A PhaseⅡ Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine

A Randomized, Blinded, Controlled Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of a COVID-19 mRNA Vaccine (ZSVG-02-O) in a Healthy Population 18 Years of Age and Older

To evaluate the immunogenicity and safety of a COVID-19 mRNA vaccine (ZSVG-02-O) in a healthy population aged 18 years and older.

Study Overview

• Status: Recruiting
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated

Detailed Description

This study uses a randomized, blinded and controlled design, with age stratification of 18-59 years and ≥60 years , including the test vaccine at different doses (30 μg and 60 μg) and an active control vaccine.

A total of 980 subjects will be enrolled in this study. 490 subjects aged 18-59 years will be randomly assigned to cohort A1 (test vaccine dose 1), A2 (test vaccine dose 2) and A3 (control vaccine) for the 2-dose regimen (0,28-day) and to cohort A4 (test vaccine dose 1), A5 (test vaccine dose 2) and A6 (active control) for the 1-dose regimen in a ratio of 3:3:1:3:3:1. Another 490 subjects aged 60 years or older will be randomized to cohort B1 (test vaccine dose 1), B2 (test vaccine dose 2) and B3 (active control) for the 2-dose regimen (0,28-day), and cohort B4 (test vaccine dose 1), B5 (test vaccine dose 2) and B6 (control vaccine) for the 1-dose regimen in a ratio of 3:3:1:3:3:1.

• Study Type: Interventional
• Enrollment (Estimated): 980
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yanxia Wang; Phone Number: +86-13613816598; Email: wangyanxia99@163.com

Study Locations

• China
  • Henan
    • Dengfeng, Henan, China
      • Recruiting
      • Dengfeng Centre for Disease Control and Prevention and Control
      • Contact: Shuaixu Guo; Phone Number: 86-18697308288; Email: dfscdcxmb@163.com
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Provincial Centre for Disease Control and Prevention
      • Contact: Yanxia Wang; Phone Number: +8613613816598; Email: wangyanxia99@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male or female subjects aged ≥18 years of age;
2. Subjects who are in good physical condition as judged by the investigator based on medical history, physical examination and clinical laboratory tests;
3. Subjects who have not been previously vaccinated with a Covid-19 vaccine or who have received the last dose (total dose ≤ 3 doses) of a Covid-19 vaccine at least 6 months ago;
4. Subjects who have not been previously infected with Covid-19, or whose nucleic acid or antigen test has turned negative for more than 3 months after previous Covid-19 infection;
5. Subjects are able to understand the study procedures, have provide written informed consent, and are able to comply with the requirements of the clinical study protocol.

