A Cohort Study of COVID-19 mRNA Vaccine, Bivalent in Participants in China

Study Overview
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Brief Summary
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This is a cohort study to evaluate safety and immunogenicity of COVID-19 mRNA Vaccine, Bivalent (LVRNA021) in participants aged 18 years and over in China

Official Title
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A Cohort Study to Evaluate Safety and Immunogenicity of COVID-19 mRNA Vaccine, Bivalent (LVRNA021) in Participants Aged 18 Years and Over in China

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: SARS-CoV-2 mRNA Vaccine, Bivalent Low dose
* Biological: SARS-CoV-2 mRNA Vaccine, Bivalent High dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at the time of first dose of vaccine: adults aged 18-59 years (including boundary values), elderly ≥60 years, both sexes; Armpit temperature <37.3℃ on the day of enrollment; Based on the medical history and relevant physical examination and laboratory examination results, the investigator clinically determined that the patient was in good health; Subjects have independent judgment ability, can read, understand and complete vaccination diary cards, and they participate voluntarily and sign an informed consent form. Exclusion Criteria: The subject has a history of SARS-CoV-2 or SARS infection, or has a history of contact with SARS-CoV-2 infected persons (nucleic acid test positive) or suspected infected persons within 30 days before screening, or living abroad within 30 days before screening history, or a positive SARS-CoV-2 nucleic acid test or a positive SARS-CoV-2 IgM or IgG test before the first dose of vaccine; History of allergy to any component of the study vaccine or a history of a severe allergic reaction to the vaccine or drug (including but not limited to anaphylactic shock, anaphylactic laryngeal edema, anaphylactic purpura, thrombocytopenic purpura, or local anaphylactic necrosis [Arthus reaction]); Upon questioning, have a history of COVID-19 vaccination, or have received other inactivated vaccines within 14 days before screening, and received live attenuated vaccines within 28 days; Patients have a medical history or family history of epilepsy, convulsions, neurological diseases and mental diseases; There are contraindications for intramuscular injection, such as: thrombocytopenia that has been diagnosed, any coagulation disorder or receiving anticoagulant treatment, etc.; The investigator judges that he is known or suspected of having more serious diseases at the same time, including but not limited to: respiratory diseases (tuberculosis, lung failure, etc.), liver and kidney diseases, cardiovascular diseases (heart failure, severe hypertension, etc.), Malignant tumor, infection or allergic skin disease, HIV infection (test report can be provided), or during the active period of acute infection or chronic disease (within 3 days before vaccination); Congenital malformations, developmental disorders, or chronic diseases that the investigator judges are not suitable for participating in this study (such as Downs syndrome, sickle cell anemia or neurological disorders, Guillain-Barre syndrome, etc.), excluding stable diabetes/hypertension ); Patients with known immunological impairment or low immunological function diagnosed by the hospital before enrollment, or functional asplenia or splenectomy caused by any situation; Smokers (≥20 cigarettes per day on average in the past 30 days), alcoholics (≥61 grams of pure alcohol per day on average for men and ≥41 grams of pure alcohol per day for women in the past 30 days) and drug abuse; Female: those who have a positive blood pregnancy test, are pregnant, breastfeeding, or have a pregnancy plan within one year; men: whose spouse has a pregnancy plan within one year; Patients have participated in other clinical trials (drugs, biological products or devices) within 3 months before the first dose of vaccine, or plan to participate in other clinical trials during the research period; Patients received immune enhancement or immunosuppressive therapy within 6 months before the first dose of vaccine (continuous oral or instillation for more than 14 days); Patients donated blood ≥400 ml within 28 days before screening, or received whole blood, plasma and immunoglobulin therapy within 6 months before screening; Currently receiving research drug treatment to prevent COVID-19; Patients are taking antipyretic, analgesic and anti-allergic drugs within 3 days before enrollment; The investigator judges that the subjects cannot follow the research procedures, comply with the agreement, or plan to permanently relocate from the area before the end of the research, or plan to leave the local area for a long time during the scheduled visit period; The relevant staff involved in this study or their immediate family members (such as spouses, parents, siblings or children); According to the investigator's judgment, there are other situations that are not suitable for participating in this clinical trial.

