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

Primary Purpose

SARS-CoV-2 Infection

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Azvudine
Placebo
Sponsored by
Shanghai Henlius Biotech
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for SARS-CoV-2 Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: ≥18 years old at the signing of informed consent. 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. 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. Subject expects to be living in the same household with the symptomatic COVID-19 cases during the whole study period. Willing and able to comply with study visits and study-related procedures/assessments. Provide informed consent signed by study subject or legally acceptable representative. Exclusion Criteria: Subject with a history of SARS-CoV-2 vaccinations within 6 months before randomization. Subject with a history of SARS-CoV-2 infection within 6 months before randomization. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×Upper Limit of Normal (ULN) ,or total bilirubin (TBIL) >2×ULN. Creatinine clearance (Ccr, calculated by Cockcroft-Gault equation)<60 ml/min or Creatinine >1.2×ULN. With any serious infection requiring systemic anti-infective therapy within 14 days before randomization. Allergic to the investigational agent or any components of the formulation. Pregnant or breast-feeding women. Previous administration of any antiretroviral drugs (e.g., antiretroviral drugs for HIV, HBV, or HCV) within 7 days before randomization. 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. Have other conditions not suitable for inclusion as judged by the investigator.

Sites / Locations

  • University of Malaya Medical Centre
  • International Islamic University Malaysia
  • ALPS Medical Center
  • Klinik Kesihatan Cheras
  • Klinik Kesihatan Greentown
  • Klinik Kesihatan Kuala Kedah
  • Klinik Kesihatan Mahmoodiah
  • Cebu Doctors' University HospitolRecruiting
  • Perpetual Succour Hospital
  • University of the East Ramon Magsaysay Memorial Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

cohort A (Phase II)

cohort B (Phase II)

cohort C (Phase II)

Arm 1 (Phase III)

Arm 2 (Phase III)

Arm Description

Azvudine 5 mg, QD PO, D1-D7

Azvudine 3 mg + placebo 2 mg, QD PO, D1-D7

placebo 5 mg, QD PO, D1-D7

Azvudine, dose to be determined according to phase II, QD PO, D1-D7

Placebo, dose to be the same as Arm1, QD PO, D1-D7

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
Duration of symptoms
Duration of symptoms in participants with COVID-19.
Adverse events
Number of participants with adverse events after administration of Azvudine will be evaluated.
Maximum serum concentration (Cmax)
The Cmax of Azvudine after administration in participants will be evaluated.
Time to reach maximum serum concentration (Tmax)
The Tmax of Azvudine after administration in participants will be evaluated.
Terminal half-life (T1/2)
The T1/2 of Azvudine after administration in participants will be evaluated.
Apparent total clearance (CL/F)
The CL/F of Azvudine after administration in participants will be evaluated.
Apparent volume of distribution based on terminal phase (Vz/F)
The Vz/F of Azvudine after administration in participants will be evaluated.
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.
Area under the concentration-time curve from time 0 to infinity (AUC0-∞)
The AUC0-∞ of Azvudine after administration in participants will be evaluated.

Full Information

First Posted
November 30, 2022
Last Updated
January 5, 2023
Sponsor
Shanghai Henlius Biotech
Collaborators
Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd., HeNan Sincere Biotech Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05633433
Brief Title
Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Household Contacts of Covid-19
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 29, 2022 (Actual)
Primary Completion Date
June 15, 2024 (Anticipated)
Study Completion Date
July 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Henlius Biotech
Collaborators
Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd., HeNan Sincere Biotech Co., Ltd

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
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2 Infection