Exclusion criteria

1. Axillary temperature ≥37.3°C;
2. Positive polymerase chain reaction (PCR) test results within the last 48 hours;
3. Women of childbearing potential with a positive urine pregnancy test result, or who are pregnant or breastfeeding, or who have not used effective contraception within 2 weeks prior to enrolment, or women and men who plan to have children within 12 months after full immunisation;
4. History of epilepsy, convulsions or seizures, psychosis or family history of psychosis;
5. Have a history of severe allergy to any medication or vaccination (e.g. acute allergic reaction, urticaria, skin eczema, dyspnoea, angioneurotic oedema, or abdominal pain) or allergy to known components of a Covid-19 vaccine;
6. Have a history of hospital-diagnosed thrombocytopenia or other coagulation disorders;
7. Have a history of hospital-diagnosed known immunological impairment or hypofunction;
8. Subjects who have received whole blood, plasma or immunoglobulin therapy within 3 months;
9. Known or suspected concomitant serious diseases, including: respiratory diseases, acute infections or active chronic diseases, liver and kidney diseases, severe diabetes, malignant tumours, infectious or allergic skin diseases, and HIV infection (with test report);
10. Have serious cardiovascular diseases, cardiopulmonary failure, hypertension that cannot be controlled by medication (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg on physical examination);
11. Received live attenuated vaccine within 1 month prior to vaccination or other vaccines within 14 days prior to vaccination;
12. Participation in a clinical trial of another drug within 3 months prior to the first dose of vaccine or planning to participate in a clinical trial of another drug during the study period;
13. Any other conditions that the investigator considers inappropriate for participation in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test vaccine dose 1, 2 dose	Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); 30 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); 60 μg
Experimental: Test vaccine dose 2, 2 dose	Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); 30 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); 60 μg
Active Comparator: Active Comparator, 2 dose	Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated; COVILO
Experimental: Test vaccine dose 1, 1 dose	Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); 30 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); 60 μg
Experimental: Test vaccine dose 2, 1 dose	Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); 30 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); 60 μg
Active Comparator: Active Comparator,1 dose	Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated; COVILO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titre (GMT) and 4-fold increasing rate of neutralizing antibodies (NAbs) against SARS-CoV-2 on 28 days after full vaccination	Geometric mean titre (GMT) and 4-fold increasing rate of neutralizing antibodies (NAbs) against SARS-CoV-2 on 28 days after full vaccination	28 days after full immunisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMT and 4-fold increasing rate of NAbs against SARS-CoV-2 on 14 days after full vaccination	GMT and 4-fold increasing rate of NAbs against SARS-CoV-2 on 14 days after full vaccination	14 days after full immunisation
GMT and 4-fold increasing rate of NAbs against SARS-CoV-2 on 7 days after the first immunisation	GMT and 4-fold increasing rate of NAbs against SARS-CoV-2 on 7 days after the first immunisation	7 days after the first immunisation
Proportion of NAbs against SARS-CoV-2 titres≥1:16, ≥1:32 and ≥1:64 on 14 and 28 days after full immunisation	Proportion of NAbs against SARS-CoV-2 titres≥1:16, ≥1:32 and ≥1:64 on 14 and 28 days after full immunisation	14 days and 28 days after full immunisation
Incidence and severity of adverse reactions/events 0-14 days after each dose of vaccination	Incidence and severity of adverse reactions/events 0-14 days after each dose of vaccination	Day 0~Day 14 after each immunisation
Incidence and severity of adverse reactions/events 15-28 days after each dose of vaccination	Incidence and severity of adverse reactions/events 15-28 days after each dose of vaccination	Day 15~Day 28 after each immunisation
GMT, 4-fold increasing rate and ratio of antibody titres ≥1:16, ≥1:32 and ≥1:64 for NAbs against SARS-CoV-2 on 90 and 180 days after full immunisation	GMT, 4-fold increasing rate and ratio of antibody titres ≥1:16, ≥1:32 and ≥1:64 for NAbs against SARS-CoV-2 on 90 and 180 days after full immunisation	90 days and 180 days after full immunisation
Incidence and severity of adverse event (AE) within 30 minutes of each dose of vaccination	Incidence and severity of AE within 30 minutes of each dose of vaccination	From the start of each immunisation until 30 minutes after each immunisation
Incidence of serious adverse event (SAE) from the start of vaccination to 12 months after full vaccination	Incidence of SAE from the start of vaccination to 12 months after full vaccination	From the first dose of immunisation to 12 months after full immunisation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cross-neutralisation against different SARS-CoV-2 variants	The cross-neutralization effect of the mRNA vaccine (Omicron strain) against different SARS-CoV-2 variants (ancestral strain, Omicron strain and main circulating strain)	From the first dose of immunisation to 28 days after full immunisation
Changes in cytokine levels in Th1/Th2 cells induced by S protein	Cytokine [IFN-γ, interleukin(IL)-4, IL-2] levels in Th1/Th2 cells changed from pre-dose to 28 days after the full immunisation	From before the first dose of immunisation to 28 days after full immunisation

Collaborators and Investigators

• Sponsor: CNBG-Virogin Biotech (Shanghai) Ltd.
• Investigators: Study Chair: Yunkai Yang, China National Biotec Group Company Limited

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Actual): October 30, 2023
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: October 31, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: ZSVG-02-O-2022-P2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No