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Safety, Tolerability and Immunogenicity of Recombinant COVID-19 Vaccine Betuvax-CoV-2

Phase 1
Conditions
COVID-19
Interventions
Biological: Betuvax-CoV-2
Drug: Placebo
Registration Number
NCT05270954
Lead Sponsor
Human Stem Cell Institute, Russia
Brief Summary

Randomized, double-blind, multicenter parallel-group clinical study of safety, tolerability and immunogenicity of the Betuvax-CoV-2 vaccine. The aim of this study is to investigate the safety, tolerability and immunogenicity of the Betuvax-CoV-2 Recombinant vaccine for the prevention of coronavirus infection caused by the SARS-CoV-2 virus, suspension for intramuscular administration, 10 μg/ml and 40 μg/ml (Ltd. Institute of New Medical Technologies, Russia) in healthy adult volunteers, aged 18 to 60 (inclusive).

Detailed Description

Participation of the volunteers in the study includes Visit 0 (screening), Visits 1-4 and Visits 10-13 (on an inpatient basis), Visits 5-9 and Visits 14-20 (on an outpatient basis). During Visits 2 and 11, volunteers receive either a study drug (one of two dosages) or a placebo.

The study includes 116 healthy male and female volunteers aged 18 to 60 (inclusive) years who meet the inclusion criteria.

All volunteers are enrolled in two stages of the study and at each stage they are randomized into two or three groups, respectively.

Taking into account the estimated number of volunteers found by the screening results as not meeting the inclusion criteria (54 people), 170 volunteers are screened in the First and Second stage.

The vaccination course includes two intramuscular injections within a 28-day period.

The first stage of the study:

* Group 1 (10 people) will be intramuscularly administered the study drug Betuvax-CoV-2 according to the following scheme: the first injection of 20 μg (0.5 ml of suspension for intramuscular administration of 40 μg/ml), the second injection of 5 μg (0.5 ml of suspension for intramuscular injection of 10 μg/ml) in 28 days.

* Group 2 (10 people) will be intramuscularly administered the study drug Betuvax-CoV-2 according to the following scheme: the first and second injection of 20 μg (0.5 ml of solution for intramuscular injection of 40 μg/ml) within a 28-day period.

The second stage of the study:

* Group 3 (32 people) will be intramuscularly administered the study drug Betuvax-CoV-2 according to the following scheme: the first injection of 20 μg (0.5 ml of the suspension for intramuscular administration of 40 μg/ml), the second injection of 5 μg (0.5 ml of the suspension for intramuscular injection of 10 μg/ml) in 28 days.

* Group 4 (32 people) will be intramuscularly administered the study drug Betuvax-CoV-2 according to the following scheme: the first and second injection of 20 μg (0.5 ml of solution for intramuscular injection of 40 μg/ml) within a 28-day period.

* Group 5 (32 people) will receive a placebo according to the following scheme: the first and second injections (0.5 ml of sodium chloride 0.9% solution, intramuscularly) within a 28-day period.

Study participants will be closely monitored for their intended outcomes. Key safety outcomes will be centrally reviewed by the Independent Data Monitoring Committee (ICMD). Investigators will be required to report anticipated safety outcomes in a timely manner (within 24 hours if possible) and to record these outcomes in the CRF in a timely manner (within 24 hours if possible).

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
116
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 1 (Phase 1)Betuvax-CoV-2All volunteers randomized to Group 1 will be administered the Betuvax-CoV-2 drug according to the following scheme: 20 μg + 5 μg, twice, within a 28-day period.
Group 2 (Phase 1)Betuvax-CoV-2All volunteers randomized to Group 2 will be administered the Betuvax-CoV-2 drug according to the following scheme: 20 μg + 20 μg, twice, within a 28-day period.
Group 3 (Phase 2)Betuvax-CoV-2All volunteers randomized to Group 3 will be administered the Betuvax-CoV-2 drug according to the following scheme: 20 μg + 5 μg, twice, within a 28-day period.
Group 4 (Phase 2)Betuvax-CoV-2All volunteers randomized to Group 4 will be administered the Betuvax-CoV-2 drug according to the following scheme: 20 μg + 20 μg, twice, within a 28-day period.
Group 5 (Phase 2)PlaceboVolunteers randomized to Group 5 will be administered a placebo reference drug (0.9% aqueous sodium chloride solution), twice, within a 28-day period.
Primary Outcome Measures
NameTimeMethod
Adverse eventsWithin 50 days of the first dose of the study drug/placebo

The proportion of the volunteers with any adverse events

Severe adverse eventsWithin 50 days of the first dose of the study drug/placebo

The proportion of the volunteers with severe adverse events

Neutralizing anti-SARS-CoV-2 antibodies90±5 days after the first administration of the study drug/placebo

The proportion of the volunteers tested positive for the presence of neutralizing anti-SARS-CoV-2 antibodies (SARS-CoV-2 Surrogate Virus Neutralization Test)

Total specific anti-SARS-CoV-2 antibodies90±5 days after the first administration of the study drug/placebo

The proportion of the volunteers with an increased level of the total specific anti-SARS-CoV-2 antibodies by 4 times or more (ELISA test)

Secondary Outcome Measures
NameTimeMethod
Geometric mean titers of the IgM-specific anti-SARS-CoV-2 antibodies180±5 days after the first administration of the study drug/placebo

