Study to Evaluate the Safety, Immunogenicity, and Efficacy of Nanocovax Vaccine Against COVID-19

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, immunogenicity, and efficacy of Nanocovax vaccine in volunteer subjects 18 years of age and older.

Detailed Description
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This is a phase 3, adaptive, multicenter, randomized, double-blind, placebo control study to evaluate the safety, immunogenicity, and efficacy of the Nanocovax vaccine against COVID-19 in volunteer subjects 18 years of age and older. Age stratified as 18-45, 45-60, and > 60 years of age. The assessment of immunogenicity will be further expanded in a subset of Phase 3 (1000 participants). Randomly assigned to vaccine or placebo group with a ratio of 2:1 (2 subjects injected with Nanocovax 25 mcg : 1 subject injected with placebo).

Official Title
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a Phase 3, Adaptive, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Immunogenicity, and Efficacy of the Nanocovax Vaccine Against COVID-19 in Volunteer Subjects 18 Years of Age and Older.

Conditions
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SARS-CoV-2 Infection, COVID-19

Intervention / Treatment
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* Biological: Nanocovax
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be a male or female 18 years of age or older. For females: Be of non-childbearing potential or willing to use appropriate contraceptive measures for 30 days prior to vaccination through 6 months after completion of the vaccine series. Willingness to provide a signed, printed, and dated informed consent form. Able and willing to participate in all activities in the clinical trial. Participants with HIV, HBV, HCV should have a health record, determined to be stable for 6 months prior to the screening. Exclusion Criteria: Participants with unstable pre-existing medical conditions over the three months before enrollment (condition that has worsened to require hospitalization or significant changes in therapy). Planned administration/administration of a vaccine not foreseen by the study protocol from within 45 days before the first dose of study vaccine. Previous vaccination with any Covid-19 vaccine. History of COVID-19 disease. History of allergic reactions or anaphylaxis to previous immunizations or allergies to any components of the vaccine. Planning to become pregnant or planning to discontinue contraceptive precautions during the vaccination phase through 6 months after the second immunization. History of bleeding disorders/hemostasis or use of anticoagulants. Currently having cancer or undergoing cancer treatment. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 3 months prior to the first vaccine dose (inhaled and topical steroids are allowed). Women who are pregnant or breastfeeding.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mcg Dose<br>Intramuscular injection, two doses given 28 days apart | Biological: Nanocovax<br>* Recombinant Protein spike (s) SARS-CoV-2 and 0,5 mg Aluminum adjuvant<br>|
| Placebo Comparator: Placebo<br>Intramuscular injection, two doses given 28 days apart | Biological: Placebo<br>* 0,5 mg Aluminum adjuvant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity | Per 1000 person-years of follow-up | From 14 days after the second dose of study intervention to the end of the study, up to 1 year | 
| Percentage of participants reporting Serious adverse events or medically attended adverse events |  | From dose 1 through one year after the last dose | 
| Geometric mean of Anti-S IgG concentrations at each time point in a subset of participants |  | days 0, 42, 180, 365 after vaccination | 
| Geometric mean of SARS-CoV-2 serum neutralizing titers by Plaque reduction neutralization test (PRNT) at each time point in a subset of participants |  | days 0, 42 after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants reporting solicited local and systemic reactions |  | 7 days after each study vaccination | 
| Percentage of participants reporting unsolicited vaccine-related ≥ Grade 2 adverse events |  | 28 days after each study vaccination | 
| Proportion of participants achieving ≥4-fold rise of Anti-S IgG at each time point in a subset of participants |  | days 0,42, 180, 365 after vaccination | 
| T-cell responses (intracellular cytokine staining) | Change from baseline in the cell-mediated immune response in a subset of participants | days 0, 42 after vaccination | 
| Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} asymptomatic case of COVID-19 | Per 1000 person-years of follow-up | From 14 days after the second dose of study intervention to the end of the study, up to 1 year | 
| Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} mild case of COVID-19 | Per 1000 person-years of follow-up | From 14 days after the second dose of study intervention to the end of the study, up to 1 year | 
| Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} moderate to severe case of COVID-19 | Per 1000 person-years of follow-up | From 14 days after the second dose of study intervention to the end of the study, up to 1 year | 
| Number of participants who death due to covid-19 confirmed with (RT-PCR) positive | Per 1000 person-years of follow-up | From 14 days after the second dose of study intervention to the end of the study, up to 1 year |