NOi receives FDA approval to begin the trial on its new drug NOviricid to treat COVID 19

Nitric Oxide Innovations (NOi), LLC has received Investigational New Drug (IND #150758) clearance and Fast Track approval from the U.S. FDA to begin a Phase 2b/3a outpatient clinical study testing the safety and efficacy of its new drug, NOviricid. NOviricid is the first oral Nitric Oxide (NO) generating drug to be clinically tested to treat African Americans diagnosed with COVID-19.

This is the first and only COVID-19 study specifically addressing the health disparities in people of color 
one of the most affected, high-risk populations of the virus.

 

NOviricid offers a fast-acting, Nitric Oxide therapeutic, with proven vasodilatory and anti-viral properties, targeting the effects of the novel Coronavirus. NOviricid is a proactive treatment, to be administered at the early onset of symptoms to prevent the rapid progression of the virus, improve recovery and survival of African Americans, or anyone who is symptomatic. NOviricid promises an easily administered, safe, affordable, and effective treatment.

BACKGROUND

To date, the COVID-19 pandemic has infected over 36 million people worldwide and is responsible for over 1 million deaths. In the U.S., African Americans are one of the most affected, high-risk populations. According to the Centers for Disease Control and Prevention (CDC), African Americans experience a 2.8x higher infection rate, a 4.7x higher hospitalization rate, and 2.1x higher death rate than Caucasians. Those with comorbidities such as hypertension, diabetes, obesity, history of smoking, kidney disease, and respiratory illnesses are most at risk for infection and rapid progression of the disease.

Dr. Nathan S. Bryan, Founder, and CEO of NOi states, “Everything we have learned about COVID-19 over the past 10 months reveals that diminished nitric oxide production in patients is what is thought to be responsible for the increased risk of infection and rapid disease progression. This applies directly to the African American population, which often suffers from diminished nitric oxide production. A lack of nitric oxide explains the multi-system disease and dysfunction that persists long after the active infection is gone, including increased risk of blood clots, endotheliitis, kidney, and lung dysfunction. Restoration of nitric oxide appears to be a very safe and effective solution.”

In recent, and ongoing, studies using inhaled nitric oxide, it has been shown that nitric oxide inhibits Coronavirus replication. While inhaled nitric oxide has been used very successfully to treat critically ill patients on ventilators, it is expensive and difficult to deliver outside of the hospital setting making it impractical to treat patients recently diagnosed with COVID-19. By contrast, NOviricid, an orally disintegrating nitric oxide therapeutic, is administered before the patient is critically ill, ideally within 72 hours of a positive COVID-19 test.

We believe that early intervention with NOviricid will prevent hospitalization, the need for ventilation and death.

NOi to FAST TRACK of Oral Nitric Oxide Therapeutic in Fight Against COVID 19

Although severe COVID-19 infections can lead to Acute Respiratory Distress Syndrome (ARDS), its vascular effects should not be overlooked. COVID-19’s effects on the vascular system affect the brain and heart and can lead to lethal effects on the blood clotting system. A key underlying mechanism of COVID-19 appears to be vascular endothelial dysfunction which causes an excessive cardiovascular disease burden. This makes the restoration of nitric oxide a key strategy for the early treatment of COVID-19, especially in those with pre-existing conditions. Nitric oxide has been proven to be a potent vasodilator for small blood vessels, supplying healthy alveoli and potentially reducing the AV shunt seen in COVID-19 patients with severe ARDS on ventilators.

  • An organic NO donor, S-nitroso-N-acetylpenicillamine, significantly inhibited the replication cycle of SARS CoV in a
    concentration-dependent manner.

  • NO inhibits viral protein and RNA synthesis.

  • NO generated by inducible nitric oxide synthase, an enzyme that produces NO, inhibits the SARS CoV replication cycle.

Nitric Oxide Inhibits the Replication Cycle of Severe Acute Respiratory Syndrome Coronavirus (SARS)

Sara Åkerström, Mehrdad Mousavi-Jazi, J

DOI: 10.1128/JVI.79.3.1966-1969.2005

 

NOi has received FDA approval to Fast Track an orally disintegrating nitric oxide generating drug

to restore and replete NO production in at-risk patients to improve patient outcomes,

reduced hospitalization, need for ventilation, and death from Coronavirus COVID 19 infection.

