An Open Label Study With an Open Dose Selection Period to Assess the Safety, Tolerability and Immunogenicity of the Drug "Gam-COVID-Vac, a Combined Vector Vaccine for the Prevention of Coronavirus Infection Caused by the SARS-CoV-2 Virus", With the Participation of Adolescent Volunteers
试验速览
- 阶段
- 2 期
- 入组人数
- 3,000
- 试验地点
- 2
- 主要终点
- Geometric mean titer of antigen-specific IgGs
研究概览
简要总结
Double-blind, placebo-controlled study with open dose selection period for safety assessment, tolerance and immunogenicity of the drug "GamKOVID-Vac M, a combined vector vaccine for prevention of coronavirus infection caused by the virus SARS-CoV-2" in adolescents
详细描述
The study will include healthy volunteers aged 12-17 years inclusive. Volunteers will be recruited in at least two clinical centers. Teams will be divided into subgroups to ensure the safety of volunteers during hospitalization amid the ongoing pandemic.
Stage 1 (Phase I-II) - 100 volunteers will be included in two dosing groups (50 in each group), a sufficient number of volunteers should be screened (no more than 7 days before inclusion in the study). To ensure the required number of volunteers who have completed screening procedures (pre-screening procedures can be organized).
The conditions of the study were the selection of doses (administration of the drug and observation for 48 hours) in a hospital setting, the rest of the visits were outpatient.
It is planned to start the study with a dose of 1/10 of the full adult dose. Volunteers will be hospitalized the day before vaccination. It is allowed to carry out screening procedures the day before vaccination in a hospital setting, subject to the prior approval of the volunteer based on the results of pre-screening. The first dose will be administered on day 1. After that, the volunteer will be monitored in the hospital for 48 hours. on days 3 and 7, a telephone consultation will be held. With a favorable safety profile after 7 days after the 1/10 dose, the Principal Investigators present a consolidated decision to escalate the dose to 1/5 of the adult dose on ICMD.
The transition to the next stage is planned on the basis of the report on the safety and tolerability of ILS on the 28th day after the introduction of the first component. The selected dose will be determined based on the immunogenicity scores at day 28, which should be consistent with the immunogenicity in adults after receiving the full dose of ILP.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Availability of written informed consent of the research subject and parents / adoptive parents of the subject to participate in the research;
- •Boys and girls aged 12-17 inclusive;
- •Negative test result for HIV, hepatitis, syphilis;
- •A negative test result for the presence of IgM and IgG antibodies to SARS CoV2 by enzyme immunoassay, as well as, if available, the result of an examination performed in medical institutions of the Moscow City Health Department 7 days prior to inclusion in the study can be taken into account;
- •A negative test result for COVID-2019, determined by the PCR method at the screening visit, and, if available, can be taken into account the result of the examination performed in the medical organizations of the Moscow City Health Department 7 days before being included in the study;
- •No history of COVID-2019;
- •Absence of contact of the research subject with COVID-2019 patients for at least 14 days prior to inclusion in the research (according to the research participant, parents / adoptive parents of the subject);
- •Consent to the use of effective contraceptive methods during the entire period of participation in the study;
- •Negative pregnancy test based on urine test results at the screening visit (for all girls - study participants);
- •Negative test for the presence of drugs and psychostimulants in the urine at the screening visit;
- •Negative alcohol test at screening visit;
- •No history of pronounced post-vaccination reactions or post-vaccination complications after the use of immunobiological drugs;
- •Absence of acute infectious and / or respiratory diseases for at least 14 days prior to enrollment in the study
排除标准
- •Any vaccination / immunization carried out within 30 days prior to enrollment in the study.
- •Therapy with steroids (with the exception of hormonal contraceptive drugs) and / or immunoglobulins or other blood products, not completed 30 days before enrollment in the study;
- •Immunosuppressive therapy and systemic therapy with corticosteroid drugs, completed in less than 3 months. prior to inclusion in the study.
- •Postponed acute coronary syndrome or stroke less than one year before inclusion in the study
- •Any immunodeficiency (for example, hereditary immunodeficiency, acquired immunodeficiency syndrome [AIDS], etc.).
- •Infectious diseases:
- •history of HIV (antibodies to HIV type 1 or 2), positive test for HBsAg or HCV RNA [qualitative]), active form of syphilis;
- •Tuberculosis;
- •Active infection (with the exception of onychomycosis), or any significant episode of infection requiring intravenous antibiotic treatment for 4 weeks before screening or by mouth for 2 weeks before screening;
- •A history of a serious recurrent or chronic infection not listed above.
- •Major surgery within 4 weeks prior to screening.
- •Chronic autoimmune diseases or systemic collagenoses in history, requiring the appointment of immunosuppressive therapy.
- •Volunteers who have undergone organ transplants, including bone marrow or peripheral blood stem cell (PBC) transplants, and are receiving immunosuppressive therapy.
- •History of splenectomy.
- •Volunteers with a previous or concomitant history of neoplasms (ICD codes C00-D09).
- •A burdened allergic history (history of anaphylactic shock, Quincke's edema and other life-threatening conditions), hypersensitivity or allergic reactions to the administration of immunobiological preparations, known allergic reactions to any component of a vaccine or vaccine containing similar components, exacerbation of allergic diseases on the day of inclusion in the study.
- •Neutropenia (decrease in the absolute number of neutrophils less than 1000 cells / mm3), agranulocytosis, significant blood loss, severe anemia (hemoglobin concentration less than 80 g / l), thrombocytopenia (decrease in the absolute number of platelets less than 50,000 cells / mm3).
- •Anorexia, protein deficiency of any origin.
- •Volunteers with a BMI <18 (low body weight) or a BMI ≥ 35 kg / m
- •Extensive tattoos at the injection sites (deltoid muscle area), which do not allow assessing the local response to the injection of ILP.
- •Chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, as well as diseases of the gastrointestinal tract, liver, kidneys, muscle and connective tissue in the stage of exacerbation or decompensation.
- •Presence or suspicion of drug, alcohol or drug addiction and other mental disorders.
- •Diseases, the presence of which, from the point of view of the medical researcher, puts the health of the participant at risk if participating in the study or potentially complicates the interpretation of the results of the examination.
- •Family members of staff of research centers directly involved in the conduct of research, etc.
- •Participation in other clinical trials and use of other investigational drugs within 28 days of screening.
- •Planned vaccination against COVID-19 with any vaccine, both in the framework of other studies and in the framework of civil appeal.
- •Female subjects during pregnancy or lactation
- •Inability to read in Russian; inability or unwillingness to understand the essence of the research. Any other conditions that limit the eligibility of obtaining informed consent or that may affect the volunteer's ability to participate in the study affect the volunteer's ability to take part in the study
结局指标
主要结局
Geometric mean titer of antigen-specific IgGs
时间窗: 21, 28, 42, 90, 180 days
To define geometric mean titer of antigen-specific IgGs after vaccination
IFN-gamma secretion by T lymphocytes
时间窗: 21, 28, 42, 90, 180 days
To define changes in level of IFN-gamma secretion by T lymphocytes under antigen stimulation
Geometric mean titer of neutralizing antibodies
时间窗: 21, 28, 42, 90, 180 days
To define geometric mean titer of neutralizing antibodies against SARS-Cov-2 virus after vaccination
Frequency of adverse reactions
时间窗: 365+/-14 days
Frequency of vaccine-related adverse reactions
Severity of adverse reactions
时间窗: 365+/-14 days
Severity of vaccine-related adverse reactions
次要结局
- Incidence of COVID-19 cases(within 28 to 365 days)