Clinical trial NCT05633433: 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
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: SARS-CoV-2 Infection
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
name: Henan Genuine Biotech Co., Ltd.
First posted: 2022-12-01
Enrollment: 1550
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy-Incidence of SARS-CoV-2 infection in 7 days
timeFrame: Day 2 to Day 7
Secondary outcomes:
measure: Incidence of asymptomatic SARS-CoV-2 infection in 7 days
timeFrame: Day 2 to Day 7
measure: Incidence of symptomatic SARS-CoV-2 infection in 7 days
timeFrame: Day 2 to Day 7
measure: Incidence of SARS-CoV-2 infection in 14 days
timeFrame: Day 2 to Day 14
measure: Incidence of asymptomatic SARS-CoV-2 infection in 14 days
timeFrame: Day 2 to Day 14
measure: Incidence of symptomatic SARS-CoV-2 infection in 14 days
timeFrame: Day 2 to Day 14
measure: Incidence of severe COVID-19
timeFrame: Day 1 to Day 28
measure: Incidence of all-cause mortality
timeFrame: Day 1 to Day 28
measure: Time to SARS-CoV-2 infection
timeFrame: Day 1 to Day 28
measure: Duration of symptoms
timeFrame: Day 1 to Day 28
measure: Adverse events
timeFrame: Day 1 to Day 28
measure: Maximum serum concentration (Cmax)
timeFrame: Day 1 to Day 28
measure: Time to reach maximum serum concentration (Tmax)
timeFrame: Day 1 to Day 28
measure: Terminal half-life (T1/2)
timeFrame: Day 1 to Day 28
measure: Apparent total clearance (CL/F)
timeFrame: Day 1 to Day 28
measure: Apparent volume of distribution based on terminal phase (Vz/F)
timeFrame: Day 1 to Day 28
measure: Area under the concentration-time curve from time 0 to the last concentration-measurable time point (AUC0-t)
timeFrame: Day 1 to Day 28
measure: Area under the concentration-time curve from time 0 to infinity (AUC0-∞)
timeFrame: Day 1 to Day 28
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Kuantan
country: Malaysia
facility: International Islamic University Malaysia
city: Shah Alam,
country: Malaysia
facility: ALPS Medical Center
city: Shah Alam
country: Malaysia
facility: Klinik Kesihatan Cheras
city: Shah Alam
country: Malaysia
facility: Klinik Kesihatan Greentown
city: Shah Alam
country: Malaysia
facility: Klinik Kesihatan Kuala Kedah
city: Shah Alam
country: Malaysia
facility: Klinik Kesihatan Mahmoodiah
city: Cebu City
country: Philippines
facility: Cebu Doctors' University Hospitol
city: Cebu City
country: Philippines
facility: Perpetual Succour Hospital
city: Quezon City
country: Philippines
facility: University of the East Ramon Magsaysay Memorial Medical Center
Study officials:
affiliation: Cebu Doctor's University Hospital
name: Gerard S. Garcia, M.D.
role: PRINCIPAL_INVESTIGATOR
References: