A Phase 1b Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine Against COVID-19

A Randomized, Blinded, Positive Control Phase 1b Trial to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 mRNA Chimera Vaccine (RQ3013) in Healthy Adults Completed a Two-dose Primary Series of Inactivated Vaccine

This is a phase 1b, randomized, double-blind, positive control trial in healthy adults, intended to evaluate the safety and immunogenicity profile of RQ3013 in healthy adults primed with a two-dose inactivated vaccine 6-9 months earlier. The study vaccine is administered IM in the upper arm deltoid as single booster shot on day 0.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: RQ3013; Biological: Comirnaty

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy participants 18-59 years and 60 years and older, and both males and females should be included;
2. Participants who agree to participate in this clinical trial voluntarily and sign the informed consent form, are capable of providing valid identification, understanding and complying with the requirements of the clinical protocol.
3. Participants who have been primed with a two-dose inactivated vaccine 6-9 months earlier, and the intervals between the two inactivated vaccines was between 21 and 42 days.
4. For female participants of childbearing potential, effective contraception measures should be used within 2 weeks prior to participation in this study and the results of the pregnancy test must be negative. Participants must voluntarily agree to use effective contraceptive measures from the time of signing the informed consent form to the end of the study (effective contraceptive measures including oral contraceptives (excluding emergency contraceptives), injectable or implantable contraceptives, sustained-release topical contraceptives, hormonal patches, intrauterine device, sterilization, abstinence, condoms (for males), diaphragms, cervical caps, etc.).

Exclusion Criteria:

1. Receipt of any COVID-19 prophylactic medication other than a primary series of inactivated vaccine (e.g., receipt history of any approved or under developing COVID-19 vaccines, or other COVID-19 prophylactic medication, etc.), or non-standard primary series of inactivated vaccine;
2. Abnormal vital signs with clinical significance at screening, with systolic blood pressure ≥140 mmHg (≥150 mmHg for participants aged ≥ 60 years) and/or diastolic blood pressure ≥90 mmHg, or axillary body temperature ≥ 37.3°C, or abnormal results of laboratory screening tests which was clinically significant at screening;
3. Known allergy, or history of anaphylaxis or other serious adverse reactions to the study vaccine or its excipients;
4. History of severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS);
5. History of COVID-19, or history of close contact with confirmed/suspected COVID-19 patients, or positive results for SARS-CoV-2 nucleic acid tests at screening;
6. Administration of antipyretics or painkillers within 24 hours prior to vaccination;
7. Receipt of any live attenuated vaccine within 28 days prior to vaccination, or subunit and inactivated vaccine within 14 days prior to vaccination;
8. Receipt of blood or blood-related products, including immunoglobulins, within 3 months prior to vaccination; or any planned use during the study period.

