Clinical trial NCT05812014: Clinical Trail of SARS-CoV-2 Bivalent mRNA Vaccine (LVRNA021) in Participants Aged 18 Years and Older
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: SARS-CoV-2
Lead sponsor: AIM Vaccine Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: LiveRNA Therapeutics Inc.
name: Ningbo Rongan Biological Pharmaceutical Co., Ltd.
First posted: 2023-04-13
Enrollment: 9800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

1. Adults aged 18 years and older;
2. 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);
3. Participants who are willing and able to comply with all scheduled visits, vaccination plan, laboratory tests, lifestyle considerations, and other study procedures;
4. 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.);
5. 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；
6. On the day of vaccination and 24 hours prior to vaccination, axillary temperatures\<37.3°C/99.1°F;
7. Healthy participants or participants with mild underlying disease \[in a stable state without exacerbation (no admission to hospital or no major adjustment to treatment regimen, etc.) for at least 3 months prior to enrollment in this study\];
8. 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:

1. History of Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), or other coronavirus infections at any time;
2. History of hepatitis A, hepatitis B, hepatitis C, syphilis infection based on medical inquiry.;
3. 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);
4. Receipt of medications intended to treat COVID-19 within 6 months;
5. Virologically confirmed SARS-CoV-2 diagnosis within 6 months before screening visit;
6. Positive nasopharyngeal/oropharyngeal swab SARS-CoV-2 RT-PCR test result at screening;
7. Positive HIV test result at screening;
8. A history or family history of convulsions, epilepsy, encephalopathy and psychosis;
9. Malignant tumors in the active phase, malignant tumors not receiving adequate treatment, malignant tumors at potential risk of recurrence during the study period;
10. Asplenia or functional asplenia, complete or partial splenectomy from any cause;
11. 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;
12. 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;
13. 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;
14. Blood donation or blood loss ≥ 450 mL within 1 month prior to enrollment or planned to donate blood during the study period;
15. Participation in other studies involving study intervention within 28 days prior to study entry, and/or during the study;
16. Women who are pregnant or breastfeeding;
17. Participants deemed unsuitable for participation in this study based on the investigator's assessment.

Primary outcomes:
measure: Person-year incidence density of first episodes of virologically-confirmed symptomatic cases of COVID-19
timeFrame: 14 days after vaccination or placebo
Secondary outcomes:
measure: Person-year incidence density of first episodes of virologically-confirmed moderate to severe cases of COVID-19
timeFrame: 14 days after vaccination or placebo
measure: Person-year incidence density of first episodes of virologically-confirmed severe cases of COVID-19
timeFrame: 14 days after vaccination or placebo
measure: Person-year incidence density of first episodes of virologically-confirmed cases of COVID-19
timeFrame: 14 days after vaccination or placebo
measure: 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)
timeFrame: 14 days after vaccination or placebo
measure: Incidence of each solicited (local and systemic) AE in all participants.
timeFrame: within 14 days after vaccination or placebo
measure: Severity of each solicited (local and systemic) AE in all participants.
timeFrame: within 14 days after vaccination or placebo
measure: Duration of each solicited (local and systemic) AE in all participants.
timeFrame: within 14 days after vaccination or placebo
measure: Incidence of unsolicited AEs in all participants.
timeFrame: 0-28 days after vaccination or placebo
measure: Severity of unsolicited AEs in all participants.
timeFrame: 0-28 days after vaccination or placebo
measure: Causality of unsolicited AEs in all participants.
timeFrame: 0-28 days after vaccination or placebo
measure: Incidence of SAEs in all participants.
timeFrame: within 12 months after vaccination or placebo
measure: Severity of SAEs in all participants.
timeFrame: within 12 months after vaccination or placebo
measure: Incidence of AESIs in all participants.
timeFrame: within 12 months after vaccination or placebo
measure: Severity of AESIs in all participants.
timeFrame: within 12 months after vaccination or placebo
measure: Incidence of pregnancy events in all participants.
timeFrame: within 12 months after vaccination or placebo
measure: Severity of pregnancy events in all participants.
timeFrame: within 12 months after vaccination or placebo
measure: Causality of SAEs, AESIs, and pregnancy events in all participants.
timeFrame: within 12 months after vaccination or placebo
measure: Geometric mean titer (GMT)of SARS-CoV-2 (Omicron subvariants) virus neutralizing antibody (live virus neutralizing assay) responses in subjects in the immunization subgroup.
timeFrame: 14 days,28 days,3 months and 6 months after vaccination or placebo
measure: Seroconversion rate (SCR) of SARS-CoV-2 (Omicron subvariants) virus neutralizing antibody (live virus neutralizing assay) responses in subjects in the immunization subgroup.
timeFrame: 14 days,28 days,3 months and 6 months after vaccination or placebo
measure: Geometric mean Increase (GMI) of SARS-CoV-2 (Omicron subvariants) virus neutralizing antibody (live virus neutralizing assay) responses in subjects in the immunization subgroup.
timeFrame: 14 days,28 days,3 months and 6 months after vaccination or placebo
measure: GMT of S-protein IgG antibodies in subjects in the immunization subgroup.
timeFrame: 14 days, 28 days,3 months,6 months and 12 months after vaccination or placebo
measure: GMI of S-protein IgG antibodies in subjects in the immunization subgroup.
timeFrame: 14 days, 28 days,3 months,6 months and 12 months after vaccination or placebo
measure: SCR of S-protein IgG antibodies in subjects in the immunization subgroup.
timeFrame: 14 days, 28 days,3 months,6 months and 12 months after vaccination or placebo
Other outcomes:
measure: Person-year incidence density of first episodes of virologically-confirmed cases of COVID-19 of any severity caused by individual VOCs.
timeFrame: 14 days after vaccination or placebo
measure: Cellular immune subgroup:viral antigen IL-2 levels
timeFrame: 7 days, 14 days, 28 days and 3 months after vaccination or placebo
measure: Cellular immune subgroup:viral antigen IL-4 levels
timeFrame: 7 days, 14 days, 28 days and 3 months after vaccination or placebo
measure: Cellular immune subgroup:viral antigen IL-13 levels
timeFrame: 7 days, 14 days, 28 days and 3 months after vaccination or placebo
measure: Cellular immune subgroup:viral antigen IFN-γ levels
timeFrame: 7 days, 14 days, 28 days and 3 months after vaccination or placebo
measure: Cross-neutralization subgroup:the cross-neutralizing ability of serum neutralizing antibodies in subjects.
timeFrame: 14 days, 28 days after vaccination or placebo
measure: The immunological correlation of risk and protection against symptomatic COVID-19 and SARS-CoV-2 infection after booster vaccination.
timeFrame: after vaccination or placebo
Locations:
city: Islamabad
country: Pakistan
facility: Sindh Infectious Diseases Hospital & Research Center Dow University of Health Sciences
Study officials:
affiliation: AIM Vaccine Co., Ltd.
name: Fan Zhang
role: STUDY_DIRECTOR
References: