SARS-CoV-2 Infection
Conditions
Brief summary
A multicenter, randomized, double-blinded, placebo-controlled, phase 3 clinical efficacy study evaluating nitric oxide nasal spray (NONS) as prevention for treatment of individuals at risk of exposure to COVID-19 infection.
Detailed description
This is a multicenter, randomized, double-blinded, placebo-controlled, Phase 3 clinical efficacy study evaluating NONS in adult volunteers as a prevention treatment for individuals at risk from COVID-19 infection. Up to 13 000 adult participants aged 18 or over with no known history of SARS-CoV-2 infection will be randomized into one of 2 cohorts of this study in a ratio of 1:1 (Treatment: Placebo Control). Participants with or without underlying medical conditions will be eligible to enroll. The NONS formulation proposed for use in this COVID-19 clinical study will be self-administered at a maximum of 3 times per day, morning, noon, and night for 28 days. Participants will be on study for 4 weeks of treatment (to include 5 days of Screening, 1 week of Follow-Up, participants will be followed for a total of approximately 5 weeks) as a viricidal Investigational Medical Product. Participants will self-administer a nasal spray containing either blinded study treatment or placebo (herein called study treatment). Nitric oxide nasal spray will be delivered from manual pump nasal spray container with 25 mL of solution with each nasal spray dispensing approximately 130-150 µL of solution. After the participant blows their nose, each treatment will require 2 sprays per nostril, or about 0.5 mL per treatment. The primary endpoint is to assess the efficacy of NONS in the prevention of symptomatic COVID-19 infection as determined by a positive COVID-19 test (antigen or reverse-transcriptase polymerase chain reaction \[RT-PCR\]),
Interventions
DRUGNitric Oxide
The Sponsor designed a dual chamber nasal spray bottle for NORS administration. Components are mixed from two chambers to create the final NO-producing formulation. The liquid contains NO at 0.11 ppm\*hour, which acts as a viricidal agent. Instructions for storing, preparing, and administering the study treatment will be provided to participants.
The Sponsor designed a dual chamber nasal spray bottle for NORS administration. The bottle will be filled with normal saline before being provided to the participant.
Sponsors
Sanotize Research and Development corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Identical labeled nasal spray bottles
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Each participant must meet the following criteria to be enrolled in this study. 1. At least aged 18 years old at the time of consent. 2. If female, be surgically sterile or post-menopausal (no menses for at least 12 months), or if of childbearing potential, must be using an acceptable method of contraception such as a combination estrogen/progestin hormonal contraceptive (oral or injected) for at least 1 month prior to Day 1, or such items as an IUD, intrauterine system (IUS), transdermal hormonal implant, vaginal hormonal ring, or 2 forms of the following: diaphragm, cervical cap, patch, condom, spermicide, or sponge. Total abstinence is permitted. If local regulations deviate from the previously listed contraception methods to prevent pregnancy, local requirements will apply. In addition, females of childbearing potential must agree to continue to use their method of birth control for the duration of the study and 12 weeks following discharge from the study. 3. If male, be surgically sterile, or agree to use appropriate contraception (latex condom with spermicide) when engaging in sexual activity and agree to not donate sperm for the duration of the study and 12 weeks following discharge from the study. 4. Be in good health (ie, no acute illnesses or hospitalizations within 30 days of the study start, no planned procedures during study participation, and no newly diagnosed chronic illnesses that are not deemed stable by the participant's primary care physician), in the opinion of the Investigator, based on medical history (ie, absence of any clinically relevant abnormality) during Screening. 5. Be able to understand and provide written, informed consent. 6. Access to a telephone, the internet, a device that reliability connects to the internet, and able to dial into telehealth checkups and study-related assessments. If access to the internet precludes involvement, then paper diaries may be completed and promptly entered into the data capture system at the study centers as part of the regular follow-up visits. 7. Must be able to receive study product shipments directly to their home (ie, no Post Office Boxes), unless in a region (EU) or other location where the participant must receive the study product directly from the sites' staff/physician.
