The purpose of this study is to test the safety of multiple doses of a Q-GRFT nasal spray in healthy volunteers. This Q-GRFT nasal spray is "investigational and not approved by the FDA for general use" and is being developed to prevent the transmission of COVID-19 and other coronaviruses.
This is an open-label dose-escalation study to assess the safety, tolerability, and pharmacokinetics (PK) of a multiple dosing schedule of Q GRFT intranasal spray DP. Up to 24 healthy participants will be enrolled and assigned to either of 2 groups to receive treatment. In Group 1, up to 12 participants will receive a dose of 3.0 mg intranasal Q-GRFT administered once daily, as 2 sprays (100 µL/ spray) in each nostril, for 7 days. The initial dose will be administered in the clinic by a study clinician. Participants will be taught how to self-administer the study product at the clinic and receive written instructions for at-home self-administration. Subsequent doses will be self-administered either at the clinic or at home. Group 1 participants will undergo PK sampling (nasal and nasopharyngeal fluids) at baseline (enrollment visit), on day 1 (1 hour, 6 hours, and 10 hours after the initial dose), day 2 (24±1 hours after initial dose), day 4 (pre-dose and 1-hour post-dose), day 7 (pre-dose, 1 hour, 6 hours, and 10 hours after the final dose, day 8 (24±1 hours) and day 9 (48±2 hours) following the final dose. Blood for evaluation of systemic exposure will be collected at baseline, day 1 and day 4 (1 hour post-dose), and on day 8, upon dose completion. In Group 2, up to 12 participants will be enrolled to receive a total of 6.0 mg intranasal Q-GRFT administered as 3.0 mg twice daily (3.0 mg BID), with 2 sprays (100 µL/ spray) in each nostril approximately every 12 hours, for 7 days. Administration of the third dose among Group 2 participants will be delayed to permit obtaining a 24-hour PK timepoint for one completed 6.0 mg BID treatment. The initial dose will be administered in the clinic by a study clinician. Participants will be taught to self-administer the study product at the clinic and receive written instructions for at-home self-administration. Subsequent doses will be self-administered either at the clinic or at home. Participants in this group will undergo PK sampling (nasal and nasopharyngeal fluids) at baseline (enrollment visit), on day 2 (1 hour, 6 hours, and 10 hours after the second dose), day 3 (24±1 hours after the second dose), day 5 (pre-dose after 3 completed doses of 6 mg and 1 hour post-dose), day 8 (pre-dose, 1 hour, 6 hours, and 10 hours after the final dose), day 9 (24±1 hours) and day 10 (48±2hours) following the final dose. Blood for evaluation of systemic exposure will be collected at baseline, on day 2 and day 5 (1 hour post-dose), and on day 9 after the final dose completion. Safety assessment for both groups will be conducted after 3 days of dosing, upon completion of the final dose, and within 3-4 weeks of dose completion. An optional rectal fluids sampling procedure using a sponge will be performed 1 day after the final dose, to assess for any study product in the gastrointestinal tract. Blood draws for anti-drug antibodies/ immunogenicity assays will be performed at baseline, 24±1 hours after the final dose and 3-4 weeks after the final dose administration. Additional participants will be enrolled in case any subjects do not complete all safety or primary PK assessments, in order to assure that a minimum of 9 subjects is available for full analysis. All sampling procedures will be performed in the clinic. This sample size is appropriate for a Phase 1b clinical study to gather additional multi-dosing safety data and preliminary PK data following completion of the single-dose treatment Phase 1a trial. The proposed studies will allow a careful selection of the ideal dose that will be administered to subjects in future Phase 2 studies.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
24
This is an open-label dose-escalation study to assess the safety, tolerability, and pharmacokinetics (PK) of a multiple dosing schedule of low dose Q GRFT intranasal spray DP
This is an open-label dose-escalation study to assess the safety, tolerability, and pharmacokinetics (PK) of a multiple dosing schedule of high dose Q GRFT intranasal spray DP
University of Louisville Clinical Trials Unit
Louisville, Kentucky, United States
RECRUITINGPharmacokinetic levels
Q-GRFT Study Product (SP) concentration will be assessed in nasopharyngeal fluids.
Time frame: Nasopharyngeal fluids on days 1, 2, 4, 7, 8, 9 for group 1; Days 2, 3, 5, 8, 9 for group 2
Safety of product by measuring number of subjects that experience Adverse Events greater than Grade 3.
Incidence of AEs Grade 3 or higher as defined by the Division of AIDS (DAIDS) Table or Grading the Severity of Adult and Pediatric Adverse Events, V2.1 (July 2017).
Time frame: 3-4 weeks
Smell Assessment by Brief Smell Identification Test
Smell Assessment will be performed using the Sensonics International Brief Smell Identification Test (BSIT) to evaluate the impact of Q GRFT SP intranasal treatment on the sensation. This is a "scratch and sniff" type test with a set number of defined odors that participants should be able to identify. Modification of smell perception can be identified by changes in the results of the BSIT\>
Time frame: Visit 0, 6 or 7 (Day 9)
Acceptability
The product acceptability will be assessed to determine perception of use by participants. This is achieved through a assessing participants' responses to defined questions on a questionnaire that asks how the participants feel about their experiences with the investigational nasal spray product, and how likely they might be to use the product if it is approved for use. A majority of answers indicating a negative impression of the user experience will alert the study team to the possibility that the product will not be acceptable for use if approved and marketed as a nasal spray to prevent virus infection.
Time frame: 3 - 4 weeks
Quality of life outcome
Quality of Life will be evaluated with the SF-12 battery of questions. The SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. It is often used as a quality of life measure.
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Time frame: Visit 0, 6 or 7 (Day 9)
Anti-drug antibody levels
Anti-drug antibodies (ADA) will be measured in collected plasma to assess if any anti-QGRFT antibodies are generated after multiple Q-GRFT SP treatment
Time frame: Day 8 or 9
Pharmacokinetic levels
Q-GRFT Study Product (SP) concentration will be assessed in plasma.
Time frame: 3 - 4 weeks