Exploratory Clinical Study to Evaluation of the Safety and Immunogenicity of Bivalent Vaccine V-01D-351

Study Overview
=================
Brief Summary
-----------------
It is a single center, randomized, open-labeled, blind endpoint evaluation, exploratory clinical study to evaluate the safety and immunogenicity of bivalent vaccine V-01D-351 as a booster.

Official Title
-----------------
A Single Center, Randomized, Open-labeled, Blind Endpoint Evaluation, Exploratory Clinical Study to Evaluate the Safety and Immunogenicity of Bivalent Vaccine V-01D-351 as a Booster Dose in Participants Aged 18 Years and Older Vaccinated 2-dose or 3-dose Inactivated COVID-19 Vaccine

Conditions
-----------------
COVID-19 Pandemic

Intervention / Treatment
-----------------
* Biological: V-01D-351
* Biological: V-01D-351
* Biological: CoronaVac
* Biological: CoronaVac


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults aged 18 years and older at time of consent, male or female; Normal body temperature; Meet either of the following conditions: Received completed primary immunization of 2 doses of CoronaVac 6-15 months ago; Received completed 3 doses of CoronaVac 5-9 months ago; Female participants who are not pregnant at the time of enrollment (urine pregnancy test is negative), nor during lactating; and has no birth plan and agree to take effective contraception in 7 months after enrollment; and took effective and acceptable contraceptive methods in the previous 2 weeks before the enrollment; Be able and willing to complete the study during the entire study and follow-up period; Participants who have the ability to understand the study process, sign the informed consent form voluntarily , and be able to comply with the requirements of the clinical study protocol. Exclusion Criteria: Serious chronic diseases or uncontrolled diseases; Uncontrolled neurological disorders, epilepsy; Received any inactivated vaccine within 1 week or received any attenuated vaccines within 4 weeks; Patients with congenital or acquired immunodeficiency; History of severe allergy or be allergic to any components of the test vaccines; History of hereditary hemorrhagic tendency or coagulation dysfunction; Patients with malignant tumors and other patients have a life expectancy less than 1 year; Refuse to sign the informed consent form or inability to complete follow-ups as required by the protocol; History of previous COVID-19 infection; Pregnant or breastfeeding women, or females of childbearing potential who not agree to or able to take effective and acceptable contraceptive methods during the study; Participants who have participated in other clinical trials within 3 months or are participating in other clinical trials; Those considered by the investigator as inappropriate to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br> | Biological: V-01D-351<br>* One dose of V-01D-351 on participants received 2 doses of inactivated vaccine (CoronaVac) 6-15 months ago<br>|
| Experimental: Cohort 2<br> | Biological: V-01D-351<br>* One dose of V-01D-351 on participants received 3 doses of inactivated vaccine (CoronaVac) 5-9 months ago<br>|
| Active Comparator: Cohort 3<br> | Biological: CoronaVac<br>* One dose of CoronaVac on participants received 2 doses of inactivated vaccine (CoronaVac) 6-15 months ago<br>|
| Active Comparator: Cohort 4<br> | Biological: CoronaVac<br>* One dose of CoronaVac on participants received 3 doses of inactivated vaccine (CoronaVac) 5-9 months ago<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing antibody GMT of Omicron BA.5 | Neutralizing antibody GMT of the most prevalent SARS-CoV-2 variant (Omicron BA.5) | 28 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing antibody GMT of other SARS-CoV-2 variants | Neutralizing antibody GMT of Delta variant and Omicron variants (BA.2, BA.4, BA.5) | 7 days, 14 days, 28 days, 3 months, 6 months and 12 months after vaccination | 
| Neutralizing antibody titer of other SARS-CoV-2 variants (MRNT) | Neutralizing antibody titer of Delta variant and Omicron variants (BA.2, BA.4, BA.5) by MRNT | 7 days, 14 days, 28 days, 3 months, 6 months and 12 months after vaccination | 
| Neutralizing antibody titer of other SARS-CoV-2 variants (SVNT) | Neutralizing antibody titer of Delta variant and Omicron variants (BA.2, BA.4, BA.5) by SVNT | 7 days, 14 days, 28 days, 3 months, 6 months and 12 months after vaccination | 
| Total IgG antibody level | Total IgG antibody level of SARS-CoV-2 | 7 days, 14 days, 28 days, 3 months, 6 months and 12 months after vaccination | 
| Spike protein antibody level | Antibody level of anti-SARS-CoV-2 spike protein | 7 days, 14 days, 28 days, 3 months, 6 months and 12 months after vaccination | 
| RBD antibody level | Anti-SARS-CoV-2 RBD antibody level | 7 days, 14 days, 28 days, 3 months, 6 months and 12 months after vaccination | 
| Specific cytokine secretion levels | Specific cytokine secretion levels such as IFN-γ | 7 days, 14 days, 28 days, 3 months, 6 months and 12 months after vaccination | 
| AEs | Observe the AEs occurs at different time point after vaccination | 30 minutes, 0-7 days, 0-28 days after vaccination | 
| SAE and AESI | Observe the SAE and AESI after vaccination | Within 12 months after vaccination |