Back to resultsStudy on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected)
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
AZVUDINE
AZVUDINE placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring AZVUDINE, SARS-CoV-2, COVID-19, FNC
Eligibility Criteria
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;
Sites / Locations
- Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute
- Hospital Moacyr Gomes de Azevedo
- Hospital Santa Casa de Misericórdia de Campos
- Unidade de Pesquisa Clínica / Centro de Alta Complexidade
- Unidade Pré Hospitalar São José
- Hospital de Itaocara
- Hospital Armando Vidal
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZVUDINE
AZVUDINE placebo
Arm Description
Experimental: AZVUDINE 1mg tablet Interventions: AZVUDINE 1mg tablet, 5 tablets QD + standard treatment, for up to 14 days
Control: AZVUDINE placebo Intervention: AZVUDINE placebo tablet, 5 tablets QD + standard treatment, for up to 14 days
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Improvement in clinical status in at least one category compared to screening
Ordinal Scale of Clinical Improvement (WHO, Jun/2020)
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)
Changes in kidney function
Change in urea/creatinine
Changes in liver function
Changes in ALT/AST
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.
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.
Occurrence of drug interactions
Monitoring of concomitant medication
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.
All-cause mortality rate during the study
mortality and its causes
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)
Proportion of comorbidity-related worsening [Obesity, diabetes, alcoholism, smoking, lung disease]
relationship between comorbidities and aggravations
hospitalization for all causes occurring in post-treatment period
hospitalization for all causes after treatment
To assess the tolerability of using AZVUDINE (FNC) at 5mg/day
calculation of participants who completed treatment
Full Information
NCT ID
NCT05033145
First Posted
December 4, 2020
Last Updated
August 10, 2022
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
1. Study Identification
Unique Protocol Identification Number
NCT05033145
Brief Title
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
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
January 15, 2022 (Actual)
Primary Completion Date
July 27, 2022 (Actual)
Study Completion Date
July 27, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the 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
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
AZVUDINE, SARS-CoV-2, COVID-19, FNC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, parallel, placebo-controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation
Randomized
Enrollment
312 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZVUDINE
Arm Type
Experimental
Arm Description
Experimental:
AZVUDINE 1mg tablet
Interventions:
AZVUDINE 1mg tablet, 5 tablets QD + standard treatment, for up to 14 days
Arm Title
AZVUDINE placebo
Arm Type
Placebo Comparator
Arm Description
Control:
AZVUDINE placebo
Intervention:
AZVUDINE placebo tablet, 5 tablets QD + standard treatment, for up to 14 days
Intervention Type
Drug
Intervention Name(s)
AZVUDINE
Other Intervention Name(s)
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
Intervention Description
AZVUDINE 5 tablets QD + standard treatment, for up to 14 days
Intervention Type
Drug
Intervention Name(s)
AZVUDINE placebo
Other Intervention Name(s)
Placebo
Intervention Description
5 tablets QD + standard treatment, for up to 14 days
Primary Outcome Measure Information:
Title
Proportion of patients hospitalized during the study through day 28
Description
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.
Time Frame
Day 14 to Day 30
Title
Proportion of participants with a clinical outcome of CURE during the study;
Description
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.
Time Frame
Day 14 to Day 30
Secondary Outcome Measure Information:
Title
Improvement in clinical status in at least one category compared to screening
Description
Ordinal Scale of Clinical Improvement (WHO, Jun/2020)
Time Frame
Day 14 to Day 30
Title
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.
Description
Intensity (1= Mild; 2= Moderate; 3= Severe; 4= Critical)
Time Frame
Day 1 to Day 14
Title
Changes in kidney function
Description
Change in urea/creatinine
Time Frame
Day 1 to Day 30
Title
Changes in liver function
Description
Changes in ALT/AST
Time Frame
Day 1 to Day 30
Title
Time of use of AZVUDINE until the second negative conversion of RT-PCR
Description
Rate of change in biochemical markers of inflammatory function in relation to the physiological reference intervals between the AZVUDINA and PLACEBO groups.
Time Frame
Day 1 to Day 14
Title
Evaluation of SARS-CoV-2 viral load negative conversion time by RT-PCR between AZVUDINE group (FNC) and control group
Description
RT-PCR performed on treatment days.
Time Frame
Day 1 to Day 28
Title
Occurrence of drug interactions
Description
Monitoring of concomitant medication
Time Frame
Day 1 to Day 14
Title
Assessment of liver function biochemical markers (AST/TGO, ALT/TGP, ALP, GGT, BIL total, and direct BIL)
Description
Rate of change in biochemical markers of hepatic function in relation to the physiological reference intervals between the AZVUDINA and PLACEBO groups.
Time Frame
Day 1 to Day 60
Title
All-cause mortality rate during the study
Description
mortality and its causes
Time Frame
Day 1 to Day 60
Title
Frequency and intensity of adverse events, unexpected adverse events, and serious adverse events
Description
Intensity of adverse events (1= Mild; 2= Moderate; 3= Severe; 4= Critical)
Time Frame
Day 1 to Day 30
Title
Proportion of comorbidity-related worsening [Obesity, diabetes, alcoholism, smoking, lung disease]
Description
relationship between comorbidities and aggravations
Time Frame
Day 1 to Day 30
Title
hospitalization for all causes occurring in post-treatment period
Description
hospitalization for all causes after treatment
Time Frame
Day 1 to Day 60
Title
To assess the tolerability of using AZVUDINE (FNC) at 5mg/day
Description
calculation of participants who completed treatment
Time Frame
Day 1 to Day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sheila P Figueiredo, Nurse,MSc
Organizational Affiliation
Galzu Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Clinical Research Unit / High Complexity Center (CRU/HCC) / Galzu Institute
City
Campos Dos Goytacazes
State/Province
Rio De Janeiro
ZIP/Postal Code
28110-000
Country
Brazil
Facility Name
Hospital Moacyr Gomes de Azevedo
City
Cambuci
State/Province
RJ
Country
Brazil
Facility Name
Hospital Santa Casa de Misericórdia de Campos
City
Campos Dos Goytacazes
State/Province
RJ
Country
Brazil
Facility Name
Unidade de Pesquisa Clínica / Centro de Alta Complexidade
City
Campos dos Goytacazes
State/Province
RJ
Country
Brazil
Facility Name
Unidade Pré Hospitalar São José
City
Campos Dos Goytacazes
State/Province
RJ
Country
Brazil
Facility Name
Hospital de Itaocara
City
Itaocara
State/Province
RJ
Country
Brazil
Facility Name
Hospital Armando Vidal
City
São Fidelis
State/Province
RJ
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study on Safety and Clinical Efficacy of AZVUDINE in Initial Stage COVID-19 Patients (SARS-CoV-2 Infected)
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