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

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

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

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: AZVUDINE; Drug: AZVUDINE placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Cambuci, RJ, Brazil
      • Hospital Moacyr Gomes de Azevedo
    • Campos Dos Goytacazes, RJ, Brazil
      • Hospital Santa Casa de Misericórdia de Campos
    • Campos Dos Goytacazes, RJ, Brazil
      • Unidade Pré Hospitalar São José
    • Campos dos Goytacazes, RJ, Brazil
      • Unidade de Pesquisa Clínica / Centro de Alta Complexidade
    • Itaocara, RJ, Brazil
      • Hospital de Itaocara
    • São Fidelis, RJ, Brazil
      • Hospital Armando Vidal
  • Rio De Janeiro
    • Campos Dos Goytacazes, Rio De Janeiro, Brazil, 28110-000
      • Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZVUDINE; Experimental: AZVUDINE 1mg tablet Interventions: AZVUDINE 1mg tablet, 5 tablets QD + standard treatment, for up to 14 days	Drug: AZVUDINE; AZVUDINE 5 tablets QD + standard treatment, for up to 14 days; Other Names: AZVUDINE 1 mg tablets; FNC; 4-amino-1-((2R,3S,4R,5R)-5-azido-3-fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2(1H)-one; 1-(4-Azido-2-deoxy-2-fluoro-beta-D- arabino Ribo-furanosyl) cytosine, FNC
Placebo Comparator: AZVUDINE placebo; Control: AZVUDINE placebo Intervention: AZVUDINE placebo tablet, 5 tablets QD + standard treatment, for up to 14 days	Drug: AZVUDINE placebo; 5 tablets QD + standard treatment, for up to 14 days; Other Names: Placebo

What is the study measuring?

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
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
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
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

Collaborators and Investigators

• Sponsor: HRH Pharmaceuticals Limited
• Collaborators: GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil; Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute
• Investigators: Study Chair: Sheila P Figueiredo, Nurse,MSc, Galzu Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2022
• Primary Completion (Actual): July 27, 2022
• Study Completion (Actual): July 27, 2022

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: August 31, 2021
• First Posted (Actual): September 2, 2021

Study Record Updates

• Last Update Posted (Actual): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; AZVUDINE; FNC
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: FNC IGZ-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No