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

NCT04337918 | Completed Phase 2

• 1 other identifier: COVID-CTP-01
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 5

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.

Conditions

Corona Virus Infection

Keywords

Antiviral; Virucidal; Nitric Oxide

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  14 days

• Treatment Sub Study: Measure the efficacy of NORS at reducing the progression of COVID- 19

  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.

  21 days

Secondary Outcomes (6)

• Prevention Study: Measure the effect of NORS on the prevention of progression of COVID- 19

  21 days

• Prevention Study: Measure the tolerability of NORS treatments

  21 days

• Treatment Sub Study: Measure the virucidal effect of NORS Treatments

  21 days

• Treatment Sub Study: Determine effect of NORS on the speed of clinical recovery

  21 days

• Treatment Sub Study: Determine the reduction in clinical symptoms

  21 days

Study Arms (3)

Prevention - Standard Precautions

NO INTERVENTION

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

Prevention - NORS + Standard Precautions

EXPERIMENTAL

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.

Drug: NORS (Nitric Oxide Releasing Solution)

Treatment Sub-Study

OTHER

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.

Drug: NORS (Nitric Oxide Releasing Solution)

Interventions

NORS (Nitric Oxide Releasing Solution) 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.

Also known as: NOG, NONI, NONS

Prevention - NORS + Standard Precautions

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
• Men and Women ≥ 19 years of age unless local laws dictate otherwise;
• English speaking;
• 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.
• Be symptom-free at screening/baseline.
• 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.

You may not qualify if:

• Prior Tracheostomy;
• Concomitant treatment of respiratory support (involving any form of oxygen therapy);
• Any clinical contraindications, as judged by the attending physician;
• Any symptoms consistent with COVID-19;
• Pregnant;
• Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
• Prior COVID-19 infection.
• Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
• Men and Women ≥ 19 years of age unless local laws dictate otherwise;
• English speaking;
• 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;
• Positive COVID-19 test or presentation of clinical symptoms defined as fatigue with either fever \>37.2 (oral) and/or a persistent cough.
• Prior Tracheostomy;
• Concomitant treatment of respiratory support (involving any form of oxygen therapy); Any clinical contraindications, as judged by the attending physician;
• Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;

Sponsors & Collaborators

• Sanotize Research and Development corp.: lead
• The Emmes Company, LLC: collaborator
• Keyrus Life Science: collaborator

Study Sites (5)

BC Diabetes

Vancouver, British Columbia, V5Y 3W2, Canada

Location

LMC Manna

Pointe-Claire, Quebec, H9R 4S3, Canada

Location

Diex Recherche Québec

Québec, Quebec, G1N 4V3, Canada

Location

Diex Recherche Joliette

Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

Location

Diex Recherche Sherbrooke

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Related Publications (8)

• 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.

  PMID: 9573217 BACKGROUND

• 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.

  PMID: 10791912 BACKGROUND

• 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.

  PMID: 26861246 BACKGROUND

• 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.

  PMID: 23481089 BACKGROUND

• 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.

  PMID: 22520076 BACKGROUND

• 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.

  PMID: 16253152 BACKGROUND

• 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.

  PMID: 23562771 BACKGROUND

• 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.

  PMID: 25975664 BACKGROUND

MeSH Terms

Conditions

Coronavirus Infections

Interventions

noggin protein

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• Jeremy Road, MD

  Private Practice

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multi-center, prospective, randomized, controlled, phase II, parallel group

Study Record Dates

• First Submitted: April 6, 2020
• First Posted: April 8, 2020
• Study Start: May 8, 2020
• Primary Completion: January 31, 2021
• Study Completion: February 2, 2021
• Last Updated: February 10, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)