Clinical Trial of Efficacy, Safety, and Immunogenicity of Gam-COVID-Vac Vaccine Against COVID-19

Study Overview
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Brief Summary
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Randomized, double-blind (blinded for the trial subject and the study physician), placebo controlled, multi-center clinical trial in parallel assignment of efficacy, immunogenicity, and safety of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection in adults in the SARS-СoV-2 infection prophylactic treatment.

Detailed Description
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Randomized, double-blind (blinded for the trial subject and the study physician), placebo controlled, multi-center clinical trial in parallel assignment of efficacy, immunogenicity, and safety of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection in adults in the SARS-СoV-2 infection prophylactic treatment. The trial will include 40,000 volunteers aged 18+. After screening, they will be randomized (3:1) into two groups - a reference group of 10,000 volunteers receiving placebo and a study group of 30,000 volunteers receiving the Gam-COVID-Vac combined vector vaccine against the SARS-СoV-2-induced coronavirus infection. The trial subjects will be randomized into five age strata: 18-30, 31-40, 41-50, 51-60, and 60+ years. The PCR test for SARS-CoV-2 RNA detection at the visit is performed during screening and before the second administration of the vaccine/placebo Each subject will participate in the trial for 180±14 days after the first dose of the study drug/placebo and will have one screening visit and five on-site visits to the study physician during the said period. The study drug/placebo will be administered intramuscularly during vaccination visits 1 and 2 (day 0 and day 21±2). Subsequent observation visits 3, 4, and 5 will be made on days14±2, 28±2, 35±2,42±2, and 180±14 respectively. During the observation visits, vital signs will be assessed in all trial subjects and changes in the subjects' condition and wellbeing compared to the previous visit will be recorded. Observation visits may be remote, through the telemedicine consultation (TMC). Additionally, the trial subjects will be able to have remote consultations with the physician through the TMC. Blood samples will be taken from certain subjects during the following visits to assess the immunogenicity parameters listed below: Virus-neutralizing activity (300 subjects) ×3 Interferon gamma (107 subjects) ×3 CD4 and CD8 cell count and ratio (50 subjects) SARS-CoV-2 glycoprotein-specific antibodies titer (9,520 subjects) ×3 Determination of the titer of SARS-CoV-2 nucleocleocapsid protein-specific antibodies(9,520 subjects) ×3 Blood sampling will be performed on the day of injecting the first dose of the study drug/placebo immediately prior to the study drug administration Blood sampling for immunogenicity parameters assessment will be only carried out in specially selected study centers. Blood samples will be taken from 9,520 trial subjects. All four immunogenicity parameters may be assessed in one trial subject. Trial subjects data will be collected using electronic case report forms and electronic questionnaires to be filled by trial subjects.

Official Title
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Randomized Double-blind Placebo-controlled Multi-center Clinical Trial in Parallel Assignment of Efficacy, Safety, and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine in SARS-СoV-2 Infection Prophylactic Treatment

Conditions
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Covid19 Prevention

Intervention / Treatment
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* Biological: Gam-COVID-Vac
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent of a subject to participate in the trial Males and females aged ≥18 y.o.; Negative HIV, hepatitis, and syphilis test results Negative anti-SARS CoV2 IgM and IgG antibodies test carried out with the enzyme immunoassay method Negative COVID-2019 PCR test result at the screening visit No COVID-2019 in the past medical history No contact with COVID-2019 diseased persons within at least 14 days before the enrollment (according to trial subjects) Consent to use effective contraception methods during the trial Negative urine pregnancy test at the screening visit (for child-bearing age women) Negative drugs or psychostimulants urine test at the screening visit Negative alcohol test at the screening visit No evident vaccine-induced reactions or complications after receiving immunobiological products in the past medical history No acute infectious and/or respiratory diseases within at least 14 days before the enrollment. Exclusion Criteria: Any vaccination/immunization within 30 days before the enrollment; Steroids (except hormonal contraceptives) and/or immunoglobulins or other blood products therapy not finished 30 days before the enrollment Immunosuppressors therapy finished within 3 months before the enrollment Pregnancy or breast-feeding Acute coronary syndrome or stroke suffered less than one year before the enrollment Tuberculosis, chronic systemic infections Drug allergy (anaphylactic shock, Quincke's edema, polymorphic exudative eczema, atopy, serum disease), hypersensitivity or allergic reaction to immunobiological products, known allergic reactions to study drug components, acute exacerbation of allergic diseases on the enrollment day Neoplasms in the past medical history (ICD codes C00-D09) Donated blood or plasma (450+ ml) within 2 months before the enrollment History of splenectomy; Neutropenia (absolute neutrophil count <1,000/mm3), agranulocytosis, significant blood loss, severe anemia (hemoglobin <80 g/L), immunodeficiency in the past medical history within 6 months before the enrollment Active form of a disease caused by the human immunodeficiency virus, syphilis, hepatitis B or C Anorexia, protein deficiency of any origin Big-size tattoos at the injection site (deltoid muscle area), which does not allow assessing the local response to the study drug/placebo administration Alcohol or drug addiction in the past medical history Participation in any other interventional clinical trial Any other condition that the study physician considers as a barrier to the trial completion as per the protocol Study center staff or other employees directly involved in the trial, or their families. If a subject has any contraindications to vaccination based on the Guidelines on Detection, Investigation and Prevention, of Vaccination-induced Side Reactions (approved by the Ministry of Healthcare of Russia on Apr. 12, 2019, the vaccination may be postponed for a period of time specified in the document.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 111 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double-blind placebo-controlled
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary Group<br>Gam-COVID-Vac combined vector vaccine, 0,5ml/dose+0,5 ml/dose prime-boost immunization in days 1 (component I rAd26-S) and 21(component II rAd5-S) | Biological: Gam-COVID-Vac<br>* vaccine for intramuscular injection<br>|
| Placebo Comparator: Control Group<br>placebo, 0,5ml/dose+0,5 ml/dose immunization in days 1 and 21 | Other: placebo<br>* placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose | Demonstrate the superiority of Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the second dose of the study drug/placebo, as confirmed with the method of polymerase chain reaction (PCR) | through the whole study, an average of 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the severity of the clinical course of COVID-19 | Assess the efficacy of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus compared to placebo, based on the severity of the clinical course of COVID-19 | through the whole study, an average of 180 days | 
| Changing of antibody levels against the SARS-CoV-2 glycoprotein S | Assess the immunogenicity of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the geometric mean titer of SARS-CoV-2 glycoprotein-specific antibodies | day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose | 
| Changing of antigen-specific cellular immunity level | Describe the strength of cell-mediated immune response induced by the use of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo | the drug administration day before injecting the first dose of the study drug/placebo and 28±2 days after the first dose | 
| Changing of of virus neutralizing antibody titer | Geometric mean virus-neutralizing antibodies titer | the drug administration day before injecting the first dose of the study drug/placebo and 42±2 days after the first dose | 
| Incidence of adverse events in trial subjects | Incidence of adverse events in trial subjects compared to placebo | through the whole study, an average of 180 days | 
| Severity of adverse events in trial subjects | Severity of adverse events in trial subjects compared to placebo | through the whole study, an average of 180 days | 
| estimation of the proportion of study subjects with antibodies to the N-protein of the virus SARS-CoV-2 | Percentage of study subjects with antibodies to the N-protein of the SARS - CoV-2 virus that appeared after vaccination | day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, vector vaccine, SARS-CoV-2, adenoviral vector