Safety and Acceptability of Q GRFT Nasal Spray for COVID-19 Prophylaxis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 1 Clinical Trial of a Q GRFT Nasal Spray

Conditions
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Safety, COVID-19, Pharmacokinetics

Intervention / Treatment
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* Drug: Q-Griffithsin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent In general good health as determined by the site clinician Negative SARS-CoV-2 test at screening Fully vaccinated for SARS-CoV-2 (does not include booster vaccination) Agree to abstain from any other investigational drug studies for the duration of the study Agree to abstain from nasally administered products, including over-the-counter products, for the duration of the study 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: Males: Male condoms, sterilization of participant or partner, partner use of hormonal contraception or intrauterine device, 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 Females: Hormonal methods at the time of enrollment, intrauterine device 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. Agree to participate in all study-related assessments and procedures Exclusion Criteria: Abnormal nasal or throat exam at enrollment If female, pregnancy, or within 42 days of last pregnancy at screening If female, breastfeeding Diagnosed with SARS-CoV-2 in the past 42 days at screening Diagnosed or suspected respiratory tract infection in the past 14 days at screening (including asymptomatic SARS-CoV-2) Participation in an investigational drug study in past 30 days at screening 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 Use of any intranasal product in the 14 days prior to enrollment Surgical procedure involving the nose or throat 90 days prior to enrollment Any of the following laboratory abnormalities at screening: Hgb < 12g/dL (men) and < 11g/dL (women) Serum creatinine > 1.1 x upper limit of normal alanine transaminase, aspartate aminotransferase, and total bilirubin > 1.1 x upper limit of normal Grade 2 or higher seasonal allergies at the time of enrollment Reported use of illicit drugs Non-therapeutic injection drug use in the 12 months prior to screening Any use of methamphetamine, gamma hydroxybutyrate, cocaine or heroin in the 12 months prior to screening Use of systemic prescription immunomodulatory medications within the 4 weeks prior to the enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Q-GRFT Nasal Spray<br>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. | Drug: Q-Griffithsin<br>* 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.<br>|
| Placebo Comparator: Placebo Nasal Spray<br>Placebo Nasal Spray. Two metered doses of 100μL into each nostril, administered once daily for 14 consecutive days. | Drug: Placebo<br>* A matched vehicle solution manufactured and dispensed in same applicators as the active comparator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Related Grade 2 or Higher Adverse Events | Number of participants with Grade 2 or higher adverse events deemed related to study product | Approximately 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Q-GRFT Concentration from Nasopharyngeal Swab Eluent Collected at 24 Hours | Q-GRFT concentration from nasopharyngeal swab eluent collected 24 hours after intranasal application of a single dose of study product | Approximately 24 hours | 
| Q-GRFT Plasma Concentration Collected at 24 Hours | Q-GRFT concentration in plasma collected 24 hours after intranasal application of a single dose of study product | Approximately 24 hours | 
| Area Under the Nasopharyngeal Swab Eluent Concentration versus Time Curve of Q-GRFT | Area under the nasopharyngeal swab eluent concentration versus time curve of Q-GRFT collected after 13 consecutive daily intranasal applications of study product. Q-GRFT concentrations will be measured prior to the first application of study product and at 7-days, 14-days, and 28-days after the first of thirteen applications of study product. | Approximately 28 days | 
| Area Under the Plasma Concentration versus Time Curve of Q-GRFT | Area under the plasma concentration versus time curve of Q-GRFT collected after 13 consecutive daily intranasal applications of study product. Q-GRFT concentrations will be measured prior to the first application of study product and at 7-days, 14-days, and 28-days after the first of thirteen applications of study product. | Approximately 28 days | 
| Acceptability of the Intranasal Spray | The acceptability of the nasal spray use by the participant will be assessed on a 5 point Likert scale, with 1 being do not agree at all and 5 being completely agree. | Approximately 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intranasal spray, Prophylaxis