Efficacy, Immunogenicity, and Safety of the Inactivated COVID-19 Vaccine (TURKOVAC) Versus the CoronaVac Vaccine

Covid19 Clinical Trial

Official title:

Efficacy, Immunogenicity, and Safety of the Two-Dose Inactivated COVID-19 Vaccine (TURKOVAC) Versus the Two-Dose CoronaVac (Sinovac) Vaccine in Healthy Subjects: A Randomized, Observer-Blinded, Phase III Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04942405
• Other study ID #: TSB-VAC-COV-TUR-F3.01
• Status: Completed
• Phase: Phase 3
• Start date: June 21, 2021
• Est. completion date: February 1, 2024

Study information

• Verified date: February 2024
• Source: Health Institutes of Turkey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a randomized, double-blinded, and active-controlled phase III clinical trial of the SARS-CoV-2 inactivated vaccine. The purpose of this study is to evaluate the efficacy, safety, and immunogenicity of the experimental vaccine in healthy adults aged 18~55 years.

Description:

This study is a randomized, double-blinded, multi-center, active-controlled phase III clinical trial in adults aged 18~55 years. The purpose of this study is to evaluate the efficacy, safety, and immunogenicity of the experimental SARS-CoV-2 inactivated vaccine. A total of 40.800 subjects will be enrolled. The participant will be assigned to receive two doses of experimental vaccine or CoronaVac on the schedule of days 0, 28.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1290
• Est. completion date: February 1, 2024
• Est. primary completion date: March 8, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

Each subject must meet all the following criteria to be enrolled in this study:

1. Subjects consented voluntarily to participate the study,

2. 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),

3. Subjects agreed to adhere to the prohibitions and restrictions specified in this protocol,

4. Subjects, who are sexually active and have childbearing potential, agreed to comply with the contraceptive requirements to be applied in the study,

5. Adult males or females of at least 18 years of age and not older than 55 years of age on the date of the informed consent signature,

6. Subjects who are medically stable (those without severe pain, severe swelling, severe movement limitation, persistent high fever, severe headache or other systemic or local reactions) such that who are not anticipated to hospitalize within the study period, according to the judgment of the Investigator, and the subjects appears likely to be able to continue the study until the follow-up period specified in the protocol,

7. Subjects who are excluded from the criteria to receive the COVID-19 vaccine approved in the scope of Emergency Use Approval in Turkey or subjects who meet the vaccination criteria, but voluntarily chose not to be vaccinated and agreed to receive one of the vaccines to be used in this study.

Exclusion Criteria:

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

1. 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).

2. Subjects who are pregnant or breastfeeding.

3. Known history of SARS-CoV-2 infection.

4. 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.

5. 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.

6. Subjects determined as ineligible to the study protocol.

7. Subjects with a history of cardiac diseases (cardiovascular disease, serious arrythmia, coronary artery disease, heart failure, cardiomyopathies, pulmonary hypertension etc).

8. Subjects with uncontrolled hypertension.

9. Subjects with a family history of coronary artery disease at early ages (presence of before age 55 in men and before age 65 in women).

10. Subjects with morbid obesity (Body mass index (BMI) = 40).

11. Subjects who have a travel plan to out of the city up to 28 days after the second vaccine dose.

12. 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.

13. 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.

14. Subjects who has bleeding disorder considered a contraindication to intramuscular injection or phlebotomy.

15. Immunosuppressive or immunodeficient state (including HIV), asplenia, recurrent severe infections.

16. Subjects who have medical conditions that prioritize them for receipt of approved COVID-19 vaccine in Turkey and has a valid vaccination right within the Ministry of Health vaccination programme.

17. 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 first study vaccination or a licensed inactivated or non-replicating vaccine (any vaccine other than the COVID-19 vaccine) within 14 days before or after first study vaccination.

18. 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.

19. Subjects who received systemic immunoglobulins or blood products within 3 months prior to the Day 0 or plans to receive such products during the study.

20. Investigator site staff members, 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.

Exclusion criteria for the second dose of vaccine:

1. Laboratory-confirmed SARS-CoV-2 infection after the first vaccination.

2. In case of an acute disease that has not recovered before the second vaccination or at acute phase of a chronic disease, the investigator should exclude COVID-19, and assess if the acute disease can recover in a short term.

3. New or newly occurred non-compliance with the inclusion/exclusion criteria after the first dose, which will be assessed by the investigator whether the study participation can continue or not.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Biological:
• TURCOVAC
Two doses at 28-day interval, each inoculation dose is 0.5 mL. Two doses of dosage (vaccine contains 600 subunit of SARS-CoV-2 virus antigen) experimental vaccine at the schedule of day 0,28
• CoronaVac
Two doses at 28-day interval, each inoculation dose is 0.5 mL. Two doses of dosage (vaccine contains 600 subunit of SARS-CoV-2 virus antigen) vaccine at the schedule of day 0, 28

Locations

Country	Name	City	State
Turkey	Çukurova University Faculty of Medicine, Department of Infectious Diseases	Adana
Turkey	Ankara University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Ankara
Turkey	Gazi University Faculty of Medicine, Department of Infectious Diseases	Ankara
Turkey	Hacettepe University Faculty of Medicine Department of Infections Diseases and Clinical Microbiology	Ankara
Turkey	T.R. Ministry of Health Ankara City Hospital, Infectious Diseases and Clinical Microbiology Clinic	Ankara	Turkey Region
Turkey	T.R. Ministry of Health Ankara Keçiören Sanatorium Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital	Ankara
Turkey	T.R. Ministry of Health Ankara Training and Research Hospital Infectious Diseases Clinic	Ankara
Turkey	Akdeniz University Faculty of Medicine, Department of Infectious Diseases	Antalya
Turkey	Uludag University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Bursa
Turkey	Dicle University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Diyarbakir
Turkey	Gaziantep University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Gaziantep
Turkey	Acibadem Atakent Hospital, Infectious Diseases and Clinical Microbiology	Istanbul
Turkey	Cerrahpasa Faculty of Medicine, Department of Internal Medicine - Department of Infectious Diseases and Clinical Microbiology	Istanbul
Turkey	Istanbul University Istanbul Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Istanbul
Turkey	T.R. Ministry of Health Basaksehir Çam ve Sakura City Hospital	Istanbul
Turkey	T.R. Ministry of Health Istanbul Provincial Health Directorate Bakirkoy Dr. Sadi Konuk Training and Research Hospital (Yesilköy Prof.Dr. Murat Dilmener Emergency Hospital)	Istanbul
Turkey	T.R. Ministry of Health Istanbul Provincial Health Directorate Prof. Dr. Cemil Tasçioglu City Hospital, Infectious Diseases Clinic	Istanbul
Turkey	T.R. Ministry of Health Istanbul Provincial Health Directorate Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital (Prof. Dr. Feriha Öz Emergency Hospital)	Istanbul
Turkey	T.R. Ministry of Health Istanbul Sisli Hamidiye Etfal Training and Research Hospital, Clinical Microbiology Clinic	Istanbul
Turkey	University of Health Sciences Istanbul Ümraniye Training and Research Hospital	Istanbul
Turkey	Ege University Faculty of Medicine Hospital, Department of Infectious Diseasesaculty of Medicine Hospital, Department of Infectious Diseases	Izmir
Turkey	T.R. Ministry of Health Izmir Provincial Health Directorate Health Sciences University Dr Suat Seren Chest Diseases And Chest Surgery Training And Research Hospital	Izmir
Turkey	T.R. Ministry of Health Izmir Provincial Health Directorate Izmir Health Sciences University Tepecik Training and Research Hospital, Infectious Diseases	Izmir
Turkey	Erciyes University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Kayseri
Turkey	T.R. Ministry of Health Kayseri City Training and Research Hospital, Infectious Diseases and Clinical Microbiology Department	Kayseri
Turkey	Kocaeli University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Kocaeli
Turkey	Malatya Inönü University Faculty of Medicine, Department of Infectious Diseases	Malatya
Turkey	Ondokuz Mayis University Istanbul Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Samsun
Turkey	Karadeniz Technical University Medical Faculty Hospital, Department of Infectious Diseases and Clinical Microbiology	Trabzon

Sponsors (1)

Lead Sponsor	Collaborator
Health Institutes of Turkey

Country where clinical trial is conducted

Turkey, 

References & Publications (1)

Pavel STI, Yetiskin H, Aydin G, Holyavkin C, Uygut MA, Dursun ZB, Celik I, Cevik C, Ozdarendeli A. Isolation and characterization of severe acute respiratory syndrome coronavirus 2 in Turkey. PLoS One. 2020 Sep 16;15(9):e0238614. doi: 10.1371/journal.pone.0238614. eCollection 2020. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Protection Indexes of Two Vaccine Doses For Symptomatic COVID-19.	To evaluate the efficacy of two-dose regimen of TURKOVAC and two-dose regimen of CoronaVac vaccines for Real Time-PCR confirmed symptomatic COVID-19 disease.	2 weeks after the second dose of vaccination
Secondary	To evaluate the efficacy of one dose of CoronaVac with one dose of TURKOVAC for Real Time-PCR-confirmed symptomatic COVID-19 disease.	The protection rate of, at least, one dose of SARS-CoV-2 vaccine against Real Time-PCR confirmed symptomatic COVID-19.	after one dose of vaccination
Secondary	To assess the safety of TURKOVAC and CoronaVac vaccines.	The incidence of adverse reactions after one dose of vaccination.	after one dose of vaccination
Secondary	To assess the immunogenicity of TURKOVAC and CoronaVac vaccines.	The seroconversion rate, seropositivity rate 14 days after each dose vaccination.	14 days after each dose vaccination
Secondary	To determine the seropositivity rate of SARS-CoV2 specific binding antibody at 42, 56, 70, 168 and 224 days after the first dose.	The seroconversion rate, seropositivity rate at 42, 56, 70, 168 and 224 days after the first dose.	at 42, 56, 70, 168 and 224 days after the first dose.
Secondary	To evaluate SARS-CoV2 neutralizing antibodies by neutralization test on the first dose day and at 42, 56, 70, 168 and 224 days after the first dose among the subjects vaccinated with TURKOVAC and the subjects vaccinated with CoronaVac.	Geometric mean titer and Geometric mean intensity of neutralizing antibody and immunoglobulin G at 42, 56, 70, 168 and 224 days after the first dose.	at 42, 56, 70, 168 and 224 days after the first dose
Secondary	To evaluate the efficacy and hospitalization and death rates of two doses of TURKOVAC vaccine against severe cases of COVID-19.	The protection rate of a two-dose of SARS-CoV-2 vaccine against rates of hospitalization, disease severity/and death two weeks after the second dose of vaccination.	2 weeks after the second dose of vaccination
Secondary	To determine the incidence of adverse reactions and serious adverse events.	The incidence of adverse reactions within after one dose of vaccination.	after one dose of vaccination
Secondary	To evaluate the SARS-CoV2 protein peptide pool-specific T cells (T cell activation) on the first dose day and at 42, 70, 168 and 224 days after the first dose.	Geometric mean percentage of SARS-CoV2 protein peptide pool specific T-cell determined by flow cytometry.	at 42, 70, 168 and 224 days after the first dose