Clinical Study of SARS-CoV-2 Variant mRNA Vaccine in Healthy Participants

Study Overview
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Brief Summary
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An Open-Label, Phase 1 Clinical Study to Determine the Safety and Preliminary Immunogenicity of SARS-CoV-2 Variant mRNA Vaccine (LVRNA010)

Official Title
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An Open-Label, Phase 1 Clinical Study to Determine the Safety and Preliminary Immunogenicity of SARS-CoV-2 Variant mRNA Vaccine (LVRNA010) in Healthy Participants Aged 18 Years and Older

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: SARS-CoV-2 variant mRNA vaccine low dose
* Biological: SARS-CoV-2 variant mRNA vaccine high dose


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 (1st dose of) vaccination and must agree to continue such precautions during the study until 3 months after (full) 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 (each dose of) vaccination in this study. On the day of vaccination and 24 hours prior to (each dose of) vaccination, axillary temperatures<37.3℃/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]. (For group 2 and group 3 only) Participants who have received full primary vaccination of licensed SARS-CoV-2 vaccine (3-8 weeks between 2 doses of COVID-19 inactivated vaccine or 2 doses of COVID-19 mRNA vaccine) and whose last dose was given >6 mony (For group 1 only) Not have received any COVID-19 vaccine prior to enrollment. Exclusion Criteria: Any screening hematology and/or blood biochemistry laboratory value that meets the definition of a ≥Grade 1 abnormality, (For group 1 only) Confirmed SARS-CoV-2 diagnosis within 1 years before screening visit. History of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), or other coronavirus infections. Receipt of medications intended to treat COVID-19 with 1 year. History of server adverse reaction associated with a vaccine or drug and/or severe allergic reaction (e.g., anaphylaxis) to any component of the study intervention(s). SARS-CoV-2 RT-PCR positive nasopharyngeal/oropharyngeal swab specimens at screening. Positive HIV test 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 of 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 the investigational vaccination, or planned administration of vaccine(s) within 28 days after (full) vaccination. Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, form 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 ≥450ml 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. (For group 1 only: Criteria for delay of 2nd dose of vaccination) Fever within 24 hours prior to the 2nd dose of vaccination (axillary body temperature ≥37.3℃/99.1°F). (For group 1 only: Criteria for delay of 2nd dose of vaccination) During treatment/recovery from illness. (For group 1 only: Criteria for delay of 2nd dose of vaccination) Other conditions considered by the investigator to be unsuitable for vaccination. (For group 1 only: Criteria for termination of 2nd dose of vaccination) Participants with a positive urine pregnancy or blood pregnancy test (women of childbearing age only). (For group 1 only: Criteria for termination of 2nd dose of vaccination) Serious allergic reactions or serious adverse events related to vaccination (as assessed by the investigator) following a previous dose of vaccine. (For group 1 only: Criteria for termination of 2nd dose of vaccination) Positive result for SARS-CoV-2 (positive RT-PCR test). (For group 1 only: Criteria for termination of 2nd dose of vaccination) The investigator considers inappropriate for the participants to continue participation in the study.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1A: 50μg SARS-CoV-2 variant mRNA vaccine<br>Participants who have not received any COVID-19 vaccines will vaccinate two doses of study vaccine with 28 days apart. | Biological: SARS-CoV-2 variant mRNA vaccine low dose<br>* 50μg/dose<br>|
| Experimental: 1B: 100μg SARS-CoV-2 variant mRNA vaccine<br>Participants who have not received any COVID-19 vaccines will vaccinate two doses of study vaccine with 28 days apart. | Biological: SARS-CoV-2 variant mRNA vaccine high dose<br>* 100μg/dose<br>|
| Experimental: 2A: 50μg SARS-CoV-2 variant mRNA vaccine<br>Participants who have received 2 dose of COVID-19 inactivated vaccines will vaccinate 1 doses of study vaccine. | Biological: SARS-CoV-2 variant mRNA vaccine low dose<br>* 50μg/dose<br>|
| Experimental: 2B: 100μg SARS-CoV-2 variant mRNA vaccine<br>Participants who have received 2 dose of COVID-19 inactivated vaccines will vaccinate 1 doses of study vaccine. | Biological: SARS-CoV-2 variant mRNA vaccine high dose<br>* 100μg/dose<br>|
| Experimental: 3A: 50μg SARS-CoV-2 variant mRNA vaccine<br>Participants who have received 2 dose of COVID-19 mRNA vaccines will vaccinate 1 doses of study vaccine. | Biological: SARS-CoV-2 variant mRNA vaccine low dose<br>* 50μg/dose<br>|
| Experimental: 3B: 100μg SARS-CoV-2 variant mRNA vaccine<br>Participants who have received 2 dose of COVID-19 mRNA vaccines will vaccinate 1 doses of study vaccine. | Biological: SARS-CoV-2 variant mRNA vaccine high dose<br>* 100μg/dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity, and duration of each solicited (local and systemic) AE. |  | Within 30 minutes and 7 days after (each dose of) vaccination | 
| Incidence, severity, and duration of each unsolicited AE. |  | Within 28 days after (each dose of) vaccination | 
| The percentage of participants with abnormal hematology and chemistry laboratory values. |  | 4 days after (each dose of) vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of SARS-CoV-2 Virus Neutralizing Antibody (VNA) (live virus assay). |  | Before (each dose of) vaccination, 14 days and 28 days after (each dose of) vaccination | 
| Seroconversion Rate (SCR) of SARS-CoV-2 Virus Neutralizing Antibody (VNA) (live virus assay). |  | Before (each dose of) vaccination, 14 days and 28 days after (each dose of) vaccination | 
| Geometric Mean Increase (GMI) of SARS-CoV-2 Virus Neutralizing Antibody (VNA) (live virus assay). |  | Before (each dose of) vaccination, 14 days and 28 days after (each dose of) vaccination | 
| GMT of S-protein specific IgG antibodies (ELISA) |  | Before (each dose of) vaccination, 14 days and 28 days after (each dose of) vaccination | 
| SCR of S-protein specific IgG antibodies (ELISA) |  | Before (each dose of) vaccination, 14 days and 28 days after (each dose of) vaccination | 
| GMI of S-protein specific IgG antibodies (ELISA) |  | Before (each dose of) vaccination, 14 days and 28 days after (each dose of) vaccination | 
| The incidence, severity, and causality of Serious Adverse Events (SAEs) |  | Within 12 months after (full) vaccination | 
| The incidence, severity, and causality of Adverse Events of Special Interest (AESI) |  | Within 12 months after (full) vaccination | 
| The incidence, severity, and causality of the occurrence of pregnancy events |  | Within 12 months after (full) vaccination |