Efficacy, Immunogenicity, and Safety of TURKOVAC Vaccine Versus the CoronaVac Vaccine Against COVID-19 in Healthy Adolescent

Multicenter,Randomized,Observational Blind Phase IIB Clinical Trial to Evaluate the Effectiveness,Immunogenicity and Safety of Two Doses of CoronaVac (Sinovac) Vaccine Against Two Doses of Inactivated COVID-19 Vaccine (TURKOVAC) in Healthy Adolescent (12-18 Years) Subjects

This study is a multi-center, randomized, national, observer-blinded, active-controlled phase IIB clinical trial to determine the efficacy, immunogenicity, and safety of two-doses of inactive COVID-19 vaccine (TURKOVAC) vaccine versus the two-doses CoronaVac (Sinovac) vaccine in healthy adolescents aged 12-18 years.

The primary aim of the study is to evaluate the clinical efficacy of two-doses of TURKOVAC and two-doses of CoronaVac vaccines against symptomatic COVID-19 disease confirmed by real time-polymerase chain reaction (RT-PCR) in adolescents (12-18 years of age).

After the second dose of vaccine administration, the immunological responses of TURKOVAC and CoronaVac vaccines will be demonstrated by neutralizing antibodies and anti-spiked antibodies.

A total of 644 subjects will be enrolled. Subjects will be assigned according to randomization (1:1) for 2 different arms. The assigned vaccine will be administered to subjects in two doses on days 0 and 28.

Inclusion Criteria:

Each subject must meet all the following criteria to be enrolled in this study:

1. Subjects who can voluntarily consent to participate in the study with their parents or legal representatives,
2. Subjects agreed to comply with all study visits and procedures (consented to give blood sample and nasopharyngeal swab, and receiving automated telephone calls from the study site),
3. No history of SARS-CoV-2 (within the last 12 months),
4. Consent of sexually active females to use effective contraception during the study,
5. Adolescent males or females who were at least 12 years old and not older than 18 years of age on the date of the informed consent signature,
6. In the opinion of the investigator, subjects who can comply with the study protocol during the study,
7. According to the vaccination program of the Ministry of Health, meeting the criteria for vaccination however, who voluntarily choose not to be vaccinated when rights are granted and subjects who agreed to receive one of the vaccines to be used in this study,
8. Not participating in another clinical trial.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

1. Is acutely ill or febrile within 48 hours before or use of antipyretic or analgesic medication within 24 hours before planned administration of study vaccine. (Fever is defined as a body temperature is 38.0 °C. Subjects with mild illness and fever may be enrolled in the study at the discretion of the investigator),
2. Those who have used more than a single dose of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in the last 24 hours for a reason other than fever,
3. Subjects who are pregnancy or breastfeeding plan within (at least) 1 year following the second dose of vaccine,
4. Those with a history of SARS-CoV-2 (within the last 12 months),
5. Individuals with a current positive (PCR-based viral RNA detection) or past positive (serological testing or PCR-based viral RNA detection) diagnostic test result for SARS-CoV-2 infection,
6. Prior administration of an investigational or approved coronavirus (SARS-CoV, SARS-CoV-2, MERS-CoV) vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID-19,
7. Subjects with a history of cardiac diseases (cardiovascular disease, serious arrythmia, coronary artery disease, heart failure, cardiomyopathies, pulmonary hypertension etc.),
8. Subjects with uncontrolled hypertension,
9. Subjects with a first-degree relative with a history of coronary artery disease at an early age (presence of coronary artery disease before 55 years of age in males and 65 years of age in females),
10. Subjects with morbid obesity (Body Mass Index (BMI) ≥ 40),
11. Subjects with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to: systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain-Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), psoriasis, and autoimmune bullous diseases,
12. Subjects with history of severe allergic reaction (i.e., anaphylaxis, generalized urticaria, angioedema, or other significant reaction) to any licensed or investigational vaccine or to any of the constituents of CoronaVac or TURKOVAC,
13. Subjects who have bleeding disorder considered a contraindication to intramuscular injection or phlebotomy,
14. Subjects who have immunosuppressive or immunodeficiency state (including HIV), asplenia, recurrent severe infections,
15. Subjects who received or planned to receive a licensed, live replicating vaccine (any vaccine other than the COVID-19 vaccine) within 28 days before or after the first study vaccination or a licensed inactivated or nonreplicating vaccine (any vaccine other than the COVID-19 vaccine) within 14 days before or after first study vaccination,
16. Subjects who receive treatment with immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, e.g., for cancer or an autoimmune disease, within 6 months prior to screening, or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until corticosteroid therapy has been discontinued for at least 28 days before study vaccine administration. Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted,
17. To be using an immunostimulant, immune-modifying supplementary drug or herbal product or to have used it in the last month,
18. Subjects who have received systemic immunoglobulin or blood products in the past 12 months, or who plan to receive such products during the study,
19. Investigator, site coordinators, employees of TUSEB or the Clinical Research Organization (CRO) directly involved in the conduct of the study, or site staff members otherwise supervised by the Investigator or immediate family members of any of the previously mentioned individuals.
20. Subjects who have previously received any COVID-19 vaccines.

Exclusion criteria for the second dose of vaccine:

1. Before the second vaccination, in the case of an unresolved acute illness or in the acute phase of a chronic illness, the investigator should exclude COVID-19 and assess if the acute disease can recover in a short term.
2. If there is an adverse event after the first dose or newly occurred non-compliance with the inclusion/exclusion criteria which will be assessed by the investigator whether the study subjects can continue or not.