Clinical Trail of SARS-CoV-2 Bivalent mRNA Vaccine (LVRNA021) in Participants Aged 18 Years and Older
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study Vaccine Group
|
Biological: SARS-CoV-2 Bivalent mRNA vaccine (LVRNA021)
One dose was administered by intramuscular injection, 100μg，1.0ml/dose
|
| Placebo Comparator: Control Group
|
Drug: 0.9% sodium chloride solution
One dose was administered by intramuscular injection, 1.0ml/dose
|
Outcome Measures
Primary Outcome Measures
- Person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19 [14 days after vaccination or placebo]
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.
Secondary Outcome Measures
- Person-year incidence density of first episodes of virologically-confirmed moderate to severe cases of COVID-19 [14 days after vaccination or placebo]
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.
- Person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19 [14 days after vaccination or placebo]
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.
- Person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 [14 days after vaccination or placebo]
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.
- 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) [14 days after vaccination or placebo]
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).
- Incidence of each solicited (local and systemic) AE in all participants. [within 14 days after vaccination or placebo]
Incidence of each solicited (local and systemic) AE within 14 days after booster vaccination in all participants.
- Severity of each solicited (local and systemic) AE in all participants. [within 14 days after vaccination or placebo]
Severity of each solicited (local and systemic) AE within 14 days after booster vaccination in all participants.
- Duration of each solicited (local and systemic) AE in all participants. [within 14 days after vaccination or placebo]
Duration of each solicited (local and systemic) AE within 14 days after booster vaccination in all participants.
- Incidence of unsolicited AEs in all participants. [0-28 days after vaccination or placebo]
Incidence of unsolicited AEs occurring 0-28 days after booster vaccination in all participants.
- Severity of unsolicited AEs in all participants. [0-28 days after vaccination or placebo]
Severity of unsolicited AEs occurring 0-28 days after booster vaccination in all participants.
- Causality of unsolicited AEs in all participants. [0-28 days after vaccination or placebo]
Causality of unsolicited AEs occurring 0-28 days after booster vaccination in all participants.
- Incidence of SAEs in all participants. [within 12 months after vaccination or placebo]
Incidence of SAEs from the day of booster vaccination to 12 months after booster vaccination in all participants.
- Severity of SAEs in all participants. [within 12 months after vaccination or placebo]
Severity of SAEs from the day of booster vaccination to 12 months after booster vaccination in all participants.
- Incidence of AESIs in all participants. [within 12 months after vaccination or placebo]
Incidence of AESIs from the day of booster vaccination to 12 months after booster vaccination in all participants.
- Severity of AESIs in all participants. [within 12 months after vaccination or placebo]
Severity of AESIs from the day of booster vaccination to 12 months after booster vaccination in all participants.
- Incidence of pregnancy events in all participants. [within 12 months after vaccination or placebo]
Incidence of pregnancy events from the day of booster vaccination to 12 months after booster vaccination in all participants.
- Severity of pregnancy events in all participants. [within 12 months after vaccination or placebo]
Severity of pregnancy events from the day of booster vaccination to 12 months after booster vaccination in all participants.
- Causality of SAEs, AESIs, and pregnancy events in all participants. [within 12 months after vaccination or placebo]
Causality of SAEs, AESIs, and pregnancy events from the day of booster vaccination to 12 months after booster vaccination in all participants.
- 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]
Other Outcome Measures
- Person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 of any severity caused by individual VOCs. [14 days after vaccination or placebo]
The person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 of any severity from 14 days after booster vaccination caused by individual VOCs.
- Cellular immune subgroup:viral antigen IL-2 levels [7 days, 14 days, 28 days and 3 months after vaccination or placebo]
Cellular immune subgroup:viral antigen IL-2 levels at 7 days, 14 days, 28 days and 3 months booster vaccination. (ELISpot assay)
- Cellular immune subgroup:viral antigen IL-4 levels [7 days, 14 days, 28 days and 3 months after vaccination or placebo]
Cellular immune subgroup:viral antigen IL-4 levels at 7 days, 14 days, 28 days and 3 months booster vaccination. (ELISpot assay)
- Cellular immune subgroup:viral antigen IL-13 levels [7 days, 14 days, 28 days and 3 months after vaccination or placebo]
Cellular immune subgroup:viral antigen IL-13 levels at 7 days, 14 days, 28 days and 3 months booster vaccination. (ELISpot assay)
- Cellular immune subgroup:viral antigen IFN-γ levels [7 days, 14 days, 28 days and 3 months after vaccination or placebo]
Cellular immune subgroup:viral antigen IFN-γ levels at 7 days, 14 days, 28 days and 3 months booster vaccination. (ELISpot assay)
- Cross-neutralization subgroup:the cross-neutralizing ability of serum neutralizing antibodies in subjects. [14 days, 28 days after vaccination or placebo]
The cross-neutralizing ability of serum neutralizing antibodies collected 14 days and 28 days after booster vaccination in the cross neutralization subgroup.
- The immunological correlation of risk and protection against symptomatic COVID-19 and SARS-CoV-2 infection after booster vaccination. [after vaccination or placebo]
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sindh Infectious Diseases Hospital & Research Center Dow University of Health Sciences | Islamabad | Pakistan | 9216793 |
Sponsors and Collaborators
- AIM Vaccine Co., Ltd.
- LiveRNA Therapeutics Inc.
- Ningbo Rongan Biological Pharmaceutical Co. Ltd.
Investigators
- Study Director: Fan Zhang, AIM Vaccine Co., Ltd.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LVRNA021-III-01