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1550 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
cohort A (Phase II)
Arm Type
Experimental
Arm Description
Azvudine 5 mg, QD PO, D1-D7
Arm Title
cohort B (Phase II)
Arm Type
Experimental
Arm Description
Azvudine 3 mg + placebo 2 mg, QD PO, D1-D7
Arm Title
cohort C (Phase II)
Arm Type
Placebo Comparator
Arm Description
placebo 5 mg, QD PO, D1-D7
Arm Title
Arm 1 (Phase III)
Arm Type
Experimental
Arm Description
Azvudine, dose to be determined according to phase II, QD PO, D1-D7
Arm Title
Arm 2 (Phase III)
Arm Type
Placebo Comparator
Arm Description
Placebo, dose to be the same as Arm1, QD PO, D1-D7
Intervention Type
Drug
Intervention Name(s)
Azvudine
Other Intervention Name(s)
FNC
Intervention Description
Azvudine is a novel nucleoside reverse transcriptase inhibitor.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Efficacy-Incidence of SARS-CoV-2 infection in 7 days
Description
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.
Time Frame
Day 2 to Day 7
Secondary Outcome Measure Information:
Title
Incidence of asymptomatic SARS-CoV-2 infection in 7 days
Description
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.
Time Frame
Day 2 to Day 7
Title
Incidence of symptomatic SARS-CoV-2 infection in 7 days
Description
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.
Time Frame
Day 2 to Day 7
Title
Incidence of SARS-CoV-2 infection in 14 days
Description
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.
Time Frame
Day 2 to Day 14
Title
Incidence of asymptomatic SARS-CoV-2 infection in 14 days
Description
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.
Time Frame
Day 2 to Day 14
Title
Incidence of symptomatic SARS-CoV-2 infection in 14 days
Description
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.
Time Frame
Day 2 to Day 14
Title
Incidence of severe COVID-19
Description
To describe the incidence of severe COVID-19 up to 28 days after administration of Azvudine for prevention of SARS-CoV-2 infection.
Time Frame
Day 1 to Day 28
Title
Incidence of all-cause mortality
Description
To describe the incidence of all-cause mortality during the 28 days after administration of Azvudine for prevention of SAR-CoV-2 infection.
Time Frame
Day 1 to Day 28
Title
Time to SARS-CoV-2 infection
Description
The time to SARS-CoV-2 infection after the the first dose of Azvudine will be evaluated in the RT-PCR positive participants.
Time Frame
Day 1 to Day 28
Title
Duration of symptoms
Description
Duration of symptoms in participants with COVID-19.
Time Frame
Day 1 to Day 28
Title
Adverse events
Description
Number of participants with adverse events after administration of Azvudine will be evaluated.
Time Frame
Day 1 to Day 28
Title
Maximum serum concentration (Cmax)
Description
The Cmax of Azvudine after administration in participants will be evaluated.
Time Frame
Day 1 to Day 28
Title
Time to reach maximum serum concentration (Tmax)
Description
The Tmax of Azvudine after administration in participants will be evaluated.
Time Frame
Day 1 to Day 28
Title
Terminal half-life (T1/2)
Description
The T1/2 of Azvudine after administration in participants will be evaluated.
Time Frame
Day 1 to Day 28
Title
Apparent total clearance (CL/F)
Description
The CL/F of Azvudine after administration in participants will be evaluated.
Time Frame
Day 1 to Day 28
Title
Apparent volume of distribution based on terminal phase (Vz/F)
Description
The Vz/F of Azvudine after administration in participants will be evaluated.
Time Frame
Day 1 to Day 28
Title
Area under the concentration-time curve from time 0 to the last concentration-measurable time point (AUC0-t)
Description
The AUC0-t of Azvudine after administration in participants will be evaluated.
Time Frame
Day 1 to Day 28
Title
Area under the concentration-time curve from time 0 to infinity (AUC0-∞)
Description
The AUC0-∞ of Azvudine after administration in participants will be evaluated.
Time Frame
Day 1 to Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: ≥18 years old at the signing of informed consent. 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. 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. Subject expects to be living in the same household with the symptomatic COVID-19 cases during the whole study period. Willing and able to comply with study visits and study-related procedures/assessments. Provide informed consent signed by study subject or legally acceptable representative. Exclusion Criteria: Subject with a history of SARS-CoV-2 vaccinations within 6 months before randomization. Subject with a history of SARS-CoV-2 infection within 6 months before randomization. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×Upper Limit of Normal (ULN) ,or total bilirubin (TBIL) >2×ULN. Creatinine clearance (Ccr, calculated by Cockcroft-Gault equation)<60 ml/min or Creatinine >1.2×ULN. With any serious infection requiring systemic anti-infective therapy within 14 days before randomization. Allergic to the investigational agent or any components of the formulation. Pregnant or breast-feeding women. Previous administration of any antiretroviral drugs (e.g., antiretroviral drugs for HIV, HBV, or HCV) within 7 days before randomization. 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. Have other conditions not suitable for inclusion as judged by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gerard S. Garcia, M.D.
Phone
+63324169341
Email
cduhrec@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerard S. Garcia, M.D.
Organizational Affiliation
Cebu Doctor's University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Malaya Medical Centre
City
Kuala Lumpur
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohd Idzwan bin Zakaria, Ph.D.
Phone
03-79493209
Ext
2251
First Name & Middle Initial & Last Name & Degree
Mohd Idzwan bin Zakaria, Ph.D.
Facility Name
International Islamic University Malaysia
City
Kuantan
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nur Syazwani Binti Jamhuri, Dr.
First Name & Middle Initial & Last Name & Degree
Nur Syazwani Binti Jamhuri, Dr.
Facility Name
ALPS Medical Center
City
Shah Alam,
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin George, Dr.
First Name & Middle Initial & Last Name & Degree
Benjamin George, Dr.
Facility Name
Klinik Kesihatan Cheras
City
Shah Alam
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Siti Shafiatun Siti Shafiatun, Dr.
First Name & Middle Initial & Last Name & Degree
Siti Shafiatun Siti Shafiatun, Dr.
Facility Name
Klinik Kesihatan Greentown
City
Shah Alam
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
V. Paranthaman, Dr.
First Name & Middle Initial & Last Name & Degree
V. Paranthaman, Dr.
Facility Name
Klinik Kesihatan Kuala Kedah
City
Shah Alam
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fazlin Suhana Othman, Dr.
First Name & Middle Initial & Last Name & Degree
Fazlin Suhana Othman, Dr.
Facility Name
Klinik Kesihatan Mahmoodiah
City
Shah Alam
Country
Malaysia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wan Fadhilah Binti Wan Ismail, Dr.
First Name & Middle Initial & Last Name & Degree
Wan Fadhilah Binti Wan Ismail, Dr.
Facility Name
Cebu Doctors' University Hospitol
City
Cebu City
Country
Philippines
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gerard S. Garcia, M.D.
First Name & Middle Initial & Last Name & Degree
Gerard S. Garcia, M.D.
Facility Name
Perpetual Succour Hospital
City
Cebu City
Country
Philippines
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jemela Anne Sanchez, Dr.
First Name & Middle Initial & Last Name & Degree
Jemela Anne Sanchez, Dr.
Facility Name
University of the East Ramon Magsaysay Memorial Medical Center
City
Quezon City
Country
Philippines
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nina Marnie Beltran-Yap, M.D.
First Name & Middle Initial & Last Name & Degree
Nina Marnie Beltran-Yap, M.D.

12. IPD Sharing Statement

Plan to Share IPD
No

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

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