Efficacy, Immunogenicity, and Safety of the Inactivated COVID-19 Vaccine (TURKOVAC) Versus the CoronaVac Vaccine

This study is a randomized, double-blinded, multi-center, active-controlled phase III clinical trial in adults aged 18~55 years. The purpose of this study is to evaluate the efficacy, safety, and immunogenicity of the experimental SARS-CoV-2 inactivated vaccine. A total of 40.800 subjects will be enrolled. The participant will be assigned to receive two doses of experimental vaccine or CoronaVac on the schedule of days 0, 28.

Inclusion criteria

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

• Subjects consented voluntarily to participate the study,
• 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),
• Subjects agreed to adhere to the prohibitions and restrictions specified in this protocol,
• Subjects, who are sexually active and have childbearing potential, agreed to comply with the contraceptive requirements to be applied in the study,
• Adult males or females of at least 18 years of age and not older than 55 years of age on the date of the informed consent signature,
• Subjects who are medically stable (those without severe pain, severe swelling, severe movement limitation, persistent high fever, severe headache or other systemic or local reactions) such that who are not anticipated to hospitalize within the study period, according to the judgment of the Investigator, and the subjects appears likely to be able to continue the study until the follow-up period specified in the protocol,
• Subjects who are excluded from the criteria to receive the COVID-19 vaccine approved in the scope of Emergency Use Approval in Turkey or subjects who meet the vaccination criteria, but voluntarily chose not to be vaccinated and agreed to receive one of the vaccines to be used in this study.

Exclusion criteria

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

• 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).
• Subjects who are pregnant or breastfeeding.
• Known history of SARS-CoV-2 infection.
• 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.
• 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.
• Subjects determined as ineligible to the study protocol.
• Subjects with a history of cardiac diseases (cardiovascular disease, serious arrythmia, coronary artery disease, heart failure, cardiomyopathies, pulmonary hypertension etc).
• Subjects with uncontrolled hypertension.
• Subjects with a family history of coronary artery disease at early ages (presence of before age 55 in men and before age 65 in women).
• Subjects with morbid obesity (Body mass index (BMI) ≥ 40).
• Subjects who have a travel plan to out of the city up to 28 days after the second vaccine dose.
• 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.
• 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.
• Subjects who has bleeding disorder considered a contraindication to intramuscular injection or phlebotomy.
• Immunosuppressive or immunodeficient state (including HIV), asplenia, recurrent severe infections.
• Subjects who have medical conditions that prioritize them for receipt of approved COVID-19 vaccine in Turkey and has a valid vaccination right within the Ministry of Health vaccination programme.
• 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 first study vaccination or a licensed inactivated or non-replicating vaccine (any vaccine other than the COVID-19 vaccine) within 14 days before or after first study vaccination.
• 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.
• Subjects who received systemic immunoglobulins or blood products within 3 months prior to the Day 0 or plans to receive such products during the study.
• Investigator site staff members, 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.

Exclusion criteria

for the second dose of vaccine:

• Laboratory-confirmed SARS-CoV-2 infection after the first vaccination.
• In case of an acute disease that has not recovered before the second vaccination or at acute phase of a chronic disease, the investigator should exclude COVID-19, and assess if the acute disease can recover in a short term.
• New or newly occurred non-compliance with the inclusion/exclusion criteria after the first dose, which will be assessed by the investigator whether the study participation can continue or not.