Clinical Trial to Assess Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Сov-2) Infection

Study Overview
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Brief Summary
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Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Centre Phase II/III Adaptive Clinical Trial to Assess the Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for SARS-Сov-2 Infection in Indian Healthy Subjects.

Detailed Description
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Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Centre Phase II/III Adaptive Clinical Trial to Assess the Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for SARS-Сov-2 Infection in Indian Healthy Subjects. In phase II trial, 100 subjects of immunogenicity group will be enrolled in 3:1 (Test:Placebo) ratio. These 100 subjects will be assessed for safety and immunogenicity outcomes till Day 28 post the first dose of investigational medicinal product (IMP)/placebo administration and will continue with study assessments till Day 180. Safety and immunogenicity data collected till Day 28 will be submitted to the regulatory authority for recommendation to proceed with Phase III recruitment. In Phase III trial, 1500 subjects will be enrolled and randomized in the ratio of 3:1 (Gam-COVID--Vac : Placebo). Each subject will participate in this adaptive study phase II/III clinical trial for 180±14 days after the first dose of the IMP/placebo and will have one screening visit and seven on-site visits during the trial period. The IMP/placebo will be administered intramuscularly during vaccination Visits 1 and 3 (Day 1 and Day 21±2). The observation Visits 2, 4, 5, 6, and 7 will be made on Day 19±2, Day 28±2, Day 42±2, Day 90±7, and Day 180±14, respectively. During the observation visits, vital indicators will be assessed in all subjects and changes in the subjects' condition and well being compared to the previous visit will be recorded. The schedule of examination procedures is mentioned in the Schedule of Event tables. Additionally, the subjects will be able to have remote consultations with the study physician through the weekly telephonic follow-up. Blood samples will be taken from immunogenicity group of phase II (all 100) and phase III (284 out of 1500) trials during the following visits to assess the immunogenicity parameters.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase II/III Adaptive Clinical Trial to Assess the Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for SARS-Сov-2 Infection in Indian Healthy Subjects

Conditions
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COVID-19 Prevention

Intervention / Treatment
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* Biological: Gam-COVID-Vac
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent of a subject to participate in the trial Males and females aged 18+ years Negative human immunodeficiency virus (HIV 1 & 2) and hepatitis B and C test results Negative immunoglobulin M (IgM) and immunoglobulin G (IgG) SARS-CoV-2 antibodies through enzyme immunoassay test result Negative COVID-2019 Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) test result at the screening visit (72 hours prior to Visit 1 [Day 1]) No COVID-2019 in the medical history History of no contact with COVID-2019 persons within at least 14 days before the enrolment (according to subjects) Consent for using effective methods of contraception during the entire trial 1 Negative urine pregnancy test at the screening visit (for child-bearing age women) No evident vaccine-induced reactions or complications after receiving immunobiological products in the medical history No acute infectious and/or respiratory diseases within at least 14 days before the enrolment. Exclusion Criteria: Any vaccination/immunization within 30 days before the enrolment Steroids (except hormonal contraceptives) and immunoglobulins or other blood products therapy not finished 30 days before the enrolment Immunosuppressors therapy finished within 3 months before the enrolment Pregnancy or breast-feeding Acute coronary syndrome or stroke suffered less than one year before the enrolment Tuberculosis, chronic systemic infections Drug allergy (anaphylactic shock, Quincke edema, polymorphic exudative eczema, atopy, serum disease),hypersensitivity or allergic reaction to immunobiological products, known allergic reactions to study product components, acute exacerbation of allergic diseases on the enrolment day Subjects who are on drugs that could have potential drug interactions with adenovirus vaccine Medical history of malignancy Donated blood or plasma (450+ mL) within 2 months before the enrolment Splenectomy in the medical history Neutropenia (absolute neutrophil count less than 1,000 mm3), agranulocytosis, significant blood loss,severe anaemia (haemoglobin less than 80 g/L), immunodeficiency including autoimmune disorders in the medical history within 6 months before the enrolment Active form of a disease caused by the HIV and hepatitis B or C Anorexia, protein deficiency of any origin Tattoos at the injection site (deltoid muscle area), which does not allow assessing the local response to the IMP or placebo administration Alcohol or drug addiction in the medical history. Participation in any other interventional clinical trial within 1 month prior to the Screening Any other medical condition that would limit the participation of the subject as per Investigator discretion Study centre staff or other employees directly involved in the trial and their families Subjects contraindicated for vaccination

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary Group<br>Gam-COVID-Vac combined vector vaccine, 0.5 ml/dose + 0.5 ml/dose prime-boost immunization on day 1 (component I rAd26-S) and on day 21 (component II rAd5-S) | Biological: Gam-COVID-Vac<br>* Vaccine for intramuscular injection<br>|
| Placebo Comparator: Control Group<br>Placebo, 0.5 ml/dose + 0.5 ml/dose immunization on days 1 and 21 | Other: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | For Phase II study - - Incidence & severity of adverse events (AEs) after first dose of IMP/Placebo For Phase III study - - Incidence of related serious adverse events (SAEs) following vaccination during the study | For Phase II study - at Day 28; For Phase III study - till day 180 after first dose | 
| Immunogenicity | For Phase II study - - Seroconversion rate of SARS-CoV-2 glycoprotein-specific antibodies in immunogenicity group | For Phase II study - Day 28 after first dose | 
| Immunogenicity | For Phase III study - Geometric mean titre ratio of SARS-CoV-2 glycoprotein-specific antibodies between IMP and placebo in immunogenicity group | For Phase III study - Day 42 after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Incidence and severity of adverse events after injecting the first dose of the IMP/placebo Incidence of SAE following vaccination | Baseline to Day 180 | 
| Immunogenicity assessment | Seroconversion rate of SARS-CoV-2 glycoprotein-specific antibodies in immunogenicity group Seroconversion rate of SARS-CoV-2 virus-neutralizing antibodies in immunogenicity group | Baseline, Day 21, Day 28, Day 42, Day 90, and Day 180 | 
| Immunogenicity assessment | Geometric mean virus-neutralizing antibodies titre in immunogenicity group | Baseline, Day 21, Day 28, Day 42, Day 90, and Day 180 | 
| Immunogenicity assessment | Interferon gamma concentration in T-cells after restimulation with the SARS-CoV-2 glycoprotein in cell mediated immunogenicity group | Baseline, Day 28, Day 42, Day 90 and Day 180 | 
| Immunogenicity assessment | The number of proliferating cluster of differentiation 4 (CD4) cell and cluster of differentiation 8 (CD8) cells in response to mitogen stimulation in cell mediated immunogenicity group | Baseline, Day 28, Day 42, Day 90 and Day 180 | 
| Percentage of subjects with mild, moderate, severe coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose of the vaccine/placebo | Comparing percentage of subjects developing COVID-19 disease between Gam-COVID-Vac combined vector vaccine and placebo based on severity course | Baseline to Day 180 | 
| Incidence of coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose in trial subjects | Comparing incidence of COVID-19 disease between Gam-COVID-Vac combined vector vaccine and placebo | Baseline to Day 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sputnik, Gamaleya