Open-label, Non-randomized, Non-comparative, Phase II Study of Safety and Immunogenicity of Combination of AZD1222 and rAd26-S for COVID-19 Prevention

1. Known past confirmed SARS-CoV-2 infection less than 6 month prior to screening (the date of diagnosis must be confirmed by an official document).

2. Positive SARS-CoV-2 Reverse transcriptase polymerase chain reaction (RT-PCR) test at screening.

3. Significant infection or other illness including fever \> 37.8 °C on the day prior to or day of vaccination.

4. Thrombocytopenia of grade ≥ 2 (i.e., \<100,000/ mm3)

5. Clinically significant neutropenia (as determined by the investigator).

6. Clinically significant anemia (as determined by the investigator).

7. Any confirmed or suspected immunosuppressive or immunodeficient condition including infection caused by human immunodeficiency virus (HIV); asplenia; recurring and severe infections and administration of chronic immunosuppressive drugs within previous 6 months ( ≥ 20 mg/day of prednisone or another steroid at an equivalent dose used daily or every other day for ≥ 15 days within the 30-day period preceding immunization) except for topical/inhalation steroids or short-term oral steroids (courses ≤14 days).

1. Note: enrollment of HIV-positive subjects with CD4 levels \> 500 cells/mL3 ≥12 months receiving stable antiretroviral therapy for HIV therapy is allowed.

2. Note: topical use of tacrolimus is permitted unless it was used within 14 days prior to enrollment.

8. History of allergic reactions to any of the product ingredients.

9. History of anaphylaxis or angioedema.

10. Current diagnosis of a malignant neoplasm and therapy thereof (except for basal-cell skin carcinoma or cervical cancer in situ).

11. History of serious mental conditions which are expected to impair participation in this study.

12. Bleeding disorders (e.g. coagulation factor deficiency, coagulopathy or impaired platelet disorders) or history of relevant hemorrhages or subcutaneous bruises after intramuscular injections or vein punctures.

13. Suspected alcohol or psychoactive drug addiction or a known current addiction.

14. History of Guillain-Barre syndrome or other demyelinating conditions.

15. Any other relevant diseases, disorders or findings which may significantly increase the risk due to participation in this study, restrict the subject's participation in it or impair interpretation of the study data.

(Note: upon assessment of the subject for exclusion criterion No. 13, adverse events of special interest should be considered which are outlined in appendix F of the study protocol as these adverse events of special interest, particularly with no treatment or control, may pose a risk for the subject's safety. Restrict his/her participation in the study or impair interpretation of the study data. The investigator should be aware of the list of conditions given in Appendix E of the study protocol and take it into account. If any of these conditions are found in the subject, the Investigator will be asked to use his/her clinical judgement to decide on the subject's eligibility for the study. If a subject with conditions outlined in Appendix E of the study protocol is enrolled into the study, the Investigator will be asked to document the final justification for the enrollment in the site's medical document.)

16. Severe and/or uncontrollable cardiovascular diseases, respiratory diseases, gastrointestinal disorders, hepatic, renal, endocrine and nervous system diseases (mild/moderate adequately controlled co-morbidities are acceptable).

17. Prior splenectomy.

18. History of cerebral venous sinus thrombosis or experienced major venous and/or arterial thrombosis.

19. Any vaccines (authorized or experimental) other than the investigational ones within 30 days prior to and after each vaccination.

20. Previous or scheduled investigational or authorized vaccines or a product which may affect the interpretation of the study data (e.g. adenoviral vector-based vaccines, any coronavirus vaccines).

21. Administration of immunoglobulins and/or any blood components within 3 months prior to scheduled administration of the study vaccine.

22. Ongoing use of anticoagulants, e.g. coumarin and related ones (i.e. warfarin) or novel oral anticoagulants (e.g. apixaban, rivaroxaban, dabigatran and edoxaban).

23. Participation in studies of medicinal products for prevention of COVID-19 throughout the study.

24. Participation in planning and/or performance of this study (applicable to both Sponsor's personnel and/or study site personnel).

25. According to the Investigator, an individual should not participate in the study if the probability of compliance with study procedures, restrictions and requirements is low.

26. Previous participation in this study (undergoing screening and study inclusion procedures).

27. Female subjects only: current pregnancy (verified by positive pregnancy test) or breastfeeding.

28. Unwilling to refrain from blood donation during the course of the study.

What this study is about