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

NCT ID: NCT04337918

Last Updated: 2021-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 143 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-08
• Study Completion Date: 2021-02-02

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.

Conditions

Corona Virus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Prevention - Standard Precautions

Participants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Prevention - NORS + Standard Precautions

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.

Group Type: EXPERIMENTAL

NORS (Nitric Oxide Releasing Solution)

Intervention Type: DRUG

NORS treatment will consist of daily self-administration of three routes; Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day.

Treatment Sub-Study

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.

Group Type: OTHER

NORS (Nitric Oxide Releasing Solution)

Intervention Type: DRUG

Up to ten 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. NORS treatment will consist of daily self-administration of three routes; Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day.

Any participants enrolled in the Prevention study who meet the criteria for the sub study will roll over into the Treatment Sub-Study but must remain in their randomly assigned group.

Interventions

NORS (Nitric Oxide Releasing Solution)

NORS treatment will consist of daily self-administration of three routes; Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day.

Intervention Type: DRUG

NORS (Nitric Oxide Releasing Solution)

Up to ten 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. NORS treatment will consist of daily self-administration of three routes; Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day.

Any participants enrolled in the Prevention study who meet the criteria for the sub study will roll over into the Treatment Sub-Study but must remain in their randomly assigned group.

Intervention Type: DRUG

Other Intervention Names

NOG, NONI, NONS; NOG, NONI, NONS

Eligibility Criteria

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.

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.

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.

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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Emmes Company, LLC

INDUSTRY

Sponsor Role: collaborator

Keyrus Life Science

NETWORK

Sponsor Role: collaborator

Sanotize Research and Development corp.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeremy Road, MD

Role: PRINCIPAL_INVESTIGATOR

Private Practice

Locations

BC Diabetes

Vancouver, British Columbia, Canada

LMC Manna

Pointe-Claire, Quebec, Canada

Diex Recherche Québec

Québec, Quebec, Canada

Diex Recherche Joliette

Saint-Charles-Borromée, Quebec, Canada

Diex Recherche Sherbrooke

Sherbrooke, Quebec, Canada

Countries

Canada

References

Reiss CS, Komatsu T. Does nitric oxide play a critical role in viral infections? J Virol. 1998 Jun;72(6):4547-51. doi: 10.1128/JVI.72.6.4547-4551.1998. No abstract available.

Reference Type: BACKGROUND

PMID: 9573217 (View on PubMed)

Colasanti M, Persichini T, Venturini G, Ascenzi P. S-nitrosylation of viral proteins: molecular bases for antiviral effect of nitric oxide. IUBMB Life. 1999 Jul;48(1):25-31. doi: 10.1080/713803459.

Reference Type: BACKGROUND

PMID: 10791912 (View on PubMed)

Deppisch C, Herrmann G, Graepler-Mainka U, Wirtz H, Heyder S, Engel C, Marschal M, Miller CC, Riethmuller J. Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study. Infection. 2016 Aug;44(4):513-20. doi: 10.1007/s15010-016-0879-x. Epub 2016 Feb 9.

Reference Type: BACKGROUND

PMID: 26861246 (View on PubMed)

Miller CC, Hergott CA, Rohan M, Arsenault-Mehta K, Doring G, Mehta S. Inhaled nitric oxide decreases the bacterial load in a rat model of Pseudomonas aeruginosa pneumonia. J Cyst Fibros. 2013 Dec;12(6):817-20. doi: 10.1016/j.jcf.2013.01.008. Epub 2013 Mar 6.

Reference Type: BACKGROUND

PMID: 23481089 (View on PubMed)

Miller C, Miller M, McMullin B, Regev G, Serghides L, Kain K, Road J, Av-Gay Y. A phase I clinical study of inhaled nitric oxide in healthy adults. J Cyst Fibros. 2012 Jul;11(4):324-31. doi: 10.1016/j.jcf.2012.01.003. Epub 2012 Apr 18.

Reference Type: BACKGROUND

PMID: 22520076 (View on PubMed)

McMullin BB, Chittock DR, Roscoe DL, Garcha H, Wang L, Miller CC. The antimicrobial effect of nitric oxide on the bacteria that cause nosocomial pneumonia in mechanically ventilated patients in the intensive care unit. Respir Care. 2005 Nov;50(11):1451-6.

Reference Type: BACKGROUND

PMID: 16253152 (View on PubMed)

Regev-Shoshani G, Vimalanathan S, McMullin B, Road J, Av-Gay Y, Miller C. Gaseous nitric oxide reduces influenza infectivity in vitro. Nitric Oxide. 2013 May 31;31:48-53. doi: 10.1016/j.niox.2013.03.007. Epub 2013 Apr 2.

Reference Type: BACKGROUND

PMID: 23562771 (View on PubMed)

Regev-Shoshani G, McMullin B, Nation N, Church JS, Dorin C, Miller C. Non-inferiority of nitric oxide releasing intranasal spray compared to sub-therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine respiratory disease complex in low to moderate risk beef cattle arriving at a commercial feedlot. Prev Vet Med. 2017 Mar 1;138:162-169. doi: 10.1016/j.prevetmed.2015.04.008. Epub 2015 Apr 20.

Reference Type: BACKGROUND

PMID: 25975664 (View on PubMed)

Other Identifiers

COVID-CTP-01

Identifier Type: -

Identifier Source: org_study_id