Mortality, Risk Factors of Patients With Cardiac Injury and COVID-19

The evaluation of Nitric Oxide generating lozenges on outcome in COVID-19 patient of African American Origin


IMPACT
This the first and only study to address the health disparities of African Americans with COVID. Furthermore, in this outpatient study, we will capture at-risk patients early on in the disease process and prevent the progression of the disease.  Nitric oxide drug therapy will address all of the underlying risk factors for African Americans with COVID and protect from the long term complications of COVID, including the risk of blood clots, embolism, heart attack, and stroke.

 
INTRODUCTION
Coronavirus disease (COVID-19), is now a worldwide pandemic affecting millions of people around the world.  As of Mid-April, over 2 million people have been infected with over 130,000 deaths.  Early data coming out of China revealed patients with underlying cardiovascular disease were more susceptible to infection, greater disease severity, and a ten times higher mortality. Among the patients studied, the median (range) age was 64 (21-95) years, female (50.7% and the median time to symptom onset was 10 days (interquartile range [IQR]), 1-30). Of this group, 82 (19.7%) had some type of cardiac injury.  It was apparent as the study went on that patients with cardiac injury and COVID-19 fared worse than the patients with COVID-19 but no history of cardiac injury. Patients with cardiac injury with diagnosed COVID-19, compared with patients without cardiac injury, had a higher mortality rate (51.2% vs 4.5%) and risk of death [1]. These observations have been supported by data reported in the U.S., especially those reported for NYC. 
Recent reports from the U.S. database compiled by CDC reports mortality from COVID-19 to have a racial disparity [2].  A disproportionate number of COVID-19 fatalities among African Americans has been observed. While this has been attributed to known disparities in health care, low economic resources, and issues associated with social distancing: occupation, crowded residential spaces, and transportation crowding. Additionally, African Americans have a high incidence of pre-existing and often untreated cardiovascular conditions [3]. However, all these issues are seen in other populations and the higher prevalence of cardiovascular conditions would not explain why African Americans would still be at higher mortal risk than Caucasians with cardiovascular risk factors.  What may be increasing risk for the African American community is some unique physiologic condition(s). Hypertension is highly prevalent in African Americans with an association with diminished nitric oxide (NO) levels [4]. Hypertension often leads to the development of a cardiomyopathy and heart failure [5].  Additionally, there are unique manifestations to the COVID-19 disease that make African Americans with low NO potentially at higher risk.
First coronavirus has a spike protein that affords the virus access to cells by a receptor, the angiotensin-converting enzyme 2(ACE2). In an earlier SARS-CoV-2 virus access to cells was also through the ACE2 receptor. NO was reported to alter the surface protein of SARS-1 (spike protein) preventing attachment to the ACE2 receptor and thus entrance into the cell [6].  It is likely that for the new COVID-19 virus NO may well prevent cellular penetration. 
Nitric oxide is reported to improve oxygenation [7, 8], an action needed as the COVID-19 disease progresses and acute respiratory disease syndrome (ARDS) develops. NO decreases the propensity of blood to clot [9], a problem leading to multi-system damage in patients severely ill with COVID-19 virus. In fact, high D-dimer levels, an indication of enhanced clotting is a strong predictor of death in infected patients.  All these factors; decreased oxygenation, low NO levels in African American patients, decreased oxygenation in severely ill COVID-19 patients, increased clotting, leads one to hypothesize that increasing NO levels in patients with COVID-19 would have a salutatory benefit.  
This current clinical trial aims to test the efficacy of a more potent nitric oxide lozenge (30 mg sodium nitrite) on patients diagnosed with COVID-19 infection to investigate if restoring nitric oxide can prevent the progression of the disease, reduced need for ventilation, and decreased death. 


SELECTION OF STUDY POPULATION 
The target population for this study consists of 840 African American subjects with positive COVID-19 diagnosis (positive by PCR testing).  Each subject will have to fulfill the inclusion criteria listed in Section 4.1. Subjects will not be included in the study if they meet any of the exclusion criteria listed in Section 4.2.

Inclusion Criteria
1.    Male or female of 18-75 years of age
2.    Subjects with recent COVID-19 diagnosis (within 72 hours), that are symptomatic (fever, cough, SOB, weakness, flu-like symptoms).
3.    Agrees to comply with study procedures   
4.    Has given voluntary, written, informed consent to participate in the study
5.    Identifies as African American.
6.    Patients must have at least 1 risk factor (hypertension (BP> 140/99) for at least 1 year by history) CHF history, angina, prior MI, coronary angiography with ASHD finding, or diabetes mellitus. 


Patients will be monitored for 30 days with rate of hospitalization, ventilation, and death a primary endpoint.  Oxygen saturation will be monitored for both safety and efficacy of the lozenge as a secondary endpoint.

Impact:  
REFERENCES
1.    Shi, S., et al., Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA Cardiol, 2020.
2.    Yancy, C.W., COVID-19 and African Americans. JAMA, 2020.
3.    Carnethon, M.R., et al., Cardiovascular Health in African Americans: A Scientific Statement From the American Heart Association. Circulation, 2017. 136(21): p. e393-e423.
4.    Brothers, R.M., P.J. Fadel, and D.M. Keller, Racial disparities in cardiovascular disease risk: mechanisms of vascular dysfunction. Am J Physiol Heart Circ Physiol, 2019. 317(4): p. H777-H789.
5.    Drazner, M.H., The progression of hypertensive heart disease. Circulation, 2011. 123(3): p. 327-34.
6.    Akerstrom, S., et al., Dual effect of nitric oxide on SARS-CoV replication: viral RNA production and palmitoylation of the S protein are affected. Virology, 2009. 395(1): p. 1-9.
7.    Allen, B.W., J.S. Stamler, and C.A. Piantadosi, Hemoglobin, nitric oxide, and molecular mechanisms of hypoxic vasodilation. Trends Mol Med, 2009. 15(10): p. 452-60.
8.    Zhang, R., et al., Hemoglobin betaCys93 is essential for cardiovascular function and an integrated response to hypoxia. Proc Natl Acad Sci U S A, 2015. 112(20): p. 6425-30.
9.    Radomski, M.W., R.M. Palmer, and S. Moncada, The anti-aggregating properties of vascular endothelium: interactions between prostacyclin and nitric oxide. Br J Pharmacol, 1987. 92(3): p. 639-46.
 

NOi COVID-19 MULTI-SITE CLINICAL TRIAL DESIGN

 

840 African American patients testing positive for COVID-19 within the previous 72 hours, will be selected for participation. Study participants must present with one or more comorbidities including but not limited to:

  • High blood pressure 

  • COPD

  • heart failure

  • Diabetes

  • Obesity

  • Others

Subjects will participate in a double-blinded, placebo-controlled study to determine the effectiveness of NOviricid. All study patients will be provided with digital pulse oximeters and blood pressure monitoring equipment. These devices will be monitored remotely for changes in their oxygen levels. Primary endpoints are hospitalization, need for ventilation, and death.

​NOi’s outpatient study will collect real-time data via eCare21’s telemedicine platform to identify disease progression in at-risk patients. Nitric oxide drug therapy will address all of the underlying risk factors for African Americans with COVID-19 and help protect them from the long-term complications, including the risk of blood clots, embolism, heart attack, and stroke. 

Those meeting the criteria above, residing locally to one of the test sites are encouraged to contact.

TEXAS

Texas Center for Lifestyle Medicine 

Ruan Cheng, M.D.

5252 Hollister St #201, Houston, TX 77040

(713) 690-1991

Appointments: texascenterforlifestylemedicine.org

Email:  admin@ruanmedicalgroup.com

CHICAGO

Premier Urgent Care

Michael McGee, M.D.

1301 E 47th Street

Building #2

Chicago, IL, 60653
Phone:(773) 891-2890

MISSISSIPPI

TrustCare Health

William Whitton, M.D.

1051 Highland Colony Parkway, Suite E

Ridgeland, MS 39157

Phone: 601-707-3737

For additional clinical study details
Contact NOi.

(512) 773-9097‬

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Email: info@nitricoxideinnovations.com

Phone: (512) 773-9097

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