Clinical trial NCT04582344: Clinical Trial For SARS-CoV-2 Vaccine (COVID-19)
Official title: Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial For Evaluation of Efficacy and Safety of SARS-CoV-2 Vaccine (Vero Cell), Inactivated
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: COVID-19, SARS-CoV-2 Vaccine
Lead sponsor: Health Institutes of Turkey
Sponsor class: OTHER_GOV
First posted: 2020-10-09
Enrollment: 10214
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial
Primary purpose: PREVENTION

Brief summary: This study is a randomized, double-blinded, and placebo controlled phase III clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research \& Development Co., Ltd. The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the experimental vaccine in healthy adults aged 18\~59 Years.

Detailed description: This study is a randomized, double-blinded, multi-center, placebo-controlled phase III clinical trial in adults aged 18\~59 years. The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the experimental SARS-CoV-2 inactivated vaccine. The experimental vaccine and placebo were both manufactured by Sinovac Research \& Development Co., Ltd. A total of 13.000 subjects will be enrolled. Participant will be assigned to receive two doses of experimental vaccine or placebo on the schedule of day 0,14. It is planned that the study will be conducted with two separate cohorts. The first cohort will be healthcare workers in the high risk group (K-1) and the second cohort will be people at normal risk (K-2). After 2 doses of vaccination of 1300 volunteers are completed, safety data will be evaluated by the data safety monitoring board without breaking the blinding, and if there is no safety issue, the K2 cohort will continue to be vaccinated.1.300 volunteers, including 650 volunteers SARS-CoV-2 vaccine and placebo arms, will be included in the K-1 cohort. In the K-2 cohort (normal risk group for COVID-19), 7.650 volunteers were planned to be included in the SARS-CoV-2 vaccine group, and 3.500 volunteers in the placebo group.

Eligibility criteria: Inclusion Criteria:

* 18-59 years of age (including 18 and 59 years of ages),
* For only K1 cohort, health care workers such as medical doctor, nurse, ward boy, cleaner, hospital technician, administrative personnel who work in any department of a hospital.
* Signed informed consent

Exclusion Criteria:

* Previously PCR positive for COVID-19
* IgG or IgM is positive
* For females: Pregnancy (confirmed by positive beta-hCG test), breastfeeding or intent to engage in sexual relations with reproductive intent without use of birth control methods in the three months following vaccination
* Known allergy to components of the study vaccine or control
* Use of immunosuppressant therapy regimens within the six months prior to enrollment in the study or planned use within the two years following enrollment. Immunosuppressant therapy regimens include: antineoplastic chemotherapy, radiation therapy and immunosuppressants to induce transplant tolerance, among others
* Use of immunosuppressive doses of corticosteroids within the three months prior to the enrollment in the study and planned use of immunosuppressive doses of corticoids within the three months following enrollment in the study. Immunosuppressive doses of corticosteroids will be considered the equivalent prednisone 20 mg/day for adults, for longer than one week. Continued use of topical or nasal corticosteroids is not considered an immunosuppressant
* History of asplenia
* History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture
* Any alcohol or drug abuse over the 12 months prior to enrollment in the study that has caused medical, professional or family problems, indicated by clinical history
* Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
* Participation in another clinical trial with an investigational product in the six months prior to enrollment in the study or planned participation in another clinical trial within the two years following enrollment
* Received live attenuated virus vaccine 14 days prior to enrollment in the study
* Inactivated vaccine or sub unit vaccine 7 days prior to enrollment in the study
* Fever (oral temperature \>37.2℃, axillary temperature will not be accepted) within the past 24 hours
* Any other condition that, in the opinion of the principal investigator or his/her representative physician, could put the safety/rights of potential participants at risk or prevent them from complying with this protocol.
* Any confirmed or suspected autoimmune disease or immunodeficiency disease, including human immunodeficiency virus (HIV) infection.

