COVID-19, Pharmacokinetics, Safety
Conditions
Keywords
Intranasal spray, Prophylaxis
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.
Interventions
DRUGQ-Griffithsin
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.
DRUGPlacebo
A matched vehicle solution manufactured and dispensed in same applicators as the active comparator.
Sponsors
National Cancer Institute (NCI)
Sharon Hillier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Brief Smell Identification Test (BSIT) Score | Approximately 14 days | Mean change in Brief Smell Identification Test (BSIT) score between the score measured before the first application of study product and measured after 13 consecutive daily applications. The BSIT score is the number of odors that a participant correctly recognizes, ranging from 0 to 12. A negative value in the change score indicates a decrease in BSIT score from the pre-dose measurement, while a positive value indicates an increase in BSIT score. |
| Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours | Approximately 24 hours | Q-GRFT concentration from nares swab eluent collected 24 hours after intranasal application of a single dose of study product. |
| Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | Approximately 14 days | Q-GRFT concentration from nasopharyngeal swab eluent collected 24 hours after the last dose of 13 consecutive daily intranasal applications of study product. |
| Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | Approximately 14 days | Q-GRFT concentration from nares swab eluent collected 24 hours after the last dose of 13 consecutive daily intranasal applications of study product. |
| Q-GRFT Concentration From Rectal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | Approximately 14 days | Q-GRFT concentration from rectal swab eluent collected 24 hours after the last dose of 13 consecutive daily intranasal applications of study product. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Q-GRFT Nasal Spray 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.
Q-Griffithsin: 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. | 33 |
| Placebo Nasal Spray Placebo Nasal Spray. Two metered doses of 100μL into each nostril, administered once daily for 14 consecutive days.
Placebo: A matched vehicle solution manufactured and dispensed in same applicators as the active comparator. | 17 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Q-GRFT Nasal Spray | Placebo Nasal Spray | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 17 Participants | 49 Participants |
| Age, Continuous | 28.4 years STANDARD_DEVIATION 7.7 | 27.6 years STANDARD_DEVIATION 6.3 | 28.1 years STANDARD_DEVIATION 7.2 |
| COVID-19 Diagnosis No | 22 Participants | 11 Participants | 33 Participants |
| COVID-19 Diagnosis Yes | 11 Participants | 6 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 17 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 12 Participants | 33 Participants |
| Region of Enrollment United States | 33 participants | 17 participants | 50 participants |
| Sex: Female, Male Female | 23 Participants | 12 Participants | 35 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 15 Participants |
| Sex/Gender, Customized Female | 23 Participants | 11 Participants | 34 Participants |
| Sex/Gender, Customized Male | 10 Participants | 4 Participants | 14 Participants |
| Sex/Gender, Customized Nonbinary | 0 Participants | 1 Participants | 1 Participants |
| Sex/Gender, Customized Transgender male to female | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 17 |
| other Total, other adverse events | 29 / 33 | 14 / 17 |
| serious Total, serious adverse events | 0 / 33 | 0 / 17 |
Outcome results
Primary
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
Time frame: Approximately 8 weeks
Population: All participants randomized to study product are included in this analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Q-GRFT Nasal Spray | Number of Participants With Related Grade 2 or Higher Adverse Events | Participants with related Grade 2 or higher | 6 Participants |
| Q-GRFT Nasal Spray | Number of Participants With Related Grade 2 or Higher Adverse Events | Participants without related Grade 2 or higher | 27 Participants |
| Placebo Nasal Spray | Number of Participants With Related Grade 2 or Higher Adverse Events | Participants with related Grade 2 or higher | 2 Participants |
| Placebo Nasal Spray | Number of Participants With Related Grade 2 or Higher Adverse Events | Participants without related Grade 2 or higher | 15 Participants |
p-value: 0.7Fisher Exact
Secondary
Acceptability of the Intranasal Spray
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.
Time frame: Approximately 14 days
Population: The 3 participants in the Q-GRFT arm that withdrew from the study were excluded.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Q-GRFT Nasal Spray | Acceptability of the Intranasal Spray | Unacceptable (Completely, somewhat, or neutral) | 4 Participants |
| Q-GRFT Nasal Spray | Acceptability of the Intranasal Spray | Acceptable (Highly or somewhat) | 26 Participants |
| Placebo Nasal Spray | Acceptability of the Intranasal Spray | Unacceptable (Completely, somewhat, or neutral) | 0 Participants |
| Placebo Nasal Spray | Acceptability of the Intranasal Spray | Acceptable (Highly or somewhat) | 17 Participants |
p-value: 0.28Fisher Exact
Secondary
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 daily applications of study product.
Time frame: Approximately 28 days
Population: The 3 participants in the Q-GRFT arm that withdrew from the study were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Q-GRFT Nasal Spray | Area Under the Plasma Concentration Versus Time Curve of Q-GRFT | NA ng x day/mL |
| Placebo Nasal Spray | Area Under the Plasma Concentration Versus Time Curve of Q-GRFT | NA ng x day/mL |
Secondary
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.
Time frame: Approximately 24 hours
Population: All participants on whom a nasopharyngeal swab was collected 24 hours after intranasal application of a single dose of study product.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Q-GRFT Nasal Spray | Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours | 1007 ng/mL |
| Placebo Nasal Spray | Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours | NA ng/mL |
Comparison: Concentrations that were below the lower limit of quantification (\<15 ng/mL) were set to 7.5 ng/mL for analyses.p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Q-GRFT Plasma Concentration Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications
Q-GRFT concentration in plasma collected 24 hours after the final intranasal application of 13 consecutive once daily administrations of study product.
Time frame: 24 hours after final dose of study product
Population: The 3 participants in the Q-GRFT arm that withdrew from the study were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Q-GRFT Nasal Spray | Q-GRFT Plasma Concentration Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | NA ng/mL |
| Placebo Nasal Spray | Q-GRFT Plasma Concentration Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | NA ng/mL |
Other Pre-specified
Mean Change in Brief Smell Identification Test (BSIT) Score
Mean change in Brief Smell Identification Test (BSIT) score between the score measured before the first application of study product and measured after 13 consecutive daily applications. The BSIT score is the number of odors that a participant correctly recognizes, ranging from 0 to 12. A negative value in the change score indicates a decrease in BSIT score from the pre-dose measurement, while a positive value indicates an increase in BSIT score.
Time frame: Approximately 14 days
Population: The 3 participants in the Q-GRFT arm that withdrew from the study were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Q-GRFT Nasal Spray | Mean Change in Brief Smell Identification Test (BSIT) Score | -0.40 score on a scale | Standard Deviation 1.1 |
| Placebo Nasal Spray | Mean Change in Brief Smell Identification Test (BSIT) Score | -0.24 score on a scale | Standard Deviation 0.83 |
p-value: 0.6t-test, 2 sided
Other Pre-specified
Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours
Q-GRFT concentration from nares swab eluent collected 24 hours after intranasal application of a single dose of study product.
Time frame: Approximately 24 hours
Population: All participants on whom a nares swab was collected 24 hours after intranasal application of a single dose of study product.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Q-GRFT Nasal Spray | Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours | 1488 ng/mL |
| Placebo Nasal Spray | Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours | NA ng/mL |
Comparison: Concentrations that were below the lower limit of quantification (\<15 ng/mL) were set to 7.5 ng/mL for analyses.p-value: <0.001Wilcoxon (Mann-Whitney)
Other Pre-specified
Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications
Q-GRFT concentration from nares swab eluent collected 24 hours after the last dose of 13 consecutive daily intranasal applications of study product.
Time frame: Approximately 14 days
Population: The 3 participants in the Q-GRFT arm that withdrew from the study were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Q-GRFT Nasal Spray | Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | 1586 ng/mL |
| Placebo Nasal Spray | Q-GRFT Concentration From Nares Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | NA ng/mL |
Comparison: Concentrations that were below the lower limit of quantification (\<15 ng/mL) were set to 7.5 ng/mL for analyses.p-value: <0.001Wilcoxon (Mann-Whitney)
Other Pre-specified
Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications
Q-GRFT concentration from nasopharyngeal swab eluent collected 24 hours after the last dose of 13 consecutive daily intranasal applications of study product.
Time frame: Approximately 14 days
Population: The 3 participants in the Q-GRFT arm that withdrew from the study were excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Q-GRFT Nasal Spray | Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | 974 ng/mL |
| Placebo Nasal Spray | Q-GRFT Concentration From Nasopharyngeal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | NA ng/mL |
Comparison: Concentrations that were below the lower limit of quantification (\<15 ng/mL) were set to 7.5 ng/mL for analyses.p-value: <0.001Wilcoxon (Mann-Whitney)
Other Pre-specified
Q-GRFT Concentration From Rectal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications
Q-GRFT concentration from rectal swab eluent collected 24 hours after the last dose of 13 consecutive daily intranasal applications of study product.
Time frame: Approximately 14 days
Population: Twenty out of 50 participants consented to provide a rectal swab sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Q-GRFT Nasal Spray | Q-GRFT Concentration From Rectal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | 106.7 ng/mL |
| Placebo Nasal Spray | Q-GRFT Concentration From Rectal Swab Eluent Collected at 24 Hours After 13 Consecutive Daily Intranasal Applications | 3.4 ng/mL |
p-value: <0.001Wilcoxon (Mann-Whitney)