Efficacy, Immunogenicity, and Safety of the Inactivated COVID-19 Vaccine (TURKOVAC) in Healthy Pregnant Women

Open-Label, Phase 2b Clinical Trial to Determine Efficacy, Safety, and Immunogenicity of Inactivated COVID-19 Vaccine (TURKOVAC) Against SARS-CoV-2 in Healthy Pregnant Women

This study is an open-label and Phase 2b clinical trial of the COVID-19 inactivated TURKOVAC vaccine against SARS-CoV-2 in healthy pregnant women.

The main purpose of this study is pregnant women who are at least in the second (13th to 27th weeks) and third (28th to 40th weeks) trimesters, to evaluate of the safety of two doses of TURKOVAC vaccine in who are naive (never vaccinated) and previously vaccinated with two doses of inactivated COVID-19 vaccine.

It is planned to include 30 healthy pregnant subjects between the ages of 18-45 (including both age groups) in the study. After the safety and immunogenicity data obtained from the interim analysis of 30 pregnant female subjects, it will be planned to increase the number of subjects.

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to be eligible for inclusion in the study:

1. Subjects willing and able to give signed informed consent to participate in study,
2. Healthy pregnant female subjects aged 18 - 45 years (including both groups),
3. Females in the second trimester of pregnancy (weeks 13 to 27) and in the third trimester (from week 28 to week 40),
4. Females who were previously vaccinated with two doses of inactivated vaccine also 3 months after their last menstrual period and more than 3 months have passed since they have vaccinated for their last dose,
5. Females without a current positive (real time-polymerase chain reaction (RT-PCR) - based viral RNA (Ribonucleic Acid) detection) or past (serological test or real time-polymerase chain reaction (RT-PCR -based viral RNA (Ribonucleic Acid) detection) positive diagnostic test result for SARS-CoV-2 infection,
6. In the opinion of the investigator, subjects capable and willing to comply with all study requirements,
7. Subjects who agree to comply with all study visits and procedures (who consent to blood and nasopharyngeal swab collection and who can answer automated phone calls from the study center).

Exclusion Criteria:

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

1. Subjects with fever (above 37,8°C) at the time of vaccination and/or up to 72 hours before (subjects may be screened again after acute condition has resolved),
2. Possible history of allergic disease or reaction (e.g. to the active substance) by any component of the study vaccines,
3. Any history of anaphylaxis,
4. Subjects with a medical or obstetric history that puts them at higher risk for maternal or fetal complications (e.g. chronic pregnancy-related disorders, birth defects, or genetic conditions during a previous pregnancy),
5. Subjects with an abnormal uterine cavity shown on hysterosalpingography or hysteroscopy,
6. Subjects with an abnormal pregnancy screening test (e.g. ultrasound fetal abnormalities, maternal blood screening),
7. Subjects with a history of malignancy within 2 years prior to screening (exceptions are squamous, basal cell carcinomas of the skin, carcinomas in situ of the cervix, or malignancy considered treated with minimal risk of recurrence),
8. Females with the presence of hydrosalpinx or endometrial polyp that are not treated surgically,
9. Females with the poor ovarian response (less than 3 mature follicles),
10. Females currently participating in a similar study of another inactive investigational product and currently using this investigational product or who have taken an inactive investigational product in the 28 days before their last menstruation period,
11. In case of clinical necessity, subjects with positive COVID-19 real time-polymerase chain reaction (RT-PCR) test results to be requested from the subjects,
12. Insufficient level of Turkish to perform the informed consent, except where briefing by an independent witness can be provided and is available,
13. 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),
14. 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,
15. 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,
16. Continued use of anticoagulants such as coumarins and related anticoagulants (e.g. warfarin) or new oral anticoagulants (e.g. apixaban, rivaroxaban, dabigatran and edoxaban),
17. Subjects with cerebral venous sinus thrombosis, antiphospholipid syndrome, or a history of heparin-induced thrombocytopenia and thrombosis (HITT or HIT type 2),
18. Suspected or known current alcohol or drug addiction,
19. History of active or previous autoimmune neurological disorders (e.g. multiple sclerosis, Guillain-Barre syndrome, transverse myelitis) (Lumbar palsy will not be an exclusion criterion),
20. Subjects with severe renal impairment or liver failure,
21. Acute respiratory disease (moderate or severe illness with or without fever). (Subjects may be screened again after acute condition has resolved).