The proportion of the volunteers with geometric mean titers of the IgM-specific anti-SARS-CoV-2 antibodies (ELISA test)

Severe or extremely severe course of COVID-19, or lethal outcomeFrom the 7th day after the second administration of the study drug/placebo till the 180±5 day after the first dose of the study drug/placebo

The proportion of the volunteers with COVID-19 of severe or extremely severe course, or with a lethal outcome, and a PCR-confirmed SARS-CoV-2 infection

Any adverse eventsWithin 180±5 days after the first dose of the study drug/placebo

The proportion of the volunteers with any adverse events

IgG-specific anti-SARS-CoV-2 antibodies180±5 days after the first dose of the study drug/placebo

The proportion of the volunteers with an increased level of the IgG-specific anti-SARS-CoV-2 antibodies by 4 times or more (ELISA test)

IgM-specific anti-SARS-CoV-2 antibodies180±5 days after the first dose of the study drug/placebo

The proportion of the volunteers with an increased level of the IgM-specific anti-SARS-CoV-2 antibodies by 4 times or more (ELISA test)

Neutralizing anti-SARS-CoV-2 antibodies180±5 days after the first administration of the study drug/placebo

The proportion of the volunteers tested positive for the presence of neutralizing anti-SARS-CoV-2 antibodies (SARS-CoV-2 Surrogate Virus Neutralization Test)

Geometric mean titers of the total anti-SARS-CoV-2 antibodies180±5 days after the first administration of the study drug/placebo

The proportion of the volunteers with geometric mean titers of the total anti-SARS-CoV-2 antibodies (ELISA test)

Geometric mean titers of the IgG-specific anti-SARS-CoV-2 antibodies180±5 days after the first administration of the study drug/placebo

The proportion of the volunteers with geometric mean titers of the IgG-specific anti-SARS-CoV-2 antibodies (ELISA test)

Specific anti-SARS-CoV-2 cellular immune response (Phase 1)90±5 days after the first dose of the study drug (only in Phase 1)

The proportion of the volunteers with a specific anti-SARS-CoV-2 cellular immune response (flow cytometry)

Specific anti-SARS-CoV-2 cellular immune response180±5 days after the first dose of the study drug/placebo

The proportion of the volunteers with a specific anti-SARS-CoV-2 cellular immune response (ELISPOT)

COVID-19 symptomsFrom the 7th day after the second administration of the study drug/placebo till the 180±5 day after the first dose of study drug/placebo

The proportion of the volunteers with at least one COVID-19 symptom (fever, chills, dyspnoea, difficulty breathing, cough, sore throat, fatigue, muscle pain, loss or decrease in taste and/or odor, nasal congestion, runny nose, headache, nausea, vomiting, diarrhea) and a PCR-confirmed SARS-CoV-2 infection

Moderate, severe or extremely severe course of COVID-19, or lethal outcomeFrom the 7th day after the second administration of the study drug/placebo till the 180±5 day after the first dose of the study drug/placebo

The proportion of the volunteers with COVID-19 of moderate, severe or extremely severe course, or with a lethal outcome, and a PCR-confirmed SARS-CoV-2 infection

Lethal outcomeFrom the 7th day after the second administration of the study drug/placebo till the 180±5 day after the first dose of the study drug/placebo

The proportion of the volunteers with lethal outcome, and a PCR-confirmed SARS-CoV-2 infection

Allergic reactionsWithin 2 hours of the second study drug/placebo administration

The proportion of the volunteers with immediate side effects (allergic reactions)

Local post-vaccination reactionsWithin 7 days after the second administration of the study drug/placebo

The proportion of the volunteers with local post-vaccination reactions

Systemic post-vaccination reactionsWithin 7 days after the second administration of the study drug/placebo

The proportion of the volunteers with systemic post-vaccination reactions

Total specific anti-SARS-CoV-2 antibodies180±5 days after the first administration of the study drug/placebo

The proportion of the volunteers with an increased level of the total specific anti-SARS-CoV-2 antibodies by 4 times or more (ELISA test)

Severe local post-vaccination reactionsWithin 7 days of the second study drug/placebo administration

The proportion of the volunteers with \>grade 3 of local post-vaccination reactions

Adverse events of special interestWithin 180±5 days after the first dose of the study drug/placebo

The proportion of the volunteers with adverse events of special interest, adverse reactions that require medical attention, with newly developed chronic diseases

Prematurely terminated participationWithin 180±5 days after the administration of the first dose of the study drug/placebo

The proportion of the volunteers who prematurely terminated their participation in the study due to the development of adverse events or severe adverse events associated with the use of the study drug

Severe systemic post-vaccination reactionsWithin 7 days after the second administration of the study drug/placebo

The proportion of the volunteers with \>grade 3 of severe systemic post-vaccination reactions

Severe adverse eventsWithin 180±5 days after the first dose of the study drug/placebo

The proportion of the volunteers with severe adverse events

Trial Locations

Locations (3)

"Eco-Safety" R&D center

🇷🇺

Saint Petersburg, Russian Federation

Center of professional medicine

🇷🇺

Perm, Russian Federation

Department of Vaccinology, Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation

🇷🇺

Saint Petersburg, Russian Federation

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