Safety and Immunogenicity Study of COVID-19 Protein Subunit Recombinant Vaccine Adjuvanted With Alum+CpG 1018

Study Overview
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Brief Summary
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The study is an observer-blind, randomized, controlled prospective intervention study of Phase I. The primary objective is to evaluate the safety and immunogenicity of the SARS-CoV-2 protein subunit recombinant vaccine adjuvanted with Alum+CpG1018

Detailed Description
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This trial is observer blinded, comparative, randomized, phase I study. Approximately 175 subjects will be recruited (18 years and above). The investigational product is 0.5 ml in two dose-regimen (for all subjects) with 28 days apart between doses, compare to an active control (inactivated SARS-CoV-2 vaccine). There will be 4 formula of investigational product used with different concentration of Receptor Binding Domain (RBD) antigen and adjuvant CpG 1018.

Official Title
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A Phase I, Observer-Blind, Randomized, Controlled Study of the Safety and Immunogenicity of SARS-CoV-2 Protein Subunit Recombinant Vaccine (Adjuvanted With Alum+CpG 1018) in Healthy Populations Aged 18 Years and Above in Indonesia

Conditions
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COVID-19

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically healthy subjects aged 18 years and above. 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: Subjects concomitantly enrolled or scheduled to be enrolled in another trial. History of vaccination with any investigational product against COVID-19 (based on anamnesis) Subjects who have history of COVID-19 (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). The result of RT-PCR test for SARS-CoV-2 is positive. Women who are lactating, pregnant or planning to become pregnant during the study period (judged by self-report of subjects and urine pregnancy test results). Abnormality hematology and biochemical test results (for main study subset). 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
Maximum Age: 70 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine Candidate Formula A<br>2 doses of vaccine candidate formula A administered with 28 days interval (0.5 mL per dose) | Biological: SARS-CoV-2 protein subunit recombinant vaccine<br>* candidate vaccine manufactured by PT. Bio Farma<br>|
| Experimental: Vaccine Candidate Formula B<br>2 doses of vaccine candidate formula B administered with 28 days interval (0.5 mL per dose) | Biological: SARS-CoV-2 protein subunit recombinant vaccine<br>* candidate vaccine manufactured by PT. Bio Farma<br>|
| Experimental: Vaccine Candidate Formula C<br>2 doses of vaccine candidate formula C administered with 28 days interval (0.5 mL per dose) | Biological: SARS-CoV-2 protein subunit recombinant vaccine<br>* candidate vaccine manufactured by PT. Bio Farma<br>|
| Experimental: Vaccine Candidate Formula D<br>2 doses of vaccine candidate formula D administered with 28 days interval (0.5 mL per dose) | Biological: SARS-CoV-2 protein subunit recombinant vaccine<br>* candidate vaccine manufactured by PT. Bio Farma<br>|
| Active Comparator: Active Control<br>2 doses of active control administered with 28 days interval (0.5 mL per dose) | Biological: SARS-CoV-2 inactivated vaccine<br>* active control manufactured by Sinovac Life Sciences Co.Ltd<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the vaccine within 7 days after each dose | percentage of subjects with solicited and unsolicited Adverse Events (AE) | 7 days after each dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of the vaccine within 28 days after each dose | percentage of subjects with solicited and unsolicited AE | 28 days after each dose | 
| Serious Adverse Event (SAE) of the vaccine | percentage of subjects with at least 1 SAE | 6 months after the last dose | 
| Comparison of safety between vaccine and active control | percentage of subjects with AE and SAE between vaccine and active control group | 28 days after each dose and 6 months after the last dose | 
| Deviation of laboratory evaluation | Any deviation from routine laboratory evaluation that probably related to the dosing | 7 days after the first dose and 14 days after the last dose | 
| Inflammatory factor evaluation | The change of interleukin-6 (IL-6) in serum | 7 days after the first dose and 14 days after the last dose | 
| Immunogenicity profile after the last dose | GMT of IgG antibody and neutralization antibody | 14 days and 28 days after the last dose | 
| Immunogenicity profile after the last dose | seroconversion rate of IgG antibody and neutralization antibody | 14 days and 28 days after the last dose | 
| Comparison of immunogenicity profile | GMT of IgG antibody and neutralization antibody | 14 days and 28 days after the last dose | 
| Comparison of immunogenicity profile | seroconversion rate of IgG antibody and neutralization antibody | 14 days and 28 days after the last dose | 

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