Safety, Tolerability and Immunogenicity of Gam-COVID-Vac Vaccine in a Nasal Spray

Study Overview
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Brief Summary
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Randomized, double-blind, placebo-controlled trial to evaluate safety and immunogenicity of intranasal Gam-COVID-Vak combined vector vaccine for the prevention of coronavirus infection caused by the SARS-CoV-2 virus. The duration of participation in the study for one subject will be 180±14 days after the first dose of vaccine, during which each subject will undergo a screening visit (within a week) and face-to-face visits according to the study plan. Intranasal vaccine administration will be done at day 1 vaccination visits and day 21±2 days on an outpatient basis. During the follow-up visits key vital signs will be assessed, and will collect data on changes in the state and well-being subjects from a previous visit. Subject data will be collected using electronic forms of individual registration cards, as well as with using questionnaires (diaries) filled by the subjects of the study. Immunogenicity will be assessed on day 1, 10, 28, 42 and 90 days. Humoral and cellular immune response will be evaluated.

Official Title
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A Randomized Double-blind Placebo-controlled Multi-center Clinical Trial in Parallel Assignment of Safety, Tolerability and Immunogenicity of a Vaccine Gam-COVID-Vac, a Combined Vector Vaccine for the Prevention of Coronavirus Infection Caused by the SARS-CoV-2 Virus in a Nasal Spray Dosage Form With the Participation of Adult Volunteers

Conditions
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COVID-19, SARS-CoV-2 Acute Respiratory Disease

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: The presence of a written informed consent of the subject to participate in the study; Adult volunteers over 18; Negative test result for HIV, hepatitis, syphilis; Negative test result for COVID-2019, determined by PCR at the visit screening, and, if available, the result of the examination performed in medical organizations that are research centers 7 days before inclusion into research; The result of the study for the presence of IgG antibodies to SARS CoV2 up to 10 VGR, which corresponds to value up to 100 BAU, regardless of the immune status before; Absence of contact of the research subject with patients with COVID-2019 for at least 14 days before enrollment in the study (according to the study participant); Consent to use effective methods of contraception during the entire period of participation in research; Negative Urine Pregnancy Test at Screening Visit (for women of childbearing age); Negative test for the presence of narcotic and psychostimulant drugs in the urine for screening visit; Negative alcohol test at screening visit; No history of severe post-vaccination reactions or post-vaccination complications after the use of immunobiological preparations; Absence of acute infectious and/or respiratory diseases for at least within 14 days prior to enrollment in the study. Exclusion Criteria: Inability to give informed consent, inability to understand the essence of the study Any vaccination/immunization carried out within 30 days prior to inclusion in study; Steroid therapy (excluding hormonal contraceptives) and/or immunoglobulins or other blood products, not completed 30 days before inclusion in the study; COVID-2019 disease or vaccination to prevent COVID-2019 in less than six months before inclusion in the study Immunosuppressive drug therapy completed less than 3 months before inclusion in the study; Postponed less than one year prior to enrollment in the study acute coronary syndrome or stroke; Tuberculosis, chronic systemic infections; Exacerbation of rhinitis Burdened allergic history (presence in the anamnesis of information about anaphylactic shock, angioedema, polymorphic exudative eczema, serum sickness), hypersensitivity or allergic reactions to the introduction of immunobiological drugs, known allergic reactions to drug components, exacerbation allergic diseases on the day of inclusion in the study; History of neoplasms (ICD codes C00-D09); Donation of blood or plasma (in a volume of 450 ml or more) less than 2 months before inclusion in the study; Splenectomy in history; Neutropenia (decrease in the absolute number of neutrophils less than 1000/mm3), agranulocytosis, significant blood loss, severe anemia (hemoglobin less than 80 g/l), immunodeficiency in history within 6 months prior to enrollment in the study; Subjects with active human immunodeficiency virus disease syphilis, hepatitis B and C; Anorexia, protein deficiency of any origin; History of alcoholism and drug addiction; Participation of the subject in any other interventional clinical trial during this study; Any other condition of the research subject that, in the opinion of the research physician, may prevent completion of the study in accordance with the protocol; Staff of research centers and other staff directly involved in conducting the study (principal investigator and members of the research team) and members of their families.

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rAd26 single administration<br> | Biological: Gam-COVID-Vac<br>* two-component combined vector vaccine for the prevention of coronavirus infection caused by the SARS-CoV-2 virus<br>|
| Experimental: rAd5 single administration<br> | Biological: Gam-COVID-Vac<br>* two-component combined vector vaccine for the prevention of coronavirus infection caused by the SARS-CoV-2 virus<br>|
| Experimental: prime-boost regimen with rAd26 followed rAd5 administration<br> | Biological: Gam-COVID-Vac<br>* two-component combined vector vaccine for the prevention of coronavirus infection caused by the SARS-CoV-2 virus<br>|
| Placebo Comparator: placebo<br> | Other: Placebo<br>* solution with same composition as for vaccine formulation except rAds<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in geometric mean titer of IgGs specific to S protein | Change from baseline in Geometric mean titer of IgGs specific to S protein at different time points after vaccination | 0, 10, 28, 42, 90 day | 
| Change from baseline in number of participants with detected specific IgGs | Change from baseline in Number of participants with detected specific IgGs at different time points after vaccination | 0, 10, 28, 42, 90 day | 
| Change from baseline in Number of participants with detected specific IgAs | Change from baseline in Number of participants with detected specific IgAs at different time points after vaccination | 0, 10, 28, 42 day | 
| Change from baseline in Geometric mean titer of neutralizing antibodies to SARS-Cov-2 virus | Change from baseline in Geometric mean titer of neutralizing antibodies to SARS-Cov-2 virus at different time points after vaccination | 0, 28, 42, 90 day | 
| Change from baseline in Number of participants with detected neutralizing antibodies to SARS-Cov-2 virus | Change from baseline in Number of participants with detected neutralizing antibodies to SARS-Cov-2 virus at different time points after vaccination | 0, 28, 42, 90 day | 
| Proportion of participants with any adverse events | AEs evaluation during the whole period of the study | 1-180 days | 
| Proportion of participants with severe adverse events | SAEs evaluation during the whole period of the study | 1-180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of symptomatic COVID-19 prevention | Efficacy of symptomatic COVID-19 prevention | 28-180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, Sputnik, adenoviral vector vaccine, intranasal vaccine