Nitric Oxide Nasal Spray (NONS) as Prevention for Treatment of Individuals at Risk of Exposure to COVID-19 Infection

Study Overview
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Brief Summary
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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
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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]),

Official Title
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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

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Drug: Nitric Oxide
* Device: Nasal spray with isotonic saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Each participant must meet the following criteria to be enrolled in this study. At least aged 18 years old at the time of consent. 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. 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. 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. Be able to understand and provide written, informed consent. 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. 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. 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. Participants with any respiratory infection, flu-like symptoms, or unexplained fever or chills during the week prior to Screening (see Section 6.6.2). Participants with any prior history of SARS-CoV-2 infection. Participants who use intranasally dosed drugs, prescriptions or over-the-counter medications such as fluticasone within the last 7 days. Participants who underwent a previous tracheostomy. Participants who are receiving any form of oxygen therapy. Females who are breastfeeding, pregnant, or attempting to become pregnant. 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.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nitric Oxide Releasing Solution<br>Nasal spray with nitric oxide releasing solution (NORS) delivered up to 3 times daily morning, mid-day, and evening. Maximum volume delivered: 0.56 mL NORS @ 0.11ppm*hrs | Drug: Nitric Oxide<br>* 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.<br>* Other names: Nasal Spray;|
| Placebo Comparator: Placebo<br>Nasal spray with isotonic saline delivered up to 3 times daily morning, mid-day, and evening. Maximum volume delivered: 0.56 mL Saline @ 0.9% | Device: Nasal spray with isotonic saline<br>* 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.<br>* Other names: Normal saline, 0.9% saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of NONS in the reduction of risk of COVID-19 infection. | Confirmed positive COVID-19 test (Both antigen and SARS-CoV-2 RT-PCR acceptable) by Day 28. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of NONS in prevention of severe COVID-19. | Hospitalization or ER/ED visits for COVID-19/flu-like symptoms by Day 28. | 28 days | 
| Assess tolerability of NONS in participants with all participants including those with COVID-19. | AEs and discontinuation of treatment. | 28 days |