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

NCT ID: NCT04668235

Last Updated: 2022-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-23
• Study Completion Date: 2022-08-10

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.

Detailed Description

Hypothesis:

AZVUDINE has therapeutic potential and safety profile for the treatment of patients infected with SARS-CoV-2.

Goals:

Primary objective • To assess the efficacy and safety of AZVUDINE (FNC) in relation to placebo, in patients infected with SARS-COV-2 in moderate to severe stage;

Secondary objective

• To evaluate the clinical outcome of the AZVUDINE group (FNC) compared to the placebo group in patients infected by SARS-COV-2 in moderate to severe stage;

Pharmaceutical form of the experimental medicine:

AZVUDINE 1 mg tablets

Comparators:

AZVUDINE placebo

Statistical planning:

The analyzes will be performed by FAS, PPS and SS and should be stratified by the severity of the disease (moderate, severe) and age (<60 years, ≥ 60 years), to assess the following parameters:

• Progression of the disease (moderate to severe, severe type);
• Negative viral load conversion rate;
• Time of negative conversion of viral load;
• Temperature recovery time;
• Time necessary to improve diarrhea, myalgia, fatigue, and other symptoms;
• Time to improve the pulmonary image;
• Frequency of supplemental oxygenation or non-invasive ventilation;
• Frequency of AEs;
• Mortality rate.

All statistical tests will be bilateral tests. If the P value is ≤0.05, it is considered that there is statistical significance between the difference in the tests.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm AZVUDINE

Experimental:

AZVUDINE 1mg tablet,

Interventions:

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

Group Type: EXPERIMENTAL

AZVUDINE

Intervention Type: DRUG

5 tablets QD + standard treatment for up to 14 days

Arm Placebo

Control:

AZVUDINE placebo,

Interventions:

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

Group Type: PLACEBO_COMPARATOR

AZVUDINE placebo

Intervention Type: DRUG

5 tablets QD + standard treatment for up to 14 days

Interventions

AZVUDINE

5 tablets QD + standard treatment for up to 14 days

Intervention Type: DRUG

AZVUDINE placebo

5 tablets QD + standard treatment for up to 14 days

Intervention Type: DRUG

Other Intervention 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

Eligibility Criteria

Inclusion Criteria

1. Individuals aged 18 or over, regardless of gender;

2. Patients hospitalized in moderate to severe stages in line with the Ministry of Health classification;

3. 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;

4. Time of onset of symptoms and inclusion ≤ 14 days;

5. Internation within 48 hours after inclusion in the study;

6. Follow-up availability during the study period;

7. Voluntary membership to participate in the study and signing the Informed Consent Form.

Exclusion Criteria

1. Patients known or suspected of being sensitive to AZVUDINE or excipients (inactive ingredients: microcrystalline cellulose, hydrated lactose, polyvinylpyrrolidone K30, croscarmellose sodium, magnesium stearate);

2. Patients diagnosed with pneumonia caused by other pathogens;

3. Patients with liver disease (total bilirubin ≥2 times above the normal limit, ALT / TGP and AST / TGO ≥5 times above the normal limit)

4. Patients with renal failure (glomerular filtration rate ≤60mL / min / 1.73 m2) or are receiving continuous renal replacement therapy, hemodialysis or peritoneal dialysis;

5. 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;

6. 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;

7. Patients already included in other clinical trials;

8. Patient under treatment for HIV;

9. Patients being treated with other antivirals (eg lopinavir / ritonavir, remdesivir, umifenovir / arbidol, favipiravir, interferon-α)

10. Patients undergoing treatment with monoclonal antibodies (eg tocilizumab and sarilumab / kevzara);

11. 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;

12. Patients who require invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at the time of randomization;

13. Any clinically significant medical condition or medical history that, in the investigator's opinion, might discourage participation in the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GALZU INSTITUTE OF RESEARCH, TEACHING, SCIENCE AND APPLIED TECHNOLOGY, Brazil

UNKNOWN

Sponsor Role: collaborator

UNIVERSIDADE ESTADUAL DO NORTE FLUMINENSE (UENF), Brazil

UNKNOWN

Sponsor Role: collaborator

HRH Pharmaceuticals Limited

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sheila P Figueiredo, MSc

Role: STUDY_DIRECTOR

Galzu Institute

Locations

Santa Casa de Misericordia de Campos

Campos dos Goytacazes, Rio de Janeiro, Brazil

Countries

Brazil

References

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.

Reference Type: DERIVED

PMID: 37928473 (View on PubMed)

Other Identifiers

FNC IGZ-1

Identifier Type: -

Identifier Source: org_study_id