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: Low dose<br>Two doses were administered by intramuscular injection, 28 days apart | Biological: SARS-CoV-2 mRNA Vaccine, Bivalent Low dose<br>* 50μg/dose<br>|
| Experimental: High dose<br>Two doses were administered by intramuscular injection, 28 days apart | Biological: SARS-CoV-2 mRNA Vaccine, Bivalent High dose<br>* 100μg/dose<br>|
| Placebo Comparator: Placebo<br>Two doses were administered by intramuscular injection, 28 days apart | Drug: Placebo<br>* Saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SARS-CoV-2 Novel coronavirus S protein antibody (IgG) level |  | At 28 days after full immunization | 
| The levels of neutralizing antibodies of SARS-CoV-2 anti-Novel coronavirus 2019 (Omicron BA.2, BA.4, BA.5 and Delta strains) true virus |  | At 28 days after full immunization | 
| The levels of neutralizing antibodies of SARS-CoV-2 anti-Novel coronavirus 2019 (Omicron BA.2, BA.4, BA.5 and Delta strains) pseudovirus |  | At 28 days after full immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events |  | Within 14 days and 28 days after each dose of immunization | 
| Incidence of adverse events associated with the study vaccine |  | Within 14 days and 28 days after each dose of immunization | 
| Incidence of SAE |  | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization | 
| Incidence of AESI |  | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization | 
| Incidence of SAE associated with the study vaccine |  | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization | 
| Incidence of AESI associated with the study vaccine |  | Within 28 days, 3 months, 6 months, and 12 months after the first dose of immunization to full immunization | 
| Incidence of grade ≥3 adverse events |  | Within 28 days after each dose/full dose | 
| Incidence of grade ≥3 adverse events associated with the study vaccine |  | Within 28 days after each dose/full dose | 
| Statistics of withdrawal from the study due to adverse events |  | Within 28 days after each dose/full dose | 
| The level of SARS-CoV-2 S protein antibody (IgG) |  | At 14 days, 3 months, 6 months, and 12 months after full immunization | 
| The positive conversion rate of SARS-CoV-2 S protein antibody |  | At 14 days, 28 days, 3 months, 6 months, and 12 months after full immunization | 
| True virus neutralizing antibody levels of SARS-CoV-2 (Omicron strain BA.2, BA.4, BA.5, Delta strain) |  | At 14 days, 3 months, 6 months, and 12 months after full immunization | 
| Pseudovirus neutralizing antibody levels of SARS-CoV-2 (Omicron strain BA.2, BA.4, BA.5, Delta strain) |  | At 14 days, 3 months, 6 months, and 12 months after full immunization | 
| Positive conversion rates of neutralizing antibodies against true virus of SARS-CoV-2 (Omicron strain BA.2, BA.4, BA.5, Delta strain) |  | At 14 days, 28 days, 3 months, 6 months, and 12 months after full immunization | 
| Positive conversion rates of neutralizing antibodies against pseudovirus of SARS-CoV-2 (Omicron strain BA.2, BA.4, BA.5, Delta strain) |  | At 14 days, 28 days, 3 months, 6 months, and 12 months after full immunization | 
| Level of cellular immune response levels (IFN-γ) against Novel coronavirus (2019-nCoV) (ELISPOT) |  | At 7 days , 14 days , and 28 days after complete immunization | 
| Level of cellular immune response levels ( IL-2) against Novel coronavirus (2019-nCoV) (ELISPOT) |  | At 7 days , 14 days , and 28 days after complete immunization | 
| Level of cellular immune response levels (IL-4) against Novel coronavirus (2019-nCoV) (ELISPOT) |  | At 7 days , 14 days , and 28 days after complete immunization | 
| Level of cellular immune response levels (IL-13) against Novel coronavirus (2019-nCoV) (ELISPOT) |  | At 7 days , 14 days , and 28 days after complete immunization | 
| PBMC transcriptome status at each visit for non-cellular immune subgroup subjects |  | At 7 days , 14 days , and 28 days after complete immunization |