Safety, and Immunogenicity Study of the Recombinant Two-component COVID-19 Vaccine (CHO Cell)

Study Overview
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Brief Summary
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Part 1: Primary Vaccination in Adults Part 1 will evaluate the safety and immunogenicity of the recombinant two component COVID-19 vaccine (CHO cell) (ReCOV for short) in adults aged 18 years and older, when administered as 2 intramuscular doses, 21 days apart. Part 2: Booster Vaccination in Adults Part 2 will evaluate the immunogenicity and safety and of one booster dose of ReCOV in adult participants who have received primary vaccination with 2 doses of an inactivated COVID-19 vaccine (CoronaVac®). COMIRNATY®, an mRNA COVID-19 vaccine will be used as the active control.

Detailed Description
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Part 1: Primary Vaccination in Adults Around 340 participants aged 18 years and older who do not have known COVID-19 or COVID-19 vaccination history will be randomized into ReCOV group (40 μg) or placebo group in a ratio of 2:1. Accordingly, around 227 participants will receive 40 μg ReCOV and 113 participants will receive matching placebo, respectively. Participants will be stratified by age (18 59 years, ≥60 years) and status of SARS-CoV-2 antibody at baseline. After randomization, participants will enter into a double-blinded period (until all participants complete V6) and an open-label long-term follow-up period (after all participants complete V6 until end of the study). After all participants complete the visit at 7 days after the 2nd vaccination, the safety and reactogenicity data will be summarized by an independent statistic group, while the sponsor, investigators and all study participants will be kept blinded. The safety summary will be submitted to DSMB for review and recommendation on the initiation of Part 2. The primary analysis of Part 1 is planned after all participants complete the Visit 6 (V3 + 28 days, +7 days) and are unblinded, to evaluate the safety and immunogenicity during the double-blinded period. The final analysis of Part 1 will be conducted after all participants of the ReCOV group complete the follow-up visit at 6 months after the 2nd vaccination, to evaluate the safety and immunogenicity during this study stage. Part 2: Booster Vaccination in Adults This study part will enroll participants who have received primary vaccination by an inactivated COVID-19 vaccine (CoronaVac®) within 3 to 12 months (90 365 days). The mRNA COVID-19 vaccine, COMIRNATY ®, will be used as the active control. The immunogenicity induced by the booster vaccination of ReCOV (commercial batch, Lot# TC202205002) will be compared with that of COMIRNATY®. In addition, the immunogenicity of one dose booster of commercial batch ReCOV (Lot# TC202205002) will be compared with that of pilot batch ReCOV (Lot# HA202107009). About 588 participants will be enrolled into the study. Eligible participants will be 1:1:1 randomized to receive 20 μg ReCOV (Lot# HA202107009), 20 μg ReCOV (Lot# TC202205002), or 30 μg COMIRNATY®, stratified by age (18 59 years, ≥60 years) and the duration since the last primary vaccination (90 180 days, 181 365 days). All participants will be followed up for safety and reactogenicity. Participants will be observed for 30 minutes at study site after the vaccination. Before leaving the study site, participants will be given participant diaries to record solicited AEs within 7 days after dosing, and unsolicited AEs within 28 days after dosing. The occurrence of SAEs and AESIs will also be monitored till 6 months after the study vaccination. The interim analysis is planned after all participants complete the Visit 5 at 28 days after the dosing, to evaluate the immunogenicity and safety within this period. The final analysis will be conducted after all participants complete the follow-up visit at 6 months post the booster vaccination, to evaluate the immunogenicity and safety.

Official Title
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A Randomized, Blinded, Two-part, Phase II Trial to Evaluate the Safety and Immunogenicity of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) in Adults 18 Years and Older

