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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Drug: Azvudine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |