical trial of the intranasal formulation. The intranasal formulation of this 
compound could provide an effective prophylactic for SARS-CoV-2 infection. Furthermore, this 
product addresses a much larger need of ensuring that the community is equipped with broadly 
effective antiviral products in the event of the emergence of new coronaviruses. The broad-
spectrum activity of Q- GRFT could provide protection not only against SARS-CoV-2, but also any 
future threats from similar viral pathogens. This product is highly applicable to frontline healthcare 
workers and at- risk populations, including those that are not responsive to vaccines, such as 
immunocompromised people. We hypothesize that prophylactic use of Q-GRFT against SARS- 
CoV-2 via a nasal spray can lead to virus inactivation at the sites of viral entry and replication. 
 
2.4 
Safety Data: Q-GRFT 
Pre-Clinical Safety 
The safety profile of GRFT and Q-GRFT lectins in PBS, saline enema solution and rectal gel 
formulations was found to be excellent. Various published studies had shown absence of 
immunotoxicity in vitro and in murine models2-4. GRFT and Q-GRFT are not mitogenic, do not 
activate T-cells, and induce very little alteration in secretion of inflammatory cytokines in treated 
PBMC from 11 different human donors2,4 (IND 130697 Module 4 Study Report UL-20180925). 
These studies also showed no production of inflammatory cytokines in mucosal secretions of 
rabbits treated with free API and mice treated with GRFT gel formulations. 
 
Upon repeated administration GRFT and Q-GRFT induce antibody responses at low titers. 
However, GRFT polyclonal antibodies raised in rabbits do not neutralize GRFT’s antiviral activity 
(D. Montefiori and K.E. Palmer, unpublished). More importantly, Q-GRFT was found to elicit a 


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systemic antibody response only in the rabbit model and not in rat after 21 consecutive days of 
once-daily intrarectal administration of Q-GRFT gels (IND 130697 Module 4 Study Reports UL- 
20180126 and UL-20180416). However, there was no localized or systemic toxicity observed at 
any dose of drug administered. Hence, Q-GRFT is immunogenic but is not immunotoxic (IND 
130697 Module 4 Study Report M334-17). Moreover, studies described in IND 130697 Module 2 
Sections 2.6.2 and 2.6.4, show that despite these developments, effective antiviral concentrations 
of drug remain in situ after intrarectal application of Q-GRFT (gel or saline enema formulations). 
Intranasal Q-GRFT delivery to rabbits showed ADA in few animals (M495-21), but none in the rat 
model (Study 1901-005). These results further suggest the species difference and the observed 
immunogenicity is likely due to the sensitivity of rabbit model. 
 
The toxicology program for Q-GRFT for IND 130697 assessed gels at 0.3%, 1.0% and 3.0% drug 
concentrations in multi-species studies. No toxicity was observed in any model at any dose of 
drug evaluated. Extrapolating to humans, the 1.0% concentration in a gel (10 mg/mL drug) 
delivered at 4 mL application volume, equates to a 40 mg Q-GRFT dose. This level of drug was 
selected as the clinical dose as it was flanked by lower and higher concentrations in nonclinical 
safety studies, none of which showed toxicity. The drug formulation for clinical administration was 
changed during development from a gel to a saline enema due to gel compatibility issues with 
condoms. Hence, the saline enema solution was administered in a Phase 1 clinical study: 
PREVENT HIV consists of 40 mg Q-GRFT in 125 mL final volume. 
 
Intranasal administration of Q-GRFT nasal spray has been tested in rats and rabbits in Good 
Laboratory Practice (GLP)-compliant toxicity studies. Additionally, genotoxicity was assessed in 
a mouse micronucleus assay and ocular irritation was assessed in NZW rabbits. 
 
Study 1901-005 was a 30-day repeat dose study in CD® rats with a 14-day recovery period. Q- 
GRFT (7.5 mg/mL) was administered by intranasal instillation once daily (SID) or twice daily (BID). 
Control groups included SID and BID vehicle control (formulation without Q GRFT) and negative 
control groups (phosphate-buffered saline only). The dose was 0.3375 mg Q-GRFT per 
administration (0.3375 mg/day for the SID group; 0.675 mg/day for the BID group), corresponding 
to approximately 1X and 2X the planned human dose on an API (mg Q GRFT) per nasal surface 
area basis. The second dose for the BID groups was administered 12 hours after the first dose. 
Evaluations included mortality, clinical signs, body weight, food consumption, ophthalmology, 
clinical pathology parameters (hematology, coagulation, clinical chemistry, and urinalysis), 
toxicokinetic parameters, anti-drug antibody parameters, organ weights, and macroscopic and 
microscopic examinations. Results show no Q GRFT related effects on any parameter examined. 
 
Once or twice daily intranasal administration of Q-GRFT for 30 days at dose levels of 0 (placebo) 
and 0.3375 mg/dose (0, 0.3375, and 0.675 mg/day) to Sprague-Dawley rats resulted in no test 
article-related findings for evaluated parameters (mortality, clinical signs, or effects on body weight 
or macroscopic findings); as well as a lack of immunogenic response. The No-Observed- 
Adverse-Effect-Level (NOAEL) was considered to be 0.675 mg/day (0.3375 mg/dose BID). On 
Day 30, the mean Cmax values at the NOAEL were BLQ and 4.20 ng/mL, for males and females 
respectively. 
 
Study M495-21 is a fifteen-day repeat-dose intranasal and intravenous toxicity study of Q-GRFT 
in New Zealand White Rabbits with a two-week recovery period. Immunogenicity and 
toxicokinetics assessment was conducted to determine potential toxic effects, identify target organ 
of toxicity, and estimate the maximum tolerated dose (MTD) and the NOAEL of test article 
following a single-day (Interim Arm, Phase A) or once daily intranasal or intravenous (IV) dose 
administration to New Zealand White rabbits for 15 days followed by a two-week recovery period 
(Main and Recovery Arms, Phase B). 
 
The IV route of administration was proposed to determine the potential systemic toxicity of the 
test article and allow the highest dose of the test article to be administered. The test articles for 
IV 


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administration was Q-GRFT in Phosphate-buffered Saline (PBS) and corresponding vehicle. IV 
arms included vehicle control Group 2 (IV vehicle, 0 mg API) and Q-GRFT IV treatment Group 5 
(IV, 1.29 mg API, corresponding to approximately 10X the proposed human intranasal dose on a 
weight basis). 
 
The intranasal route is the proposed route for prevention of SARS-CoV-2 in humans. The test 
articles used for intranasal administration in this study matches the clinical drug product 
formulation and corresponding vehicle control. Intranasal dose treatment of vehicle control was 
administered on Day 1 to animals in Group 1 (intranasal vehicle, 0 mg API), and test article Q-
GRFT was administered to Group 3 (intranasal, 1.5 mg API; approximately 1.5X the human 
intranasal dose on a mg/surface area basis) and Group 4 (intranasal, 3 mg API; 3X the human 
intranasal dose on a mg/surface area basis). Each intranasal -dose volume was administered in 
0.05 ml treatment increments alternating briefly, pausing between nares to deliver the entire 
volume. Each treatment group consisted of a single dose arm (Phase A) and a 15-day multidose 
arm (Phase B). 
 
The results of the Phase A single dose interim analysis found that there were no toxicologically 
relevant changes seen in clinical observations, body weights, clinical chemistry, hematology, 
coagulation or urinalysis parameters. There were no macroscopic or microscopic findings 
identified in histology that were considered test article related. The multidose Phase B portion of 
the study showed no test article-related mortalities or macroscopic findings. No toxicologically 
relevant differences were seen in clinical observations, body weights, clinical chemistry, 
hematology, coagulation, or urinalysis parameters. There were incidences of test-article related 
microscopic findings noted for intranasally treated animals, however, these incidences were 
scored “minimal” to “mild”. Specifically, intranasally treated rabbits showed increased incidences 
and/or severity of mixed cell inflammation and increased alveolar macrophages in the lung of low 
dose and high dose males and females. A complete recovery was observed in male rabbits and 
partial recovery in female rabbits. Of note, the same effects were observed sporadically in control 
animals, although at lower severity. This effect may be due to dosing material entering the lungs 
and may therefore be an indirect effect of the protein drug substance in the lungs, and not a direct 
effect due to Q-GRFT’s mode of action. Some evidence of systemic immunogenicity was seen 
with detectable and/or low yet quantifiable amounts of anti-drug antibodies (ADAs) noted in 11 
rabbits following the 15-day intranasal or IV Q-GRFT dose treatment and 14-day recovery period. 
This mild induction of ADA is in contrast to the lack of ADA observed in the 30-day rat exposure 
study. The results also underpin the sensitivity of the species, with the rabbit model showing 
higher sensitivity than rat for immunological and other toxicological findings. Based on these 
findings, the MTD of Q-GRFT is considered equal to or greater than 3 mg API when given 
intranasally and equal to or greater than 1.29 mg API when given intravenously daily for 15 days. 
The NOAEL was not observed for intranasal dose treatment and is therefore considered to be 
less than 1.5 mg API when given intranasally once a day for 15 days. The NOAEL for intravenous 
administration was greater than 1.29 mg API when given once daily for 15 days. 
 
Study M494-21 was a five day repeat dose eye irritation study Q-GRFT intranasal dose 
formulation in New Zealand White Rabbits. The objective of this study was to determine the ocular 
irritation potential of Q-GRFT, formulated for intranasal delivery, after once daily single ocular 
(topical drops) treatment at 0.75 or 1.5 mg administered to the right eye, or twice daily (BID) 
treatment at 1.5 mg to the right eye (total dose of 3 mg/day) administered for 5 consecutive days 
to New Zealand White rabbits. Control Group 1 received twice daily administration of the control 
vehicle to the right eye. The left eye served as the untreated control eye for each animal. Three 
male and female rabbits were assigned to each treatment group. The human dose is 3 mg/ 
intranasal administration and hence the BID animals received the full human clinical dose daily 
for 5 consecutive days. 
 
No animal morbidities or deaths occurred. Clinical observations conducted once daily post-dose 
showed that all animals appeared normal with no adverse findings. No statistically significant 


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changes in group mean body weight was observed compared with controls and all animals 
maintained or gained weight over the course of the study. 
 
No adverse ocular effects were observed following once daily administration of Q GRFT at 0.75 
or 1.5 mg once daily, or twice daily administration of 1.5 mg (3 mg total) for 5 consecutive days. 
Because no adverse ocular effects were observed, the MTD of Q GRFT cannot be determined 
but is considered to be at least 3 mg (1.5 mg twice daily). 
 
Study G529-21 evaluated the effect of Q-GRFT on mouse bone marrow to rule out potential 
genetic toxicity caused by exposure to Q-GRFT API. The objective of this study was to evaluate 
the capacity of Q-GRFT to induce chromosomal or mitotic spindle abnormalities in bone marrow 
cells of treated mice, as indicated by an increased incidence of micronuclei in newly formed, RNA- 
containing erythrocytes (polychromatic erythrocytes, PCE). Male and female Swiss Webster mice 
(Mus musculus) 6-8 weeks of age were the test species (5M/5F per group). Doses ranged from 0 
to 20 mg/kg Q-GRFT; the highest dose equated to 465-times Human Equivalent Dose (20 mg/kg 
mouse/0.043 mg/kg human) if the 3 mg of clinically administered drug (IN) were to be totally 
absorbed. The animals were administered Q GRFT PBS solution or PBS vehicle control solution 
intravenously on Day 1, or urethane positive control solution by oral gavage, via a single 
administration of test article on Day 1. Mortality and morbidity were observed twice daily and 
clinical observations once daily. Body weights were measured at pre-dose for the purpose of dose 
calculation. Necropsies were on Days 2 and 3. Q-GRFT was judged to be negative for the 
induction of micronuclei under the test conditions used in the mouse bone marrow micronucleus 
assay. By this assay, Q-GRFT is not genotoxic. 
 
Clinical Safety 
Q-GRFT has been tested in two clinical studies as part of development for a separate indication 
(prevention of HIV infection). The PREVENT HIV rectal microbicide Phase 1 study was initiated 
in 2019 at the University of Pittsburgh. The study is entitled: “A Randomized, Double-Blind Phase 
1 Safety and Pharmacokinetic Study of Q-Griffithsin Enema Administered Rectally to HIV-1 
Seronegative Adults” (NCT04032717). The purpose of this first in human (FIH) Phase 1 clinical 
study was to assess the safety, tolerability, and acceptability of a single dose of Q-GRFT enema 
in healthy adult participants (aged 18-45 years), practicing receptive anal intercourse (RAI). Study 
participants were topically administered a single rectal dose of study product consisting of either 
40 mg of Q-GRFT in a 125 ml saline enema or a 125 mL saline placebo. The study enrolled 21 
participants, with 15 participants receiving the Q-GRFT enema. To date, the study has reported 
three mild (Grade 2 or lower) AEs with all lab values being within reference ranges. Q-GRFT was 
not detectable in plasma after administration in any participant. Although preliminary, the findings 
of this FIH study of mucosally administered Q-GRFT antiviral lectin are reassuring from the 
standpoint of safety and tolerability. 
 
GRFT has also been investigated by the Population Council (www.popcouncil.org) as a potential 
HIV prophylactic. In a FIH study in 15 female volunteers, griffithsin/carrageenan gel administered 
vaginally for up to 14 days was found to have a favorable safety profile, and no GRFT was 
detected in plasma samples. The results of this study have not yet been published but were 
presented at the HIV R4P conference in October 20185. 
 
2.5 
PK Data: Q-GRFT 
Intranasal administration of Q-GRFT to rats and rabbits indicated low levels of Q-GRFT reach 
systemic circulation with this route of administration. In a rat PK/BA study of Q-GRFT, very low 
levels of systemic exposure were observed after QD and BID intranasal administration, with 
highest plasma level of 14.44 ng/mL, which corresponds to an estimated 0.15% of dose 
administered In a 30 day multi-dose study, rats with once daily or twice daily intranasal 
administration, low levels of Q-GRFT in plasma (1.02 – 21.6 ng/mL) were detected in some 
animals up to 14 hours post-dose. Single day intranasal administration of Q-GRFT nasal solution 
(same as clinical formulation) to rabbits showed mean apparent Cmax of 17.1 ng/ml (male) at a 


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dose of 1.5 mg and 137 ng/ml (males) and 63.2 ng/ml (females) at the 3 mg dose. Q-GRFT was 
eliminated with a mean terminal t1/2 of 15.8 hr (males) and 18.8 hr (females) in the 3 mg intranasal 
group. Repeated daily intranasal administration of Q-GRFT nasal solution to rabbits for 15 days 
showed that the mean apparent Cmax on Day 15 was 61.7 ng/ml (female) at a dose of 1.5 mg, 
and 63.3 ng/ml (males) and 147 ng/ml (females) at a dose of 3 mg. Plasma exposure to Q-GRFT 
was 2.5-fold greater with the BID regimen versus the QD regimen in the intranasal groups on Day 
15, based on AUClast values. The mean AUClast was 1,866 hr*ng/ml in 3 mg dosed females and 
733 hr*ng/ml in 1.5 mg dosed females on Day 15. The bioavailability of intranasal Q-GRFT is 
0.1% in Phase B after repeated administrations, and therefore, accumulation is unlikely to be an 
issue in human studies. A slight (~2x single exposure), increase in exposure was seen with repeat 
dose intranasal (3 mg dose), however, this increase was statistically non-significant (P>0.05) and 
observed in only few animals. 
 
Results of a single-administration PK/BA study showed that the average t1/2 of Q-GRFT DS 
delivered intravenously (IV) in male and female Sprague-Dawley rats is 6-7 hours (Study B949- 
17; see IND 130697). Single dose of IV administered Q-GRFT in male and female rabbits also 
showed a similar terminal t1/2 of 7.7-9.4 h. Whereas, 15-day daily IV administration of Q-GRFT 
had a mean terminal t1/2 of 29.0 h in males and 26.0 h in females after IV administration on Day 
15 and was longer than that observed on Day 1 of single dose study. Although not evaluated in 
same animals, repeat dose administration of Q-GRFT for 15 days seems to have resulted in Q- 
GRFT accumulation in plasma. The mean AUClast on Day 15 (74,825 h*ng/ml in males and 96,992 
h*ng/ml in females) was over 5-fold greater than the mean AUClast on Day 1 (13,454 h*ng/ml in 
males and 17,329 h*ng/ml in females) in IV Group 5 (1.29 mg Q-GRFT). The accumulation of Q- 
GRFT on Day 15 in the IV group might be due to a saturation of metabolism and/or elimination 
pathways of the API. Q-GRFT was not bioavailable intrarectally at either the 0.3% (2.5 mg/kg) or 
3.0% (25 mg/kg) Q-GRFT formulations. The amount of Q-GRFT to be applied intranasally is 
significantly less than the rectal dose and Q-GRFT is not expected to be systemically absorbed 
in significant levels from the nasal application. 
 
Similarly, analyses of rat and rabbit sera from animals administered Q-GRFT carbopol 
formulations in GLP-compliant studies (21-day repeat-dose plus 14-day recovery, Studies M333- 
17 and M334-17) showed no Q-GRFT in any of the samples. These results demonstrated that 
neither Q-GRFT DS nor gel-formulated DP are absorbed systemically when delivered intrarectally 
to rats and rabbits for up to 21-consecutive days at doses up to 3% API. 
 
In PREVENT HIV, the Phase 1 study examining safety and tolerability of rectal administration of 
Q-GRFT, Q-GRFT was not detectable in plasma after administration in any participant. 
 
The length of time that Q-GRFT persists in the nasal mucosa after intranasal administration in 
humans is currently not known and will be examined in this trial. Based on in vivo studies in rats 
and rabbits, intranasal administration of Q-GRFT may result in low levels of systemic exposure. 
 
2.6 
Summary 
Q-GRFT has demonstrated excellent safety in prior in vitro and ex vivo tissue studies, in vivo 
animal studies in three species and preliminarily in human rectal studies. Although there are 
differences between the rectal and nasal mucosae, there are also similarities, and we believe that 
much of the nonclinical information generated for topical microbicide should translate and inform 
the development and use of the nasal formulation. Mucosal surface area exposure in the proposed 
Phase 1 study is lower by a factor of 6-7 than previous studies. These results are sufficient to 
initiate a Phase 1 study for intranasal application of Q-GRFT spray as a prophylactic for SARS-
CoV-2. The successful completion of this study will inform decisions about whether nasal 
administration of Q-GRFT is safe. 
3 
OBJECTIVES 
 
3.1 
Primary Objective: 


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• 
To assess the local and systemic safety of intranasal Q-GRFT after 14 doses 
 
3.2 
Primary Endpoint: 
• 
The proportion of participants who experience a related Grade 2 or higher adverse event 
 
3.3 
Secondary Objectives: 
• 
Persistence: To determine the persistence of Q-GRFT in the respiratory tract after a 
single dose and after 13 days of daily use as assessed by nasopharyngeal swab 
• 
Pharmacokinetics: To determine the systemic absorption of Q-GRFT after administration 
of a single dose and after 13 days of daily use 
• 
Acceptability: To assess the acceptability of a Q-GRFT nasal spray 
 
3.4 
Secondary Endpoints: 
• 
Persistence: Q-GRFT concentrations from nasopharyngeal swabs collected 24 hours 
after a single dose and 24 hours after 13 consecutive daily doses 
• 
Pharmacokinetics: Q-GRFT concentrations in plasma 24 hours after the first dose and 
24 hours after the 13th consecutive daily dose 
• 
Acceptability: Self-reported assessment of qualities of the experience with the nasal 
spray through a Likert scoring of acceptability questions 
 
3.5 
Exploratory Objectives: 
• 
To assess the impact of Q-GRFT nasal spray on smell 
• 
Persistence: Q-GRFT concentrations from oropharyngeal and nares swabs collected 24 
hours after a single dose and 24 hours after 13 consecutive daily doses 
• 
Presence of Q-GRFT in the gastrointestinal tract after 13 days of consecutive use 
• 
Determine the potential of the Q-GRFT study drug product to induce an immune response by 
measuring the generation of anti-drug antibodies (ADAs) in plasma/blood samples after 
multiple Q-GRFT intranasal spray treatments 
 
3.6 
Exploratory Endpoints: 
• 
Change in Brief Smell Identification Test (BSIT) score after 13 days of consecutive daily 
doses compared to baseline 
• 
Persistence: Q-GRFT concentrations from oropharyngeal and nares swabs collected 24 
hours after first dose and 24 hours after the 13th consecutive daily dose 
• 
Presence: Q-GRFT concentrations from rectal swab collected 24 hours after the 13th 
consecutive daily dose 
• 
Immunogenicity of Q-GRFT study product delivered by an intranasal spray system 
• 
Humoral antibody responses to Q-GRFT in plasma/blood by ELISA 
 
 
4 
STUDY DESIGN 
 
4.1 
Identification of Study Design 
This is a phase I randomized, placebo-controlled, single site safety study 
 
 
4.2 
Summary of Major Endpoints 
The proportion of participants who experience a related Grade 2 or higher adverse event. 
 


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4.3 
Description of Study Population 
The study population will be people who meet criteria outlined in Section 5. 
 
4.4 
Time to Complete Accrual 
Accrual is expected to be completed in approximately 6 months. 
 
4.5 
Study Groups 
Participants will be randomized 2:1 to Q-GRFT or placebo intranasal spray. 
 
4.6 
Expected Duration of Participation 
The duration of study participation is expected to be approximately 6-8 weeks. This includes the 
screening period. 
 
4.7 
Site 
There is a single study site: UPMC Magee-Womens Hospital, Pittsburgh, PA. 
 
5 
STUDY POPULATION 
 
5.1 
Selection of the Study Population 
The inclusion and exclusion criteria will be utilized to ensure the appropriate selection of study 
participants. 
 
5.2 
Recruitment 
Participants will be recruited using a combination of outreach for instance through research 
registries at the University of Pittsburgh, use of IRB approved informational flyers and posters,  
and through outreach in the areas and clinics of UPMC Magee-Womens Hospital. This 
combination of recruitment strategies has proven to successfully provide an adequate number of 
eligible participants for a wide range of studies evaluating investigational products. The study 
team includes research staff members who can provide potential study participants with a concise 
synopsis of the study objectives and rationale. If potential participants contact the study office by 
telephone, text or email, the study staff will review the study objectives and review the inclusion 
and exclusion criteria with the potential participants utilizing an IRB approved script. 
 
5.3 
Retention 
Retention of study participants is a high priority and retention of participants in other phase 1 
studies of investigational products has been high (>95%) within our research group. This is 
accomplished through the development of strong locator information including alternative contacts 
including friends and family members, telephone reminders prior to study visits and the 
development of rapport with participants. 
 
5.4 
Inclusion Criteria 
Participants must meet all the following criteria to be eligible for inclusion in the study: 
 
1) Age 18-55 
2) Willing and able to provide written informed consent 
3) In general good health as determined by the site clinician 
4) Willing to have SARS-CoV-2 test performed at screening 
Note regarding positive SARS-CoV-2 test result at screening visit:   
Positive result and asymptomatic: participants may enroll 14 days after a positive test result if they 
remain asymptomatic 
Positive test result and is/becomes symptomatic: participants may enroll 14 days after the start of 


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symptoms or positive results (whichever occurred later) as long as afebrile for 24 hours 
 
5) Fully vaccinated for SARS-CoV-2 (does not include booster vaccination) 
6) Agree to abstain from any other investigational drug studies for the duration of the  study 
7) Agree to abstain from nasally administered products, including over-the-counter products, for 
the duration of the study 
8) Report use of an effective method of contraception at enrollment and intending to continue 
use of an effective method for the duration of study participation. Acceptable methods 
include: 
a) Males: Male condoms, sterilization of participant or partner, partner use of hormonal 
contraception or intrauterine device [IUD], identifies as a man who has sex with men 
exclusively, and/or sexually abstinent for the past 60 days and agrees to remain 
abstinent for the study duration 
b) Females: Hormonal methods at the time of enrollment, IUD inserted prior to 
enrollment, sterilization of participant or partner, consistent condom use of male 
partner for at least 28 days (reports using condoms 10 times in the last 10 acts of 
intercourse), identifies as a woman who has sex with women exclusively, and/or 
sexually abstinent for the past 60 days and agrees to remain abstinent for the study 
duration. 
NOTE:  Male and Female refer to Sex at Birth, not self-identified gender.  
Sexually abstinent refers to penile-vaginal intercourse only. 
9) Agree to participate in all study-related assessments and procedures 
 
5.5 
Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from the study: 
1) Abnormal nasal or throat exam at enrollment 
2) If female, pregnancy, or within 42 days of last pregnancy at screening 
3) If female, breastfeeding 
4) Diagnosed with SARS-CoV-2 in the past 42 days prior to screening 
5) Diagnosed or suspected respiratory tract infection in the past 14 days prior to screening  
6) Participation in an investigational drug study in past 30 days at screening 
7) Any condition that, in the opinion of the Investigator would preclude provision of consent, 
make participation in the study unsafe, complicate interpretation of study outcome data, 
or otherwise interfere with achieving the study objectives 
8) Use of any intranasal product in the 14 days prior to enrollment 
9) Surgical procedure involving the nose or throat 90 days prior to enrollment 
10) Any of the following laboratory abnormalities at screening: 
a.) Hgb < 12g/dL (men) and < 11g/dL (women) 
b.) Serum creatinine > 1.1 x ULN 
c.) ALT, AST, and total bilirubin > 1.1 x ULN 
11) Grade 2 or higher seasonal allergies at the time of enrollment 
12) Reported use of illicit drugs 
a. Non-therapeutic injection drug use in the 12 months prior to screening 
b. Any use of methamphetamine, gamma hydroxybutyrate, cocaine or heroin in the 
12 months prior to screening 
13) Use of systemic prescription immunomodulatory medications within the 4 weeks prior to 
the enrollment 


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6 
STUDY PRODUCTS 
 
6.1 
Regimen 
Each participant will receive a total of 14 doses of intranasal Q-GRFT. A dose consists of two 
sprays into each naris (400 μL total). 
 
6.2 
Administration 
To ensure appropriate placement, the clinician will administer the study product for the first 
application. Participants will be instructed on the proper use of the applicator and have an 
opportunity to practice spraying into a paper towel. Thereafter, participants will administer the 
product themselves. 
 