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Part1:Recombinant two-component COVID-19 vaccine (CHO cell)
* Biological: Part1: Placebo
* Biological: Part2: Recombinant two-component COVID-19 vaccine (CHO cell)
* Biological: Part2: COVID-19 Vaccine, mRNA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years and older. All participants are able and willing to comply with all study requirements. Willing to allow investigators to discuss the medical history with his/her general practitioner/personal doctors and access all medical records which are relevant to study procedures. Healthy participants, or participants with stable medical condition who have a pre-existing medical condition that does not meet any exclusion criteria. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment. For Part 1, participants should have not received any COVID-19 vaccine before the screening. For Part 2, participants should have received complete 2-dose primary vaccination with an inactivated COVID-19 vaccine (CoronaVac®), 90 365 days (included) prior to the study vaccination. Provide written informed consent form (ICF) prior to study enrollment. Exclusion Criteria Laboratory confirmed SARS-CoV-2 infection, defined by RT-PCR assay. Medical history of severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and COVID-19 within 12 months prior to the randomization. Fever (oral temperature ≥ 37.5°C / axillary temperature ≥ 37.3°C) on the day of vaccination or within recent 72 hours. History of severe allergic disease or reactions likely to be exacerbated by any component of ReCOV or the control vaccine, such as allergic shock, allergic laryngeal edema, allergic purpura, thrombocytopaenic purpura, local hypersensitive necrosis reaction (Arthus reaction), or prior history of serious adverse reaction to any vaccine or drug, such as allergy, urticaria eczema, dyspnea, and angioneurotic edema. Have malignant tumor (except for skin basal cell carcinoma or carcinoma uterine cervix in situ) and immune disease (e.g., human immunodeficiency virus [HIV] infection, systemic lupus erythematosus, rheumatoid arthritis, asplenia or splenectomy, and other immune disease that may influence immune response at investigator's discretion). Have other severe and/or uncontrolled conditions, including but not limited to, acute infectious disease, cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, hematology disease, endocrine disorder, psychiatric condition and neurological illness. Mild/moderate well-controlled comorbidities are allowed to participate as deemed appropriate by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: Part1: 2 arms Part2: 2 arms
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part1: Recombinant two-component COVID-19 vaccine (CHO cell)<br>Antigen: NTD-RBD-foldon protein, sodium dihydrogen phosphate, disodium hydrogen phosphate, sucrose, glycine, polysorbate 80 Adjuvant (BFA03): squalene, alpha-tocopherol, polysorbate 80, sodium chloride, potassium chloride, disodium hydrogen phosphate, potassium dihydrogen phosphate | Biological: Part1:Recombinant two-component COVID-19 vaccine (CHO cell)<br>* 2 doses. Before reconstitution:Lyophilized powder for reconstitution in single-use vials; After reconstitution with BFA03 adjuvant: Milk-white solution with no visible foreign matter; Unite Does Strengths: 40ug/vial; Does Volume: 0.5ml/dose Routine of administration: Intramuscular (IM) injection<br>* Other names: Part1: ReCOV;|
| Placebo Comparator: Part1: Placebo control<br>Antigen: sodium dihydrogen phosphate, disodium hydrogen phosphate, sucrose, glycine, polysorbate 80 Adjuvant (BFA03): squalene, alpha-tocopherol, polysorbate 80, sodium chloride, potassium chloride, disodium hydrogen phosphate, potassium dihydrogen phosphate | Biological: Part1: Placebo<br>* 2 doses. Before reconstitution: Lyophilized powder for reconstitution in single-use vials; After reconstitution with BFA03 adjuvant: Milk-white solution with no visible foreign matter; Unite Does Strengths: Not Applicable; Does Volume: 0.5ml/dose; Routine of administration: IM injection;<br>|
| Experimental: Part2: Recombinant two-component COVID-19 vaccine (CHO cell)<br>(Lot# HA202107009 and Lot# TC202205002) Recombinant two-component COVID-19 vaccine (CHO cell) Antigen: NTD-RBD-foldon protein, sodium dihydrogen phosphate, disodium hydrogen phosphate, sucrose, glycine, polysorbate 80 Adjuvant (BFA03): squalene, alpha-tocopherol, polysorbate 80, sodium chloride, potassium chloride, disodium hydrogen phosphate, potassium dihydrogen phosphate | Biological: Part2: Recombinant two-component COVID-19 vaccine (CHO cell)<br>* 1 dose.Before reconstitution:Lyophilized powder for reconstitution in single-use vials; After reconstitution with BFA03 adjuvant: Milk-white solution with no visible foreign matter; Unite Does Strengths: 40ug/vial; Does Volume: 0.5ml/dose Routine of administrati<br>* Other names: Part2: ReCOV;|
| Active Comparator: Part2: COMIRNATY® COVID-19 Vaccine, mRNA<br>Antigen: nucleoside-modified messenger RNA (mRNA) encoding the viral Spike (S) glycoprotein of SARS-CoV-2, called tozinameran. Others: ((4-hydroxybutyl) azanediyl) bis (hexane-6,1-diyl) bis (2-hexyldecanoate), 2-[(polyethylene glycol)-2000]-N, N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol, potassium chloride, potassium dihydrogen phosphate, sodium chloride, disodium phosphate dihydrate, sucrose. | Biological: Part2: COVID-19 Vaccine, mRNA<br>* 1 dose. Intramuscular injection, 30 μg/0.3 mL.<br>* Other names: Part2: COMIRNATY®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part1, Primary Safety | Number of Participants with AEs | Day 7 after first dose and up to Day 28 after second dose | 
| Part1, Primary immunogenicity | To evaluate SARS-CoV-2 Specific Neutralizing Antibody | 14 days after 2 doses vaccination | 
| Part2, Primary immunogenicity | To evaluate SARS-CoV-2 Specific Neutralizing Antibody | 14 days after 2 doses vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part1, Immunogenicity | To evaluate other immunogenicity variables of ReCOV in adults aged 18 years and older. | 14 days, 3 months and 6 months after 2 doses vaccination | 
| Part2, safety and reactogenicity | The occurrence of AEs | 7 days, 28days and 6 months after the booster vaccination |