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

NCT04668235 | Completed Phase 3 DMC

• 1 other identifier: FNC IGZ-1
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Estimated number of participants: 342 participants with COVID-19 Design: Phase III, single-center, randomized, double-blind, parallel, placebo-controlled clinical study. In December 2021, there was a drop in the number of hospitalizations and the cases of COPD, tuberculosis and HIV associated with COVID-19, which are outside the inclusion criteria of this study. After the initial data of the study, there was a discussion with Anvisa and the size of the sample calculation was revised by amendment 4 (180 participants), and the methodology of statistical analysis for a new sample calculation was "a formula for sample calculation for superiority studies using proportions, according to the book do Chow et al (Chow, S.-C., Shao, J., Wang, H., \&Lokhnygina, Y. Eds. 2017. Sample Size Calculations in Clinical Research: Third Edition, Chapman and Hall/CRC). Thus, Anvisa concluded that the adjustments are in accordance with the agency's guidelines, approving E4, which was later also approved by the Ethics Committee.

Conditions

COVID-19

Keywords

AZVUDINE; SARS-CoV-2; COVID-19; FNC

Outcome Measures

Primary Outcomes (1)

• Evaluation of clinical improvement of AZVUDINE (FNC) in COVID-19 treatment

  Rate of participants who reduced at least one level of the Clinical Progression Ordinal Scale category compared to the enrollment status (WHO, Jun/2020)

  Day 1 to Day 15

Secondary Outcomes (32)

• Clinical cure outcome rate

  Day 1 to Day 15

• Recovery of body temperature

  Day 1 to Day 28

• Clinical improvement of diarrhea, myalgia fatigue and other symptoms

  Day 1 to Day 28

• Assessment of inflammatory biochemical markers (Reactive C Protein, erythrocyte sedimentation rate, and Procalcitonin)

  Day 1 to Day 60

• Assessment of immunological function biochemical markers (IL-6, IgG, IgM, IgA, and complement factor C3 and C4)

  Day 1 to Day 60

Study Arms (2)

Arm AZVUDINE

EXPERIMENTAL

Experimental: AZVUDINE 1mg tablet, Interventions: AZVUDINE 1mg tablet, 5 tablets QD + standard treatment for up to 14 days

Drug: AZVUDINE

Arm Placebo

PLACEBO COMPARATOR

Control: AZVUDINE placebo, Interventions: AZVUDINE placebo, 5 tablets QD + standard treatment for up to 14 days

Drug: AZVUDINE placebo

Interventions

AZVUDINE DRUG

5 tablets QD + standard treatment for up to 14 days

Also known as: 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

Arm AZVUDINE

AZVUDINE placebo DRUG

5 tablets QD + standard treatment for up to 14 days

Also known as: Placebo

Arm Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals aged 18 or over, regardless of gender;
• Patients hospitalized in moderate to severe stages in line with the Ministry of Health classification;
• Positive diagnosis for SARS-CoV-2 by molecular amplification of the virus in RT-PCR diagnosed from a respiratory sample (nasopharynx, oropharyngeal, lower respiratory tract \[eg, sputum\]) collected \<96 hours before randomization;
• Follow-up availability during the study period;
• Voluntary membership to participate in the study and signing the Informed Consent Form.

You may not qualify if:

• Patients known or suspected of being sensitive to AZVUDINE or excipients (inactive ingredients: microcrystalline cellulose, hydrated lactose, polyvinylpyrrolidone K30, croscarmellose sodium, magnesium stearate);
• Patients diagnosed with pneumonia caused by other pathogens;
• Patients with liver disease (total bilirubin ≥2 times above the normal limit, ALT / TGP and AST / TGO ≥5 times above the normal limit)
• Patients with renal failure (glomerular filtration rate ≤60mL / min / 1.73 m2) or are receiving continuous renal replacement therapy, hemodialysis or peritoneal dialysis;
• Individuals with malabsorption syndrome, or other conditions that affect gastrointestinal absorption, and circumstances in which patients need intravenous nutrition, or cannot take drugs orally or nasogastrically;
• Pregnant or lactating women, or women with the potential to become pregnant during the study period and within 6 months after the end of administration;
• Patients already included in other clinical trials;
• Patient under treatment for HIV;
• Patients being treated with other antivirals (eg lopinavir / ritonavir, remdesivir, umifenovir / arbidol, favipiravir, interferon-α)
• Patients undergoing treatment with monoclonal antibodies (eg tocilizumab and sarilumab / kevzara);
• Patients who are on a clinical treatment plan that includes the concomitant administration of any other experimental treatment or off-label use of drugs already on the market (eg hydroxychloroquine sulfate;
• Patients who require invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at the time of randomization;
• Any clinically significant medical condition or medical history that, in the investigator's opinion, might discourage participation in the study.

Sponsors & Collaborators

• HRH Pharmaceuticals Limited: lead
• GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil: collaborator
• UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil: collaborator

Study Sites (1)

Santa Casa de Misericordia de Campos

Campos dos Goytacazes, Rio de Janeiro, Brazil

Location

Related Publications (1)

• de Souza SB, Cabral PGA, da Silva RM, Arruda RF, Cabral SPF, de Assis ALEM, Viana Junior AB, Degrave WMS, Moreira ADS, Silva CG, Chang J, Lei P. Phase III, randomized, double-blind, placebo-controlled clinical study: a study on the safety and clinical efficacy of AZVUDINE in moderate COVID-19 patients. Front Med (Lausanne). 2023 Oct 19;10:1215916. doi: 10.3389/fmed.2023.1215916. eCollection 2023.

  PMID: 37928473 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

azvudine; Cytosine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sheila P Figueiredo, MSc

  Galzu Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: December 16, 2020
• Study Start: April 23, 2021
• Primary Completion: August 10, 2022
• Study Completion: August 10, 2022
• Last Updated: August 12, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)