A Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SARS-CoV-2 Bivalent mRNA Vaccine (LVRNA021)

Randomized, Blinded, Positive and Placebo-controlled Phase II Clinical Trial to Evaluate the Immunogenicity and Safety of SARS-CoV-2 Bivalent mRNA Vaccine (LVRNA021) Booster Vaccination in People 18 Years of Age and Older Who Have Received SARS-CoV-2 Vaccine.

This trial is a phase II clinical trial of SARS-CoV-2 Bivalent mRNA Vaccine (LVRNA021). The trial was randomized, blinded, positive and placebo controlled. To evaluate the safety and immunogenicity of the study vaccine in participants aged 18 years and older who have received SARS-CoV-2 Vaccine.

Study Overview

• Status: Not yet recruiting
• Conditions: SARS-CoV-2
• Intervention / Treatment: Biological: SARS-CoV-2 Bivalent mRNA Vaccine; Other: Saline; Biological: Recombinant SARS-CoV-2 vaccine

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fan Zhang; Phone Number: 021-33360772; Email: fan.zhang@aimbio.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Provincial Center for Disease Control and Prevention
      • Contact: Fengcai Zhu; Email: jszfc@jscdc.cn
      • Contact: Hongxing Pan; Email: panhongxing@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy adults aged 18 years and older, both male and female, who can provide legal identity certificate of participants;
2. The subject understands the contents of the Informed Consent Form and the vaccination situation of this vaccination, voluntarily signs the Informed Consent Form, and has the ability to use the thermometer, scale and fill in the Diary Card and Contact Card as required (if the subject is unable to sign the Informed Consent Form by himself/herself due to limited reading and writing ability, the informed consent form and signature of the Informed Consent Form can be completed under the witness' s witness);
3. Able to communicate well with investigators and understand and comply with the requirements of this trial;
4. Completion of basic immunization with SARS-CoV-2 vaccine ≥ 6 months;
5. Negative nucleic acid test for SARS-CoV-2 within 3 days prior to vaccination;
6. Women who have used effective contraception within 2 weeks prior to inclusion in this trial, have a negative pregnancy test (pregnancy test can be exempted for those who have been amenorrheic for at least 1 year or have a documented history of surgical sterilization), and voluntarily agree to continue using at least 1 effective contraception within 6 months after vaccination [effective contraception includes: oral contraceptives, injected or implanted contraception, sustained-release local contraceptives, hormonal patches, intrauterine device (IUD), sterilization, abstinence, condoms (men), diaphragms, cervical caps, etc.];
7. Healthy participants or participants with mild underlying disease [stable condition without worsening (requiring no hospitalization or major modification of treatment regimen, etc.) for at least 3 months prior to inclusion in this trial].

Exclusion Criteria:

