Clinical trial NCT05726084: Immunogenicity, Efficacy and Safety Trial of the Convacell Vaccine in Healthy Volunteers Aged 18 Years and Older
Official title: Multicentre, Double-blind, Randomized, Prospective, Placebo-controlled Trial to Assess the Immunogenicity, Efficacy and Safety of the Coronavirus Vaccine in Healthy Volunteers Aged 18 Years and Older
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: COVID-19
Coronavirus Infections
Respiratory Tract Infections
COVID-19 Respiratory Infection
Keywords: COVID-19
cellular immunity
nucleocapsid protein
recombinant vaccine
SPbSRIVS
SARS-CoV-2
Convacell
Lead sponsor: St. Petersburg Research Institute of Vaccines and Sera
Sponsor class: OTHER_GOV
First posted: 2023-02-13
Enrollment: 16304
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to assess the immunogenicity, efficacy and safety of the Convacell vaccine in healthy adult volunteers aged 18 years and older. The main questions it aims to answer are:

* To assess the immunogenicity and safety of single and double dose intramuscular administration of the Convacell vaccine;
* To assess the epidemiological effectiveness of the Convacell vaccine in the prevention of SARS-CoV-2 infection and development of severe COVID-19 compared with placebo when single or double intramuscular injection.

Detailed description: The trial will be conducted in two stages (Stage IIb and Stage III).

• Stage IIb

Participants will be vaccinated one dose or two doses of the Convacell vaccine. Investigators will compare one dose and two doses groups and will choose the best vaccine dosage regimen in terms of immunogenicity and safety.

• Stage III

Participants will be vaccinated the Convacell vaccine or Placebo. Investigators will use the dosage regimen chosen in IIb stage.

Eligibility criteria: Inclusion Criteria:

* Men and women aged 18 Years and Older
* Written informed consent of the volunteer to participate in the clinical trial (in paper or electronic form)
* BMI within the range of 18.5 ≤ BWI ≤ 30 kg/m2 with the body weight of not less than 55 kg for men, not less than 45 kg for women and not more than 100 kg for volunteers of both sexes
* Absence of clinically significant (according to the investigator) deviations from the reference values of clinical, laboratory and instrumental methods of examination at screening
* Hemodynamic and other vital signs are within normal limits (reference intervals are 60-90 beats/min at rest for HR, up to 22 per minute for RR, body temperature from 35.5 to 36.9 °C; systolic blood pressure (SBP) is considered normal in the range of 100-139 mmHg, diastolic blood pressure (DBP) - in the range of 60-89 mmHg)
* Volunteers able to fulfill requirements of the Protocol (i.e., fill in the electronic patient's diary, come to follow-up visits)
* Abstinence from alcohol from the start of screening until completion of Visit 7 procedures (day 42 ± 2) - for stage 2b
* For fertile women - a negative result of the pregnancy test and consent to observe adequate methods of contraception during the trial and at least two months after vaccination
* For fertile men - consent to observe adequate methods of contraception during the trial and at least two months after vaccination, except for men after vasectomy with documented azoospermia, and their sexual partners should use methods of contraception that ensure more than 90% reliability or be incapable of conception after a surgical sterilization or have a natural menopause for at least 2 years
* Throughout the study, the opportunity to use own smartphone with the ability to fill in the electronic patient's diary

Exclusion Criteria:

* History of influenza or acute respiratory viral infection (ARVI) within 2 months before the start of the trial;
* A serious post-vaccination reaction (temperature above 40 °C, hyperemia or edema more than 8 cm in diameter) or complications (collapse or shock-like condition that developed within 48 hours after vaccination; convulsions accompanied or not accompanied by a fever due to any previous vaccination);
* Fever, cough, and shortness of breath within 30 days before vaccination;
* History of COVID-19 within 6 months before screening;
* The level of IgG antibodies to the SARS-CoV-2 N-protein according to semi-quantitative test (Architect, Abbott) ≥ 3 (positivity rate) at screening;
* Positive result of the COVID-19 PCR test or antigen COVID-19 test (rapid test);
* Body temperature ≥ 37,3°C.
* History of allergies;
* Any vaccination within 30 days before the screening;
* History of leukemia, tuberculosis, cancer, autoimmune diseases;
* History of Quincke's edema;
* Positive blood test results for HIV, syphilis, hepatitis B/C according to the examination during the screening period (only for Stage IIb) or according to the history (for Stage III). It is acceptable to use the results of previously performed tests, if their prescription does not exceed 60 days before the date of the screening or based on history;
* Volunteers who received immunoglobulin during the last three months before the trial;
* History of long-term use (more than 14 days) of immunosuppressants or other immunomodulatory drugs for six months before the trial;
* Treatment with glucocorticosteroids, including in small doses, as well as local use of drugs containing steroids (\> 10 mg of prednisolone or its equivalent for more than 14 days before the screening);
* History of any confirmed or suspected immunosuppressive or immunodeficiency condition;
* History of splenectomy;
* History of chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, the gastrointestinal tract, liver, kidneys, hematopoietic or immune systems, mental disease in the acute stage or in the decompensation stage (according to history and / or examination on the screening);
* Transfusion of blood or blood components within 4 months before screening;
* Any acute infectious diseases during the screening period or past illnesses within 3 months before the screening visit, any chronic infectious diseases in the acute stage during the screening period;
* Consumption of more than 10 units of alcohol per week or history of alcohol addiction, drug addiction or abuse of pharmaceutical products;
* Smoking of more than 10 cigarettes per day;
* Participation in another clinical trial within the last 90 days;
* Pregnancy or lactation;
* Coagulopathy, hemophilia, bleeding disorder;
* Participation in previous clinical trials of the Convacell vaccine, a subunit recombinant vaccine for the prevention of coronavirus infection caused by SARS-CoV-2 virus, or any other vaccines to prevent coronavirus infection caused by the virus SARS-CoV-2 for 6 months before screening;
* History of anticovid plasma use;
* Vaccination against COVID-19 within 6 months before screening.

