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

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

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

Study Overview

• Status: Recruiting
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Drug: Placebo; Drug: Azvudine

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 1550
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Gerard S. Garcia, M.D.; Phone Number: +63324169341; Email: cduhrec@gmail.com

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia
    • Not yet recruiting
    • University of Malaya Medical Centre
    • Contact: Mohd Idzwan bin Zakaria, Ph.D.; Phone Number: 2251 03-79493209
    • Principal Investigator: Mohd Idzwan bin Zakaria, Ph.D.
  • Kuantan, Malaysia
    • Not yet recruiting
    • International Islamic University Malaysia
    • Contact: Nur Syazwani Binti Jamhuri, Dr.
    • Principal Investigator: Nur Syazwani Binti Jamhuri, Dr.
  • Shah Alam, Malaysia
    • Not yet recruiting
    • Klinik Kesihatan Cheras
    • Contact: Siti Shafiatun Siti Shafiatun, Dr.
    • Principal Investigator: Siti Shafiatun Siti Shafiatun, Dr.
  • Shah Alam, Malaysia
    • Not yet recruiting
    • Klinik Kesihatan Greentown
    • Contact: V. Paranthaman, Dr.
    • Principal Investigator: V. Paranthaman, Dr.
  • Shah Alam, Malaysia
    • Not yet recruiting
    • Klinik Kesihatan Kuala Kedah
    • Contact: Fazlin Suhana Othman, Dr.
    • Principal Investigator: Fazlin Suhana Othman, Dr.
  • Shah Alam, Malaysia
    • Not yet recruiting
    • Klinik Kesihatan Mahmoodiah
    • Contact: Wan Fadhilah Binti Wan Ismail, Dr.
    • Principal Investigator: Wan Fadhilah Binti Wan Ismail, Dr.
  • Shah Alam,, Malaysia
    • Not yet recruiting
    • ALPS Medical Center
    • Contact: Benjamin George, Dr.
    • Principal Investigator: Benjamin George, Dr.
• Philippines
  • Cebu City, Philippines
    • Recruiting
    • Cebu Doctors' University Hospitol
    • Contact: Gerard S. Garcia, M.D.
    • Principal Investigator: Gerard S. Garcia, M.D.
  • Cebu City, Philippines
    • Not yet recruiting
    • Perpetual Succour Hospital
    • Contact: Jemela Anne Sanchez, Dr.
    • Principal Investigator: Jemela Anne Sanchez, Dr.
  • Quezon City, Philippines
    • Not yet recruiting
    • University of the East Ramon Magsaysay Memorial Medical Center
    • Contact: Nina Marnie Beltran-Yap, M.D.
    • Principal Investigator: Nina Marnie Beltran-Yap, M.D.

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:

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cohort A （Phase II）; Azvudine 5 mg, QD PO, D1-D7	Drug: Azvudine; Azvudine is a novel nucleoside reverse transcriptase inhibitor.; Other Names: FNC
Experimental: cohort B （Phase II）; Azvudine 3 mg + placebo 2 mg, QD PO, D1-D7	Drug: Placebo; Placebo; Drug: Azvudine; Azvudine is a novel nucleoside reverse transcriptase inhibitor.; Other Names: FNC
Placebo Comparator: cohort C （Phase II）; placebo 5 mg, QD PO, D1-D7	Drug: Placebo; Placebo
Experimental: Arm 1 (Phase III); Azvudine, dose to be determined according to phase II, QD PO, D1-D7	Drug: Azvudine; Azvudine is a novel nucleoside reverse transcriptase inhibitor.; Other Names: FNC
Placebo Comparator: Arm 2 (Phase III); Placebo, dose to be the same as Arm1, QD PO, D1-D7	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
Duration of symptoms	Duration of symptoms in participants with COVID-19.	Day 1 to Day 28
Adverse events	Number of participants with adverse events after administration of Azvudine will be evaluated.	Day 1 to Day 28
Maximum serum concentration (Cmax)	The Cmax of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Time to reach maximum serum concentration (Tmax)	The Tmax of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Terminal half-life (T1/2)	The T1/2 of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
Apparent total clearance (CL/F)	The CL/F of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28
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
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
Area under the concentration-time curve from time 0 to infinity (AUC0-∞)	The AUC0-∞ of Azvudine after administration in participants will be evaluated.	Day 1 to Day 28

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech
• Collaborators: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd
• Investigators: Principal Investigator: Gerard S. Garcia, M.D., Cebu Doctor's University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2022
• Primary Completion (Anticipated): June 15, 2024
• Study Completion (Anticipated): July 15, 2024

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 1, 2022

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: FNC-Covid304

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