Study of Safety and Immunogenicity of BVRS-GamVac-Combi

Study Overview
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Brief Summary
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The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of  34.5%. The aim of the study is to assess the safety and immunogenicity of heterologous adenoviral-based vaccine against MERS - BVRS-GamVac-Combi.

Detailed Description
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The study will include volunteers of both sexes, aged 18-55 years inclusive. The study will involve 268 (will receive the vaccine or placebo) healthy volunteers. At the first stage, it is planned: study the safety of component 1 - 40 volunteers and 4 spares * study the safety of prime-boost vaccination with component 1 and component 2 with an interval of 21 days in half and full dose - 40 volunteers and 4 spares * At the second phase, it is planned to study the safety and immunogenicity of the vaccine as part of a placebo-controlled randomized trial - 188 people, of whom 138 will receive the vaccine, and 50 will make up the control group of observation - they will be given a placebo. Data from 20 volunteers from the first phase who received the drug in selected dose will be included in the analysis of safety and immunogenicity of the second phase. Volunteers are replaced by spares before the introduction of the drug, if the volunteer took the drug, then the replacement is not performed. Any volunteer who received a dose of the vaccine will be considered as included in the study, the data available on it will be used in assessing the safety and tolerability of the drug.

Official Title
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Double-blind, Placebo-controlled Study With an Open Dose Selection Period for Assessing the Safety and Immunogenicity of the Drug BVRS-GamVac-Combi, a Combined Vector Vaccine for the Prevention of the Middle East Respiratory Syndrome, Lyophilisate for the Preparation of a Solution for Intramuscular Administration, With the Participation of Healthy Volunteers

Conditions
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MERS, MERS (Middle East Respiratory Syndrome)

Intervention / Treatment
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* Drug: BVRS-GamVac-Combi
* Other: placebo


Participation Criteria
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Eligibility Criteria
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IInclusion Criteria written informed consent; absence of a history, as well as according to a screening examination of pathology from the gastrointestinal tract, liver, kidneys, cardiovascular system, central nervous system, musculoskeletal system, urogenital, immune and endocrine systems, blood, which may affect volunteer safety and evaluation of the results of the study (clinical, instrumental and laboratory studies did not reveal diseases or clinically significant deviations); males and females within the age range from 18 to 55 years; Consent to the use of effective methods of contraception during the entire period of participation in the study; subject body mass index (BMI): 18.5 ≤ BMI ≤ 30; absence of acute infectious diseases at the time of vaccination and 7 days before vaccination; absence of severe allergic diseases in the medical history no serious post-vaccination complications in patient's history following the earlier administration of immunobiological products; subject has a negative result of the blood or urine pregnancy test (for females of childbearing age); subject has negative tests for HIV, hepatitis B and С, syphilis; subject has a negative result of the urine test for residual narcotic drugs; Negative alcohol test; The indicators of the complete blood count test and biochemical analysis of blood on the screen within 1,1*ULN/LLN (upper limit of normal/lower limit of normal) absence of inflammatory or dystrophic myocardial changes based on ECG data Exclusion Criteria: Volunteer participation in any other study over the past 90 days; Any vaccination in the last 30 days; Acute infectious and non-infectious diseases, exacerbations of chronic diseases within 4 weeks prior to screening; subject has received treatment with steroids for the last 10 days; subject has received immunoglobulins or other blood products over the last 3 months; subject has received immunosuppressive and/or immunomodulating agents within 6 months prior to the start of the study; Pregnancy or lactation; subject has systolic blood pressure less than 100 mm Hg or greater than 139 mm Hg; diastolic blood pressure less than 60 mm Hg or greater than 90 mm Hg; heart rate lower than 60 beats per minute or above 100 beats per minute; A burdened allergic history (anaphylactic shock, Quincke's edema, polymorphic exudative eczema, atopy, a history of serum sickness, hypersensitivity or allergic reactions to the introduction of any vaccines in history, known allergic reactions to vaccine components, etc.); Diabetes mellitus or other forms of impaired glucose tolerance; presence of a concomitant illness in decompensation stage which might affect the course of the study (CNS organic lesion, decompensated cardiovascular diseases, any manifestations of kidney or acute liver failure, oncological diseases, diabetes mellitus); subject has a a history of neoplasms (ICD codes C00-D09); blood donation (at least 450 ml of blood or plasma) by subject in less than 2 months prior to the start of the study; Reception of narcotic and psychostimulating drugs at present or in the anamnesis; subject has a history of the consumption of more than 5 units alcohol per week, alcohol intake within 48 hours before the injection of the test drug; subject smokes more than 10 cigarettes a day; subject has a planned hospitalization and / or surgery during the period of participation in the study, as well as 4 weeks before the estimated date of vaccination. subject has any condition that, according to the researcher's doctor, may be a contraindication to participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: phase 1, component 1<br>component 1 of vaccine | Drug: BVRS-GamVac-Combi<br>* BVRS-GamVac-Combi, a combined vector vaccine for the prevention of Middle East respiratory syndrome, lyophilisate for the preparation of a solution for intramuscular administration<br>|
| Experimental: phase 1, half dose<br>prime-boost vaccination with component 1 and component 2 with an interval of 21 days in half dose | Drug: BVRS-GamVac-Combi<br>* BVRS-GamVac-Combi, a combined vector vaccine for the prevention of Middle East respiratory syndrome, lyophilisate for the preparation of a solution for intramuscular administration<br>|
| Experimental: phase 1, full dose<br>prime-boost vaccination with component 1 and component 2 with an interval of 21 days in full dose | Drug: BVRS-GamVac-Combi<br>* BVRS-GamVac-Combi, a combined vector vaccine for the prevention of Middle East respiratory syndrome, lyophilisate for the preparation of a solution for intramuscular administration<br>|
| Experimental: phase 2, selected dose<br>prime-boost vaccination with component 1 and component 2 with an interval of 21 days in selected dose | Drug: BVRS-GamVac-Combi<br>* BVRS-GamVac-Combi, a combined vector vaccine for the prevention of Middle East respiratory syndrome, lyophilisate for the preparation of a solution for intramuscular administration<br>|
| Placebo Comparator: phase 2, placebo<br>vaccination with placebo with an interval of 21 days | Other: placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Determination of Number of Participants With Adverse Events | through the whole study, an average of 180 days | 
| Number of Participants With Serious Adverse Events | Determination of Number of Participants With Serious Adverse Events | through the whole study, an average of 180 days | 
| Number of Participants with Solicited Local and Systemic Adverse Events | Determination of Number of Participants with Solicited Local and Systemic Adverse Events | through the whole study, an average of 180 days | 
| Antibody levels against the MERS-CoV glycoprotein S measured by an enzyme-linked immunosorbent assay (ELISA) | Determination of antibody levels against the MERS-CoV glycoprotein S measured by an ELISA vs. baseline values (phase 1, phase 2) and placebo (phase 2) | Time Frame for group 1 phase 1: at days 0, 7, 14, 21, 28, 42, 56 and 90. Time Frame for group 2 phase 1 and phase 2: at days 0, 7, 14, 21, 28, 35, 42, 56 and 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of antigen-specific cell-mediated immune response | determination of specific T-cell- mediated response vs. baseline values and placebo | at 0, 14 and 28 days from the start of vaccination compared to baseline values (phase 1, phase 2) and placebo (phase 2) | 
| Neutralizing antibody levels | Determination of the neutralizing antibody titer for a virus in virus neutralization reaction vs. baseline values and placebo | at days 0, 14 and 28 from the start of vaccination compared to baseline values | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, vector based vaccine, Immunologic Factors, MERS-CoV, Middle East respiratory syndrome