Study on Safety and Clinical Efficacy of AZVUDINE in COVID-19 Patients (SARS-CoV-2 Infected)

Hypothesis:

AZVUDINE has therapeutic potential and safety profile for the treatment of patients infected with SARS-CoV-2.

Goals:

Primary objective • To assess the efficacy and safety of AZVUDINE (FNC) in relation to placebo, in patients infected with SARS-COV-2 in moderate to severe stage;

Secondary objective

• To evaluate the clinical outcome of the AZVUDINE group (FNC) compared to the placebo group in patients infected by SARS-COV-2 in moderate to severe stage;

Pharmaceutical form of the experimental medicine:

AZVUDINE 1 mg tablets

Comparators:

AZVUDINE placebo

Statistical planning:

The analyzes will be performed by FAS, PPS and SS and should be stratified by the severity of the disease (moderate, severe) and age (<60 years, ≥ 60 years), to assess the following parameters:

• Progression of the disease (moderate to severe, severe type);
• Negative viral load conversion rate;
• Time of negative conversion of viral load;
• Temperature recovery time;
• Time necessary to improve diarrhea, myalgia, fatigue, and other symptoms;
• Time to improve the pulmonary image;
• Frequency of supplemental oxygenation or non-invasive ventilation;
• Frequency of AEs;
• Mortality rate.

All statistical tests will be bilateral tests. If the P value is ≤0.05, it is considered that there is statistical significance between the difference in the tests.

Inclusion criteria

• Individuals aged 18 or over, regardless of gender;
• Patients hospitalized in moderate to severe stages in line with the Ministry of Health classification;
• Positive diagnosis for SARS-CoV-2 by molecular amplification of the virus in RT-PCR diagnosed from a respiratory sample (nasopharynx, oropharyngeal, lower respiratory tract [eg, sputum]) collected <96 hours before randomization;
• Time of onset of symptoms and inclusion ≤ 14 days;
• Internation within 48 hours after inclusion in the study;
• Follow-up availability during the study period;
• Voluntary membership to participate in the study and signing the Informed Consent Form.

Exclusion criteria

• Patients known or suspected of being sensitive to AZVUDINE or excipients (inactive ingredients: microcrystalline cellulose, hydrated lactose, polyvinylpyrrolidone K30, croscarmellose sodium, magnesium stearate);
• Patients diagnosed with pneumonia caused by other pathogens;
• Patients with liver disease (total bilirubin ≥2 times above the normal limit, ALT / TGP and AST / TGO ≥5 times above the normal limit)
• Patients with renal failure (glomerular filtration rate ≤60mL / min / 1.73 m2) or are receiving continuous renal replacement therapy, hemodialysis or peritoneal dialysis;
• Individuals with malabsorption syndrome, or other conditions that affect gastrointestinal absorption, and circumstances in which patients need intravenous nutrition, or cannot take drugs orally or nasogastrically;
• Pregnant or lactating women, or women with the potential to become pregnant during the study period and within 6 months after the end of administration;
• Patients already included in other clinical trials;
• Patient under treatment for HIV;
• Patients being treated with other antivirals (eg lopinavir / ritonavir, remdesivir, umifenovir / arbidol, favipiravir, interferon-α)
• Patients undergoing treatment with monoclonal antibodies (eg tocilizumab and sarilumab / kevzara);
• Patients who are on a clinical treatment plan that includes the concomitant administration of any other experimental treatment or off-label use of drugs already on the market (eg hydroxychloroquine sulfate;
• Patients who require invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at the time of randomization;
• Any clinically significant medical condition or medical history that, in the investigator's opinion, might discourage participation in the study.