Clinical Trail of SARS-CoV-2 Bivalent mRNA Vaccine (LVRNA021) in Participants Aged 18 Years and Older

Study Overview
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Brief Summary
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This is a multi-center, randomized, blinded, placebo-controlled, phase 3 clinical study to evaluate the efficacy, safety and immunogenicity of SARS-CoV-2 bivalent mRNA vaccine (LVRNA021) as booster in participants aged 18 years and older who completed primary/1 booster dose(s) of SARS-CoV-2 vaccination.

Official Title
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A Multi-center, Randomized, Blinded, Placebo-controlled, Phase 3 Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of SARS-CoV-2 Bivalent mRNA Vaccine (LVRNA021) as Booster in Participants Aged 18 Years and Older Who Completed Primary/1 Booster Dose(s) of SARS-CoV-2 Vaccination

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: SARS-CoV-2 Bivalent mRNA vaccine (LVRNA021)
* Drug: 0.9% sodium chloride solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 years and older; Understand the content of the ICF, and voluntarily sign the ICF (If the participant is unable to sign the ICF on his/her own due to illiteracy, an impartial witness is needed); Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures; Female participants of childbearing potential or partners of male participants: voluntarily agree to use effective contraception with their partners prior to the first vaccination and must agree to continue such precautions during the study until 3 months after booster vaccination [Effective contraception includes oral contraceptives, injectable or implantable contraception, extended-release topical contraceptives, hormonal patches, intrauterine devices (IUDs), sterilization, abstinence, condoms (for male), diaphragms, cervical caps, etc.); For female participants: without childbearing potential (amenorrhea for at least 1 year or documented surgical sterilization) or have used effective contraception with a negative pregnancy test before booster vaccination in this study； On the day of vaccination and 24 hours prior to vaccination, axillary temperatures<37.3°C/99.1°F; Healthy participants or participants with mild underlying disease [in a stable state without exacerbation (no admission to hospital or no major adjustment to treatment regimen, etc.) for at least 3 months prior to enrollment in this study]; Participants who have received primary/1 booster dose(s) of SARS-CoV-2 vaccination (including primary series of inactivated vaccine, mRNA vaccine, adenovirus vaccine or 1 homologous/heterologous booster), with the last dose received at least 6 months before enrolment. Documented confirmation of prior SARS-CoV-2 vaccination receipt must be obtained prior to randomization; Exclusion Criteria: History of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), or other coronavirus infections at any time; History of hepatitis A, hepatitis B, hepatitis C, syphilis infection based on medical inquiry.; History of severe adverse reaction associated with a vaccine or drug and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention(s); Receipt of medications intended to treat COVID-19 within 6 months; Virologically confirmed SARS-CoV-2 diagnosis within 6 months before screening visit; Positive nasopharyngeal/oropharyngeal swab SARS-CoV-2 RT-PCR test result at screening; Positive HIV test result at screening; A history or family history of convulsions, epilepsy, encephalopathy and psychosis; Malignant tumors in the active phase, malignant tumors not receiving adequate treatment, malignant tumors at potential risk of recurrence during the study period; Asplenia or functional asplenia, complete or partial splenectomy from any cause; Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids (if systemic corticosteroids are administered for ≥14 days at a dose of ≥20 mg/day of prednisone or equivalent), e.g., for cancer or an autoimmune disease, or planned receipt throughout the study. Inhaled/nebulized, intra-articular, epidural, or topical (skin or eyes) corticosteroids are permitted; Any other licensed vaccines given within 28 days prior to vaccination, planned administration of any other vaccines within 28 days after vaccination, or planned administration of other COVID-19 vaccines during the entire study duration; Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before vaccine administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before vaccine administration, or planned receipt throughout the study; Blood donation or blood loss ≥ 450 mL within 1 month prior to enrollment or planned to donate blood during the study period; Participation in other studies involving study intervention within 28 days prior to study entry, and/or during the study; Women who are pregnant or breastfeeding; Participants deemed unsuitable for participation in this study based on the investigator's assessment.

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: Study Vaccine Group<br> | Biological: SARS-CoV-2 Bivalent mRNA vaccine (LVRNA021)<br>* One dose was administered by intramuscular injection, 100μg，1.0ml/dose<br>|
| Placebo Comparator: Control Group<br> | Drug: 0.9% sodium chloride solution<br>* One dose was administered by intramuscular injection, 1.0ml/dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 | The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity meeting the case definition for the primary efficacy analysis occurring from 14 days after booster vaccination. | 14 days after vaccination or placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Person-year incidence density of first episodes of virologically-confirmed moderate to severe cases of COVID-19 | The person-year incidence density of first episodes of virologically-confirmed moderate to severe cases of COVID-19 from 14 days after booster vaccination meeting the case definition for the primary efficacy analysis. | 14 days after vaccination or placebo | 
| Person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 | The person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 from 14 days after booster vaccination meeting the case definition for the primary efficacy analysis. | 14 days after vaccination or placebo | 
| Person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 | The person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 leading to death from 14 days after booster vaccination meeting the case definition for the primary efficacy analysis. | 14 days after vaccination or placebo | 
| Person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 for participants in different age strata (18-59 years, ≥ 60 years) | The person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 of any severity occurring from 14 days after booster vaccination for participants in different age strata (18-59 years, ≥ 60 years). | 14 days after vaccination or placebo | 
| Incidence of each solicited (local and systemic) AE in all participants. | Incidence of each solicited (local and systemic) AE within 14 days after booster vaccination in all participants. | within 14 days after vaccination or placebo | 
| Severity of each solicited (local and systemic) AE in all participants. | Severity of each solicited (local and systemic) AE within 14 days after booster vaccination in all participants. | within 14 days after vaccination or placebo | 
| Duration of each solicited (local and systemic) AE in all participants. | Duration of each solicited (local and systemic) AE within 14 days after booster vaccination in all participants. | within 14 days after vaccination or placebo | 
| Incidence of unsolicited AEs in all participants. | Incidence of unsolicited AEs occurring 0-28 days after booster vaccination in all participants. | 0-28 days after vaccination or placebo | 
| Severity of unsolicited AEs in all participants. | Severity of unsolicited AEs occurring 0-28 days after booster vaccination in all participants. | 0-28 days after vaccination or placebo | 
| Causality of unsolicited AEs in all participants. | Causality of unsolicited AEs occurring 0-28 days after booster vaccination in all participants. | 0-28 days after vaccination or placebo | 
| Incidence of SAEs in all participants. | Incidence of SAEs from the day of booster vaccination to 12 months after booster vaccination in all participants. | within 12 months after vaccination or placebo | 
| Severity of SAEs in all participants. | Severity of SAEs from the day of booster vaccination to 12 months after booster vaccination in all participants. | within 12 months after vaccination or placebo | 
| Incidence of AESIs in all participants. | Incidence of AESIs from the day of booster vaccination to 12 months after booster vaccination in all participants. | within 12 months after vaccination or placebo | 
| Severity of AESIs in all participants. | Severity of AESIs from the day of booster vaccination to 12 months after booster vaccination in all participants. | within 12 months after vaccination or placebo | 
| Incidence of pregnancy events in all participants. | Incidence of pregnancy events from the day of booster vaccination to 12 months after booster vaccination in all participants. | within 12 months after vaccination or placebo | 
| Severity of pregnancy events in all participants. | Severity of pregnancy events from the day of booster vaccination to 12 months after booster vaccination in all participants. | within 12 months after vaccination or placebo | 
| Causality of SAEs, AESIs, and pregnancy events in all participants. | Causality of SAEs, AESIs, and pregnancy events from the day of booster vaccination to 12 months after booster vaccination in all participants. | within 12 months after vaccination or placebo | 
| Geometric mean titer (GMT)of SARS-CoV-2 (Omicron subvariants) virus neutralizing antibody (live virus neutralizing assay) responses in subjects in the immunization subgroup. |  | 14 days,28 days,3 months and 6 months after vaccination or placebo | 
| Seroconversion rate (SCR) of SARS-CoV-2 (Omicron subvariants) virus neutralizing antibody (live virus neutralizing assay) responses in subjects in the immunization subgroup. |  | 14 days,28 days,3 months and 6 months after vaccination or placebo | 
| Geometric mean Increase (GMI) of SARS-CoV-2 (Omicron subvariants) virus neutralizing antibody (live virus neutralizing assay) responses in subjects in the immunization subgroup. |  | 14 days,28 days,3 months and 6 months after vaccination or placebo | 
| GMT of S-protein IgG antibodies in subjects in the immunization subgroup. |  | 14 days, 28 days,3 months,6 months and 12 months after vaccination or placebo | 
| GMI of S-protein IgG antibodies in subjects in the immunization subgroup. |  | 14 days, 28 days,3 months,6 months and 12 months after vaccination or placebo | 
| SCR of S-protein IgG antibodies in subjects in the immunization subgroup. |  | 14 days, 28 days,3 months,6 months and 12 months after vaccination or placebo |