Clinical trial NCT05033145: Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: AZVUDINE
SARS-CoV-2
COVID-19
FNC
Lead sponsor: HRH Pharmaceuticals Limited
Sponsor class: OTHER
Collaborators: name: GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil
name: Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute
First posted: 2021-09-02
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, parallel, placebo-controlled trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Proportion of patients hospitalized during the study through day 28
timeFrame: Day 14 to Day 30
measure: Proportion of participants with a clinical outcome of CURE during the study;
timeFrame: Day 14 to Day 30
Secondary outcomes:
measure: Improvement in clinical status in at least one category compared to screening
timeFrame: Day 14 to Day 30
measure: 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.
timeFrame: Day 1 to Day 14
measure: Changes in kidney function
timeFrame: Day 1 to Day 30
measure: Changes in liver function
timeFrame: Day 1 to Day 30
measure: Time of use of AZVUDINE until the second negative conversion of RT-PCR
timeFrame: Day 1 to Day 14
measure: Evaluation of SARS-CoV-2 viral load negative conversion time by RT-PCR between AZVUDINE group (FNC) and control group
timeFrame: Day 1 to Day 28
measure: Occurrence of drug interactions
timeFrame: Day 1 to Day 14
measure: Assessment of liver function biochemical markers (AST/TGO, ALT/TGP, ALP, GGT, BIL total, and direct BIL)
timeFrame: Day 1 to Day 60
measure: All-cause mortality rate during the study
timeFrame: Day 1 to Day 60
measure: Frequency and intensity of adverse events, unexpected adverse events, and serious adverse events
timeFrame: Day 1 to Day 30
measure: Proportion of comorbidity-related worsening [Obesity, diabetes, alcoholism, smoking, lung disease]
timeFrame: Day 1 to Day 30
measure: hospitalization for all causes occurring in post-treatment period
timeFrame: Day 1 to Day 60
measure: To assess the tolerability of using AZVUDINE (FNC) at 5mg/day
timeFrame: Day 1 to Day 14
Other outcomes:
Locations:
city: Campos Dos Goytacazes
country: Brazil
facility: Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute
state: Rio De Janeiro
city: Cambuci
country: Brazil
facility: Hospital Moacyr Gomes de Azevedo
state: RJ
city: Campos Dos Goytacazes
country: Brazil
facility: Hospital Santa Casa de Misericórdia de Campos
state: RJ
city: Campos dos Goytacazes
country: Brazil
facility: Unidade de Pesquisa Clínica / Centro de Alta Complexidade
state: RJ
city: Campos Dos Goytacazes
country: Brazil
facility: Unidade Pré Hospitalar São José
state: RJ
city: Itaocara
country: Brazil
facility: Hospital de Itaocara
state: RJ
city: São Fidelis
country: Brazil
facility: Hospital Armando Vidal
state: RJ
Study officials:
affiliation: Galzu Institute
name: Sheila P Figueiredo, Nurse,MSc
role: STUDY_CHAIR
References: