UNAIR Inactivated COVID-19 Vaccine Phase III (Immunobridging Study)

Study Overview
=================
Brief Summary
-----------------
This study is a multicenter, randomized, double blind, controlled, phase III clinical trial (Immunobridging Study) to evaluate the immunogenicity and safety of Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) in healthy populations aged 18 years and above. Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) is an inactivated vaccine made of SARS-CoV-2 virus isolated from a patient in Surabaya, composed with aluminium hydroxy gel, tween 80, and L-histidine, and this study will be the first phase III in human.

Detailed Description
-----------------
This is a double blind randomized controlled trial - immunobridging study. There will be 2 groups in the study. One adult group (18 year-old and above) with 5 µg dose, and 1 control group using CoronaVac Bio Farma. Both vaccines will be administered with 2-dose schedule, intramuscularly. All cohorts will be followed for 6 months. This study will have two interim and one full analysis The main focus is immunogenicity and safety or reactogenicity issues. Data Safety Monitoring Board will be commissioned for this study to evaluate safety data over the study period and to review any events that meet a specific study pausing rule or any other safety issue that may arise. They will review the blinded 7 and 28 days safety data following the first dose of vaccine, and then the 7 and 28 days after the second dose. The immunogenicity data will be evaluated until 6 months after the second dose

Official Title
-----------------
A Multicenter, Randomized, Double Blind, Controlled, Phase III Clinical Trial (Immunobridging Study) of Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) in Healthy Population Aged 18 Years and Above

Conditions
-----------------
COVID-19 Pandemic, COVID-19 Vaccines

Intervention / Treatment
-----------------
* Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg
* Biological: CoronaVac Biofarma COVID-19 Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adults and elderly, males and females, 18 years of age and above. Healthy status will be determined by the investigator based on medical history, clinical laboratory results, vital sign measurements, and physical examination at screening. Subjects have been informed properly regarding the study and signed the informed consent form. Subject will commit to comply with the instructions of the investigator and the schedule of the trial Participants agree not to donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine. Participants must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study. Exclusion Criteria: Subjects concomitantly enrolled or scheduled to be enrolled in another vaccine trial. Evolving mild, moderate, and severe illness, especially infectious diseases or fever (axillary temperature 37.5 degree Celcius or more) concurrent or within 7 days prior to first study vaccination. This includes respiratory or constitutional symptoms consistent with SARS-CoV-2 (cough, sore throat, difficulty in breathing, etc) Known history of allergy to any component of the vaccines. History of uncontrolled coagulopathy or blood disorders contraindicating intramuscular injection. Any autoimmune or immunodeficiency disease/condition Subjects who have received in the previous 4 weeks a treatment likely to alter the immune response (intravenous immunoglobulin, blood derived products, long term corticosteroid - more than 2 weeks, and so on), OR anticipation of the need for immunosuppressive treatment within 6 months after last vaccination. The use of topical or nasal steroid will be permitted. Unstable chronic disease, inclusive of uncontrolled hypertension, congestive heart failure, chronic obstructive pulmonary disease, asthma, chronic urticaria, diabetes requiring use of medicine. The final decision regarding this condition will be decided by the attending field clinicians or investigator. Any abnormality or chronic disease which according to the investigator might interfere with the assessment of the trial objectives. Individuals who previously receive any vaccines against Covid-19. Subjects already immunized with any vaccine within 4 weeks prior and expect to receive other vaccines within 60 days following the first dose. Individuals who have a previously ascertained Covid-19 in the period of 1 month (for mild, moderate, or asymptomatic people) or 3 months (for severe Covid-19) before the first recruit of this study, or in a close contact in the last 14 days with confirmed case of Covid-19. Positive test for SARS-CoV-2 (Antigen test or, if necessary, PCR test) at screening prior to first vaccination. Testing may be repeated during the screening period if exposure to positive confirmed case of SARS-CoV-2 is suspected, at the discretion of investigator. Alcohol or substance abuse HIV patients. Malignancy patients within 2 years prior to first study vaccination. Any neurological disease or history of significant neurological disorder such as meningitis, encephalitis, Guillain-Barre Syndrome, multiple sclerosis, etc Vital sign abnormalities and clinical laboratory abnormalities as decided by the investigators. Vital sign measurements and clinical laboratory testing may be repeated before the final decision. Women who are pregnant or who plan to become pregnant during the study. Participant has major psychiatric problem or illness Participant cannot communicate reliably with the investigator Participant has contraindication to intramuscular injection and blood draws, such as bleeding disorders or phobia. Participant had major surgery within 12 weeks before vaccination which will not be fully recovered, or has major surgery planned during the time participant is expected to participate in the study or within 6 months after the last dose of study vaccine administration. Any condition that in the opinion of the investigators would pose a health risk to the subject if enrolled or could interfere with the evaluation of the vaccine or interpretation of the study results Study team members. Subject planning to move from the study area before the end of study period.

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: Parallel Assignment
Interventional Model Description: There will be 2 groups in the study. One adult group (18 year-old and above) with 5 µg dose, and 1 control group using CoronaVac Bio Farma. The UNAIR vaccine group will consist of 3 sub group based on different lot. Both vaccines will be administered with 2-dose schedule, intramuscularly. All cohorts will be followed for 6 months.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg<br>Study product are provided in the form of liquid in vial single dose (0.5 ml). The vaccine will be given twice with 28 days interval. | Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg<br>* Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) contains purified S protein of SARS-CoV-2 - Dose: 5 µg, aluminium hydroxide gel, 10 mM L-Histidine buffer, 0.005%, Tween Polysorbate 80, and 0.9% Sodium chloride. Vaccine will be prepared in vial (1 ml per vial). One vial will be used for one injection only. The vial should be shaken well before injection.<br>|
| Active Comparator: CoronaVac Biofarma COVID-19 Vaccine<br>Control vaccine is CoronaVac Bio Farma vaccine, supplied by Ministry of Health of Indonesia, in the form of two doses vial. The vaccine will be given twice with 28 days interval. | Biological: CoronaVac Biofarma COVID-19 Vaccine<br>* Control vaccine in this study is existing CoronaVac-BioFarma inactivated COVID-19 vaccine which has been used widely in Indonesia<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Humoral Immunogenicity Profile | The level of SARS-CoV-2 neutralizing and non neutralizing antibody among participants | 28 days after the second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Safety Profile | Evaluate number of adverse events occur among participants | Within 30 minutes, 24 hours, 7 and 28 days following each dose and 3 and 6 months after the second doses of vaccination | 
| The Humoral Immunogenicity Profile | The level of SARS-CoV-2 neutralizing and non neutralizing antibody among participants | 3 and 6 months following the second vaccination | 
| The Cellular Immunogenicity Profile | Evaluate Th1 and Th2 immune responses including CD4+/CD8+. IL-2, IL-4, TNF alpha, IFN gamma, and other markers after stimulation of PBMC with SARS-CoV-2 protein peptides and Interferon gamma release assay (IGRA) to assess the production of IFN-γ from stimulated CD4+ and CD8+ with antigen peptides specific to SARS-CoV-2 among participants | 3 and 6 months after the second vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inactivated COVID-19 Vaccine, Immunogenicity, Safety, COVID-19, Indonesia, Immunobridging study