Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection

Phase 2

Completed

• Conditions: Corona Virus Infection
• Interventions: Drug: NORS (Nitric Oxide Releasing Solution)

• Registration Number: NCT04337918
• Lead Sponsor: Sanotize Research and Development corp.

Brief Summary

This is a multi-center, randomized, controlled, phase II clinical efficacy study evaluating a novel Nitric Oxide Releasing Solution (NORS) treatment for the prevention and treatment of COVID-19 in healthcare workers at risk of infection. Participants will be enrolled into one of two components of this study. Based on initial swabs/symptoms, volunteers who are COVID-19 negative will be enrolled in the Prevention study and randomized to receive standard institutional precautions or standard institutional precautions + NORS. Those who are COVID-19 positive will be enrolled in the open-label Treatment Sub-Study.

Detailed Description

The novel, human-infecting corona-virus, provisionally named 2019 novel corona virus (2019-nCoV) is a single-strand, positive-sense RNA virus and has a similar receptor-binding domain structure to that of SARS-CoV and MERS-CoV. The virus is transmitted via airborne droplets to the nasal mucosa. Replication occurs locally in the nasal mucosa, in ciliated epithelial cells, over a 3-day incubation period. The mucosal cells are damaged with a resultant inflammatory response similar to the common cold. During this time the virus is shed in nasal secretions causing disease in the lower respiratory tract, potentially causing fatal viral pneumonia.

The literature supports that NO or its derivatives have inhibitory effects on a variety of viral infections. This inhibitory effect was shown to be marked in Interferon (IFN) mediated inhibition manifested by activated macrophage. It was also shown to be correlated with s-nitrosylation of viral proteins such as reductases and proteases.

Based on the genetic similarities between SARS and corona viruses, similar viricidal effects of NO on COVID-19 can be hypothesized.

SaNOtize has developed an innovative approach to provide nitric oxide gas using a formulation called Nitric Oxide Releasing Solution (NORS). This patented solution releases virucidal doses of NO for a sustained period and is effective at rapidly inactivating Influenza A and SARS-CoV-2.

NORS delivered as a gargle (AM), nasal spray (PRN) or as a nasopharyngeal flush (PM) has the potential to decontaminate the upper respiratory tract that could preventing transmission and progression of COVID-19 in Healthcare Workers \& Individuals at Risk of Infection.

The randomized Prevention study will investigate the ability of NORS to prevent COVID-19 infection when used prophylactically. The open-label Treatment Sub-Study is expected to be small and will provide pilot data on the possibility of NORS as a treatment for Mild/Moderate COVID-19 infection.

Study Timeline

• Study First Submitted: 2020-04-06
• Study First Submitted QC: 2020-04-06
• Study First Posted: 2020-04-08
• Study Start: 2020-05-08
• Primary Completion: 2021-01-31
• Status Verified: 2021-02
• Study Completion: 2021-02-02
• Last Update Submitted: 2021-02-08
• Last Update Posted: 2021-02-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 143

Inclusion Criteria

1. Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
2. Men and Women ≥ 19 years of age unless local laws dictate otherwise;
3. English speaking;
4. Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP.
5. Be symptom-free at screening/baseline.
6. Work/live in contact with COVID-19 infected patients or scheduled to work in a setting with high likelihood of contact with COVID-19 infected patients.

Prevention Study

Exclusion Criteria

1. Prior Tracheostomy;
2. Concomitant treatment of respiratory support (involving any form of oxygen therapy);
3. Any clinical contraindications, as judged by the attending physician;
4. Any symptoms consistent with COVID-19;
5. Pregnant;
6. Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
7. Prior COVID-19 infection.

Treatment Sub study Inclusion Criteria:

1. Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
2. Men and Women ≥ 19 years of age unless local laws dictate otherwise;
3. English speaking;
4. Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP;
5. Positive COVID-19 test or presentation of clinical symptoms defined as fatigue with either fever >37.2 (oral) and/or a persistent cough.

Treatment Sub Study Exclusion Criteria:

1. Prior Tracheostomy;
2. Concomitant treatment of respiratory support (involving any form of oxygen therapy); Any clinical contraindications, as judged by the attending physician;
3. Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
4. Pregnant;
5. Currently hospitalized for symptoms of COVID-19.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prevention - NORS + Standard Precautions	NORS (Nitric Oxide Releasing Solution)	Participants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols) plus daily NORS treatment for 14 days.
Treatment Sub-Study	NORS (Nitric Oxide Releasing Solution)	Volunteers who are found to be COVID-19 positive during screening will be eligible to enroll in the 21-day Treatment sub-study and receive daily NORS treatment for 14 days. Ten participants can be directly enrolled in the Treatment sub-study. Participants enrolled in the Prevention study who meet the criteria in this section will roll over into the Treatment Sub-Study but must remain in their randomly assigned group.

Primary Outcome Measures

Name	Time	Method
Prevention Study: Measure the effect of NORS on the prevention of COVID-19 infection among health care professionals at risk of exposure to COVID-19	14 days	Measure the proportion of subjects with either swab positive COVID-19 or presentation of clinical symptoms as measured by fatigue with either fever \>37.2 (oral)and/or a persistent cough.
Treatment Sub Study: Measure the efficacy of NORS at reducing the progression of COVID- 19	21 days	Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.

Secondary Outcome Measures

Name	Time	Method
Treatment Sub Study: Determine effect of NORS on the speed of clinical recovery	21 days	Determine the time to clinical recovery in participants with COVID-19 by measuring the median number of days from enrollment to discharge (if admitted), or to normalization of fever (defined as \<36.6°C from axillary site, or \< 37.2°C from oral site or \< 37.8°C from rectal or tympanic site), respiratory rate (\< 24 bpm while breathing room air).
Treatment Sub Study: Determine the reduction in clinical symptoms	21 days	Measure the reduction clinical symptoms in participants with COVID- 19 by the magnitude of the change in Modified Jackson Cold Score Diary Score (5-unit change is a substantial clinical benefit).
Prevention Study: Measure the effect of NORS on the prevention of progression of COVID- 19	21 days	Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Prevention Study: Measure the tolerability of NORS treatments	21 days	Measure the tolerability of the NORS treatments as determined by number of adverse events, pain, discomfort or discontinuations of treatment.
Treatment Sub Study: Measure the virucidal effect of NORS Treatments	21 days	Measure the median number of days to negative conversion of SARS-CoV-2 RT-PCR from a nasopharyngeal swabs.
Treatment & Sub Study: Determine positive sero-conversion for SARS-CoV-2	21 days	Measure the proportion of participants that have a positive sero-conversion for SARS-CoV-2

Trial Locations

Locations (5)

BC Diabetes; 🇨🇦 Vancouver, British Columbia, Canada

Diex Recherche Joliette; 🇨🇦 Saint-Charles-Borromée, Quebec, Canada

Diex Recherche Québec; 🇨🇦 Québec, Quebec, Canada

Diex Recherche Sherbrooke; 🇨🇦 Sherbrooke, Quebec, Canada

LMC Manna; 🇨🇦 Pointe-Claire, Quebec, Canada