Primary outcomes:
measure: Change in titer of IgG antibodies to N-protein of SARS-CoV-2 (Stage IIb)
timeFrame: Days 0, 42
measure: Frequency of symptomatic COVID-19 with laboratory-confirmed infection within 6 months after vaccination compared with the placebo group (Stage III)
timeFrame: Days 0-180 (6 months)
Secondary outcomes:
measure: Change in titer of IgM antibodies to N-protein of SARS-CoV-2 on day 42 after initial vaccination (Stage IIb)
timeFrame: Days 0, 42
measure: Proportion of SARS-CoV-2 seropositive participants on day 42 after initial vaccination (Stage IIb)
timeFrame: Days 0, 42
measure: Change in titer of IgG antibodies to N-protein of SARS-CoV-2 on day 42 after initial vaccination (Stage IIb)
timeFrame: Days 0, 42
measure: The frequency of seroconversion (appearance of specific antibodies to SARS-CoV-2 N-protein) on day 42 after initial vaccination (Stage IIb)
timeFrame: Days 0, 42
measure: Change from Baseline in the Mean Specifically Sensitized T-lymphocytes (Stage IIb)
timeFrame: Days 0, 42
measure: Number of volunteers hospitalized with COVID-19 (Stage IIb)
timeFrame: through trial Stage IIb; Days 0-49
measure: Frequency of laboratory confirmed asymptomatic SARS-CoV-2 infections within 6 months. after initial vaccination compared with the placebo group (Stage III)
timeFrame: Days 0-180 (6 months)
measure: Frequency of laboratory-confirmed severe COVID-19 (Stage III)
timeFrame: Days 0-180 (6 months)
measure: Overall frequency of all AEs/SAEs (Stage IIb and III)
timeFrame: through trial Stage IIb (Days 0-49), through trial Stage III (Days 0-196)
measure: Overall frequency of all AEs/SAEs associated with the study drug (Stage IIb and III)
timeFrame: through trial Stage IIb (Days 0-49), through trial Stage III (Days 0-196)
measure: The frequency of local post-vaccination reactions at the injection site (Stage IIb and III)
timeFrame: Days 0-7 after initial vaccination and revaccination
measure: The frequency of systemic post-vaccination reactions at the injection site (Stage IIb and III)
timeFrame: Days 0-7 after initial vaccination and revaccination
measure: The frequency of local post-vaccination reactions at the injection site (Stage IIb and III)
timeFrame: Days 0-21 after initial vaccination and revaccination
measure: Frequency of systemic post-vaccination reactions (Stage IIb and III)
timeFrame: Days 0-42 after initial vaccination
measure: The frequency of toxic post-vaccination complications (Stage IIb and III)
timeFrame: through trial Stage IIb (Days 0-49), through trial Stage III (Days 0-196)
measure: The frequency of allergic post-vaccination complications (Stage IIb and III)
timeFrame: through trial Stage IIb (Days 0-49), through trial Stage III (Days 0-196)
measure: The frequency of neurological post-vaccination complications (Stage IIb and III)
timeFrame: through trial Stage IIb (Days 0-49), through trial Stage III (Days 0-196)
measure: The presence of allergic reactions (Stage IIb and III)
timeFrame: through trial Stage IIb (Days 0-49), through trial Stage III (Days 0-196)
measure: Сhange in white blood cell count and relative white blood cell count (Stage IIb)
timeFrame: Day 0 (screening), day 28 ± 2 (visit 4)
measure: Сhange in neutrophils count and relative neutrophils count (Stage IIb)
timeFrame: Day 0 (screening), day 28 ± 2 (visit 4)
measure: Сhange in lymphocytes count and relative lymphocytes count (Stage IIb)
timeFrame: Day 0 (screening), day 28 ± 2 (visit 4)
measure: Сhange in monocyte count and relative monocyte count (Stage IIb)
timeFrame: Day 0 (screening), day 28 ± 2 (visit 4)
measure: Сhange in the IgE level (Stage IIb)
timeFrame: Day 0 (screening), day 28 ± 2 (visit 4)
measure: The proportion of participants with delayed post-vaccination reactions (percent) (Stage IIb and III)
timeFrame: through trial Stage IIb (Days 0-49), through trial Stage III (Days 0-196)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Limited Liability Company "OLLA-MED"
city: Moscow
country: Russian Federation
facility: State budgetary health care institution of the city of Moscow "City Clinical Hospital No. 24 of the Department of Health of the City of Moscow"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Scientific Research Center Eco-Safety"
city: Saint Petersburg
country: Russian Federation
facility: St. Petersburg State Budgetary Health Institution "City Polyclinic No. 117"
city: Tol'yatti
country: Russian Federation
facility: Limited Liability Company "Otkrytaya Meditsina"
city: Yaroslavl
country: Russian Federation
facility: Limited Liability Company "Meditsinskiy Diagnosticheskiy Tsentr"
Study officials:
affiliation: St. Petersburg Research Institute of Vaccines and Sera
name: Ellina Ruzanova
role: STUDY_DIRECTOR
References: