Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Covid-19

SARS-CoV-2 Infection Clinical Trial

Official title:

A Phase II/III Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected With SARS-CoV-2

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05633433
• Other study ID #: FNC-Covid304
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 29, 2022
• Est. completion date: July 15, 2024

Study information

• Verified date: January 2023
• Source: Shanghai Henlius Biotech
• Contact: Gerard S. Garcia, M.D.
• Phone: +63324169341
• Email: cduhrec[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase II/III Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected with SARS-CoV-2

Description:

The study has two parts: Part 1 is a multicentre, randomized, double-blind, placebo-controlled phase II clinical study to evaluate the efficacy and safety of Azvudine versus placebo in preventing SARS-CoV-2 infection in household contacts with SARS-CoV-2 infection individuals. The population of part 1 will consist of approximately 450 adults with household contact exposure to individuals with a confirmed SARS-CoV-2 infection.A phase III study will be further conducted if any of the treatment groups reduce SARS-CoV-2 infection rate (Relative risk reduction) > 50% compared with the placebo group. Part 2 is a multicentre, randomized, double-blind, placebo-controlled phase III clinical study. The subject sample size will be calculated based on the results of the Phase II trial. Phase II and phase III studies have the same objectives and primary/secondary end points. The primary endpoint is the proportion of subjects with positive SARS-CoV-2 RT-PCR assay in 7 days. Nasopharyngeal swabs will be collected at D2, D4, D7, D10, and D14 by RT-PCR to confirm SARS-CoV-2 infection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1550
• Est. completion date: July 15, 2024
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. =18 years old at the signing of informed consent.

2. Household contacts of individual with symptomatic COVID-19. Symptomatic COVID-19 cases (index case) to be identified as those symptomatic and recently tested (rapid antigen test or RT-PCR) positive for SARS-CoV-2 and must fulfill the following criteria 1) collection of the first positive SARS-CoV-2 test sample less than 48 hours before randomization, 2) have at least one symptom attributable to COVID-19.

3. RT-PCR test negative (with nasopharyngeal [NP] swab samples) OR rapid antigen test negative at the time of screening and without any suspicious COVID-19 symptoms within 2 weeks before randomization.

4. Subject expects to be living in the same household with the symptomatic COVID-19 cases during the whole study period.

5. Willing and able to comply with study visits and study-related procedures/assessments.

6. Provide informed consent signed by study subject or legally acceptable representative.

Exclusion Criteria:

1. Subject with a history of SARS-CoV-2 vaccinations within 6 months before randomization.

2. Subject with a history of SARS-CoV-2 infection within 6 months before randomization.

3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×Upper Limit of Normal (ULN) ,or total bilirubin (TBIL) >2×ULN.

4. Creatinine clearance (Ccr, calculated by Cockcroft-Gault equation)<60 ml/min or Creatinine >1.2×ULN.

5. With any serious infection requiring systemic anti-infective therapy within 14 days before randomization.

6. Allergic to the investigational agent or any components of the formulation.

7. Pregnant or breast-feeding women.

8. Previous administration of any antiretroviral drugs (e.g., antiretroviral drugs for HIV, HBV, or HCV) within 7 days before randomization.

9. Women of childbearing potential who are unwilling to practice highly effective contraception during the study, and for at least 6 months after the study; Sexually active men who are unwilling to use medically acceptable birth control during the study period.

10. Have other conditions not suitable for inclusion as judged by the investigator.

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19
• Infections
• SARS-CoV-2 Infection

Intervention

Drug:
• Azvudine
Azvudine is a novel nucleoside reverse transcriptase inhibitor.
• Placebo
Placebo

Locations

Country	Name	City	State
Malaysia	University of Malaya Medical Centre	Kuala Lumpur
Malaysia	International Islamic University Malaysia	Kuantan
Malaysia	Klinik Kesihatan Cheras	Shah Alam
Malaysia	Klinik Kesihatan Greentown	Shah Alam
Malaysia	Klinik Kesihatan Kuala Kedah	Shah Alam
Malaysia	Klinik Kesihatan Mahmoodiah	Shah Alam
Malaysia	ALPS Medical Center	Shah Alam,
Philippines	Cebu Doctors' University Hospitol	Cebu City
Philippines	Perpetual Succour Hospital	Cebu City
Philippines	University of the East Ramon Magsaysay Memorial Medical Center	Quezon City

Sponsors (3)

Lead Sponsor	Collaborator
Shanghai Henlius Biotech	HeNan Sincere Biotech Co., Ltd, Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Countries where clinical trial is conducted

Malaysia,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy-Incidence of SARS-CoV-2 infection in 7 days	The incidence of SARS-CoV-2 infection (RT-PCR positive) up to 7 days from 2 days after administration of Azvudine for prevention of SARS-CoV-2 infection.	Day 2 to Day 7
Secondary	Incidence of asymptomatic SARS-CoV-2 infection in 7 days	The incidence of asymptomatic SARS-CoV-2 infection (RT-PCR positive) up to 7 days from 2 days after administration of Azvudine for prevention of SARS-CoV-2 infection.	Day 2 to Day 7
Secondary	Incidence of symptomatic SARS-CoV-2 infection in 7 days	The incidence of symptomatic SARS-CoV-2 infection (RT-PCR positive) up to 7 days from 2 days after administration of Azvudine for prevention of SARS-CoV-2 infection.	Day 2 to Day 7
Secondary	Incidence of SARS-CoV-2 infection in 14 days	The incidence of SARS-CoV-2 infection (RT-PCR positive) up to 14 days from 2 days after administration of Azvudine for prevention of SARS-CoV-2 infection.	Day 2 to Day 14
Secondary	Incidence of asymptomatic SARS-CoV-2 infection in 14 days	The incidence of asymptomatic SARS-CoV-2 infection (RT-PCR positive) up to 14 days from 2 days after administration of Azvudine for prevention of SARS-CoV-2 infection.	Day 2 to Day 14
Secondary	Incidence of symptomatic SARS-CoV-2 infection in 14 days	The incidence of SARS-CoV-2 infection (RT-PCR positive) up to 14 days from 2 days after administration of Azvudine for prevention of SARS-CoV-2 infection.	Day 2 to Day 14
Secondary	Incidence of severe COVID-19	To describe the incidence of severe COVID-19 up to 28 days after administration of Azvudine for prevention of SARS-CoV-2 infection.	Day 1 to Day 28
Secondary	Incidence of all-cause mortality	To describe the incidence of all-cause mortality during the 28 days after administration of Azvudine for prevention of SAR-CoV-2 infection.	Day 1 to Day 28
Secondary	Time to SARS-CoV-2 infection	The time to SARS-CoV-2 infection after the the first dose of Azvudine will be evaluated in the RT-PCR positive participants.	Day 1 to Day 28
Secondary	Duration of symptoms	Duration of symptoms in participants with COVID-19.	Day 1 to Day 28
Secondary	Adverse events	Number of participants with adverse events after administration of Azvudine will be evaluated.	Day 1 to Day 28
Secondary	Maximum serum concentration (Cmax)	The Cmax of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Secondary	Time to reach maximum serum concentration (Tmax)	The Tmax of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Secondary	Terminal half-life (T1/2)	The T1/2 of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Secondary	Apparent total clearance (CL/F)	The CL/F of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Secondary	Apparent volume of distribution based on terminal phase (Vz/F)	The Vz/F of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Secondary	Area under the concentration-time curve from time 0 to the last concentration-measurable time point (AUC0-t)	The AUC0-t of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Secondary	Area under the concentration-time curve from time 0 to infinity (AUC0-8)	The AUC0-8 of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28