Clinical trial NCT04337918: Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection
Official title: Multi-Center, Randomized, Controlled, Phase II Clinical Efficacy Study Evaluating Nitric Oxide Releasing Solution Treatment for the Prevention and Treatment of COVID-19 in Healthcare Workers and Individuals at Risk of Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Corona Virus Infection
Keywords: Antiviral
Virucidal
Nitric Oxide
Lead sponsor: Sanotize Research and Development corp.
Sponsor class: INDUSTRY
Collaborators: name: The Emmes Company, LLC
name: Keyrus Life Science
First posted: 2020-04-08
Enrollment: 143
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, prospective, randomized, controlled, phase II, parallel group
Primary purpose: PREVENTION

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.

Eligibility criteria: Prevention 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. 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.

Primary outcomes:
measure: 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
timeFrame: 14 days
measure: Treatment Sub Study: Measure the efficacy of NORS at reducing the progression of COVID- 19
timeFrame: 21 days
Secondary outcomes:
measure: Prevention Study: Measure the effect of NORS on the prevention of progression of COVID- 19
timeFrame: 21 days
measure: Prevention Study: Measure the tolerability of NORS treatments
timeFrame: 21 days
measure: Treatment Sub Study: Measure the virucidal effect of NORS Treatments
timeFrame: 21 days
measure: Treatment Sub Study: Determine effect of NORS on the speed of clinical recovery
timeFrame: 21 days
measure: Treatment Sub Study: Determine the reduction in clinical symptoms
timeFrame: 21 days
measure: Treatment & Sub Study: Determine positive sero-conversion for SARS-CoV-2
timeFrame: 21 days
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Diabetes
state: British Columbia
city: Pointe-Claire
country: Canada
facility: LMC Manna
state: Quebec
city: Québec
country: Canada
facility: Diex Recherche Québec
state: Quebec
city: Saint-Charles-Borromée
country: Canada
facility: Diex Recherche Joliette
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Recherche Sherbrooke
state: Quebec
Study officials:
affiliation: Private Practice
name: Jeremy Road, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.