Phase 3 Booster Vaccination Against COVID-19

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05077176
• Other study ID #: Inaktif_Rapel_Faz 3
• Status: Completed
• Phase: Phase 3
• Start date: October 8, 2021
• Est. completion date: February 5, 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

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4340
• Est. completion date: February 5, 2024
• Est. primary completion date: May 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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

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 CoronaVac for 2 doses and who had a minimum of 90 days and a maximum of 270 days after the second dose,

4. Subjects with minimum 28 days and maximum 42 days between CoronaVac 1st and 2nd dose vaccines,

5. 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,

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.

Subjects meeting any of the following criteria will not be included in 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. Pre-or planned use of another vaccine or product likely to affect the study (e.g. adenovirus vectored vaccines, any coronavirus vaccine),

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

4. Pregnant and puerperant subjects (subjects who become pregnant 2 months after vaccination will continue to study),

5. 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),

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 (i.e. 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. Acute respiratory disease (moderate or severe illness with or without fever). (Subjects may be screened again after acute condition has resolved),

23. Insufficient level of Turkish to perform the informed consent, except where briefing by an independent witness can be provided and is available.

Related Conditions & MeSH terms

• COVID-19
• Sars-CoV-2 Infection

Intervention

Biological:
• CoronaVac
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.
• Turkovac
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.

Locations

Country	Name	City	State
Turkey	Çukurova University Faculty of Medicine, Department of Infectious Diseases	Adana
Turkey	Diskapi SUAM Infectious Diseases and Clinical Microbiology	Ankara
Turkey	T.R. Ministry of Health Ankara City Hospital, Infectious Diseases and Clinical Microbiology Clinic	Ankara
Turkey	T.R. Ministry of Health Ankara Keçiören Sanatorium Ataturk Chest Diseases and Thoracic Surgery Training and Research Hospital	Ankara	Turkey Region
Turkey	T.R. Ministry of Health Antalya Training And Research Hospital	Antalya
Turkey	T.R. Ministry of Health Aydin State Hospital	Aydin
Turkey	T.R. Ministry of Health Balikesir Atatürk City Hospital	Balikesir
Turkey	T.R. Ministry of Health Abant Izzet Baysal University Training and Research Hospital	Bolu
Turkey	T.R. Ministry of Health Bursa City Hospital	Bursa
Turkey	Uludag University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Bursa
Turkey	T.R. Ministry of Health Denizli Acipayam State Hospital	Denizli
Turkey	T.R. Ministry of Health Elazig Fethi Sekin City Hospital	Elazig
Turkey	Erzincan Binali Yildirim University Training and Research Hospital Traditional and Complementary Medicine Application Center - GETAT	Erzincan
Turkey	T.R. Ministry of Health Erzurum Regional Training and Research Hospital	Erzurum
Turkey	Eskisehir Osmangazi University Eskisehir Osmangazi University Health, Application and Research Hospital	Eskisehir
Turkey	T.R. Ministry of Health Eskisehir City Hospital	Eskisehir
Turkey	T.R. Ministry of Health Dr. Ersin Arslan Training and Research Hospital	Gaziantep
Turkey	Cerrahpasa Faculty of Medicine, Department of Internal 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 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	T.R. Ministry of Health Kartal Dr. Lütfi Kirdar City Hospital Infectious Diseases	Istanbul
Turkey	University of Health Sciences Istanbul Ümraniye Training and Research Hospital	Istanbul
Turkey	T.R. Ministry of Health Izmir Katip Çelebi University Atatürk Training and Research Hospital, Infectious Diseases Clinic	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	Kahramanmaras Sütçü Imam University Infections Diseases	Kahramanmaras
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	Kirikkale University Faculty of Medicine, Department of Internal Medicine	Kirikkale
Turkey	Kocaeli University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology	Kocaeli
Turkey	T.R. Ministry of Health Kocaeli Health Sciences University Derince Training And Research Hospital	Kocaeli
Turkey	T.R. Ministry of Health Konya City Hospital	Konya
Turkey	Kütahya University of Health Sciences, Infectious Diseases and Clinic	Kütahya
Turkey	Malatya Inönü University Faculty of Medicine, Department of Infectious Diseases	Malatya
Turkey	T.R. Ministry of Health Manisa City Hospital	Manisa
Turkey	T.R. Ministry of Health Mersin City Training and Research Hospital	Mersin
Turkey	Sanliurfa Harran University Hospital	Sanliurfa
Turkey	T.R. Ministry of Health Tekirdag Çorlu District State Hospital	Tekirdag
Turkey	Health Sciences University Kanuni Training and Research Hospital Infectious Diseases and Clinical Microbiology	Trabzon
Turkey	Van Yüzüncü Yil University Hospital, Faculty of Medicine, Infectious Diseases and Clinical Microbiology	Van

Sponsors (1)

Lead Sponsor	Collaborator
Health Institutes of Turkey

Country where clinical trial is conducted

Turkey, 

References & Publications (6)

Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, Grifoni A, Ramirez SI, Haupt S, Frazier A, Nakao C, Rayaprolu V, Rawlings SA, Peters B, Krammer F, Simon V, Saphire EO, Smith DM, Weiskopf D, Sette A, Crotty S. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021 Feb 5;371(6529):eabf4063. doi: 10.1126/science.abf4063. Epub 2021 Jan 6. — View Citation

Doria-Rose N, Suthar MS, Makowski M, O'Connell S, McDermott AB, Flach B, Ledgerwood JE, Mascola JR, Graham BS, Lin BC, O'Dell S, Schmidt SD, Widge AT, Edara VV, Anderson EJ, Lai L, Floyd K, Rouphael NG, Zarnitsyna V, Roberts PC, Makhene M, Buchanan W, Luke CJ, Beigel JH, Jackson LA, Neuzil KM, Bennett H, Leav B, Albert J, Kunwar P; mRNA-1273 Study Group. Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19. N Engl J Med. 2021 Jun 10;384(23):2259-2261. doi: 10.1056/NEJMc2103916. Epub 2021 Apr 6. No abstract available. Erratum In: N Engl J Med. 2022 Feb 3;386(5):500. — View Citation

Kumar A, Singh R, Kaur J, Pandey S, Sharma V, Thakur L, Sati S, Mani S, Asthana S, Sharma TK, Chaudhuri S, Bhattacharyya S, Kumar N. Wuhan to World: The COVID-19 Pandemic. Front Cell Infect Microbiol. 2021 Mar 30;11:596201. doi: 10.3389/fcimb.2021.596201. eCollection 2021. — View Citation

Madhi SA, Izu A, Pollard AJ. ChAdOx1 nCoV-19 Vaccine Efficacy against the B.1.351 Variant. Reply. N Engl J Med. 2021 Aug 5;385(6):571-572. doi: 10.1056/NEJMc2110093. Epub 2021 Jul 21. No abstract available. — View Citation

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

Wu K, Werner AP, Koch M, Choi A, Narayanan E, Stewart-Jones GBE, Colpitts T, Bennett H, Boyoglu-Barnum S, Shi W, Moliva JI, Sullivan NJ, Graham BS, Carfi A, Corbett KS, Seder RA, Edwards DK. Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine. N Engl J Med. 2021 Apr 15;384(15):1468-1470. doi: 10.1056/NEJMc2102179. Epub 2021 Mar 17. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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