Efficacy, Immunogenicity, and Safety of TURKOVAC Vaccine Versus the CoronaVac Vaccine Against COVID-19 in Healthy Adolescent (12-18 Years)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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COVID-19, Sars-CoV-2 Infection

Intervention / Treatment
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* Biological: TURKOVAC
* Biological: CoronaVac


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each subject must meet all the following criteria to be enrolled in this study: Subjects who can voluntarily consent to participate in the study with their parents or legal representatives, 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), No history of SARS-CoV-2 (within the last 12 months), Consent of sexually active females to use effective contraception during the study, 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, In the opinion of the investigator, subjects who can comply with the study protocol during the study, 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, Not participating in another clinical trial. 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), 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, Subjects who are pregnancy or breastfeeding plan within (at least) 1 year following the second dose of vaccine, Those with a history of SARS-CoV-2 (within the last 12 months), 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 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 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), Subjects with morbid obesity (Body Mass Index (BMI) ≥ 40), 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 have bleeding disorder considered a contraindication to intramuscular injection or phlebotomy, Subjects who have immunosuppressive or immunodeficiency state (including HIV), asplenia, recurrent severe infections, 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, 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, To be using an immunostimulant, immune-modifying supplementary drug or herbal product or to have used it in the last month, Subjects who have received systemic immunoglobulin or blood products in the past 12 months, or who plan to receive such products during the study, 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. Subjects who have previously received any COVID-19 vaccines. Exclusion criteria for the second dose of vaccine: 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. 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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum 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
Interventional Model Description: Multi-Centered, Randomized, National, Observer-blinded, Active-controlled, Phase IIB
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TURKOVAC<br>The dose of the TURKOVAC vaccine will be 3 μg/0.5 mL. It will be administered by injection to the left deltoid muscle of the upper arm, two doses are given 28 days apart. | Biological: TURKOVAC<br>* Inactive COVID-19 Vaccine - TURKOVAC<br>|
| Active Comparator: CoronaVac<br>The dose of the CoronaVac vaccine will be 3 μg/0.5 mL. It will be administered by injection to the left deltoid muscle of the upper arm, two doses are given 28 days apart. | Biological: CoronaVac<br>* It has 600 subunit of SARS-CoV-2 virus antigen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19 Positivity Rate | The rate of positivity in a polymerase chain reaction (PCR) sample taken within 24 or 48 hours in subjects (symptomatic subject) with fever and other COVID-19 symptoms 14 days after the second vaccination dose. | 14 days after the second dose of vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protection Rates of TURKOVAC and CoronaVac Vaccines Against Symptomatic COVID-19 | Protection rates of TURKOVAC and CoronaVac vaccines against symptomatic COVID-19 confirmed by real time-polymerase chain reaction (RT-PCR), 14 days after first dose of vaccination. | 14 days after first dose of vaccination | 
| Protection rates of TURKOVAC and CoronaVac Vaccines Against Symptomatic COVID-19 | Protection rates of TURKOVAC and CoronaVac vaccines against symptomatic COVID-19 confirmed by real time-polymerase chain reaction (RT-PCR), 14 days after second dose of vaccination. | 14 days after second dose of vaccination | 
| The Protection Rates of TURKOVAC and CoronaVac Vaccines in Preventing Hospitalization and Death Against Severe COVID-19 | The protection rates of two-doses of TURKOVAC and CoronaVac vaccines in preventing hospitalization and death against severe COVID-19 disease confirmed by real time-polymerase chain reaction (RT-PCR), 14 days after the second dose of vaccination. | 14 days after second dose of vaccination | 
| The Incidence of Adverse Events (AEs) | The incidence of adverse events (AEs) within after up to 30 minutes each dose of vaccination. | Up to 30 minutes each dose of vaccination | 
| The Incidence of Undesirable Adverse Event | The incidence of an undesirable adverse event from the first day of vaccination to the following year after the last dose of vaccination. | First day of vaccination to the following year after the last dose of vaccination | 
| The Incidence of Undesirable Adverse Event | The incidence of undesirable adverse events within 7 days after each vaccination dose. | 7 days after each vaccination dose | 
| The Incidence of Serious Undesirable Adverse Events | The incidence of serious undesirable adverse events up to one year after first and second dose vaccination. | 1 year after first and second dose vaccination | 
| The Seropositivity Rate of SARS-CoV2 Specific Binding Antibody | The seropositivity rate of SARS-CoV2 specific binding antibody at 42, 56, 70, 126, 168, and 224 days after the first dose of TURKOVAC and CoronaVac vaccination. The change in the geometric mean concentration (GMC) SARS-CoV2 anti-spike protein immunoglobulin G in the 42nd and 56th day compared to the baseline is 2 times. | 42, 56, 70, 126, 168, and 224 days after the first dose of vaccination | 
| Evaluation of SARS-CoV2 Neutralizing Antibodies | To evaluate SARS-CoV2 neutralizing antibodies by neutralization test at 42, 56, 70, 126, 168, and 224 days after the first dose of TURKOVAC and CoronaVac vaccination. The change in the geometric mean concentration (GMC) and geometric mean titer (GMT) SARS-CoV2 neutralizing antibodies in the 42nd and 56th day compared to the baseline is 2 times. | 42, 56, 70, 126, 168, and 224 days after the first dose of vaccination | 
| T-Cell Evaluation | To evaluate the SARS-CoV2 protein-peptide pool-specific T cells (T cell activation) on the first dose day and at 70, 126, and 224 days after the first dose. Geometric mean percentage (minimum 25 percent, maximum 75 percent) of SARS-CoV2 protein-peptide pool-specific T-cell determined by flow cytometry. The success criterion for T cell activation is defined as the appearance of an anamnestic response. | 70, 126, and 224 days after the first dose of vaccination | 
| The Incidence of Local and Systemic Signs and Symptoms | The incidence of local and systemic signs and symptoms in TURKOVAC and CoronaVac vaccines will be evaluated with the chi-square test when the chi-square condition is provided, and the Fisher Exact Test when the chi-square condition is not provided. | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 Vaccine, Efficacy, COVID-19, Immunogenicity, Safety, Adolescent