Exclusion criteria
Participants who meet any of the following criteria will be excluded from the study. 1. Participants with acute illnesses or hospitalizations within 30 days of the study start, and/or planned procedures during study participation, and/or newly diagnosed chronic illnesses that are not deemed stable by the participant's primary care physician), based on Investigator assessment of medical history during Screening. 2. Participants with any respiratory infection, flu-like symptoms, or unexplained fever or chills during the week prior to Screening (see Section 6.6.2). 3. Participants with any prior history of SARS-CoV-2 infection. 4. Participants who use intranasally dosed drugs, prescriptions or over-the-counter medications such as fluticasone within the last 7 days. 5. Participants who underwent a previous tracheostomy. 6. Participants who are receiving any form of oxygen therapy. 7. Females who are breastfeeding, pregnant, or attempting to become pregnant. 8. Participants who have any other condition that, in the opinion of the Investigator, would interfere with a participant's ability to adhere to the protocol (eg, participants whom are mentally or neurologically disabled and whom are considered not fit to their participation in the study), interfere with assessment of the investigational product, or compromise the safety of the participant or the quality of the data.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a COVID-19 Infection. | 28 days | Confirmed positive COVID-19 test (Both antigen and SARS-CoV-2 RT-PCR acceptable) by Day 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Requiring Medical Services. | 28 days | Hospitalization or ER/ED visits for COVID-19/flu-like symptoms by Day 28. |
| Number of Participants Reporting Safety Concerns. | 28 days | Adverse events captured during treatment (i.e., systemic and local nasal/throat events \[emphasis on respiratory and nervous system disorders\]). |
Countries
Canada, Sri Lanka
Participant flow
Pre-assignment details
1393 participants screened; 1389 participants randomized, 4 screen failures due to participants' having a prior history of SARS-CoV-2 infection.
Participants by arm
| Arm | Count |
|---|---|
| Intervention Nitric oxide nasal spray (NONS) | 690 |
| Control 0.9% Sodium chloride nasal spray | 694 |
| Total | 1,384 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 10 |
| Overall Study | Information unavailable | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Intervention | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 26 Participants | 49 Participants |
| Age, Categorical Between 18 and 65 years | 667 Participants | 668 Participants | 1335 Participants |
| Age, Continuous | 40.5 years STANDARD_DEVIATION 13.9 | 39.5 years STANDARD_DEVIATION 13.68 | 40.0 years STANDARD_DEVIATION 13.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 689 Participants | 692 Participants | 1381 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 651 Participants | 652 Participants | 1303 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 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 | 34 Participants | 35 Participants | 69 Participants |
| Sex: Female, Male Female | 364 Participants | 354 Participants | 718 Participants |
| Sex: Female, Male Male | 326 Participants | 340 Participants | 666 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 690 | 0 / 694 |
| other Total, other adverse events | 129 / 690 | 130 / 694 |
| serious Total, serious adverse events | 1 / 690 | 0 / 694 |
Outcome results
Primary
Number of Participants With a COVID-19 Infection.
Confirmed positive COVID-19 test (Both antigen and SARS-CoV-2 RT-PCR acceptable) by Day 28.
Time frame: 28 days
Population: All evaluable participants randomized who received at least one dose of the test article (NONS or placebo; mITT) analyzed through the end of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nitric Oxide Releasing Solution | Number of Participants With a COVID-19 Infection. | 2 Participants |
| Placebo | Number of Participants With a COVID-19 Infection. | 2 Participants |
Secondary
Number of Participants Reporting Safety Concerns.
Adverse events captured during treatment (i.e., systemic and local nasal/throat events \[emphasis on respiratory and nervous system disorders\]).
Time frame: 28 days
Population: All randomized participants who received at least 1 dose of study intervention (Safety Population)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nitric Oxide Releasing Solution | Number of Participants Reporting Safety Concerns. | 129 Participants |
| Placebo | Number of Participants Reporting Safety Concerns. | 130 Participants |
Secondary
Number of Participants Requiring Medical Services.
Hospitalization or ER/ED visits for COVID-19/flu-like symptoms by Day 28.
Time frame: 28 days
Population: All randomized participants who received at least 1 dose of study intervention (Safety Population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nitric Oxide Releasing Solution | Number of Participants Requiring Medical Services. | 1 participants |
| Placebo | Number of Participants Requiring Medical Services. | 0 participants |