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

Study Overview
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Brief Summary
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Phase III, single-center with co-participating units, randomized, double-blind, parallel, placebo-controlled clinical study

Detailed Description
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Hypothesis: AZVUDINE has a therapeutic potential and safety profile for the treatment of patients infected with SARS-CoV-2. Goals: Main goal: To evaluate the efficacy and safety of AZVUDINE (FNC) in patients infected with SARS-COV-2, in a mild stage; Specific objective: To assess the clinical outcome of mild-stage SARS-CoV-2 infected participants treated with AZVUDINE (FNC) versus placebo Statistical planning: Statistical description: all statistical tests are performed by bilateral testing. A significance level of 5% will be adopted. Baseline analysis: including subject distribution, data demographics, and baseline analysis.

Official Title
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Evaluation of the Safety and Clinical Efficacy of AZVUDINE: Randomized, Double-blind, Placebo-controlled Study in Mild Stage Patients Infected With the SARS-CoV-2 Virus

Conditions
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COVID-19

Intervention / Treatment
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* Drug: AZVUDINE
* Drug: AZVUDINE placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who present the following characteristics will be included in this study: Age ≥18 years, regardless of gender; Fluorescence RT-PCR test result of respiratory or blood samples must be positive for COVID-19, or viral gene sequencing of respiratory tract samples must be highly homologous to COVID-19; Individuals with COVID-19 must meet the diagnostic criteria in the latest version of clinical guidelines for COVID-19 issued by the World Health Organization (WHO) on June 4, 2020; Symptomatic patients who meet the case definition for COVID-19, according to WHO, without evidence of bacterial pneumonia or hypoxia (Sat O2 < 95%) P. [score 1-3]; Voluntary participation and signing of the informed consent form. Exclusion Criteria: Individuals who present one or more of the following characteristics will not be eligible to participate in this study: Know or suspect that you are allergic to any of the components of AZVUDINE tablets (inactive ingredients: microcrystalline cellulose, lactose hydrate, polyvinylpyrrolidone K30, croscarmellose sodium, magnesium stearate); Individual presenting shortness of breath and Sat O2 < 95%; or any other symptom requiring treatment through hospital admission; Patients with liver disease (total bilirubin ≥2mg/dL, ALT/TGP e AST/TGO ≥5 times above normal limit); Pactients with a history of known liver disease (cirrhosis with ChildPugh classification B and C); Patients with a history of renal insufficiency (glomerular filtration rate < 60mL/min/1,73m2); Patients with history of congestive heart failure (NYHA ¾ grade), untreated symptomatic arrhythmias ormyocardial infarction within 6 months; Individuals with malabsorption syndrome, or other conditions affecting gastrointestinal absorption, and circumstances in which patients require intravenous nutrition, or cannot take medications orally or nasogastrically; Total neutrophil count <750 cells/L;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, parallel, placebo-controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZVUDINE<br>Experimental: AZVUDINE 1mg tablet Interventions: AZVUDINE 1mg tablet, 5 tablets QD + standard treatment, for up to 14 days | Drug: AZVUDINE<br>* AZVUDINE 5 tablets QD + standard treatment, for up to 14 days<br>* Other names: 1-(4-Azido-2-deoxy-2-fluoro-beta-D- arabino Ribo-furanosyl) cytosine, FNC;|
| Placebo Comparator: AZVUDINE placebo<br>Control: AZVUDINE placebo Intervention: AZVUDINE placebo tablet, 5 tablets QD + standard treatment, for up to 14 days | Drug: AZVUDINE placebo<br>* 5 tablets QD + standard treatment, for up to 14 days<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients hospitalized during the study through day 28 | WHO clinical progression ordinal scale (Jun/2020), Score 4 to 10.Health Organization Ordinal Clinical Progression Scale (WHO, Jun/2020; scale 0 [asymptomatic] to 10 [death]), with score 4 to 7. | Day 14 to Day 30 | 
| Proportion of participants with a clinical outcome of CURE during the study; | The clinical outcome of cure is defined in this protocol as the absence of viral RNA in samples collected and clinical conditions for outpatient discharge. | Day 14 to Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in clinical status in at least one category compared to screening | Ordinal Scale of Clinical Improvement (WHO, Jun/2020) | Day 14 to Day 30 | 
| Severity and duration of symptoms: fever, cough, fatigue or tiredness, breathlessness, myalgia, nasal congestion or runny nose, sore throat, headache, chills, nausea, vomiting, anosmia, ageusia. | Intensity (1= Mild; 2= Moderate; 3= Severe; 4= Critical) | Day 1 to Day 14 | 
| Changes in kidney function | Change in urea/creatinine | Day 1 to Day 30 | 
| Changes in liver function | Changes in ALT/AST | Day 1 to Day 30 | 
| Time of use of AZVUDINE until the second negative conversion of RT-PCR | Rate of change in biochemical markers of inflammatory function in relation to the physiological reference intervals between the AZVUDINA and PLACEBO groups. | Day 1 to Day 14 | 
| Evaluation of SARS-CoV-2 viral load negative conversion time by RT-PCR between AZVUDINE group (FNC) and control group | RT-PCR performed on treatment days. | Day 1 to Day 28 | 
| Occurrence of drug interactions | Monitoring of concomitant medication | Day 1 to Day 14 | 
| Assessment of liver function biochemical markers (AST/TGO, ALT/TGP, ALP, GGT, BIL total, and direct BIL) | Rate of change in biochemical markers of hepatic function in relation to the physiological reference intervals between the AZVUDINA and PLACEBO groups. | Day 1 to Day 60 | 
| All-cause mortality rate during the study | mortality and its causes | Day 1 to Day 60 | 
| Frequency and intensity of adverse events, unexpected adverse events, and serious adverse events | Intensity of adverse events (1= Mild; 2= Moderate; 3= Severe; 4= Critical) | Day 1 to Day 30 | 
| Proportion of comorbidity-related worsening [Obesity, diabetes, alcoholism, smoking, lung disease] | relationship between comorbidities and aggravations | Day 1 to Day 30 | 
| hospitalization for all causes occurring in post-treatment period | hospitalization for all causes after treatment | Day 1 to Day 60 | 
| To assess the tolerability of using AZVUDINE (FNC) at 5mg/day | calculation of participants who completed treatment | Day 1 to Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AZVUDINE, SARS-CoV-2, COVID-19, FNC