1. Abnormal blood pressure indicators in the screening period, and the investigator determines that the health condition is uncertain and further diagnosis is required, or the investigator determines that the vaccination is not suitable in combination with the medical history and clinical manifestations;
2. Body mass index (BMI) <18 kg/m 2 or >30 kg/m 2;
3. Individuals with any infectious disease, acute infection, acute phase of chronic infection (such as active untreated pulmonary tuberculosis, etc.) or any advanced immune disease (inquiry);
4. Infected within last 6 months or likely infected with SARS-CoV-2;
5. Positive HIV test result at screening;
6. Fever on the day of investigational vaccination (axillary temperature ≥ 37.3℃) or within 3 days, or use of antipyretic and analgesic drugs within 3 days;
7. Women with a positive pregnancy test (surgical sterilizers who are menstruating or amenorrheic for at least 1 year or have medical records may be exempted from pregnancy testing), or breastfeeding women, or women planning to become pregnant from screening through 6 months after booster vaccination, men whose partners plan to become pregnant, or plan to donate sperm and eggs;
8. Previous history of allergic or allergic reactions to vaccines or drugs, such as urticaria, severe skin eczema, dyspnea, laryngeal edema, angioneurotic edema, etc.;
9. Administration of any vaccine within 28 days prior to booster vaccination with investigational vaccine;
10. Have participated within 28 days prior to booster vaccination with investigational vaccine or plan to participate in other drug clinical trials within 12 months after booster vaccination;
11. Patients with a history of thrombocytopenia or other coagulation disorders, which may cause contraindications to subcutaneous blood sampling or injection, and patients with a history of thrombosis;
12. Known history or diagnosis of diseases affecting immune system function, such as cancer (except basal cell carcinoma of the skin), congenital or acquired immunodeficiency, uncontrolled autoimmune diseases, etc. (such as systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis);
13. Absence of spleen or functional absence of spleen;
14. Chronic use (≥14 consecutive days) of immunosuppressants or other immunomodulatory drugs (eg, corticosteroids: prednisone or drugs of the same class) within 6 months prior to booster vaccination with the investigational vaccine, but topical medications (eg, ointments, eye drops, inhalers, or nasal sprays) are allowed and should not exceed the dose recommended in the package insert;
15. Immunoglobulins and/or blood products received within 3 months prior to the investigational booster vaccination;
16. Suspected or known alcohol dependence or drug abuse that could compromise the safety evaluation or subject compliance;
17. Other conditions that the investigator considers inappropriate for participation in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline; One booster dose 1.0mL IM injection of saline.	Other: Saline; 100 μg /1.0 mL/dose, intramuscular injection into the lateral deltoid muscle of the upper arm.
Experimental: SARS-CoV-2 Bivalent mRNA Vaccine; 100 μg /1.0 mL/dose, One booster dose 1.0mL IM injection of SARS-CoV-2 Bivalent mRNA Vaccine (LVRNA021).	Biological: SARS-CoV-2 Bivalent mRNA Vaccine; 100 μg /1.0 mL/dose, slightly milky white and clear liquid, intramuscular injection into the lateral deltoid muscle of the upper arm.; Other Names: LVRNA021
Active Comparator: Recombinant SARS-CoV-2 vaccine; One booster dose 0.5mL IM injection of recombinant SARS-CoV-2 vaccine.	Biological: Recombinant SARS-CoV-2 vaccine; 1.0 mL/vial. Each human dose was 0.5 mL containing 25 ug NCP-RBD protein.Each human dose is 0.5 mL, and the recommended route of administration is intramuscular injection, with the best site being the deltoid muscle of the upper arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMT, SCR of neutralizing antibodys against SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains).	GMT, SCR of neutralizing antibodys against SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains) on day 14 after vaccination.	14 day after booster vaccination.
Incidence of solicited and unsolicited adverse events	Incidence of solicited and unsolicited adverse events within 0-28 days after booster vaccination.	0-28 days after booster vaccination.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of serious adverse events (SAEs) of special interest (AESIs).	Incidence of serious adverse events (SAEs) of special interest (AESIs) through 12 months after booster vaccination in all subjects.	12 months after booster vaccination
GMI of neutralizing antibodies against SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains).	GMI of neutralizing antibodies against SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains) on day 14 after booster vaccination.	14 day after booster vaccination.
GMT, SCR, GMI of neutralizing antibodies against SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains).	GMT, SCR, GMI of neutralizing antibodies against SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains) on days 7 and 28 after booster vaccination.	7, 28 days after booster vaccination.
GMT of neutralizing antibodies against SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains).	GMT of neutralizing antibodies against SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains) at 3, 6, 12 months after booster vaccination.	3, 6, 12 months after booster vaccination.
GMC, SCR, GMI of IgG antibodies against S proteins of SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains)	GMC, SCR, GMI of IgG antibodies against S proteins of SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains) on days 7, 14, and 28 after booster vaccination.	7, 14, 28 days after booster vaccination.
GMC of antibodies against S proteins of SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains)	GMC of antibodies against S proteins of SARS-CoV-2 (original strain, delta strain, Omicron BA.5, XBB strains and current major circulating strains) at 3 months, 6 months and 12 months after booster vaccination.	3, 6, 12 months after booster vaccination.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific T cell responses after booster vaccination.	Specific T cell responses secreting IL-2, IL-4, IL-13, IFN-γ cytokines (ELISpot) on days 7, 14, and 28 after booster vaccination in cellular immune subgroups.	7, 14, 28 days after booster vaccination.
Broad spectrum of immunogenicity against SARS-CoV-2.	Broad spectrum of immunogenicity against SARS-CoV-2 after booster vaccination.	after booster vaccination.

Collaborators and Investigators

• Sponsor: AIM Vaccine Co., Ltd.
• Collaborators: Zhejiang Provincial Center for Disease Control and Prevention
• Investigators: Study Director: fan zhang, AIM Vaccine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): August 11, 2023
• Primary Completion (Estimated): September 30, 2023
• Study Completion (Estimated): September 30, 2023

Study Registration Dates

• First Submitted: July 7, 2023
• First Submitted That Met QC Criteria: July 7, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: LVRNA021-II-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No