Phase 3 Booster Vaccination Against COVID-19

Study Overview
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Brief Summary
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The inactivated Booster Phase 3 study aims to determine the efficacy, safety, and immunogenicity of inactivated COVID-19 vaccines in subjects with a minimum of 90 days and a maximum of 270 days after the second dose of CoronaVac vaccine.

Detailed Description
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The inactivated Booster Phase 3 study aims to determine the efficacy, safety, and immunogenicity of inactivated COVID-19 vaccines in subjects with a minimum of 90 days and a maximum of 270 days after the second dose of CoronaVac vaccine. For the booster dose, subjects will be assigned open-label according to their preference for 2 different arms. The booster dose vaccine arms are as follows: CoronaVac Turkovac

Official Title
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Open Label, Multi-Center Phase 3 Clinical Trial to Determine Safety, Efficacy, and Immunogenicity of Booster Vaccination Against SARS-CoV-2

Conditions
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COVID-19, Sars-CoV-2 Infection

Intervention / Treatment
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* Biological: CoronaVac
* Biological: Turkovac


Participation Criteria
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Eligibility Criteria
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Subjects must meet all of the following inclusion criteria to be eligible for inclusion in the study: Inclusion Criteria: Subjects willing and able to give signed informed consent to participate in study, Healthy male or female aged 18 - 59 years (including both groups), Subjects who were vaccinated with CoronaVac for 2 doses and who had a minimum of 90 days and a maximum of 270 days after the second dose, Subjects with minimum 28 days and maximum 42 days between CoronaVac 1st and 2nd dose vaccines, Female subjects of childbearing potential should be willing to ensure that they or their partner use effective birth control methods continuously from 1 month before and up to 3 months after vaccination, Male subjects of potential to have children should be willing to ensure that they or their partner use effective birth control methods continuously from 1 month before and up to 3 months after vaccination, In the opinion of the investigator, subjects capable and willing to comply with all study requirements, Subjects are willing to agree to abstain from donating blood during the study. Subjects meeting any of the following criteria will not be included in the study: Exclusion Criteria: Administration of any vaccine (registered or investigational) other than study intervention within 30 days before and after each study vaccine (one week for authorized seasonal flu vaccine or pneumococcal vaccine), Pre-or planned use of another vaccine or product likely to affect the study (e.g. adenovirus vectored vaccines, any coronavirus vaccine), Known history of SARS-CoV-2 infection, Pregnant and puerperant subjects (subjects who become pregnant 2 months after vaccination will continue to study), Subjects with fever (above 37,8°C) at the time of vaccination and/or up to 72 hours before (After the acute condition has resolved, the subject can be screened again), Administration of immunoglobulins and/or any blood product within 3 months prior to vaccination, Any confirmed or suspected immunosuppressive or immunodeficiency state; asplenia; recurrent severe infections and use of immunosuppressants (less than ≤14 days) in the last 6 months, excluding topical steroids or short-term oral steroids, Possible history of allergic disease or reaction (e.g. to the active substance) by any component of the study vaccines, Any history of anaphylaxis, Current cancer diagnosis or treatment (excluding basal cell carcinoma of the skin and cervical carcinoma in situ), History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venipuncture, Continued use of anticoagulants such as coumarins and related anticoagulants (i.e. warfarin) or new oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban), Cerebral venous sinus thrombosis, antiphospholipid syndrome, or a history of heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2), Suspected or known current alcohol or drug addiction, Any other significant disease, disorder or finding that could significantly increase the subject's risk for participation in the study, affect the subject's ability to participate in the study, or impair the interpretation of study data; severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, kidney disease, endocrine disorder, and neurological disease (mild/moderate well-controlled comorbidities are permitted), History of active or previous autoimmune neurological disorders (e.g. multiple sclerosis, Guillain-Barre syndrome, transverse myelitis) (Bell's palsy will not be an exclusion criterion), Subjects with severe renal impairment or liver failure, Subjects who will undergo scheduled elective surgery during the study, Subjects with a life expectancy of less than 6 months, Subject who participated in another clinical trial study involving an investigational product in the past 12 weeks, In case of clinical necessity, a COVID-19 PCR (polymerase chain reaction) test will be requested from the subjects, and subjects who are positive will be excluded from the study, Acute respiratory disease (moderate or severe illness with or without fever). (Subjects may be screened again after acute condition has resolved), Insufficient level of Turkish to perform the informed consent, except where briefing by an independent witness can be provided and is available.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multi-Center Phase 3 Clinical Trial to Determine Safety, Efficacy, and Immunogenicity of Booster Vaccination (CoronaVac or TURKOVAC) Against SARS-CoV-2
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CoronaVac<br>Inactivated SARS-CoV-2 virus antigen, single intramuscular injection for boosting dose. | Biological: CoronaVac<br>* One dose vaccine will be administered to subjects who have passed at least 90 days and at most 270 days after the second dose of the first course of CoronaVac vaccine.<br>|
| Experimental: Turkovac<br>Inactivated SARS-CoV-2 virus antigen, single intramuscular injection for boosting dose. | Biological: Turkovac<br>* One dose vaccine will be administered to subjects who have passed at least 90 days and at most 270 days after the second dose of the first course of CoronaVac vaccine.<br>|

What is the study measuring?
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Primary 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 RT-PCR at least 14 days after booster vaccination dose. | At least 14 days after booster vaccination dose | 
| To Evaluate the SARS-CoV2 anti-spike protein immunoglobulin G | The change in the amount of SARS-CoV2 anti-spike protein immunoglobulin G in the 28th day compared to the baseline is 2 times or more | 28 days after booster vaccination dose | 
| Evaluation of SARS-CoV2 Neutralizing Antibodies | The change in the amount of SARS-CoV2 neutralizing antibodies in the 28th day compared to the baseline is 2 times or more | 28 days after booster vaccination dose | 
| T-Cell Evaluation | IL-2, TNF-alpha and IFN-gamma levels in T cells changed by 2 times or more on day 28 compared to baseline for 35 - 40 subjects | 28 days after booster vaccination dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AE) | To evaluate the safety of booster dose vaccines by determining the incidence of adverse reactions. | On days 7 and 14 days after vaccination | 
| Incidence of Serious Adverse Events (SAE) | To evaluate the safety of booster dose vaccines by determining the incidence of serious adverse reactions. | 168 days after vaccination | 

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