COVID-19
Conditions
Keywords
AZVUDINE, SARS-CoV-2, COVID-19, FNC
Brief summary
Phase III, single-center with co-participating units, randomized, double-blind, parallel, placebo-controlled clinical study
Detailed description
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.
Interventions
DRUGAZVUDINE
AZVUDINE 5 tablets QD + standard treatment, for up to 14 days
DRUGAZVUDINE placebo
5 tablets QD + standard treatment, for up to 14 days
Sponsors
GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil
Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute
HRH Pharmaceuticals Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double-blind, parallel, placebo-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Individuals who present the following characteristics will be included in this study: 1. Age ≥18 years, regardless of gender; 2. 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; 3. Symptomatic patients who meet the case definition for COVID-19, according to WHO, without evidence of bacterial pneumonia or hypoxia (Sat O2 \< 95%) P. \[score 1-3\]; 4. 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: 1. 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); 2. Individual presenting shortness of breath and Sat O2 \< 95%; or any other symptom requiring treatment through hospital admission; 3. Patients with liver disease (total bilirubin ≥2mg/dL, ALT/TGP e AST/TGO ≥5 times above normal limit); 4. Pactients with a history of known liver disease (cirrhosis with ChildPugh classification B and C); 5. Patients with a history of renal insufficiency (glomerular filtration rate \< 60mL/min/1,73m2); 6. Patients with history of congestive heart failure (NYHA ¾ grade), untreated symptomatic arrhythmias ormyocardial infarction within 6 months; 7. 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; 8. Total neutrophil count \<750 cells/L;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients hospitalized during the study through day 28 | Day 14 to Day 30 | 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. |
| Proportion of participants with a clinical outcome of CURE during the study; | Day 14 to Day 30 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in kidney function | Day 1 to Day 30 | Change in urea/creatinine |
| Changes in liver function | Day 1 to Day 30 | Changes in ALT/AST |
| Time of use of AZVUDINE until the second negative conversion of RT-PCR | Day 1 to Day 14 | Rate of change in biochemical markers of inflammatory function in relation to the physiological reference intervals between the AZVUDINA and PLACEBO groups. |
| Evaluation of SARS-CoV-2 viral load negative conversion time by RT-PCR between AZVUDINE group (FNC) and control group | Day 1 to Day 28 | RT-PCR performed on treatment days. |
| Occurrence of drug interactions | Day 1 to Day 14 | Monitoring of concomitant medication |
| Improvement in clinical status in at least one category compared to screening | Day 14 to Day 30 | Ordinal Scale of Clinical Improvement (WHO, Jun/2020) |
| All-cause mortality rate during the study | Day 1 to Day 60 | mortality and its causes |
| Frequency and intensity of adverse events, unexpected adverse events, and serious adverse events | Day 1 to Day 30 | Intensity of adverse events (1= Mild; 2= Moderate; 3= Severe; 4= Critical) |
| Proportion of comorbidity-related worsening [Obesity, diabetes, alcoholism, smoking, lung disease] | Day 1 to Day 30 | relationship between comorbidities and aggravations |
| hospitalization for all causes occurring in post-treatment period | Day 1 to Day 60 | hospitalization for all causes after treatment |
| To assess the tolerability of using AZVUDINE (FNC) at 5mg/day | Day 1 to Day 14 | calculation of participants who completed treatment |
| Assessment of liver function biochemical markers (AST/TGO, ALT/TGP, ALP, GGT, BIL total, and direct BIL) | Day 1 to Day 60 | Rate of change in biochemical markers of hepatic function in relation to the physiological reference intervals between the AZVUDINA and PLACEBO groups. |
| 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. | Day 1 to Day 14 | Intensity (1= Mild; 2= Moderate; 3= Severe; 4= Critical) |
Countries
Brazil
Outcome results
None listed