9. Participants with the following diseases:

   1. Any acute diseases or acute attacks of chronic diseases within 7 days prior to enrolment；
   2. Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.；
   3. Congenital or acquired immunodeficiency or autoimmune disease, or long-term receipt (>14 consecutive days) of glucocorticoid (reference value for dose: ≥20 mg/day prednisone or equivalent) or other immunosuppressive agents within the past 6 months, with exception of inhaled or topical steroids, or short-term use (≤14 consecutive days) of oral corticosteroids；
   4. Currently suffering from or previously diagnosed with infectious diseases, positive screening results for hepatitis B surface antigen, hepatitis C antibody, treponema pallidum antibody, human immunodeficiency virus antibody；
   5. History or family history of neurological disorders (convulsions, epilepsy, encephalopathy, etc.) or psychiatric disorders；
   6. Asplenia, or functional asplenia；
   7. Presence of severe, uncontrollable or hospitalization indicated cardiovascular diseases, diabetes, blood and lymphatic diseases, immune diseases, liver and kidney diseases, respiratory diseases, metabolic and skeletal diseases, or malignant tumors, except for history of well-controlled chronic diseases, such as diabetes, hypertension, etc.;
   8. Participants who cannot tolerate venepuncture, or have a history of needle or blood phobia;
   9. Contraindications to IM injections and blood draws, such as coagulation disorders, thrombotic or bleeding disorders, or conditions that needs continuous anticoagulant usage.
10. Drug or alcohol abuse (alcohol intake ≥ 14 units per week) which in the investigator's opinion would compromise the participant's safety or compliance with the study procedures;
11. History of a major surgery, per the investigator's judgment, within 12 weeks before vaccination, or not achieving full recovery after surgery, or any planned major surgery during the study;
12. Pregnant or lactating females; males whose partner plans to conceive; males or females who plan to donate sperm or eggs;
13. Participating or planning to participate in other clinical trials during the study period;
14. Presence of any underlying disease or condition which, in the opinion of the investigator, may place the participant at unacceptable risk, make the participant unable to meet the requirements of the protocol, or interfere with the assessment of vaccine response.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Comirnaty	Biological: Comirnaty; A single dose of 30 μg/0.3 mL
Experimental: RQ3013	Biological: RQ3013; A single dose of 30 μg/0.15 mL, a single dose of 60 μg/0.3 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Immediate AEs within 30 minutes after booster vaccination, solicited local and systemic AEs for within 7 days and unsolicited AEs within 28 days following booster vaccination	within 28 days following booster vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Live virus GMT, GMFR and seroconversion rate against Beta and Omicron strain in serum measured at pre booster dose and day 7, 14, 28 after booster dose	pre booster dose and day 7, 14, 28 after booster dose
Pseudovirus GMT, GMFR and seroconversion rate against SARS-CoV-2 Beta and Omicron strain in serum measured at pre booster dose and day 7, 14, 28 after booster dose	pre booster dose and day 7, 14, 28 after booster dose
GMT, GMFR and seroconversion rate of S-Protein Specific IgGs in serum measured at pre booster dose and day 7, 14, 28 after booster dose	pre booster dose and day 7, 14, 28 after booster dose
Live virus GMT, GMFR and seroconversion rate against Beta and Omicron strain in serum measured at 3, 6, 12 months after booster dose	3, 6, 12 months after booster dose
Pseudovirus GMT, GMFR and seroconversion rate against SARS-CoV-2 Beta and Omicron strain in serum measured at 3, 6, 12 months after booster dose	3, 6, 12 months after booster dose
GMT, GMFR and seroconversion rate of S-Protein Specific IgGs in serum measured at 3, 6, 12 months after booster dose	3, 6, 12 months after booster dose
Changes of safety laboratory measures at day 4 following booster vaccination in comparison to pre-boosting levels	day 4 following booster vaccination
SAEs and AESIs throughout the study	12 months after vaccination

Other Outcome Measures

Outcome Measure	Time Frame
Spike protein specific CD4+, CD8+, CD4+IFN-γ+, CD4+IL-2+, CD4+TNFα+, CD4+IL-4+, CD4+IL-13+, CD8+IFN-γ+, CD8+IL-2+, CD8+TNFα+ cytokine profiling (flow cytometry) by flow cytometry at baseline and day 7, 14 after booster	baseline and day 7, 14 after booster
Spike protein specific cytokine responses by enzyme-linked immunospot (ELISPOT) assay, IFN-γ, IL-2, IL-4 at baseline and day 7, 14 after booster	baseline and day 7, 14 after booster
Spike protein specific T memory cell responses: CD4+ and CD8+ TCM(CCR7+CD45RA-), TEM(CCR7-CD45RA-) and TSCM(CCR7+CD45RA+CD95+) at baseline and 28 days, 3, 6 months after booster	baseline and 28 days, 3, 6 months after booster

Collaborators and Investigators

• Sponsor: Walvax Biotechnology Co., Ltd.
• Collaborators: Shanghai RNACure Biopharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: May 26, 2022
• First Posted (Actual): May 31, 2022

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: RQ3013-005

Drug and device information, study documents

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