6.3 
Study Product Formulation 
Griffithsin (GRFT) is a non-glycosylated protein consisting of 121 amino acids. The API to be used 
in this trial contains a single amino acid substitution, M78Q variant, that is resistant to oxidation 
yet maintains the parent molecule’s pharmacological profile6. The drug product is a mixture of Q- 
GRFT API and excipients at a final concentration of 7.5 mg/mL. The Q-GRFT API used for drug 
product manufacture is available as a suspension in PBS at 10±2 mg/mL. The final drug product 
is filled into metered pump nasal spray applicator, Aptar VP7 screw-on actuator fitted to an SGD 
Type 1 Glass Amber U-Save bottle (fill volume not less than 5.5 mL), for intranasal administration. 
A matched vehicle solution is also manufactured and dispensed in same applicators. The device 
requires 5 sprays for priming before first time use and no priming required thereafter for 
subsequent administrations. Both placebo and DP should be stored at 2-8°C. The placebo and 
drug product are manufactured in the Rohan Pharmaceutics Laboratories with CBR International 
serving as the Quality Assurance as per the regulatory requirements for phase 1 products.  
Additional details regarding study product may be found in the study specific pharmacy manual.   
 
6.4 
Study Product Supply and Accountability 
cGMP Q-GRFT and placebo nasal spray bottles will be sent to the Magee-Womens Hospital 
Investigational Pharmacy, and stored at 2-8°C. 
 
The Magee research pharmacist will maintain complete accountability records of all study 
products received for this protocol and provided to participants. Additional documentation will be 
required for study product returns, destruction (if applicable). Unused (once dispensed) study 
products will be handled according to the study specific pharmacy manual.   
 
6.5 
Study Product Provision 
Study product will be provided to clinic staff only upon receipt of a written prescription signed by an 
authorized prescriber. Once the nasal spray bottles are dispensed from the pharmacy and provided to 
the participant, the bottles can be stored at room temperature.   
 
6.6 
Concomitant Medications 
Enrolled study participants may use concomitant medications during study participation except 
immunomodulating drugs and intranasal products as detailed below. All concomitant medications, 
over-the-counter preparations, vitamins and nutritional supplements, recreational drugs, and 
herbal preparations will be recorded on the concomitant medications log form. 
 
All participants will be counseled to avoid the use of intranasal products. Prohibited non-study 
intranasal products include, but are not limited to, decongestants, saline, steroid, and 
antihistamine sprays. Participant use of prohibited medications will be documented. 


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7 
STUDY PROCEDURES 
This section describes visit-specific study procedures. 
 
7.1 
Pre-Screening 
As part of participant outreach and recruitment strategies, study staff may pre-screen potential 
study participants (e.g. via telephone using an IRB approved screening script). During these 
interactions, study staff may explain the study to participants and ascertain elements of 
presumptive eligibility, to be confirmed at an on-site screening visit. If the participant is eligible 
based on a screening script the person’s name and appointment time will be placed on the script. 
If the person signs consent, the telephone script will then become part of the research record. If the 
person does not sign consent, the form will be de-identified. 
 
7.2 
Visit 1: Screening Visit 
At the Screening Visit, participants will provide written informed consent prior to study procedures. 
Study personnel will collect participant locator Information, demographic, and medical history 
information. The participants will undergo a physical examination including a visual examination 
of the nose and throat using a lighted instrument (otoscope).  Safety labs will be obtained, and for 
female participants of child-bearing potential, a urine pregnancy test will be performed. A 
nasopharyngeal swab will be collected for SARS-CoV-2 testing per local standards. Participants 
who meet all eligibility criteria will be scheduled for the enrollment visit (Visit 2) within 60 days of 
the screening visit. 
 
The table below outlines the procedures to take place at the Screening visit. 
 
Table 1: Visit 1 Procedures 
VISIT 1: SCREENING VISIT 
Component 
Procedure/Analysis 
ADMINISTRATIVE 
• 
Written Informed Consent 
• 
Informed Consent Comprehension 
• 
Assign Study Number (PTID) 
• 
Review Eligibility 
• 
Collect Contact Information 
• 
Medical History and Concomitant Medications 
• 
Visit Questionnaire 
• 
Provide Available Screening Results 
• 
Protocol Counseling 
• 
Schedule Next Study Visit, prn 
• 
Participant Reimbursement 
NASOPHARYNGEAL 
• 
SARS-CoV-2 
URINE 
• 
Pregnancy test for participants of childbearing potential 
BLOOD 
• 
CBC with platelets 
• 
ALT, AST 
• 
Creatinine 
• 
Total Bilirubin 
PHYSICAL EXAM 
• 
Full Physical Exam 
• 
Vital Signs (BP) 
• 
Height & Weight 
 
7.3 
Visit 2: Enrollment 
Subjects who meet the inclusion and exclusion criteria following the Screening visit may schedule 
an Enrollment visit. This visit is to occur within 60 days of the Screening Visit. 


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At this visit, locator information will be updated, and eligibility reviewed. Participants will undergo 
a smell assessment prior to drug delivery. The Brief Smell Identification Test (BSIT) contains 12 
odorants embedded on scent strips and released when scratched with a pencil tip. The BIST is a 
forced choice test as participants are instructed to identify an odorant even if no smell is perceived. 
The total olfaction score using the BSIT is defined as the number of odorants that are correctly 
identified.  
 
The participant will be sequence randomized to receive either Q-GRFT nasal spray or placebo 
nasal spray. The clinician will administer the first dose of study product. After reviewing 
administration instructions, the participant will try the metered dose delivery system by delivering 
product into a paper towel. Participants will be asked to wait at the research trial site for one hour 
after product administration for observation. All participants will undergo an assessment of 
adverse events, targeted physical exam, blood draw, and assessment of smell approximately 
one-hour postnasal spray administration. 
 
Interested participants may participate in an optional enrollment visit sampling (nasal, 
oropharyngeal, and nasopharyngeal) at a single timepoint between 1- and 12-hours post product 
administration. Participants must agree to all three sample collections to be eligible for this 
optional enrollment visit sampling. 
 
Table 2: Visit 2 Procedures 
VISIT 2: ENROLLMENT – PRE 
Component 
  Procedure/Analysis 
ADMINISTRATIVE 
• 
Review/Confirm Eligibility 
• 
Collect/Update Contact Information 
• 
Visit Questionnaire 
• 
Quality of Life Survey 
• 
Update Medical History and Concomitant Medications 
• 
Provide Available Screening Results 
• 
Protocol Counseling 
URINE 
• 
Pregnancy Test (participants of childbearing potential) 
PHYSICAL EXAM 
• 
Targeted Physical Exam 
• 
Assessment of Smell (BSIT) 
• 
Vital Signs (BP) 
BLOOD 
• 
Q-GRFT level 
• 
ADA test for Anti Q-GRFT antibodies 
 
NASAL 
• 
Q-GRFT level 
 
OROPHARYNGEAL 
• 
Q-GRFT level 
 
NASOPHARYNGEAL 
• 
Q-GRFT level 
 
STUDY PRODUCT 
• 
Randomized to study product 
• 
Study Product Provision 
• 
Clinician-administered 
1-HR POST-DOSE 
Component 
Procedure/Analysis 
ADMINISTRATIVE 
• 
Assess/Document Adverse Events 
• 
Schedule Next Study Visit 
• 
Participant Reimbursement 
BLOOD 
• 
Q-GRFT level 
• 
CBC with platelets 
• 
ALT, AST 
• 
Creatinine 
• 
Total Bilirubin 


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PHYSICAL EXAM 
• 
Targeted Physical Exam 
• 
Assessment of Smell (BSIT) 
• 
Vital Signs (BP) 
OPTIONAL SINGLE TIME POINT SAMPLES (1 – 12-hour post-dose) 
Component 
Procedure/Analysis 
NASAL 
• 
Q-GRFT level 
OROPHARYNGEAL 
• 
Q-GRFT level 
NASOPHARYNGEAL 
• 
Q-GRFT level 
 
7.4 
Visit 3 Follow-Up Visit 
Visit 3 will occur the day after the enrollment visit. Every effort will be made to time the study visit 
for 24 hours after dosing. At this visit, a safety assessment will be performed via medical interview, 
targeted physical exam, and repeat blood tests. An assessment of participant smell will be 
performed using the BSIT. Samples (blood, nasal, oropharyngeal, and nasopharyngeal) will be 
collected, and an acceptability questionnaire will be administered. 
 
Table 3: Visit 3 Follow-up Visit Procedures 
VISIT 3 FOLLOW-UP VISIT 
Component 
Procedure/Analysis 
ADMINISTRATIVE 
• 
Collect/Update Contact Information 
• 
Visit Questionnaire 
• 
Update Medical History and Concomitant Medications 
• 
Protocol Counseling 
• 
Assess/Document Adverse Events 
• 
Schedule Next Study Visit 
• 
Participant Reimbursement 
ACCEPTABILITY 
• 
Acceptability Questionnaire 
BLOOD 
• 
Q-GRFT level 
• 
CBC with platelets 
• 
AST, ALT 
• 
Creatinine 
• 
Total Bilirubin 
NASAL 
• 
Q-GRFT level 
OROPHARYNGEAL 
• 
Q-GRFT level 
NASOPHARYNGEAL 
• 
Q-GRFT level 
PHYSICAL EXAM 
• 
Targeted Physical Exam 
• 
Assessment of Smell (BSIT) 
• 
Vital Signs (BP) 
 
7.5 
Visit 4 [Extended Dosing; 1st week of study product provision] 
Visit 4 will occur 5-49 days after Visit 3. If any of the safety labs (e.g.Hemoglobin, AST, ALT, 
Creatinine, bilirubin) obtained at Visit 3 are returned as Grade 2 or higher, this visit will be 
postponed until the abnormal lab returns to Grade 1 or Grade 0 but within the 49-day window 
period. 
 Ideally, participants will return within the week for Visit 4 but the extended window will allow for 
flexibility for the participant or any disruptions to visit scheduling caused by external forces, for 
example a spike in SARS-CoV-2 cases at the institution prompting a pause in study visits. 
Medical history will be updated, a targeted physical exam conducted, safety labs, blood and 
respiratory sampling obtained, and study product provided to the participant. After reviewing 
administration instructions with the participant, the first dose of the 13-day course will be self-
administered under direct observation in the clinic. The participant will then self-administer 
product daily at home for the remainder of the dosing period. A one-week supply will be 
provided at Visit 4. 
Participants will be provided with an administration log to record date and time of drug 


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administration. 
 
Table 4: Visit 4 Follow-up Visit Procedures 
VISIT 4 FOLLOW-UP VISIT [week one of extended dosing] 
Component 
Procedure/Analysis 
                                                                                                                           
 
                     
Participants will be contacted in between Visit 4 and Visit 5 to assess for adverse events.  This contact 
will be considered Visit 4a.   
 
7.6 
Visit 5 [Extended dosing; second week of product provision) 
Visit 5 will occur 7 days after Visit 4. A safety assessment will be performed via medical 
interview and physical exam. An assessment of smell will be performed. The second week of 
study product will be provided.  Participants will be provided with an administration log to record 
date and time of drug administration. 
 
Table 5: Visit 5 Follow-up Visit Procedures 
VISIT 5 FOLLOW-UP VISIT [week two of extended dosing] 
Component 
Procedure/Analysis 
ADMINISTRATIVE 
• 
Collect/Update Contact Information 
• 
Visit Questionnaire 
• 
Quality of Life Survey 
• 
Update Medical History and Concomitant Medications 
• 
Protocol Counseling 
• 
Assess/Document Adverse Events 
• 
Provision of Study Product (week two supply) 
• 
Schedule Next Study Visit 
• 
Participant Reimbursement 
PHYSICAL EXAM 
• 
Targeted Physical Exam 
• 
Assessment of Smell (BSIT) 
• 
Vital Signs (BP) 
BLOOD 
• 
CBC with platelets 
• 
AST, ALT 
• 
Creatinine 
• 
Total Bilirubin 
 
ADMINISTRATIVE 
• 
Collect/Update Contact Information 
• 
Visit Questionnaire 
• 
Quality of Life Survey (pre-dose) 
• 
Update Medical History and Concomitant Medications 
• 
Protocol Counseling 
• 
Provision of Study Product (week one supply) 
• 
Assess/Document Adverse Events 
• 
Schedule Next Study Visit 
• 
Participant Reimbursement 
BLOOD 
• 
Q-GRFT level 
• 
CBC with platelets 
• 
AST, ALT 
• 
Creatinine 
• 
Total Bilirubin 
URINE 
• 
Pregnancy test (participants of childbearing potential) 
OROPHARYNGEAL 
• 
Q-GRFT level 
NASAL 
• 
Q-GRFT level 
NASOPHARYNGEAL 
• 
Q-GRFT level 
PHYSICAL EXAM 
• 
Targeted Physical Exam 
• 
Assessment of Smell (BSIT) 
• 
Vital Signs (BP) 


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Participants will be contacted in between Visit 5 and Visit 6 to assess for adverse events.  This contact 
will be considered visit 5a.   
 
7.7 
Visit 6 
Visit 6 will occur approximately 13 days after Visit 4. Every effort will be made to time the study 
visit for 24 hours after the last self-administered dose. At this visit, a safety assessment will be 
performed via medical interview, targeted physical exam, and repeat blood tests. An 
assessment of participant smell will be performed using the BSIT. Blood and respiratory 
samples will be collected. An acceptability questionnaire will be administered. Participants have 
the option to have a rectal swab collected. 
 
Table 6: Visit 6 Follow-up Visit Procedures 
VISIT 6 FOLLOW-UP VISIT [24 hours after last self-administered dose] 
Component 
Procedure/Analysis 
ADMINISTRATIVE 
• 
Collect/Update Contact Information 
• 
Visit Questionnaire 
• 
Quality of Life Survey 
• 
Update Medical History and Concomitant Medications 
• 
Protocol Counseling 
• 
Assess/Document Adverse Events 
• 
Schedule Next Study Visit 
• 
Participant Reimbursement 
BLOOD 
• 
Q-GRFT level 
• 
ADA test for Anti Q-GRFT antibodies 
• 
CBC with platelets 
• 
AST, ALT 
• 
Creatinine 
• 
Total Bilirubin 
ACCEPTABILITY 
• 
Acceptability Questionnaire 
URINE 
• 
Pregnancy test (participants of childbearing potential) 
NASAL 
• 
Q-GRFT level 
OROPHARYNGEAL 
• 
Q-GRFT level 
NASOPHARYNGEAL 
• 
Q-GRFT level 
RECTAL (optional) 
• 
Q-GRFT level 
PHYSICAL EXAM 
• 
Targeted Physical Exam 
• 
Assessment of Smell (BSIT) 
• 
Vital Signs (BP) 


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7.8 
Visit 7 
Visit 7 will occur 28 days after Visit 4. At this visit, a final safety assessment will be performed 
via medical interview, targeted physical exam, and repeat blood tests. An assessment of 
participant smell will be performed using the BSIT. Samples (blood and respiratory) will be 
collected. An acceptability questionnaire will be administered. 
 
Table 7: Visit 7 Follow-up Visit Procedures 
VISIT 7 FOLLOW-UP VISIT 
Component 
Procedure/Analysis 
ADMINISTRATIVE 
• 
Visit Questionnaire 
• 
Quality of Life Survey 
• 
Update Medical History and Concomitant Medications 
• 
Assess/Document Adverse Events 
• 
Participant Reimbursement 
ACCEPTABILITY 
• 
Acceptability Questionnaire 
BLOOD 
• 
Q-GRFT level 
• 
ADA test for Anti Q-GRFT antibodies 
• 
CBC with platelets 
• 
AST, ALT 
• 
Creatinine 
• 
Total Bilirubin 
URINE 
• 
Pregnancy test (participants of childbearing potential) 
NASAL 
• 
Q-GRFT level 
OROPHARYNGEAL 
• 
Q-GRFT level 
NASOPHARYNGEAL 
• 
Q-GRFT level 
PHYSICAL EXAM 
• 
Targeted Physical Exam 
• 
Assessment of Taste and Smell (BSIT) 
• 
Vital Signs (BP) 
 
7.9 
Visit Window Periods 
While every attempt will be made to evaluate the participant on the protocol specified date, the 
following visit windows are allowable 
 
Visit 3: 24 hours after first dose (24-48 hours) 
Visit 4: 5-49 days after Visit 3   
Visit 5: 7 days after Visit 4 (5-7 days) 
Visit 6:  13 days after Visit 4 (12-13 days) * 
Visit 7: 28 days after Visit 4 (25-32 days) 
 
*If scheduling requires that the participant be seen  12 days after Visit 4 rather than 13 days after, 
participants will be instructed to hold the final home dose and present to the clinic the next day  
7.10 Participants Who Become Pregnant 
Urine pregnancy tests will be performed at screening, enrollment Visit 4, Visit 6, and Visit 7 for 
participants of pregnancy potential. Participants who become pregnant will be referred for care. 
Participants will remain in the study for safety but study product will be discontinued, if applicable . 
Pregnant participants will be contacted after their study participation to ascertain the pregnancy 
outcome. 
 
7.11 Interim Visits 
Interim visits may be performed at any time during the study (and study procedures repeated as 
clinically indicated), for the following or other reasons: 
 
• 
In between screening and enrollment or Visits 3 and 4 if laboratory tests need to be 
repeated due to out of range values 


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• 
For administrative reasons, e.g., a participant may have questions for study staff, or may 
need to re-schedule a follow-up visit. 
• 
In response to AEs. When interim contacts or visits are completed in response to 
participant reports of AEs, study staff will assess the reported event clinically and provide 
or refer the participant to appropriate medical care. 
• 
In the event of laboratory processing issues (i.e., lost or inadequate sample) 
• 
For other reasons at participant request. 
 
Details of the interim visit will be recorded in the chart notes. 
 
7.12 Clinical Evaluations and Procedures 
Physical exams will include the following assessments. 
A targeted physical exam will include: 
• 
Vital signs: 
o Blood pressure 
• 
Measurements of: 
o Weight (at Screening only) 
o Height (at Screening only) 
 
• 
Visual assessment of nose and throat 
 
A full physical exam will include the components of the targeted exam as well as the following: 
• 
General appearance 
• 
Cardiac exam 
• 
Respiratory exam 
• 
Abdomen 
 
Additional assessments may be performed at the discretion of the examining clinician in 
response to symptoms or illnesses present at the time of the exam. 


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7.13 
Laboratory Evaluations 
Urine pregnancy test 
Clinical and Translational Research Center 
University of Pittsburgh Medical Center 
300 Halket Street Room 5521 
Pittsburgh, PA 15213 
 
CBC with platelets, AST, ALT, Creatinine, Total Bilirubin, SARS-CoV-2 testing 
UPMC Presbyterian Shadyside CP PUH 
UPMC Clinical Laboratory Building 3477 
Euler Way 
Pittsburgh, PA 15213 
 
Q-GRFT levels in blood, nasal, oropharyngeal, nasopharyngeal, and rectal samples and anti-Q-
GRFT antibodies 
Matoba Laboratory, University of Louisville, Owensboro Cancer Research Program 
 
7.14 Specimen Collection and Processing 
The site will adhere to the standards of good clinical laboratory practice and site standard 
operating procedures for proper collection, processing, labeling, handling, transport, and storage 
of specimens. In cases where laboratory results are not available due to administrative or 
laboratory error, study staff is permitted to re-draw and/or re-collect specimens. 
 
7.15 Biohazard Containment 
As the transmission of SARS-CoV-2 can occur through contact with an asymptomatic infected 
individual, site staff will use appropriate personnel protective equipment per Centers for Disease 
Control guidance. As the transmission of HIV and other blood-borne pathogens can occur through 
contact with contaminated needles, blood, and blood products, appropriate blood and secretion 
precautions will be employed by all personnel in the drawing of blood and shipping and handling 
of all specimens for this study as recommended by the CDC and NIH. All biological specimens 
will be transported using packaging mandated by CFR 42 Part 72. Biohazardous waste will be 
contained according to institutional, transportation/carrier, and all other applicable regulations. 


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8 
ASSESSMENT OF SAFETY AND CLINICAL MANAGEMENT 
 
8.1 
Safety Monitoring 
The study site investigator is responsible for continuous close safety monitoring of all study 
participants, and for alerting the Protocol Chair if unexpected concerns arise. 
 
8.2 
Clinical Data Safety Review 
Appropriate safety monitoring will be contingent upon excellent communication between study 
participants and study staff. Data collected from participants will include changes in medical 
status, concomitant medications and side effects. All adverse events will be reported as outlined 
in the study protocol and will be monitored by the study staff, investigators, and an Independent 
Safety Monitor on a regular basis. Any immediate safety concerns will be brought to the 
attention of the Principal Investigator. Adverse events will be reported to the IRB as required by 
IRB guidelines. 
 
An Independent Safety Monitor who is familiar with the pertinent scientific literature related to 
intranasal medications and potential side effects will be responsible for safety monitoring. This 
individual will be a physician independent of the study sponsor and the principal investigators 
and will be available to monitor data from this single site. The Independent Safety Monitor 
will evaluate adverse event data on a routine basis to determine whether the study protocol 
should continue as originally designed, should be changed, or should be terminated. Any 
change to the anticipated benefit-to-risk ratio identified will be reported to the IRB. In addition, 
any breaches of confidentiality will be reported for review. 
 
8.3 
Adverse Events Definitions 
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product that does not necessarily have a causal 
relationship with the study product. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease temporally associated with the 
use of a medicinal (investigational) product, whetheror not related to the medicinal 
(investigational) product (see the ICH Guideline for Clinical Safety Data Management: Definitions 
and Standards for Expedited Reporting). 
 
SAEs will be defined by the Manual for Expedited Reporting of Adverse Events to DAIDS (Version 
2.0, January 2010), as AEs occurring at any dose that: 
• Results in death 
• Is life-threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• Is an important medical event that may not result in death, be immediately life-threatening, or 
require hospitalization but may jeopardize the participant or require intervention to prevent one of 
the above 
 
Study participants will be provided instructions for contacting the study site to report any untoward 
medical occurrences they may experience, except for possible life-threatening events, for which 
they will be instructed to seek immediate emergency care. Where feasible and medically 
appropriate, participants will be encouraged to seek evaluation at UPMC Magee-Womens 
Hospital, where the study clinicians are based, and to request that a study clinician be contacted 
upon their arrival. All participants reporting a clinically significant untoward medical occurrence 
will be followed either in person or by phone until the occurrence resolves (returns to baseline) or 
stabilizes over a four-week period. 


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For each study participant, AE documentation and reporting will be undertaken throughout the 
scheduled duration of follow-up. 
 
The Protocol chair/designee will grade the severity of each AE and the relationship of the AE to 
study product: 
 
AE severity will be graded per the DAIDS Table for Grading Adult and Pediatric Adverse Events, 
Version 2.1, July 2017 
 
It is anticipated that most AEs will not be specifically identified in the DAIDS toxicity table and will 
be graded by the Estimating Severity Grade for Parameters Not Identified in the Grading Table 
row of the toxicity table. 
 
Table 8: DAIDS toxicity table 
 
 
Relatedness is an assessment made by a study clinician of whether the event is related to the 
study agent. Degrees of relatedness will be categorized according to current DAIDS-approved 
guidelines. Per the Manual for Expedited Reporting of Adverse Events to DAIDS (Version 2.0, 
January 2010), the relationship categories that will be used for this study are: 
• Related: There is a reasonable possibility that the AE may be related to the study agent(s) 
• Not Related: There is not a reasonable possibility that the AE is related to the study agent(s) 
 
All AEs will be captured through REDCap on an AE log form. The form should be reviewed at each 
study visit and updated as needed. For any serious AEs (SAEs) that are continuing at a 
participant’s study exit visit, the Protocol chair or designee must establish a clinically appropriate 
follow-up plan for the AE. At a minimum, the AE must be re-assessed by study staff at least 2 
weeks after the participant’s study exit visit; additional evaluations also may take place at the 
discretion of the PI/designee. The same approach must be taken for any AEs deemed related to 
study product that are found to have increased in severity at the study exit visit. For those AEs 
requiring re- assessment, if the AE has not resolved or stabilized at the time of re-assessment, 
study staff will continue to re-assess the participant at least once per month while the study is 
ongoing. After the study has ended, all AEs requiring re-assessment will be re-assessed at least 
once within the 30-60 days after the study end date. 
 
8.4 
Clinical Management of Adverse Events 
By definition, an adverse event can be either new finding or symptom or a worsening of a pre- 
existing condition. In order to accurately capture adverse events in follow-up, a thorough baseline 
history will be obtained at Visit 1. For example, for participants who endorse a history of headache, 
site staff will probe for and record details surrounding the condition such as frequency, location, 
duration, medication use, triggers, etc. Only by eliciting a full description will study staff be 
equipped to determine whether a subsequent event in follow-up is a clinically distinct event or not. 


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Adverse events will be elicited at each follow-up visit. Referral to appropriate care will be offered 
to participants as needed. 
Any Grade 3 AE’s that are deemed to be related to the study product will be reviewed within 5 
days by an ENT investigator.  The ENT investigator and the PI will determine whether the 
participant will continue in the study. 
If a participant experiences a Grade 4 AE related to the study product or any SAE related to the 
study product, the study product will be held. The AE will be reviewed by the ENT investigator 
within 3 days. They will be discontinued from the study and followed for safety and outcome of 
the event.   
 
8.5 
Product Removal 
In the unlikely event that a participant is intolerant of the study product immediately after 
placement, the site clinician will remove any residual drug with a sterile saline wash and a 
moistened swab if necessary. 
 
8.6 
Criteria for Early Termination of Study Participation 
Participants may voluntarily withdraw from the study for any reason at any time. The Site 
PI/designee also may withdraw participants from the study to protect their safety and/or if they are 
unwilling or unable to comply with required study procedures. Participants also may be withdrawn 
if the study sponsors, government or regulatory authorities, including the Office of Human 
Research Protections (OHRP), or site IRBs/ECs terminate the study prior to its planned end date. 
Every reasonable effort is made to complete a final evaluation of participants who withdraw or are 
withdrawn from the study prior to completing follow-up. Study staff members will record the 
reason(s) for all withdrawals in participants’ study records. 


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9 
STATISTICAL CONSIDERATIONS 
 
9.1 
Review of Study Design 
This is a first in human multi-day dose phase 1 randomized, double-blind, placebo-controlled 
study to evaluate safety after 14 doses of Q-GRFT prepared in saline. The primary aim of the 
study is to assess the local and systemic safety of nasally administered Q-GRFT in healthy 
adults. The primary endpoint is the proportion of participants who experience a Grade 2 or 
higher related adverse event. 
 
