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)

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)

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)

Study Overview

• Status: Terminated
• Conditions: COVID-19; Coronavirus Infection
• Intervention / Treatment: Biological: Low dose BCD-250 injection; Biological: High dose BCD-250 injection; Biological: Low dose or high dose BCD-250 injection; Other: Placebo injection

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation
    • UNINOVA clinic
  • Saint Petersburg, Russian Federation
    • X7 Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects with identified AAV5 in biological fluids (blood, saliva and urine)	The proportion of subjects with identified AAV5 in biological fluids (blood, saliva and urine) during the study	up to Day 365
Percentage of subjects with AAV5-specific IgG antibodies	Percentage of subjects with AAV5-specific IgG antibodies during the study	up to Day 365

Collaborators and Investigators

• Sponsor: Biocad

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2021
• Primary Completion (Actual): April 18, 2022
• Study Completion (Actual): April 18, 2022

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 8, 2021

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2 Infection; COVID-19 Vaccine; COVID-19 Virus Infection; COVID-19 Virus Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Coronavirus Infections; Infections; Communicable Diseases
• Other Study ID Numbers: BCD-250-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No