Clinical trial NCT05180500: Safety and Acceptability of Q GRFT Nasal Spray for COVID-19 Prophylaxis
Official title: Phase 1 Clinical Trial of a Q GRFT Nasal Spray
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: COVID-19
Pharmacokinetics
Safety
Keywords: Intranasal spray
Prophylaxis
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-01-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Related Grade 2 or Higher Adverse Events
timeFrame: Approximately 8 weeks
Secondary outcomes:
measure: Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours
timeFrame: Approximately 24 hours
measure: Q-GRFT Plasma Concentration Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications
timeFrame: 24 hours after final dose of study product
measure: Area Under the Plasma Concentration Versus Time Curve of Q-GRFT
timeFrame: Approximately 28 days
measure: Acceptability of the Intranasal Spray
timeFrame: Approximately 14 days
Other outcomes:
measure: Mean Change in Brief Smell Identification Test (BSIT) Score
timeFrame: Approximately 14 days
measure: Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours
timeFrame: Approximately 24 hours
measure: Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications
timeFrame: Approximately 14 days
measure: Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications
timeFrame: Approximately 14 days
measure: Q-GRFT Concentration From Rectal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications
timeFrame: Approximately 14 days
Locations:
city: Pittsburgh
country: United States
facility: Ingrid Macio
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Sharon L Hillier, PhD
role: PRINCIPAL_INVESTIGATOR
References: