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) (COVER)

• ClinicalTrials.gov Identifier: NCT05037188
• Recruitment Status: Terminated
• First Posted: September 8, 2021
• Last Update Posted: January 30, 2023
• Sponsor: Biocad
• Information provided by (Responsible Party): Biocad

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
Coronavirus Infection; COVID-19	Biological: Low dose BCD-250 injection; Biological: High dose BCD-250 injection; Biological: Low dose or high dose BCD-250 injection; Other: Placebo injection	Phase 1; Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment

Intervention 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 (Participant, Investigator)

Masking Description

Stage 1 will be open label. The participants will receive the assigned dose of BCD-250 according to the allocation.

Stage 2 will be double blind, placebo-controlled. Investigators and subjects will be unaware of the assigned treatment (BCD-250 or placebo).

• Primary Purpose: Prevention
• Official Title: 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)
• Actual Study Start Date: August 10, 2021
• Actual Primary Completion Date: April 18, 2022
• Actual Study Completion Date: April 18, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG titer from baseline [ Time Frame: Day 56 after the study drug administration ]
   Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG titer (binding and neutralizing) from baseline on Day 56

Secondary Outcome Measures :

1. Percentage of subjects with acute immediate hypersensitivity reactions [ Time Frame: 30 minutes after the study drug administration ]
   Percentage of subjects with acute immediate hypersensitivity reactions developed within 30 minutes after study drug administration.
2. Percentage of subjects with solicited local adverse reactions [ Time Frame: 7 days after the study drug administration ]
   Percentage of subjects with local post-vaccination reactions developed within 7 days after study drug administration.
3. Percentage of subjects with grade ≥3 solicited local adverse reactions [ Time Frame: 7 days after the study drug administration ]
   Percentage of subjects with grade ≥3 local post-vaccination reactions developed within 7 days after study drug administration.
4. Percentage of subjects with solicited systemic adverse reactions [ Time Frame: 7 days after the study drug administration ]
   Percentage of subjects with systemic post-vaccination reactions developed within 7 days of study drug administration.
5. Percentage of subjects with grade ≥3 solicited systemic adverse reactions [ Time Frame: 7 days after the study drug administration ]
   Percentage of subjects with grade ≥3 systemic post-vaccination reactions developed within 7 days of study drug administration.
6. Percentage of subjects with any adverse reactions [ Time Frame: 56 days after the study drug administration ]
   Percentage of subjects with any adverse reactions developed within 56 days of study drug administration.
7. Percentage of subjects with any grade ≥3 adverse reactions [ Time Frame: 56 days after the study drug administration ]
   Percentage of subjects with any grade ≥3 adverse reactions developed within 56 days of study drug administration.
8. The proportion of subjects with clinical and laboratory abnormalities [ Time Frame: 56 days after the study drug administration ]
   The proportion of subjects with clinical and laboratory abnormalities developed within 56 days after administration of the study drug
9. Percentage of subjects with adverse events of special interest [ Time Frame: up to Day 365 ]
   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
10. Percentage of subjects with SARS-CoV-2-specific IgG antibodies [ Time Frame: Days 7, 14, 21, 28, 56 after the study drug administration. ]
    Percentage of subjects with SARS-CoV-2-specific IgG (binding and neutralizing) antibodies within the main period of the study
11. Geometric mean titer of SARS-CoV-2-specific IgG antibodies [ Time Frame: Days 7, 14, 21, 28, 56 after the study drug administration ]
    Geometric mean titer of SARS-CoV-2-specific IgG (binding and neutralizing) antibodies within the main period of the study
12. Change of the SARS-CoV-2-specific IgG antibodies titer from baseline [ Time Frame: Days 7, 14, 21, 28, 56 after the study drug administration ]
    Change of the SARS-CoV-2-specific IgG (binding and neutralizing) antibodies titer from baseline within the main period of the study
13. Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG antibodies titer from baseline [ Time Frame: Days 7, 14, 21, 28 after the study drug administration ]
    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
14. Percentage of subjects with detected SARS-CoV-2-specific peripheral blood lymphocytes [ Time Frame: Days 14, 28, 56 after the study drug administration. ]
    Percentage of subjects with detected SARS-CoV-2-specific peripheral blood lymphocytes within the main period of the study
15. Mean change in SARS-CoV-2-specific peripheral blood lymphocytes count [ Time Frame: Days 14, 28, 56 after the study drug administration ]
    Mean change in SARS-CoV-2-specific peripheral blood lymphocytes count within the main period of the study
16. Percentage of subjects with SARS-CoV-2-specific IgG antibodies [ Time Frame: Days 57- 365 ]
    Percentage of subjects with SARS-CoV-2-specific IgG (binding and neutralizing) antibodies during the study
17. Geometric mean titer of SARS-CoV-2-specific IgG antibodies [ Time Frame: Days 57- 365 ]
    Geometric mean titer of SARS-CoV-2-specific IgG (binding and neutralizing) antibodies during the study
18. Change in the SARS-CoV-2-specific IgG titer from baseline [ Time Frame: Days 57- 365 ]
    Change in the SARS-CoV-2-specific IgG (binding and neutralizing) antibodies titer from baseline during the study
19. Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG (binding and neutralizing) titer from baseline [ Time Frame: Days 57- 365 ]
    Percentage of subjects with ≥ 4 fold rise of serum SARS-CoV-2-specific IgG titer from baseline during the study

Other Outcome Measures:

1. The proportion of subjects with identified AAV5 in biological fluids (blood, saliva and urine) [ Time Frame: up to Day 365 ]
   The proportion of subjects with identified AAV5 in biological fluids (blood, saliva and urine) during the study
2. Percentage of subjects with AAV5-specific IgG antibodies [ Time Frame: up to Day 365 ]
   Percentage of subjects with AAV5-specific IgG antibodies during the study

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Russian Federation

UNINOVA clinic

Saint Petersburg, Russian Federation

X7 Clinical Research

Saint Petersburg, Russian Federation

Sponsors and Collaborators

Biocad

More Information

• Responsible Party: Biocad
• ClinicalTrials.gov Identifier: NCT05037188
• Other Study ID Numbers: BCD-250-1
• First Posted: September 8, 2021
• Last Update Posted: January 30, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Biocad:

COVID-19 Vaccine; COVID-19 Virus Disease; COVID-19 Virus Infection; SARS-CoV-2 Infection

Additional relevant MeSH terms:

Infections; Communicable Diseases; COVID-19; Coronavirus Infections; Disease Attributes; Pathologic Processes; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases