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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05033145
• Other study ID #: FNC IGZ-2
• Status: Completed
• Phase: Phase 3
• Start date: January 15, 2022
• Est. completion date: July 27, 2022

Study information

• Verified date: September 2021
• Source: HRH Pharmaceuticals Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: July 27, 2022
• Est. primary completion date: July 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• AZVUDINE
AZVUDINE 5 tablets QD + standard treatment, for up to 14 days
• AZVUDINE placebo
5 tablets QD + standard treatment, for up to 14 days

Locations

Country	Name	City	State
Brazil	Hospital Moacyr Gomes de Azevedo	Cambuci	RJ
Brazil	Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute	Campos Dos Goytacazes	Rio De Janeiro
Brazil	Hospital Santa Casa de Misericórdia de Campos	Campos Dos Goytacazes	RJ
Brazil	Unidade de Pesquisa Clínica / Centro de Alta Complexidade	Campos dos Goytacazes	RJ
Brazil	Unidade Pré Hospitalar São José	Campos Dos Goytacazes	RJ
Brazil	Hospital de Itaocara	Itaocara	RJ
Brazil	Hospital Armando Vidal	São Fidelis	RJ

Sponsors (3)

Lead Sponsor	Collaborator
HRH Pharmaceuticals Limited	Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute, GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Changes in kidney function	Change in urea/creatinine	Day 1 to Day 30
Secondary	Changes in liver function	Changes in ALT/AST	Day 1 to Day 30
Secondary	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
Secondary	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
Secondary	Occurrence of drug interactions	Monitoring of concomitant medication	Day 1 to Day 14
Secondary	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
Secondary	All-cause mortality rate during the study	mortality and its causes	Day 1 to Day 60
Secondary	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
Secondary	Proportion of comorbidity-related worsening [Obesity, diabetes, alcoholism, smoking, lung disease]	relationship between comorbidities and aggravations	Day 1 to Day 30
Secondary	hospitalization for all causes occurring in post-treatment period	hospitalization for all causes after treatment	Day 1 to Day 60
Secondary	To assess the tolerability of using AZVUDINE (FNC) at 5mg/day	calculation of participants who completed treatment	Day 1 to Day 14