9.2 
Sample Size and Accrual 
Accrual of approximately 45 evaluable participants is expected to take 6 months. The expected 
duration of study participation for each participant will be approximately 6-8 weeks. This includes 
the screening period. Participants will be randomized 2:1 (Q-GRFT nasal spray: placebo nasal 
spray) resulting in 30 participants enrolled into the Q-GRFT arm and 15 participants enrolled into 
the placebo arm. 
 
The primary aim of the study is to assess the local and systemic safety of nasally administered 
Q-GRFT in healthy adults. The primary endpoint is the proportion of participants who experience 
a Grade 2 or higher adverse event deemed related to study product. The proposed total sample 
size is N=45 divided into 2 arms (Q-GRFT and placebo assigned at a 2:1 ratio). The sample size 
is based on the exact binomial probability of observing at least two Grade 2 or higher related 
adverse events in the Q-GRFT arm. Table 1 gives the upper and lower bounds for the 95% exact 
binomial confidence intervals of the true Grade 2 or higher adverse event rate at all possible 
numbers of observed events in a group of size 30. Note that the results for more than 50% of 
events in each group are not listed, but by symmetry can be calculated as 1- the listed rate and 
95% CI for the number of non-events. If none of the 30 participants experience Grade 2 or higher 
adverse events, the 95% exact 2-sided upper confidence bound for the Grade 2 adverse event 
rate is 11.6%. In a Cochrane review of intranasal steroids for rhinosinusitis, the rate of any adverse 
event was 5.5%8. If similar event rates are observed in the proposed study, we will be able to rule 
out Grade 2 or higher adverse event rates greater than 22.1% in the Q-GRFT study arm. 
 
Table 9: 95% confidence intervals for the true rate at all possible observed Grade 2 or higher 
adverse event rates 
Number of 
observed 
events 
Rate (95% CI) 
0/30 
0 (0, 11.6%) 
1/30 
3.3% (0.1%, 17.2%) 
2/30 
6.7% (0.8%, 22.1%) 
3/30 
10.0% (2.1%, 26.5%) 
4/30 
13.3% (3.8%, 30.7%) 
5/30 
16.7% (5.6%, 34.7%) 
6/30 
20.0% (7.7%, 38.6%) 
7/30 
23.3% (9.9%, 42.3%) 
8/30 
26.7% (12.3%, 45.9%) 
9/30 
30.0% (14.7%, 49.4%) 
10/30 
33.3% (17.3%, 52.8%) 
11/30 
36.7% (19.9%, 56.1%) 
12/30 
40.0% (22.7%, 59.4%) 
13/30 
43.3% (25.5%, 62.6%) 
14/30 
46.7% (28.3%, 65.7%) 
15/30 
50.0% (31.3%, 68.7%) 


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9.3 
Study Endpoints 
9.3.1 Primary Endpoint 
The proportion of participants who experience a related Grade 2 or higher adverse event. 
 
9.3.2 Secondary Endpoints 
Persistence: Q-GRFT concentrations from nasopharyngeal swabs 1) collected 24 hours after a 
single dose and 2) collected 24 hours after 13 consecutive daily doses 
Pharmacokinetics: Q-GRFT concentrations in plasma 1) 24 hours after the first dose and 2) 24 
hours after the 13th consecutive daily dose 
Acceptability: Self-reported assessment of qualities of the experience with the nasal spray as 
assessed by acceptability questionnaires. Product attributes considered likely to discourage 
future use by participants, will be dichotomized as having a rating of lower than 3 on a 5-point 
Likert scale. 
 
9.3.3 Exploratory Endpoints 
Change in Brief Smell Identification Test (BSIT) score after 13 days of consecutive daily doses 
compared to baseline 
Persistence: Q-GRFT concentrations from oropharyngeal and nares swabs collected 1) 24 
hours after first dose and 2) 24 hours after the 13th consecutive daily dose 
Presence: Q-GRFT concentrations from rectal swab collected 24 hours after the 
13th consecutive daily dose 
Immunogenicity of Q-GRFT study product delivered by an intranasal spray 
system 
Humoral antibody responses to Q-GRFT in plasma/blood by ELISA 
 
9.4 
Blinding and Unblinding 
Blinding will be maintained until all data are entered into the study database, all study endpoint 
data and other data included in the final analysis have been cleaned and verified, and the data 
are ready for final analysis. 
 
Unblinding may need to be performed on an individual basis for assessment of a serious AE 
and/or for the safety of the participant. Details of emergency unblinding are specified in an SOP. 
 
9.5 
Randomization 
The randomization scheme will be generated and maintained by a member of the Data 
Management Center at Magee-Womens Research Institute and supplied to the Pharmacy at 
Magee-Womens Hospital. Participants will be randomized to the sequence of the two nasal spray 
formulations, active or placebo, in a 2:1 ratio using a permuted block design with random block 
sizes of 3 and 6. To minimize bias in the group assignment, participants will be given study 
randomization numbers. Participants will be randomized using REDCap’s randomization module 
to obtain the sequence of product assignment. When a participant is ready to be randomized, the 
study investigator (PI/Co-I) will open the Randomization eCRF in REDCap and confirm that the 
participant is being enrolled. REDCap will then assign a randomization number which the study 
investigator (PI/Co-I) will print and take to the pharmacy to obtain the study product indicated by 
the randomization scheme. The study product will be labeled in order to mask the product 
assignment to the participants and study staff. The randomization scheme will be created for a 
total of 48 participants. 
 
9.6 
Data Monitoring and Analysis 
9.6.1 Data Monitoring 


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This clinical trial will be conducted in compliance with the protocol, GCP guidelines, and applicable 
regulatory requirements. All paper research charts are maintained in locked files in a locked room. 
The data management research staff, under the direction of the primary investigator, will create 
and maintain databases using REDCap (Research Electronic Data Capture) which is a secure, 
validated, web-based application designed for clinical trial data collection. The databases will be 
backed up nightly, weekly, and monthly onto the University of Pittsburgh’s server’s back-up 
system. Appropriate firewall and virus scanning software are installed and updated routinely by 
the university support staff. 
 
This study will utilize electronic data capture. Site staff will enter data as collected directly into a 
data entry system. Study data management staff will review the electronic data elements for 
completeness and accuracy. If there are any responses that are incomplete, unclear, or 
inconsistent with related data elements, the staff person will communicate with the clinician in 
question as soon as possible to resolve the problem. If necessary, the study staff will make the 
appropriate change in the electronic database which tracks time, date, and by whom a change is 
made. 
 
9.6.2 Statistical Analysis 
The number of adverse events will be summarized by severity, body system, and relationship to 
study product using frequencies and percent. Individual participants will contribute once to the 
calculation of event rates. Differences in the prevalence of adverse events between the study 
arms will be assessed using Fisher’s exact test. 
 
Descriptive statistics (frequency, medians, range, means, standard deviation) will be used to 
summarize the secondary and exploratory endpoints. Differences in Q-GRFT concentration and 
BSIT score between the study arms will be evaluated using Student’s t- or Mann Whitney U tests, 
where appropriate. Fisher’s exact tests will be used to assess differences in the presence of Q- 
GRFT in the gastrointestinal tract and dichotomized acceptability endpoints between the two study 
arms. Spearman’s correlation coefficients Fisher’s exact, and Mann-Whitney U tests may be used 
in exploratory analyses to evaluate the impact of gender, age and race on the pharmacokinetics 
and acceptability of the Q-GRFT nasal spray. 
 
9.6.3 Analysis Cohort 
The intent-to-treat cohort (ITT) will be defined as those who were enrolled. It will be used for 
analyses of baseline characteristics, protocol deviations and violations, and trial conduct. The 
evaluable cohort (Eval) is a subset of ITT participants. Evaluable participants will be defined as 
participants who complete Visit 6 procedures. 


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10 HUMAN SUBJECTS CONSIDERATIONS 
The investigators will make efforts to minimize risks to human subjects. Volunteers will take part 
in a thorough informed consent process throughout their participation in the study. Before 
beginning the study, the investigators will have obtained IRB approval. The investigators will 
permit audits by the NIH or any of their appointed agents. 
 
10.1 Special Populations 
Study staff will offer screening to people of all ethnic and racial groups. Members of the study staff 
are not seeking the screening or enrollment people in special or vulnerable populations. 
 
Women and Minorities 
SARS-CoV-2 uninfected women and men of all races and ethnicities represented at the Magee- 
Womens Hospital clinical site will be recruited into the clinical protocol. Men and women who 
provide written informed consent and meet the eligibility criteria will be enrolled. It is anticipated 
that gender distribution of the 45 study participants will be approximately 60% female (n=27) and 
approximately 40% male (n=18). While SARS-CoV-2 infects women and men equally, a larger 
proportion of female participants is anticipated based on the recruitment population available at 
Magee-Womens Hospital. Allegheny county, the location of Magee-Womens Hospital, has a 
population of approximately 2.2 million and is comprised of 89% white not Hispanic, 13% black or 
African American, 2% Hispanic, 4% Asian, 2% mixed race and 0.2% American Indian. The 
anticipated study population is expected to reflect the distribution of Allegheny County residents, 
except for Black or African Americans who will be recruited preferentially to comprise at least 20% 
of the study population since blacks and African Americans are disproportionately impacted by 
Covid-19. In our past phase 1 studies of investigational products, we have been able to accomplish 
recruitment of a larger proportion of black and African American study participants through 
outreach at clinics having high attendance by underrepresented minority patients and through the 
use of culturally competent and diverse study staff who have developed strong relationships with 
minority communities in Allegheny County. 
 
Children 
This clinical study is not seeking to enroll special or vulnerable populations or children < 18 years 
of age.  This clinical trial will be the first-in-human multi-day dose study of an investigational drug 
product intended to provide protection from infection by SARS-CoV-2, the virus which causes 
Covid-19. The study is designed to evaluate the safety of a new product for which the safety 
profile is not yet defined. Studies conducted in children are generally deferred until such time as 
the safety of an investigational product has been established in a healthy adult population. 
 
Prisoners 
Prisoners will not be included in this study (for screening or enrollment). Any participants 
incarcerated during participation in the trial will not be followed during their incarceration and will 
be discontinued from the study. 
 
Pregnant women 
Pregnancy is an exclusion criterion as this is a first in human multi-day dose study. Women who 
become pregnant during the study period following enrollment will not be excluded from analysis. 
Participants who become pregnant during the study will continue with follow up visits and will be 
contacted periodically after study completion in order to determine the pregnancy outcome. 
 
10.2 Informed Consent Process 
Written informed consent will be obtained from all potential study participants prior to the initiation 
of any study-related procedures. The informed consent process will give individuals all the 
relevant information they need in order to decide whether to participate, or to continue 


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participation, in this study. Potential research participants will be permitted to ask questions and 
to exchange information freely with the study investigators. Only listed study investigators may 
obtain informed consent from potential study participants. The investigators will keep research 
participants fully informed of any new information that could affect their willingness to continue 
study participation. 
 
Risk/Benefit Statement 
Risks 
It is not expected that this study will expose healthy participants to unreasonable risk. While this 
is the first in human multi-day dose assessment of Q-GRFT administered intranasally, Q-GRFT is 
under evaluation n a Phase I clinical trial as a rectal enema product for HIV prevention at Magee-
Womens Research Institute within an NIAID U19 funded collaboration between the University of 
Pittsburgh and the University of Louisville (U19 AI113182, K. Palmer Program Director). No safety 
issues have been identified to date in 15 healthy volunteers who have received a single dose 
enema containing 10mg/mL of Q-GRFT in phosphate buffered saline. 
 
As with any intranasally administered product, nasal congestion, nasal discharge, nasal burning, 
nasal irritation, increased mucus, nasal dryness, sneezing, coughing, pharyngitis, epistaxis, 
mucosal erythema, nasal ulceration, interference with taste and smell, tinnitus, and headache are 
potential risks and participants will be closely monitored for these. Hypersensitivity reactions 
(including contact dermatitis and rash) are rare risks with any product. As the drug is intended to 
work at the mucosal surface, systemic side effects are presumed to be exceptionally unlikely. 
Nonetheless, safety labs including CBC with platelets, AST, ALT, total bilirubin and creatinine will 
be checked pre and post administration. 
 
A rare but potentially life-threatening risk of exposure to nasal spray containing Q GRFT or the 
placebo spray would be anaphylaxis. Risk will be mitigated by having the single application of the 
product in the clinical research site and having people remain in the clinical trial facility for 1 hour 
after application. 
 
Additional Risks: 
Nasal specimen collection may cause mild discomfort and/or nasal spotting. Oropharyngeal swab 
collection may induce a gag reflex and cause mild discomfort. Nasopharyngeal swabs may cause 
discomfort, eyes to water, coughing/gagging. Phlebotomy may lead to discomfort, feelings of 
dizziness or faintness, bruising, swelling and/or infection. Collecting a rectal swab may cause 
discomfort. Testing positive for SARS-CoV-2 could impact a participant’s social and work 
schedule. Testing positive for pregnancy may cause anxiety. 
 
Potential participants will be screened for SARS-CoV-2 at the screening visit. Anxiety and 
depression surrounding a positive result is a risk. A positive test result will necessitate that the 
Allegheny County Health Department be notified; the potential participant will be counselled about 
this possibility which would likely result in a period of self-quarantine and disruption to his or her 
daily life. 
 
Participation in clinical research includes the risks of loss of confidentiality and discomfort with 
personal nature of questions 
 
Benefits 
Participation in these studies may have no direct benefit to volunteers. All volunteers will receive 
a SARS-CoV-2 test, which some may consider a benefit. Some volunteers may have the 
opportunity to access expedient treatment and decreased morbidity due to early diagnosis and 
treatment of abnormalities in blood count, liver or kidney function tests that would have otherwise 
not been detected. Lastly, the participant may appreciate the opportunity to contribute to the body 
of knowledge in the field of SARS-CoV-2 research. However, there is no guarantee that volunteers 
will receive any of these benefits. 


PREVENT V.5.0 
35 
07JUL 22 
 
 
 
10.3 Incentives 
 
Volunteers will not be charged for any of the study visits, study supplies or examinations. There 
are no costs to participants in this study. Pending IRB approval of compensation guidelines, 
participants will be compensated for their time and inconvenience and for their travel needs 
while participating in the protocol. The approved amounts of compensation for the time 
commitment of participants will be given out at each visit. The visits will be pro-rated and partial 
payment given if the participant only completes a portion of the study visits.  
 
10.4 Participant Confidentiality 
Members of the study staff are all trained in patient confidentiality. The log of study subject names 
and other protected health information is kept in a secure location. All computer information about 
study volunteers is kept on a computer with log-on passwords. Laboratory specimens are labeled 
with study numbers and date and are delivered by study staff. In addition to the research study 
staff, NCI, study monitors, University of Pittsburgh, University of Pittsburgh Office of Research 
Protections, and/or the University of Pittsburgh IRB may have access to participant’s health 
information. Each member of the staff has log-on identification and password, logs off before 
leaving a computer screen unattended, and closes their office door when out of the office. All 
research records will be kept for a minimum of seven years following closure of this study (per 
University of Pittsburgh policy). 
 
10.5 Communicable Disease Reporting 
Study staff members will comply with all local requirements to report communicable diseases 
including SARS-CoV-2 identified among study participants to the Allegheny County Health 
Department. Study investigators will include discussion of mandated reporting during the study 
informed consent process. 
 
10.6 Study Pause/Discontinuation 
NCI or the University of Pittsburgh Institutional Review Board may discontinue this study at any 
time. Ongoing safety monitoring will track the incidence of AEs.  
The study will be paused if the following should occur: 
• 
Two or more Grade 3 AEs that are similar in nature and related to study product 
• 
Any Grade 4 AE or SAE related to study product 
If the study is paused, the Independent Safety Monitor will evaluate the safety data and 
recommend whether the study should be discontinued or may be continued with or without a 
protocol amendment.   


PREVENT V.5.0 
36 
07JUL 22 
 
 
 
11 LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT 
 
11.1 Laboratory Specimens 
Laboratory specimens will be handled in a manner consistent with institutional, OSHA, and GLP 
guidelines. Study staff members are trained in the appropriate handling of laboratory specimens. 
 
Table 10: Laboratory Test Methods 
SAMPLE 
METHOD 
LABORATORY 
URINE 
Pregnancy test 
Clinical Research Center 
CLIA #39D1031322 
NASOPHARYNGEAL SARS-CoV-2 
UPMC Presbyterian Shadyside CP PUH 
CLIA# 39D0911193 
Q-GRFT Level 
Owensboro Cancer Research Program 
BLOOD 
CBC with platelets, AST, 
ALT, Creatinine, Total 
Bilirubin 
UPMC Presbyterian Shadyside CP PUH 
CLIA# 39D0911193 
Q-GRFT Level 
Owensboro Cancer Research Program 
Anti-Q-GRFT Antibody  
Owensboro Cancer Research Program 
OROPHARYNGEAL, 
NASAL 
Q-GRFT Level 
Owensboro Cancer Research Program 
RECTAL 
Q-GRFT Level 
Owensboro Cancer Research Program 
 
11.1.1 Urine Samples 
Urine will be tested for HCG via the Sure-Vue® test or equivalent FDA-cleared test. 
 
11.1.2 Respiratory Samples 
The assessment of SARS-CoV-2 in the nasopharynx will be assessed by Nucleic Acid 
Amplification (NAAT) test. Q-GRFT concentrations from nasal, oropharyngeal and 
nasopharyngeal swabs will be measured according to SOP. 
 
Collection will be done as gently and carefully as possible to collect an adequate sample that is 
unlikely to disturb the mucosa. 
 
11.1.3 Blood 
Q-GRFT concentrations from blood will be measured according to SOP. 
 
 


PREVENT V.5.0 
37 
07JUL 22 
 
 
 
 
11.2 Biohazard Containment 
Biohazardous waste will be contained according to institutional and all other applicable 
regulations. 
 
 
12 ADMINISTRATIVE PROCEDURES 
The study proposal for funding, this protocol, the informed consent document, data collection 
forms, and advertising flyers are all reviewed by the University of Pittsburgh Institutional Review 
Board prior to enrollment of participants in the study. 
 
12.1 Protocol Registration 
This NIH-funded clinical trial will be registered on ClinicalTrials.gov after the protocol is at 
version 1 and the submission of the protocol has been completed to the US Food and Drug 
Administration and to the University of Pittsburgh IRB. Updates of the record on 
ClinicalTrials.gov will be made to record when the study is open for accrual, when the study has 
closed to accrual as well as summaries of the results from the study. These updates are 
accomplished by Dr. Leslie Meyn who heads the Data Management group. Informed consent 
documents for the clinical trial will include a specific statement relating to posting of clinical trial 
information at ClinicalTrials.gov. The University of Pittsburgh has an internal policy in place to 
ensure that clinical trials registration and results reporting occur in compliance with policy 
requirements including reminders and updates throughout the year. 
 
12.2 Data Coordination 
Data management responsibilities will reside with the Data Management staff at Magee-Womens 
Research Institute. 
 
12.3 Study Monitoring 
The University of Pittsburgh Education and Compliance Office for Human Subject Research 
(ECO-HSR) will conduct the study monitoring. 
 
The site investigator will make study documents and REDCap as applicable (e.g., consent forms, 
drug distribution forms, eCRFs) and pertinent hospital or clinic records readily available for 
inspections by the local IRB, the site monitors, the FDA, NCI, the OHRP, and other local and US 
regulatory entities for confirmation of the study data. 
 
12.4 Protocol Compliance 
All protocol amendments will be submitted to and approved by the University of Pittsburgh IRB. 
 
12.5 Investigator’s Records 
The investigator will maintain, and store securely, complete, accurate and current study records 
throughout the study. Study records will not be destroyed prior to receiving approval for record 
destruction from the Principal Investigator and they will be maintained for a minimum of seven 
years following completion of the study, per the University of Pittsburgh IRB policy. Applicable 
records include source documents, site registration documents and reports, correspondence, 
informed consent forms, and notations of all contacts with the participant. 


PREVENT V.5.0 
38 
07JUL 22 
 
 
 
APPENDIX 1 SCHEDULE OF STUDY VISITS AND PROCEDURES 
 
Component 
Procedure/Analysis 
V1: 
Screen 
V2: 
Enroll 
V3 
V4 
V5 
V6 
V7 
ADMINISTRATIVE 
Written Informed Consent 
X 
Assign Study Number (PTID) 
X 
Review/Confirm Eligibility 
X 
X 
Collect/Update 
Contact Information 
X 
X 
X 
X 
X 
X 
X 
Medical Hx/Concomitant Meds 
X 
X 
X 
X 
X 
X 
X 
Visit Questionnaire 
X 
X 
X 
X 
X 
X 
X 
 Quality of Life Survey 
 
X 
 
X 
X 
X 
X 
Provide Screening Results 
X 
X 
Protocol counseling 
X 
X 
X 
X 
X 
X 
Assess/Document Adverse 
Events 
 
X (post) 
X 
X 
X 
X 
X 
Schedule Next Study Visit 
X 
X 
X 
X 
X 
X 
Participant Reimbursement 
X 
X 
X 
X 
X 
X 
X 
Safety/AE Assessment Contact 
 
 
X(V4a) X (V5a) 
 
 
ACCEPTABILITY 
Acceptability Questionnaire 
 
X 
X 
X 
NASAL/THROAT 
Q-GRFT level 
X 
X 
X 
X 
X 
BLOOD 
CBC with 
Platelets, AST, 
ALT,Cr, Total 
Bilirubin 
X 
X 
X 
X 
X 
X 
X 
Q-GRFT level 
X 
X 
X 
X 
X 
Anti-Q-GRFT antibody 
X 
 
 
X 
X 
NASOPHARYNGEAL 
Q-GRFT level 
X 
X 
X 
X 
X 
SARS-CoV-2 
X 
URINE 
Pregnancy Test, as applicable 
X 
X 
X 
X 
X 
PHYSICAL EXAM 
Physical Exam (full 
vs. targeted) 
X 
X 
X 
X 
X 
X 
Vital Signs (BP) 
X 
X 
X 
X 
X 
X 
Height & Weight 
X 
 BSIT 
Assessment of Smell 
X 
X 
X 
X 
X 
X 
STUDY PRODUCT 
Provision of Study Product 
X 
X 
X 


PREVENT V.5.0 
39 
07JUL 22 
 
 
 
REFERENCES 
 
1. 
WHO Coronavirus (COVID-19) Dashboard. (https://covid19.who.int/). 
2. 
O'Keefe BR, Vojdani F, Buffa V, et al. Scaleable manufacture of HIV-1 entry inhibitor 
griffithsin and validation of its safety and efficacy as a topical microbicide component. 
Proc Natl Acad Sci U S A 2009;106(15):6099-104. DOI: 10.1073/pnas.0901506106. 
3. 
Nixon B, Stefanidou M, Mesquita PM, et al. Griffithsin protects mice from genital herpes 
by preventing cell-to-cell spread. J Virol 2013;87(11):6257-69. DOI: 10.1128/JVI.00012- 
13. 
4. 
Kouokam JC, Huskens D, Schols D, et al. Investigation of griffithsin's interactions with 
human cells confirms its outstanding safety and efficacy profile as a microbicide 
candidate. PLoS One 2011;6(8):e22635. DOI: 10.1371/journal.pone.0022635. 
5. 
Lal M LM, Ugaonkar S, Wesenberg A, Kizima L, Rodriguez A, Levendosky K, Mizenina 
O, Fernández-Romero J, Zydowsky T. Self-administered Griffithsin and Carrageenan 
Containing Microbicide Fast-dissolving Insert as Pre-exposure Prophylaxis Against HIV 
and HPV Infections. HIV Research for Prevention 2018, October 21-25, 2018. Madrid, 
Spain. 
6. 
Ziolkowska NE, Wlodawer A. Structural studies of algal lectins with anti-HIV activity. 
Acta Biochim Pol 2006;53(4):617-26. (https://www.ncbi.nlm.nih.gov/pubmed/17128290). 
7. 
Doty RL, Marcus A, Lee WW. Development of the 12-item Cross-Cultural Smell 
Identification Test (CC-SIT). Laryngoscope 1996;106(3 Pt 1):353-6. DOI: 
10.1097/00005537-199603000-00021. 
8. 
Chong LY, Head K, Hopkins C, Philpott C, Schilder AG, Burton MJ. Intranasal steroids 
versus placebo or no intervention for chronic rhinosinusitis. Cochrane Database Syst 
Rev 2016;4:CD011996. DOI: 10.1002/14651858.CD011996.pub2. 

ICF_001.pdf: 
 
Phase 1 Clinical Trial of a Q GRFT Nasal Spray 
 
NCT05180500 
 
Document/IRB Approval Date: November 15, 2022 


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                                                                      Page 1 of 12                                          
Magee-Womens Hospital
of University of Pittsburgh Medical Center
     300 Halket Street   Pittsburgh, PA  15213-3180
CONSENT TO ACT AS A PARTICIPANT IN A RESEARCH STUDY
Study Title
Phase 1 Clinical Trial of a Q GRFT Nasal Spray [PREVENT COVID 101]
Consent Version
7.0  07Jul2022
Protocol Version
5.0 07Jul2022
Principal Investigator
Katherine Bunge, MD,  UPMC Magee-Womens Hospital 
Researcher’s phone #
412-641-4242 
Funding agencies
National Cancer Institute
********************************KEY INFORMATION*********************************
You are being asked to take part in a research study.  Participation is voluntary.  The study involves 
evaluating the safety of an investigational Q-GRFT nasal spray being studied as a potential future 
prevention of SARS-CoV2 (COVID) infection.  Q-GRFT nasal spray has not been Food and Drug 
Administration (FDA) approved.  Approximately 45 evaluable participants will take part in this study at 
UPMC Magee-Womens Hospital.
If you are a healthy individual between 18-55 years of age and are fully vaccinated (does not include 
booster vaccine) for SARS-CoV-2, you may be eligible to participate.  If you decide to screen for the study, 
you are under no obligation to enroll even if you are eligible.  You may also withdraw from the study at 
any time, for any reason.  
The study consists of seven visits over approximately 6-8 weeks:   
V
Visit Type
Brief description
1
Screen
to assess eligibility, includes COVID testing
2
Enrollment
to confirm eligibility, first dose of nasal spray administered by a clinician; 
optional sample collection between 1 - 12 hours post dose
3
24 hour post dose
safety assessments
4
Start multi-day dosing
begin daily use of nasal spray (for total of 13 days)
5
Multi-day dosing cont’d 
dispense second week of study medication
6
Safety assessment
24 hours after last dose, optional rectal swab for drug levels
7
Final visit
safety labs, drug levels  
You cannot take part in this study if you are a pregnant or breastfeeding, you are using nasal products, or 
you are participating in another investigational research study.  There may be other reasons you cannot 
participate, which will be explained to you by study staff. 
There are risks associated with participation in any research study.  There may be risks that are unknown 
and possibly life threatening.  The table below outlines the most common risks. 


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Study procedure
Risk
Use of study medication 
(Q-GRFT nasal spray)

This intranasal (used in the nose) spray has been tested for safety in one 
(single-dose) study. Our study will look at multi-day dose (daily for 14 
days) use of the intranasal  formulation

As with any nasal product, the following nasal side effects are possible 
with the study products (Q-GRFT nasal spray or placebo spray containing 
no active drug):  congestion, burning, irritation, increased mucus, 
dryness, sneezing, coughing, sore throat, nosebleed, redness, ulceration, 
interference with taste and smell, headaches

Rare risks include a hypersensitivity to the product, including local 
reaction or rash

As the drug is intended to work locally, systemic side effects are 
presumed to be exceptionally unlikely

Rare but potentially life-threatening risk of exposure is anaphylaxis (life-
threatening allergic reaction), but risks will be mitigated by using the first 
dose in the clinic and staying for approximately one hour
SARS-CoV-2 testing

A positive test result could impact social and work schedule

A positive test result will be reported to Allegheny County Health 
Department
There may be no direct benefit to participate, but some individuals may appreciate the opportunity to 
contribute to the body of knowledge in the field of SARS-CoV-2 (COVID) research.
******************************************************************************
INTRODUCTION/REASON FOR STUDY
This study is a randomized, placebo-controlled study of nasal Q-GRFT spray being done at a single site, 
UPMC Magee-Womens Hospital.  Q-GRFT is derived from Griffithsin and is obtained from Nicotiana 
benthamiana plants.  Q-GRFT has demonstrated an ability to inactivate viruses, including the SARS-CoV-2 
virus which causes COVID.  It has demonstrated excellent safety in prior laboratory, animal studies in 
three species, and preliminarily in human rectal studies as an HIV prevention product.  This study is the 
first multi- day dose clinical trial of the intranasal (used in the nose) formulation and is being studied for 
safety. Additional effective antiviral products are needed for the current COVID pandemic and in the 
event of the emergence of new coronaviruses.  This study will help to understand the safety of Q-GRFT 
spray and it’s potential to be studied more in the future as a prevention for SARS-CoV-2 infection.  
PARTICIPATION
You have been asked to join this study because you are a healthy individual, 18 to 55 years old, who is 
fully vaccinated for SARS-CoV2.  Your participation is voluntary.  The study team members will explain the 
study to you and will answer any questions you might have.  You should take your time to make your 
decision and discuss with others if needed. 
By participating in this study, you will be asked to use a nasal spray (two sprays in each nostril) a total of 
14 times.  You will be randomly assigned to use either Q-GRFT nasal spray or a placebo nasal spray 
(contains no active drug).  For every two participants that are assigned to Q-GRFT nasal spray, one will be 
assigned to placebo nasal spray which equates to 30 participants in the active Q-GFRT group and 15 
participants in the placebo group.  You will not get to pick your group, nor will you (or the research staff) 
know which nasal spray you will be assigned to as both will be packaged identically.  Both groups are 
important to the study.  


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The nasal spray comes in a spray pump bottle with a rounded tip that is gently inserted into each nostril 
to administer the spray.  The first dose will be administered by a research clinician at V2.  You will get to 
practice handling and using the nasal spray at V2 by spraying the product into a paper towel.  Later in the 
study (V4), you will be asked to use the assigned nasal spray for 13 additional doses.  Written and verbal 
instructions will be provided to you. You will be followed for safety, by having repeat questionnaires, 
exams and safety labs performed as described below.  
OVERVIEW OF STUDY DETAILS
Screening
Enrollment
Follow up 
Final 
VISITS →
V1
V2
V3
V4
V5
V6
V7
Timing of Visit →
Within 60 d 
of V1
24 hrs 
after V2
5-49 d 
after V3
7 d 
after V4
24 hrs after 
last dose
28 d 
after V4
Approx. length of visit
45 mins
1 ½ hrs
30 mins
1 hr
30 mins
30 mins
30 mins
Informed consent
x
Eligibility
x
x
Contact information
x
x
x
x
x
x
x
Visit questionnaire
x
x
x
x
x
x
x
Quality of Life Survey
x
x
x
x
x
Medical history
x
x
x
x
x
x
x
Medication review
x
x
x
x
x
x
x
Physical exam, vitals
x
x
x
x
x
x
x
SARS-CoV-2 Testing*
x
Urine pregnancy test*
^
^
^
^
^
Blood safety labs*
x
x
x
x
x
x
x
Blood drug levels
x
x
x
x
x
Blood drug antibody 
levels
x
x
x
Respiratory Samples**
x
x
x
x
x
Smell test
x
x
x
x
x
x
Acceptability Questions
x
x
x
Study medication
x
x
x
Study medication log
x
x
One hour observation+
x
Optional sample 
collection
Respiratory 
samples
rectal swab
Visit payment
30
80+OS
60
60
60
60+RS
60
  x Required procedure       ^ As necessary procedure        *The results of tests will be given to you     
 
  OS= $40 for 1 hour optional sample collection timepoint and $80 for 2-12 hour optional sample collection timepoints
  RS= $20 for optional rectal swab collection 
  + procedures performed approximately one hour after first dose administered include repeat blood draw, targeted physical examination,  
blood pressure and repeat smell test
  **Respiratory samples include: nasal, throat and nasopharyngeal (area just behind your nose that goes into the throat area) 
Additional details of each visit are listed below.  Procedures common to each visit include:

Contact information (phone number, email, alternate contacts) will be collected/reviewed 

Visit Questionnaire:  medical history, medication use and any issues/concerns

 Quality of Life survey will be done at V2, V4, V5, V6 and V7

Next appointment will be scheduled, as applicable

Reimbursement for the visit (amounts for each completed visit listed in table above) 


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
Counseling about protocol procedures

Reminder to call research staff with issues/concerns
V1:  SCREENING VISIT  - the following will be conducted/performed/collected:  

Review eligibility

SARS-CoV-2 test:  nasopharyngeal (NP; the area behind your nose that goes into the throat area) 
sample collected by using a narrow Q-tip like swab.  If your test is positive, you can enroll 14 days after 
the positive test result as long as you remain symptom free.  If you test positive and then develop 
symptoms, you can enroll 14 days after the start of symptoms as long as you do not have a fever for at 
least 24 hours.  

Full physical exam:  height, weight, blood pressure; exam of nose (by using an instrument to shine a 
light up your nose), throat, heart, lungs, abdomen

Urine pregnancy test, as applicable

Blood draw (approx. 1 ½ tsp) for safety labs: blood count, liver and kidney functions   
V2:  ENROLLMENT VISIT - the following will be conducted/performed/collected:  

Confirm eligibility

Urine pregnancy test, as applicable 

Targeted physical exam (exam of nose and throat using a small light to see clearly) and blood pressure

Smell test:  scratch and sniff test to identify certain smells

Blood draw for baseline drug level and anti-drug antibody testing.  This test will be done to check if 
there is any anti Q-GRFT antibodies generated in your body. (less than 1 tsp)

Collection of respiratory samples (nose, throat, and NP) for drug levels
o
Nose sample: collected with a cotton Q-tip like swab from inside the nostril
o
Throat sample:  collected with a cotton Q-tip like swab from the back of the throat

Random assignment to Q-GRFT nasal spray or placebo nasal spray 
o
Administered by a clinician
o
Participant will practice using by spraying into a paper towel
o
Wait in clinic for one hour after product administration

Approximately one hour following dosing, the following will be performed: 
o
Blood draw (less than 3 tsp):  safety labs and drug level
o
Repeat targeted physical exam and blood pressure
o
Repeat smell test

OPTIONAL SAMPLE COLLECTION:  single timepoint between 1 - 12 hours post product administration 
(as time permits); respiratory samples (nose, throat and NP) for drug levels
o
Nose sample: collected with a cotton Q-tip like swab from inside the nostril
o
Throat sample:  collected with a cotton Q-tip like swab from the back of the throat
Following V2, safety will be assessed at each visit by asking questionnaires (i.e. changes in medical history, 
medication use, any issues/concerns).  Urine pregnancy tests will be performed throughout the study, as 
applicable.  The study visits include the following:  
V3:  FOLLOW-UP VISIT – the following will be conducted/performed/collected:

NOTE:  timing of this visit is 24 hours after V2 dosing

Acceptability questionnaire:  questions about how you feel about the nasal spray


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
Blood draw (less than 3 tsp):  safety labs and drug level

Respiratory samples (nose, throat and NP) for drug levels

Targeted physical exam and blood pressure

Smell test
V4:  START MULTI- (THIRTEEEN) DAY DOSE – the following will be conducted/performed/collected:

Blood draw (less than 3 tsp):  safety labs and drug level 

Urine pregnancy test, as applicable

Respiratory samples (nose, throat and NP) for drug levels

Targeted physical exam and blood pressure

Smell test

Provide one week supply of study product with instructions on use

First dose of nasal spray administered by participant in clinic; followed by daily dosing at home

Record date and time of study product administration on provided study medication log

Contacted between V4 and V5 to assess safety (e.g.  any new issues or concerns)
V5:  PROVIDE SECOND WEEK OF PRODUCT - the following will be conducted/performed/collected:

Return 1st bottle of study product and completed study medication log

Blood draw (approx. 1 ½ tsp) for safety labs: blood count, liver and kidney function

Targeted physical exam and blood pressure

Smell test

Provide second week of study product for daily dosing at home and study medication log

Contacted between V5 and V6 to assess safety (e.g.  any new issues or concerns)
V6:  FOLLOW-UP VISIT - the following will be conducted/performed/collected:

NOTE:  timing of this visit is 24 hours after the last self-administered 13th dose.  If there is an issue with you 
coming the day after the 13th dose, the window allows for you to come 24 hours after the 12th dose (essentially 
skipping the 13th dose)

Return 2nd bottle of study product and completed study medication log

Blood draw (less than 3 tsp):  safety labs, drug level, and anti-drug antibody testing

Acceptability questionnaire

Urine pregnancy test, as applicable

Respiratory samples (nose, throat and NP) for drug levels

Optional rectal swab for drug levels:  collected using a cotton Q-tip like swab/sponge

Targeted physical exam and blood pressure

Smell test
V7:  FINAL VISIT - the following will be conducted/performed/collected:

Acceptability questionnaire  

Blood draw (less than 3 tsp):  safety labs, drug level, and anti-drug antibody testing 

Urine pregnancy test, as applicable

Respiratory samples (nose, throat and NP) for drug levels

Targeted physical exam and blood pressure

Smell test
Unscheduled Visits 


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Unscheduled visits may occur at any time during the study, for instance if you are having side effects, you 
have concerns, or to follow up on an abnormal test result.  At those visits, any of the above study 
procedures may be repeated as clinically indicated.  
 
WITHDRAWING FROM THE STUDY
You may stop taking part in this study at any time, for any reason; you can also withdraw your 
authorization for us to use your identifiable medical information. This means that you will also be 
withdrawn from further participation in this research study.  Any identifiable research or medical 
information obtained as part of this study prior to the date that you withdrew your consent will continue 
to be used and disclosed by the investigators for the purposes described above.  Your decision to 
withdraw from this study will have no effect on your current or future relationship with the University of 
Pittsburgh or UPMC.
If you decide to stop participating in the study, we encourage you to talk with the study doctor and your 
regular doctor first and continue with any safety follow-up, even if you did not complete all the days of 
study medication.
The study doctor or sponsor may decide to stop you from taking part in this study at any time.  You could 
be removed from the study for reasons related only to you (for example, if you have a bad reaction to the 
study medication) or because the entire study is stopped.  The sponsor, the study doctor or Institutional 
Review Board may stop the study at any time.
LAB TESTING OF SAMPLES
Some of the respiratory and blood collected from you will be used for research tests to determine the 
amount of study drug in these samples and the presence of anti-drug antibodies in the blood. The results 
of these respiratory/blood tests are useful only for research purposes and will not be available to you or 
your health care provider. These specimens will be sent to an outside testing laboratory.  The specimens 
will not be labeled by your name or other identifying information but rather by a unique study identifier.    
Personnel at the testing laboratory will not know your identity.  Your research information and bio-
specimens may be shared with investigators conducting other research, including the University of 
Louisville who will have access to specimens/specimen data.  Specimens will only be kept until study 
completion.  
Blood samples to test the health of your blood, liver and kidney function and SARS-CoV-2 testing will be 
sent to the clinical lab associated with Magee.  They will also be sent by your study number, however the 
results of these tests will be given to you.  At screening, abnormal test results could prevent you from 
participating.  If abnormal labs are identified during the course of the study, they may be repeated as 
clinically appropriate and/or you may be referred to your own doctor for additional evaluations.    
If you test positive for SARS-CoV-2, the Commonwealth of Pennsylvania requires that your name be given 
to the Allegheny County Health Department.  
This study does not include whole genome sequencing (DNA testing).  
CLINICAL TEST RESULTS
You will receive your results from the tests performed in this study that are conducted/processed in a 
certified clinical laboratory.  This includes urine pregnancy test results (as applicable), clinical blood tests 


