Phase 2b Booster Vaccination (TURKOVAC) Against COVID-19

Open-Label, Two Arms, Multi-Centered, Phase 2b Clinical Trial to Determine the Safety, Efficacy, and Immunogenicity of Booster Vaccination (TURKOVAC) Against SARS-CoV-2

This study is open-label, two arms, multi-centered, phase 2b clinical trial to determine the efficacy, safety, and immunogenicity of booster vaccination (TURKOVAC) against Covid-19.

The primary aim of the study is to evaluate the efficacy of a booster dose of TURKOVAC vaccine administered to subjects who have passed at least 90 days and at most 240 days after the second dose of the first course of Comirnaty (Code name: BNT162b2) vaccine.

This phase 2b study aims to determine the efficacy, safety, and immunogenicity of a booster dose of TURKOVAC vaccine administered to subjects who have passed at least 90 days and at most 240 days after the second dose of the first course of Comirnaty (Code name: BNT162b2) vaccine.

Efficacy will be evaluated by spike-specific antibody response and neutralizing antibody levels on days 0, 28 (all subjects), 48, 84 and 168 days (50% of subjects).

For the booster dose, subjects will be assigned open-label according to randomization (1:1) for 2 different arms. Comparing the efficacy, safety, and immunogenicity results of different series of TURKOVAC vaccines (TURKOVAC-Koçak and TURKOVAC-Dollvet) produced in different production facilities are the secondary objectives of the study.

The booster dose vaccine arms are as follows:

• TURKOVAC-Koçak
• TURKOVAC-Dollvet

Inclusion Criteria:

1. Subjects willing and able to give signed informed consent to participate in study,
2. Healthy male or female aged 18 - 59 years (including both groups),
3. Subjects who were vaccinated with Comirnaty (Code name: BNT162b2) for 2 doses and who had a minimum of 90 days and a maximum of 240 days after the second dose,
4. Subjects with a minimum of 28 days and a maximum of 42 days between 1st and 2nd dose of Comirnaty (Code name: BNT162b2) vaccines,
5. Female subjects of childbearing potential and male subjects of to have child potential who are willing to ensure that they or their partner use effective contraception continuously from 1 month before vaccination to 3 months after booster vaccination,
6. In the opinion of the investigator, subjects capable and willing to comply with all study requirements,
7. Subjects are willing to agree to abstain from donating blood during the study.

Exclusion Criteria:

1. 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),
2. Known history of SARS-CoV-2 infection,
3. Pre-or planned use of another vaccine or product likely to affect the study (e.g. adenovirus vectored vaccines, any coronavirus vaccine),
4. Subjects who were pregnant at the time of enrollment or who plan to become pregnant within the first 3 months following vaccination and who are breastfeeding,
5. Subjects with fever (above 38°C) at the time of vaccination and/or up to 72 hours before (subjects may be screened again after acute condition has resolved),
6. Administration of immunoglobulins and/or any blood product within 3 months prior to vaccination,
7. 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,
8. Possible history of allergic disease or reaction (e.g. to the active substance) by any component of the study vaccines,
9. Any history of anaphylaxis,
10. Current cancer diagnosis or treatment (excluding basal cell carcinoma of the skin and cervical carcinoma in situ),
11. 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,
12. Continued use of anticoagulants such as coumarins and related anticoagulants (i.e. warfarin) or new oral anticoagulants (e.g. apixaban, rivaroxaban, dabigatran and edoxaban),
13. Cerebral venous sinus thrombosis, antiphospholipid syndrome, or a history of heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2),
14. Suspected or known current alcohol or drug addiction,
15. 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),
16. 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),
17. Subjects with severe renal impairment or liver failure,
18. Subjects who will undergo scheduled elective surgery during the study,
19. Subjects with a life expectancy of less than 6 months,
20. Subject who participated in another clinical trial study involving an investigational product in the past 12 weeks,
21. 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,
22. Known history of SARS-CoV-2 infection,
23. Acute respiratory disease (moderate or severe illness with or without fever). (Subjects may be screened again after acute condition has resolved),
24. Fever (greater than 37.8°C as measured by ear) (Subjects can be enrolled again after acute condition improves),
25. Insufficient level of Turkish to perform the informed consent, except where briefing by an independent witness can be provided and is available.