Booster Study of COVID-19 Protein Subunit Recombinant Vaccine

Study Overview
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Brief Summary
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Observer-blind, randomized, active-controlled prospective intervention study of Immunogenicity & Safety of SARS-Cov-2 Protein Subunit Recombinant Vaccine (Bio Farma) as a Booster Dose Against COVID-19 in Adults 18 Years of Age and Older.

Detailed Description
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This trial is observer-blind, randomized, prospective intervention study. In this study 900 subjects who had received complete primary doses of authorized/approved inactivated (Sinovac®), mRNA (Pfizer®), or viral vector (AstraZeneca®) COVID-19 vaccine and willing to participate in the booster study by signing the consent form, will be involved in this trial. Subject will be divided into six groups, each 150 subjects per arm who had received a complete primary dose of inactivated (Sinovac®) vaccine, mRNA (Pfizer®) vaccine, or viral vector (AstraZeneca®) vaccine will receive one booster dose of SARS-CoV-2 subunit protein recombinant vaccine or active control.

Official Title
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Observer-Blind, Randomized, Controlled Study of Immunogenicity and Safety of SARS-Cov-2 Protein Subunit Recombinant Vaccine (Bio Farma) as a Booster Dose Against COVID-19 in Adults 18 Years of Age and Older

Conditions
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COVID-19

Intervention / Treatment
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* Biological: SARS-CoV-2 subunit protein recombinant vaccine
* Biological: Active Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically healthy adults 18 years of age and older. Subjects who have previously received complete primary series of authorized/approved inactivated (Sinovac®), mRNA (Pfizer®), or viral vector COVID-19 vaccine (AstraZeneca®) with the last dose administered a minimum of 6 months prior to inclusion but not longer than 12 months prior to inclusion. Subjects have been informed properly regarding the study and signed the informed consent form. Subjects will commit to comply with the instructions of the investigator and the schedule of the trial. Exclusion Criteria: Subject concomitantly enrolled or scheduled to be enrolled in another trial. Subject who has received booster dose of COVID-19 vaccine. Subject who has history of COVID-19 in the last 3 months (based on anamnesis or other examinations). Evolving mild, moderate or severe illness, especially infectious disease or fever (body temperature ≥37.5℃, measured with infrared thermometer/thermal gun). Women who are pregnant or planning to become pregnant during the study period (judged by self-report of subjects and urine pregnancy test results). History of asthma, history of allergy to vaccines or vaccine ingredients, and severe adverse reactions to vaccines, such as urticaria, dyspnea, and angioneurotic edema. History of uncontrolled coagulopathy or blood disorders contraindicating intramuscular injection. Patients with serious chronic diseases (serious cardiovascular diseases, uncontrolled hypertension and diabetes, liver and kidney diseases, malignant tumors, etc) which according to the investigator might interfere with the assessment of the trial objectives. Subjects who have any history of confirmed or suspected immunosuppressive or immunodeficient state, or received in the previous 4 weeks a treatment likely to alter the immune response (intravenous immunoglobulins, blood-derived products or long-term corticosteroid therapy (> 2 weeks)). Subjects who have history of uncontrolled epilepsy or other progressive neurological disorders, such as Guillain-Barre Syndrome. Subjects receive any vaccination (other than COVID-19 vaccine) within 1 month before and after IP immunization. Subjects plan to move from the study area before the end of study period.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary dose of inactivated (Sinovac®) vaccine (1)<br>Subject who had received a complete primary dose of inactivated (Sinovac®) vaccine | Biological: SARS-CoV-2 subunit protein recombinant vaccine<br>* SARS-CoV-2 RBD subunit recombinant protein, manufactured by PT. Bio Farma<br>|
| Experimental: Primary dose of mRNA (Pfizer®) vaccine (1)<br>Subject who had received a complete primary dose of mRNA (Pfizer®) vaccine | Biological: SARS-CoV-2 subunit protein recombinant vaccine<br>* SARS-CoV-2 RBD subunit recombinant protein, manufactured by PT. Bio Farma<br>|
| Experimental: Primary dose of Viral Vector (AstraZeneca®) vaccine (1)<br>Subject who had received a complete primary dose of viral vector (AstraZeneca®) vaccine | Biological: SARS-CoV-2 subunit protein recombinant vaccine<br>* SARS-CoV-2 RBD subunit recombinant protein, manufactured by PT. Bio Farma<br>|
| Experimental: Primary dose of inactivated (Sinovac®) vaccine (2)<br>Subject who had received a complete primary dose of inactivated (Sinovac®) vaccine | Biological: Active Comparator<br>* The Pfizer-BioNTech® COVID-19 vaccine or BNT162b2, is an mRNA vaccine encoding a P2 mutant spike protein (PS 2) and formulated as an RNA-lipid nanoparticle of nucleoside-modified mRNA (modRNA).<br>|
| Experimental: Primary dose of mRNA (Pfizer®) vaccine (2)<br>Subject who had received a complete primary dose of mRNA (Pfizer®) vaccine | Biological: Active Comparator<br>* The Pfizer-BioNTech® COVID-19 vaccine or BNT162b2, is an mRNA vaccine encoding a P2 mutant spike protein (PS 2) and formulated as an RNA-lipid nanoparticle of nucleoside-modified mRNA (modRNA).<br>|
| Experimental: Primary dose of Viral Vector (AstraZeneca®) vaccine (2)<br>Subject who had received a complete primary dose of viral vector (AstraZeneca®) vaccine | Biological: Active Comparator<br>* The Pfizer-BioNTech® COVID-19 vaccine or BNT162b2, is an mRNA vaccine encoding a P2 mutant spike protein (PS 2) and formulated as an RNA-lipid nanoparticle of nucleoside-modified mRNA (modRNA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of the candidate vaccine | Geometric Mean Titer (GMT) and GMT ratio of neutralizing antibody to the SARS-CoV-2 | 14 days after booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seropositive rate of the candidate vaccine | Seropositive rate of neutralizing antibody | Baseline, 14 days and 6 months after booster vaccination | 
| Seroconversion rate of the candidate vaccine | Seroconversion rate of neutralizing antibody | Baseline and 14 days after booster vaccination | 
| Seropositive rate and GMT of candidate vaccine | Seropositive rate and GMT of candidate vaccine | Baseline, 14 days, and 6 months after booster vaccination | 
| Seroconversion rate of the candidate vaccine | Seroconversion rate of IgG antibody (RBD) | baseline and 14 days after booster vaccination | 
| Comparison of immunogenicity between candidate vaccine and control group | Comparison of GMT, seroconversion rate, seropositive rate of neutralizing antibody and IgG antibody (RBD) between candidate vaccine and control group | Baseline, 14 days, and 6 months after booster vaccination | 
| Safety of the candidate vaccine | Percentage of subjects with solicited and unsolicited Adverse Events (AE) | 28 days after booster vaccination | 
| Serious Adverse Event (SAE) of the vaccine | Percentage of subjects with at least 1 SAE | 6 months after booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 vaccine, healthy population, Booster