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and SARS-CoV-2 testing.  You will not receive results of the testing conducted for study drug 
levels/research only laboratory testing.  There is no plan to provide participants with the overall study 
results when completed.
PROTECTION OF CONFIDENTIALITY AND PERSONAL HEALTH INFORMATION 
Identifiable medical information may be collected as part of this study and will be made available to 
members of the research team for an indefinite period of time.  Your medical information, as well as 
information obtained during this research study, may be shared with other groups, possibly including 
authorized officials from the Food and Drug Administration, National Cancer Institute, and the University 
of Pittsburgh Office of Research Protections, for the purpose of monitoring the study. Authorized 
representatives of UPMC or affiliated health care providers may also have access to this information to 
provide services and address billing and operational issues.  Results from this research may also be shared 
with other investigators, however this information will be de-identified.
To protect your confidentiality we will use a number instead of your name on all the forms for the study, 
and we will store your data in password protected files located on secure computers.  If information from 
this study is shown publicly or published in a journal, we will not mention your name, or anything else 
that could identify you.
We will make every attempt to protect the privacy and the confidentiality of your records, as described in 
this document, but cannot guarantee the confidentiality of your research records, including information 
obtained from your medical records once your personal information is disclosed to others outside UPMC 
or the University.  This authorization is valid for an indefinite period of time.  However, you can always 
withdraw your authorization to allow the research team to review your medical records by contacting the 
investigator listed on the first page and making the request in writing.  If you do so, you will no longer be 
permitted to participate in this study.  Any information obtained from you up to that point will continue 
to be used by the research team. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law. This web site will not include information that can identify you. At most, the web site will include a 
summary of the results. You can search this web site at any time.
Your data or specimens used in this research study may contribute to a new discovery or treatment. In 
some instances, these discoveries or treatments may be of commercial value and may be sold, patented, 
or licensed by the investigators and the University of Pittsburgh for use in other research or the 
development of new products.  You will not retain any property rights, nor will you share in any money 
that the investigators, the University of Pittsburgh, or outside agencies may receive.
Per University of Pittsburgh policy all research records must be maintained for at least 7 years following 
final reporting or publication of a project. In unusual cases, the investigators may be required to release 
your identifiable research information (which may include your identifiable medical record information) in 
response to an order from a court of law. If the investigators learn that you or someone with whom you 
are involved is in serious danger or potential harm, they will need to inform the appropriate agencies, as 
required by Pennsylvania law.
This research is covered by a Certificate of Confidentiality from the National Institutes of Health. The 
researchers with this Certificate may not disclose or use information, documents, or biospecimens that 
may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other action, 


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suit, or proceeding, or be used as evidence, for example, if there is a court subpoena, unless you have 
consented for this use. Information, documents, or biospecimens protected by this Certificate cannot be 
disclosed to anyone else who is not connected with the research except, if there is a federal, state, or 
local law that requires disclosure (such as to report child abuse or communicable diseases but not for 
federal, state, or local civil, criminal, administrative, legislative, or other proceedings;) if you have 
consented to the disclosure, including for your medical treatment; or if it is used for other scientific 
research, as allowed by federal regulations protecting research subjects.
  
RISKS AND DISCOMFORTS FROM TAKING PART IN THIS STUDY 
As with any research study, there may be adverse events or side effects for you that are currently 
unknown and certain of these unknown risks could be permanent, severe or life-threatening.
This is a phase 1 trial. The first human tests of investigational drugs or therapies occur in Phase 1 trials. 
Phase 1 trials are designed to determine the best dose of the study drug and to check for any potential 
side effects. These trials usually involve small numbers of volunteers. Because some Phase 1 trials use 
study treatments that have never been tested in humans, they may involve significant risks.
Q-GRFT (the study drug) has been tested for safety in one human study using a single dose of the nasal 
spray.  The risks are unknown. There is a chance that drugs like Q-GRFT may cause a hypersensitivity 
reaction. 
Studies in animals did not show any significant harmful effects from administration of the study drug. The 
study drug was given to animals nasally at up to 3 times the human dose. The animal studies did not show 
any major risk associated with the study drug, although animal studies are not always able to predict what 
will happen in humans.
As with any intranasally (used in the nose) administered product, study products (active or placebo) may 
cause nasal congestion, nasal discharge, nasal burning, nasal irritation, increased mucus, nasal dryness, 
sneezing, coughing, pharyngitis (sore throat), nose bleed, mucosal erythema (redness in the lining of the 
nose), nasal ulceration, interference with taste and smell, ringing in the ear(s) and headache are potential 
risks. Hypersensitivity reactions (including contact dermatitis and rash) are rare risks with any product. As 
the drug is intended to work at the mucosal surface, systemic side effects are presumed to be 
exceptionally unlikely. Nonetheless, safety labs will be checked before and after study medication use. 
A rare but potentially life-threatening risk of exposure to nasal spray containing Q GRFT or the placebo 
spray would be anaphylaxis (life-threatening allergic reaction). You will be asked to stay in the clinic for 1 
hour after application.  In the unlikely event of a reaction, the study team, including licensed physicians 
are available to care for you.  Medications for allergic reactions as well as a team of medical staff are 
available at the location of your study visit (UPMC Magee Womens Hospital CTRC).
Persons who are pregnant or breastfeeding may not participate in this research study. If you are pregnant 
or become pregnant, your unborn child may suffer harms that we have not seen before. If you become 
pregnant while in this study, the sponsor may ask to follow the outcome of the pregnancy. Before starting 
this research study, persons of pregnancy potential will have a pregnancy test. Testing positive for 
pregnancy may cause anxiety.  There is a risk that your unborn baby could be harmed if you become 
pregnant during your participation in the study. There is currently no data about this drug related to 
pregnancy.


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Nasal exam may cause discomfort.  Nasal specimen collection may cause mild discomfort and/or nasal 
spotting. Oropharyngeal (throat) swab collection may induce a gag reflex and cause mild discomfort. 
Nasopharyngeal (NP) swabs may cause discomfort, eyes to water, coughing/gagging.  
Drawing blood may lead to excessive bleeding, discomfort, feelings of dizziness or faintness, and/or 
bruising, swelling and/or infection. 
Collecting a(n optional) rectal swab may cause discomfort.  
As part of the study, you will be screened for SARS-CoV-2 at the screening visit. Anxiety and depression 
surrounding a positive result is a risk. A positive test result will necessitate that the Allegheny County Health 
Department be notified, which would likely result in a period of self-quarantine and disruption to your daily 
life.  
Performing the smell test can cause stress or anxiety if you are unable to detect a smell.  Some of the smells 
may be unpleasant. 
Participation in clinical research includes the risks of loss of confidentiality and discomfort with personal 
nature of questions.  Answering research questionnaires and completing study medication logs may be 
inconvenient. 
GENERAL RISKS:
You will be asked to provide personal/protected health information (PHI).  All attempts will be made to 
keep your PHI confidential within the limits of the law.  However, there is a chance that unauthorized 
persons will see your PHI.  All paper records will be kept in a locked file cabinet or maintained in a locked 
room at Magee.  Electronic files will be password protected.  Only people who are involved in the 
conduct, oversight, monitoring, or auditing of this study will be allowed access to the PHI that is collected.  
Any publications from this study will not use information that will identify participants by name.  
Organizations that may inspect and/or copy research records maintained at the participating sites for 
quality assurance and data analysis include groups such as the National Cancer Institute or its designee 
and the US Food and Drug Administration (FDA). 
BENEFITS TO TAKING PART IN THIS STUDY 
Participation may have no direct benefit. All participants will receive a SARSCoV-2 test, which some may 
consider a benefit. Some participants may have the opportunity to access expedient treatment and 
decreased morbidity due to early diagnosis and treatment of abnormalities in blood count, liver or kidney 
function tests that would have otherwise not been detected. Lastly, you may appreciate the opportunity to 
contribute to the body of knowledge in the field of SARS-CoV-2 research. However, there is no guarantee 
that volunteers will receive any of these benefits.
ALTERNATE CHOICES TO PARTICIPATION
You do not have to take part in this study.    
COST
There will be no costs to you for being in this study and there are no anticipated expenses related to your 
participation.  You will not have to pay to receive the study medication in this study.  There are no costs 
for the physical examinations, laboratory testing, or clinic visits.  They will be included as part of the study.  


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During the study, should you test positive for SARS-CoV-2, the study will not be responsible for expenses 
such as lost wages from having to miss work/quarantine.  
STUDY PAYMENT FOR PARTICIPATION
There is no cost to you to participate.  You will receive the payments as listed in the tables above for each 
visit/procedure that is completed. 
Since you are being compensated for your participation in this study, your name, address, and social 
security number will be released to the Accounting Office.  Your study payments will be loaded onto a 
UPMC cash card at the completion of each visit.  All compensation is taxable income to the participant 
regardless of the amount.  If a participant receives $600 or more in a calendar year from one organization, 
that organization is required by law to file a Form 1099-Miscellaneous with the IRS and provide a copy to 
the taxpayer.  Individuals who do not provide a social security number may still participate in the research 
but the IRS requires that 26% of the payment be sent by the institution to the IRS for “backup 
withholding”, thus you would only receive 74% of the expected payment
RIGHT TO WITHDRAW
Your participation in this study is voluntary. You do not have to take part in this research. You are free to 
withdraw your consent at any time. If you withdraw from this study, already collected data may not be 
removed from the study database.  Refusal to take part or to stop taking part in the study will involve no 
penalty or loss of benefits to which you are otherwise entitled. If you decide to stop taking part, or if you 
have questions, concerns, or complaints, or if you need to report a medical injury related to the research, 
please contact the investigator (study doctor), Dr. Katherine Bunge, and/or research staff at 412-641-
4242.  
You will be told of any significant new findings which develop during the study which may affect your 
willingness for you to participate in the study.  You may be asked to sign a revised consent form if this 
occurs.
REMOVAL FROM THE STUDY
Investigators (study doctors), the Institutional Review Board (a committee at the University of Pittsburgh 
charged with protecting the safety and rights of people taking part in research studies), or the National 
Cancer Institute can remove you from the research study without your approval. Reasons why this may 
occur include that you are unable to fulfill the requirements of the study. 
If you decide to stop participating in the study, or if your participation is ended, the study doctor or study 
staff may ask you some questions about being in the study.  Any time a participant is permanently 
discontinued from study medication you may be asked to complete the procedures listed under the study 
visits described above.   
RESEARCH-RELATED INJURY
If you believe that participating in this study has resulted in an injury to you, immediately contact the 
Principal Investigator who is listed on the first page of this form.  Emergency medical treatment for 
injuries solely and directly related to your participation in this research study will be provided to you by 
the hospitals of UPMC.  Your insurance provider may be billed for the costs of this emergency treatment, 
but none of those costs will be charged directly to you.  If your research-related injury requires medical 
care beyond this emergency treatment, you will be responsible for the costs of this follow-up care.  At this 


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time, there is no plan for any additional financial compensation.   You do not waive any legal rights by 
signing this form. 
PROBLEMS OR QUESTIONS
If you have any questions about your rights as a research subject or wish to talk to someone other the 
research team, please call the University of Pittsburgh Human Subjects Protection Advocate toll-free at 
866-212-2668.
VOLUNTARY PARTICIPATION
Your participation in this research study is entirely voluntary. You may want to discuss this study with your 
family and friends and your personal physician before agreeing to participate. If there are any words you 
do not understand, feel free to ask us. The investigators will be available to answer your current and 
future questions.
Whether or not you provide your consent for participation in this research study will have no effect on 
your current or future relationship with the University of Pittsburgh. Whether or not you provide your 
consent for your participation in this research study will have no effect on your current or future medical 
care at a UPMC hospital or affiliated health care provider or your current or future relationship with a 
health care insurance provider.


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PLEASE INITIAL YOUR CHOICE FOR THE FOLLOWING OPTIONAL PROCEDURES: 
Optional Procedure
Visit
INITIAL if you agree
INITIAL if you do 
not agree
Collection of Nasal, Throat and 
Nasopharyngeal samples for 
study drug levels between 
1-12 hours post-dose
Enrollment, 
Visit 2
Collection of a rectal sample using a 
cotton swab for study drug levels
Follow-up,
Visit 6
****************************************************************************************************************
VOLUNTARY CONSENT FOR PARTICIPANTS 
The above information has been explained to me and all of my current questions have been answered.  I 
understand that I am encouraged to ask questions, voice concerns or complaints about any aspect of this 
research study during the course of this study, and that such future questions, concerns or complaints will 
be answered by a qualified member of the research team or by the Principal Investigator listed on the first 
page.  I understand that I may always request that my questions, concerns or complaints be addressed by 
the Principal Investigator.  At any time, I may also contact the Human Subjects Protection Advocate of the 
IRB Office, University of Pittsburgh (1-866-212-2668) to discuss problems, concerns and questions; obtain 
information; offer input; or discuss situations in the event that the research team is unavailable.  By signing 
this form, I agree to participate in this research study for the purposes described above.  A copy of this 
consent form will be offered to me.
___________________________________  
Printed Name of Participant
___________________________________
_______________
______________
Participant Signature
Date
Time (am/pm)
CERTIFICATION OF INFORMED CONSENT
I certify that I have explained the nature and purpose of this research to the above individual and I have 
discussed the potential benefits and possible risks of study participation.  Any questions the individual has 
about the study have been answered, and we will always be available to address future questions as they 
arise.  I further certify that no research component of this protocol was begun until after this consent form 
was signed.  
___________________________________  
______________________
Printed name of Person Obtaining Consent
Role in Research Study
__________________________________
______________
______________
Signature of Person Obtaining Consent
Date
Time  (am/pm)