Primary outcomes:
measure: Protection Indexes of Two Vaccine Doses For Symptomatic COVID-19
timeFrame: 2 weeks after the second dose of vaccination
Secondary outcomes:
measure: Protection Indexes of One Vaccine Dose For Symptomatic COVID-19
timeFrame: 2 weeks after the second dose of vaccination
measure: Protection Indexes of Second Vaccine Dose For Hospitalization, Disease Severity/and Death
timeFrame: 2 weeks after the second dose of vaccination
measure: Protection Indexes of Two Vaccine Doses For SARS-CoV-2 infection
timeFrame: 2 weeks after the second dose of vaccination
measure: Safety indexes of adverse reactions in 28 days
timeFrame: 28 days after the second dose of vaccination
measure: Safety indexes of adverse reactions in 7 days
timeFrame: 7 days after each dose of vaccination
measure: Safety indexes of serious adverse events in 1 year
timeFrame: 1 year after second dose of vaccination
measure: Immunogenicity parameters (seroconversion rate, seropositivity rate) in 14 days
timeFrame: 14 days after each dose vaccination
measure: Immunogenicity parameters (seroconversion rate, seropositivity rate) in 28 days
timeFrame: 28 days after the second dose vaccination
measure: Immunogenicity parameters (GMT and GMI of neutralizing antibody and IgG) in 14 days
timeFrame: 14 days after each dose vaccination
measure: Immunogenicity parameters (GMT and GMI of neutralizing antibody and IgG) in 28 days
timeFrame: 28 days after the second dose vaccination
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: T.R. Ministry of Health Ankara City Hospital, Infectious Diseases and Clinical Microbiology Clinic
state: Turkey Region
city: Ankara
country: Turkey
facility: T.R. Ministry of Health Ankara Provincial Health Directorate Ankara Training and Research Hospital, Infectious Diseases
state: Turkey Region
city: Ankara
country: Turkey
facility: Ankara University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
state: Turkey Region
city: Adana
country: Turkey
facility: Çukurova University Faculty of Medicine, Department of Infectious Diseases
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine Department of Infections Diseases and Clinical Microbiology
city: Ankara
country: Turkey
facility: T.C Ministry of Health Ankara Provincial Health Directorate Health Sciences University Ankara Atatürk Chest Diseases and Thoracic Surgery Training and Research Hospital
city: Antalya
country: Turkey
facility: Akdeniz University Faculty of Medicine, Department of Infectious Diseases
city: Bursa
country: Turkey
facility: Bursa Uludağ University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
city: Diyarbakır
country: Turkey
facility: Dicle University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
city: Gaziantep
country: Turkey
facility: Gaziantep University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
city: Istanbul
country: Turkey
facility: Acıbadem Atakent Hospital, Infectious Diseases and Clinical Microbiology
city: Istanbul
country: Turkey
facility: Cerrahpaşa Faculty of Medicine, Department of Internal Medicine - Department of Infectious Diseases and Clinical Microbiology
city: Istanbul
country: Turkey
facility: Istanbul Medipol University Faculty of Medicine, Department of Internal Medicine
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
city: Istanbul
country: Turkey
facility: T.R. Ministry of Health Istanbul Provincial Health Directorate Marmara Univesity Istanbul Pendik Education and Research Hospital
city: Istanbul
country: Turkey
facility: T.R. Ministry of Health Istanbul Provincial Health Directorate Prof. Dr. Cemil Taşçıoğlu City Hospital, Infectious Diseases Clinic
city: Istanbul
country: Turkey
facility: T.R. Ministry of Health Istanbul Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital
city: Istanbul
country: Turkey
facility: University of Health Sciences İstanbul Ümraniye Training and Research Hospital
city: İzmir
country: Turkey
facility: Ege University Faculty of Medicine Hospital, Department of Infectious Diseasesaculty of Medicine Hospital, Department of Infectious Diseases
city: İzmir
country: Turkey
facility: Republic Of Turkey Ministry Of Health Izmir Provincial Health Directorate Health Sciences University Dr Suat Seren Chest Diseases And Chest Surgery Training And Research Hospital
city: İzmir
country: Turkey
facility: T.R. Ministry of Health İzmir Provincial Health Directorate İzmir Health Sciences University Tepecik Training and Research Hospital, Infectious Diseases
city: Kayseri
country: Turkey
facility: T.R. Ministry of Health Kayseri City Training and Research Hospital, Infectious Diseases and Clinical Microbiology Department
city: Kocaeli
country: Turkey
facility: Kocaeli University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology
city: Malatya
country: Turkey
facility: Malatya İnönü University Faculty of Medicine, Department of Infectious Diseases
city: Trabzon
country: Turkey
facility: Karadeniz Technical University Medical Faculty Hospital, Department of Infectious Diseases and Clinical Microbiology
Study officials:
affiliation: Faculty Member
name: Murat Akova, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Luan N, Li T, Wang Y, Cao H, Yin X, Lin K, Liu C. Th2-Oriented Immune Serum After SARS-CoV-2 Vaccination Does Not Enhance Infection In Vitro. Front Immunol. 2022 Apr 8;13:882856. doi: 10.3389/fimmu.2022.882856. eCollection 2022.
citation: Tanriover MD, Doganay HL, Akova M, Guner HR, Azap A, Akhan S, Kose S, Erdinc FS, Akalin EH, Tabak OF, Pullukcu H, Batum O, Simsek Yavuz S, Turhan O, Yildirmak MT, Koksal I, Tasova Y, Korten V, Yilmaz G, Celen MK, Altin S, Celik I, Bayindir Y, Karaoglan I, Yilmaz A, Ozkul A, Gur H, Unal S; CoronaVac Study Group. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021 Jul 17;398(10296):213-222. doi: 10.1016/S0140-6736(21)01429-X. Epub 2021 Jul 8.
citation: Akova M, Unal S. A randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the efficacy and safety of SARS-CoV-2 vaccine (inactivated, Vero cell): a structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Apr 13;22(1):276. doi: 10.1186/s13063-021-05180-1.