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

Phase 1

Completed

Conditions: Pharmacokinetics
COVID-19
Safety

Interventions: Drug: Q-Griffithsin
Drug: Placebo

Registration Number: NCT05180500

Lead Sponsor: Sharon Hillier

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 50

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:
1. 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
2. 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:
1. Hgb < 12g/dL (men) and < 11g/dL (women)
2. Serum creatinine > 1.1 x upper limit of normal
3. 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
1. Non-therapeutic injection drug use in the 12 months prior to screening
2. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Q-GRFT Nasal Spray	Q-Griffithsin	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.
Placebo Nasal Spray	Placebo	Placebo Nasal Spray. Two metered doses of 100μL into each nostril, administered once daily for 14 consecutive days.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Related Grade 2 or Higher Adverse Events	Approximately 8 weeks	Number of participants with Grade 2 or higher adverse events deemed related to study product

Secondary Outcome Measures

Name	Time	Method
Q-GRFT Plasma Concentration Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications	24 hours after final dose of study product	Q-GRFT concentration in plasma collected 24 hours after the final intranasal application of 13 consecutive once daily administrations of study product.
Area Under the Plasma Concentration Versus Time Curve of Q-GRFT	Approximately 28 days	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 daily applications of study product.
Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours	Approximately 24 hours	Q-GRFT concentration from nasopharyngeal swab eluent collected 24 hours after intranasal application of a single dose of study product.
Acceptability of the Intranasal Spray	Approximately 14 days	The acceptability of the nasal spray for use at home by the participant if it could protect against infection from coronavirus/COVID-19 will be assessed on a 5-point Likert scale, with 1 being completely unacceptable and 5 being highly acceptable. Acceptability will be assessed approximately 24 hours after the final application of 13 consecutive daily applications of the study product.