Clinical Study of the Safety and Immunogenicity of a Recombinant Viral Vector AAV5 (Adeno-Associated Virus Type 5 )-RBD (Receptor Binding Domain)-S Vaccine for the Prevention of Coronavirus Infection (COVID-19)

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled, adaptive, seamless phase I / II clinical study of the safety and immunogenicity of a recombinant viral vector AAV5-RBD-S vaccine for the prevention of coronavirus infection (COVID-19)

Detailed Description
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The study will be carried out in 2 stages. Stage 1 aims to assess the safety and immunogenicity of different doses of BCD-250 in subjects without a history of COVID-19 infection to choose the optimal dose for further investigation. Stage 2 aims to assess the immunogenicity and safety of the chosen on stage 1 optimal BCD-250 dose compared to placebo in subjects with and without the history of COVID-19 infection.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Adaptive, Seamless Phase I / II Clinical Study of the Safety and Immunogenicity of a Recombinant Viral Vector AAV5-RBD-S Vaccine for the Prevention of Coronavirus Infection (COVID-19)

Conditions
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Coronavirus Infection, COVID-19

Intervention / Treatment
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* Biological: Low dose BCD-250 injection
* Biological: High dose BCD-250 injection
* Biological: Low dose or high dose BCD-250 injection
* Other: Placebo injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form Ability to comply with the study procedures based on the Investigator's assessment Males and females aged 18-60 years, inclusive, at the date of consent. Negative pregnancy test (for females of childbearing potential) Patients of childbearing potential and their partners with preserved reproductive function must agree to use reliable contraceptive methods starting from the time of informed consent for 3 months after Visit 1. This requirement does not apply to patients and their partners who underwent surgical sterilization. Reliable contraceptive methods include one barrier method in combination with one of the following: spermicides, intrauterine device/oral contraceptives. Cohort 1 only. Negative test for SARS-CoV-2 IgM and IgG at screening Cohort 2 only. Negative test for SARS-CoV-2 IgM at screening Cohort 2 only. Confirmed by SARS-CoV-2 RNA test, history of COVID-19 with documented recovery at least 4 month prior consent date. Exclusion Criteria: Positive / uncertain test for SARS-CoV-2 RNA at screening Cohort 1 only. Documented history of COVID-19. Changes on chest X-ray suggestive for pneumonia or other lung diseases at screening, excluding clinically non-significant changes in subjects with COVID-19 history on investigator's opinion. Prior administration of SARS-CoV-2 or other coronavirus vaccine or planning of receiving SARS-CoV-2 or other coronavirus vaccine during the study participation. Known contact with SARS-CoV-2 infected person or person with known contact with SARS-CoV-2 infected person, within 14 days prior to consent date. Any acute infectious or non-infectious disease, including convalescence period, less than 4 weeks since clinical recovery Positive HIV, HBV, HCV or Syphilis tests History of splenectomy History of severe allergic reactions History of allergic or postvaccinal reactions (anaphylactic shock, fever of 40°C or more, fainting, non-febrile convulsions etc.) after vaccine administration Suspicious hypersensitivity or history of hypersensitivity to any component of investigational product Participation in other clinical studies within 90 days prior to consent date, excluding screen failures or discontinued prior to the first investigational product administration.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Sequential Assignment
Interventional Model Description: Stage 1. Subjects without history of COVID-19 infection will be randomized in two treatment groups to receive different doses of BCD-250. After the last subject completes the 28 days of the main study period the safety and immunogenicity analysis will be performed. Based on these results the optimal BCD-250 dose will be selected by the Sponsor considering the Independent Data Monitoring Committee recommendations. Stage 2. Subjects without history of COVID-19 infection (Cohort 1) and with history of COVID-19 infection (Cohort 2) will be randomized to receive either selected dose of BCD-250 or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: COVID-19 vaccine candidate (BCD-250) low dose<br>The participants will receive the low dose of BCD-250 | Biological: Low dose BCD-250 injection<br>* A recombinant viral vector AAV5-RBD-S vaccine<br>|
| Experimental: COVID-19 vaccine candidate (BCD-250) high dose<br>The participants will receive the high dose of BCD-250 | Biological: High dose BCD-250 injection<br>* A recombinant viral vector AAV5-RBD-S vaccine<br>|
| Experimental: Cohort 1/COVID-19 vaccine candidate (BCD-250)<br>The participants will receive the selected dose of BCD-250 | Biological: Low dose or high dose BCD-250 injection<br>* A recombinant viral vector AAV5-RBD-S vaccine<br>|
| Placebo Comparator: Cohort 1/Placebo<br>The participants will receive placebo | Other: Placebo injection<br>* Placebo injection<br>|
| Experimental: Cohort 2/COVID-19 vaccine candidate (BCD-250)<br>The participants will receive the selected dose of BCD-250 | Biological: Low dose or high dose BCD-250 injection<br>* A recombinant viral vector AAV5-RBD-S vaccine<br>|
| Placebo Comparator: Cohort 2/Placebo<br>The participants will receive placebo | Other: Placebo injection<br>* Placebo injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG titer from baseline | Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG titer (binding and neutralizing) from baseline on Day 56 | Day 56 after the study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with acute immediate hypersensitivity reactions | Percentage of subjects with acute immediate hypersensitivity reactions developed within 30 minutes after study drug administration. | 30 minutes after the study drug administration | 
| Percentage of subjects with solicited local adverse reactions | Percentage of subjects with local post-vaccination reactions developed within 7 days after study drug administration. | 7 days after the study drug administration | 
| Percentage of subjects with grade ≥3 solicited local adverse reactions | Percentage of subjects with grade ≥3 local post-vaccination reactions developed within 7 days after study drug administration. | 7 days after the study drug administration | 
| Percentage of subjects with solicited systemic adverse reactions | Percentage of subjects with systemic post-vaccination reactions developed within 7 days of study drug administration. | 7 days after the study drug administration | 
| Percentage of subjects with grade ≥3 solicited systemic adverse reactions | Percentage of subjects with grade ≥3 systemic post-vaccination reactions developed within 7 days of study drug administration. | 7 days after the study drug administration | 
| Percentage of subjects with any adverse reactions | Percentage of subjects with any adverse reactions developed within 56 days of study drug administration. | 56 days after the study drug administration | 
| Percentage of subjects with any grade ≥3 adverse reactions | Percentage of subjects with any grade ≥3 adverse reactions developed within 56 days of study drug administration. | 56 days after the study drug administration | 
| The proportion of subjects with clinical and laboratory abnormalities | The proportion of subjects with clinical and laboratory abnormalities developed within 56 days after administration of the study drug | 56 days after the study drug administration | 
| Percentage of subjects with adverse events of special interest | Adverse events of special interest include the following adverse events: 1) AEs demanding the medical care, 2) Newly developed chronic diseases, 3) serious adverse reactions 4) Laboratory confirmed COVID-19 cases | up to Day 365 | 
| Percentage of subjects with SARS-CoV-2-specific IgG antibodies | Percentage of subjects with SARS-CoV-2-specific IgG (binding and neutralizing) antibodies within the main period of the study | Days 7, 14, 21, 28, 56 after the study drug administration. | 
| Geometric mean titer of SARS-CoV-2-specific IgG antibodies | Geometric mean titer of SARS-CoV-2-specific IgG (binding and neutralizing) antibodies within the main period of the study | Days 7, 14, 21, 28, 56 after the study drug administration | 
| Change of the SARS-CoV-2-specific IgG antibodies titer from baseline | Change of the SARS-CoV-2-specific IgG (binding and neutralizing) antibodies titer from baseline within the main period of the study | Days 7, 14, 21, 28, 56 after the study drug administration | 
| Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG antibodies titer from baseline | Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG (binding and neutralizing) antibodies titer from baseline within the main period of the study | Days 7, 14, 21, 28 after the study drug administration | 
| Percentage of subjects with detected SARS-CoV-2-specific peripheral blood lymphocytes | Percentage of subjects with detected SARS-CoV-2-specific peripheral blood lymphocytes within the main period of the study | Days 14, 28, 56 after the study drug administration. | 
| Mean change in SARS-CoV-2-specific peripheral blood lymphocytes count | Mean change in SARS-CoV-2-specific peripheral blood lymphocytes count within the main period of the study | Days 14, 28, 56 after the study drug administration | 
| Percentage of subjects with SARS-CoV-2-specific IgG antibodies | Percentage of subjects with SARS-CoV-2-specific IgG (binding and neutralizing) antibodies during the study | Days 57- 365 | 
| Geometric mean titer of SARS-CoV-2-specific IgG antibodies | Geometric mean titer of SARS-CoV-2-specific IgG (binding and neutralizing) antibodies during the study | Days 57- 365 | 
| Change in the SARS-CoV-2-specific IgG titer from baseline | Change in the SARS-CoV-2-specific IgG (binding and neutralizing) antibodies titer from baseline during the study | Days 57- 365 | 
| Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG (binding and neutralizing) titer from baseline | Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG titer from baseline during the study | Days 57- 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Vaccine, COVID-19 Virus Disease, COVID-19 Virus Infection, SARS-CoV-2 Infection