Phase I Clinical Trial of Recombinant SARS-CoV-2 Spike Protein Vaccine (CHO Cell) for the Prevention of COVID-19

Study Overview
=================
Brief Summary
-----------------
The purpose of this double-blind, randomized, controlled study is to assess safety, reactogenicity, and preliminary immunogenicity of 202-CoV at multiple dose levels, administered as 2 injections (i.m) at 28 days apart in adult subjects 18 years of age and above.

Official Title
-----------------
A Randomized, Double-blinded, Placebo-controlled Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Preliminary Immunogenicity of the Recombinant SARS-CoV-2 Vaccine (CHO Cell) in Healthy Adults Aged 18 Years and Above

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Biological: 202-CoV low adjuvant dose
* Biological: 202-CoV low antigen dose
* Biological: 202-CoV standard dose
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy individuals aged 18-59 years as well as 60 years and above who can provide legal identification (males and females are both required). Willing to participate in the study with informed consent prior to screening Negative in SARS-CoV-2 IgG and IgM test at screening. Women of childbearing potential must be using effective method of birth control for 14 days prior to the enrollment of the study vaccine/placebo and must agree to continue such precautions during the study until 30 days after the second dose of the study vaccine/placebo. Male subjects must agree to employ acceptable contraception from the day of first dose of the study vaccine/placebo until 30 days after the second dose of the study vaccine/placebo. Exclusion Criteria: Confirmed or asymptomatic COVID-19 cases or SARS-CoV-2 infection(had positive in SARS-CoV-2 nucleic acid test or serological test). Had a history of traveling or residence in domestic area of high and moderate pandemic risk, overseas or epidemic areas, or had a history of contact with confirmed, asymptomatic or suspected COVID-19 cases within the past 14 days; History of SARS; Received SARS-CoV-2 vaccines for emergency use or approved SARS-CoV-2 vaccines; Individuals involving a clinical study within 6 months prior to the screening visit; or planning to participate in another clinical study during study period. Clinical laboratory abnormalities and with clinical significance judged by investigator Individual's systolic blood pressure ≥ 150mmHg and/or diastolic blood pressure ≥ 100mmHg at screening visit Axillary temperature >=37.3℃ prior to vaccination Individuals in other acute diseases, or in the acute phase of chronic diseases within 3 days prior to the signing of the informed consent form. Received immunoglobulin and/or blood product 3 months prior to the first vaccination. Presence of uncontrolled chronic pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic or metabolic (including diabetes mellitus) disorders, which would include the potential subject in a high-risk category for SARS-CoV-2 infection and/or its complications as judged by the investigator.. Individuals with a history of severe allergic reaction (throat swelling, difficult in breath, dyspnea, or shock). Individuals who have a history of severe adverse reaction associated with a vaccine or severe allergic reaction [e.g., anaphylaxis to any component of the study vaccines (S protein, Aluminum hydroxide, CpG adjuvant). Any autoimmune or immunodeficiency disease/condition [e.g. human immunodeficiency virus (HIV) infection, Systemic lupus erythematosus (SLE)] Received immunoglobulin, blood-derived products within 3 months prior to the first study vaccination. Abnormal coagulation function (such as coagulation factor deficiency, coagulation disease, platelet abnormality) obvious bruises or coagulopathy. Pregnant women or breastfeeding women. According to the judgment of the investigator, subject has or had any other symptoms, medical history and other factors that are not suitable for participating in this clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adult Group 1a<br>Adult healthy subjects (18 to 59 years of age, inclusive) receive 202-CoV low adjuvant dose at Day 0 and Day 28 | Biological: 202-CoV low adjuvant dose<br>* standard dose of 202-CoV with low dose CpG / alum adjuvant<br>|
| Experimental: Adult Group 1b<br>Adult healthy subjects (18 to 59 years of age, inclusive) receive 202-CoV low antigen dose at Day 0 and Day 28 | Biological: 202-CoV low antigen dose<br>* low dose 202-CoV with CpG / alum adjuvant<br>|
| Experimental: Adult Group 1c<br>Adult healthy subjects (18 to 59 years of age, inclusive) receive 202-CoV standard dose at Day 0 and Day 28 | Biological: 202-CoV standard dose<br>* standard dose 202-CoV with CpG / alum adjuvant<br>|
| Placebo Comparator: Adult Placebo<br>Adult healthy subjects (18 to 59 years of age, inclusive) receive 2 doses of placebo (saline) at Day 0 and Day 28 | Other: Placebo<br>* Normal saline solution<br>|
| Experimental: Elderly Group 1d<br>Adult healthy subjects (60 years of age and above) receive 202-CoV low adjuvant dose at Day 0 and Day 28 | Biological: 202-CoV low adjuvant dose<br>* standard dose of 202-CoV with low dose CpG / alum adjuvant<br>|
| Experimental: Elderly Group 1e<br>Adult healthy subjects (60 years of age and above) receive 202-CoV low antigen dose at Day 0 and Day 28 | Biological: 202-CoV low antigen dose<br>* low dose 202-CoV with CpG / alum adjuvant<br>|
| Experimental: Elderly Group 1f<br>Adult healthy subjects (60 years of age and above) receive 202-CoV standard dose at Day 0 and Day 28 | Biological: 202-CoV standard dose<br>* standard dose 202-CoV with CpG / alum adjuvant<br>|
| Placebo Comparator: Elderly Placebo<br>Adult healthy subjects (60 years of age and above) receive 2 doses of placebo (saline) at Day 0 and Day 28 | Other: Placebo<br>* Normal saline solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of solicited adverse events (AEs) after vaccination | Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0, 28) by intensity, relevance. | 7 days after the first or second vaccination | 
| Incidence of unsolicited AEs after vaccination | Percentage of participants with unsolicited AEs for 28 days following each vaccination | Frame: Day 0 to Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious AEs (SAEs) and adverse events of special interest (AESIs) | Percentage of participants with SAEs or AESI for 12month after last dose vaccination | Day 0 to Month 13 | 
| Proportion of subjects with abnormal markers of hematology, biochemistry, urinalysis and coagulation parameters | Safety Laboratory Values (Serum Chemistry, Hematology) | Day 4 after first or second vaccination | 
| Geometric mean titer (GMT) of SARS-CoV-2 neutralising antibodies | Neutralizing antibody activity as detected by neutralization assay expressed as GMTs at multiple time points through Day 56 | Day0, Day28, Day42 and Day56 | 
| Seroconversion rate (SCR) of SARS-CoV-2 neutralising antibodies | Neutralizing antibody activity as detected by neutralization assay expressed as seroconversion rate at multiple time points through Day 56 | Day0, Day28, Day42 and Day56 | 
| Geometric mean titer (GMT) of Serum IgG Antibody Levels | Serum IgG antibody levels specific for the SARS-CoV-2 S protein antigen as detected by ELISA expressed as GMTs at multiple time points through Day 56 | Day0, Day28, Day42 and Day56 | 
| Seroconversion rate (SCR) of Serum IgG Antibody Levels | Serum IgG antibody levels specific for the SARS-CoV-2 S protein antigen as detected by ELISA expressed as seroconversion rate at multiple time points through Day 56 | Day0, Day28, Day42 and Day56 |