A Phase Ⅱ Clinical Trial of Recombinant Corona Virus Disease-19 (COVID-19) Vaccine (Sf9 Cells)

Study Overview
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Brief Summary
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This is a phase Ⅱ, single-center, randomized, double-blind, placebo-controlled study, to evaluate the immunogenicity and safety of the recombinant COVID-19 vaccine (Sf9 cells) in the subjects from healthy adults and elderly adults aged 18 years and above (aged 18-60 and 60-85 years) with different immunization procedures (0, 21 days and 0, 14, 28 days) and doses (20μg/40μg).

Detailed Description
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This is a phase Ⅱ, single-center, randomized, double-blind, placebo-controlled study, to evaluate the immunogenicity and safety of the recombinant COVID-19 vaccine (Sf9 cells) in the subjects from healthy adults and elderly adults aged 18 years and above (aged 18-60 and 60-85 years) . The phase Ⅱ clinical trials designed 8 research group, including two immunization procedures (0, 21 days and 0, 14, 28 days), two doses (20μg/0.5ml, 40μg/1.0ml) and two ages group (adults and elder): Each group including 120 participants. Vaccination or placebo group will be randomly assigned to receive in a 5:1 ratio, 960 in total.

Official Title
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A Single-center, Randomized, Double-Blinded, Placebo-Controlled, Phase Ⅱ Clinical Trial of Recombinant COVID-19 Vaccine (Sf9 Cells), in the Subjects From Healthy Aged 18 Years and Above

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Two dose regimen
* Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Three dose regimen
* Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Two dose regimen
* Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Three dose regimen
* Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Two dose regimen
* Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Three dose regimen
* Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Two dose regimen
* Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Three dose regimen
* Biological: Low-dose placebo (18-59 years) & Two dose regimen
* Biological: Low-dose placebo (18-59 years) & Three dose regimen
* Biological: High-dose placebo (18-59 years) & Two dose regimen
* Biological: High-dose placebo (18-59 years) & Three dose regimen
* Biological: Low-dose placebo (60-85 years) & Two dose regimen
* Biological: Low-dose placebo (60-85 years) & Three dose regimen
* Biological: High-dose placebo (60-85 years) & Two dose regimen
* Biological: High-dose placebo (60-85 years) & Three dose regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years and above. Able to understand the content of informed consent and willing to sign the informed consent. Able and willing to complete all the secluded study process during the whole study follow-up period (about 7 months). Axillary temperature ≤37.0℃. General good health as established by medical history and physical examination. Exclusion Criteria: First dose exclusion criteria: Positive serum immunoglobulin M (IgM) and IgG to the SARS-CoV-2. A Known History of HIV infection Family history of seizure, epilepsy, brain or mental disease. Participant that has an allergic history to any ingredient of vaccines. Woman who is pregnant, breast-feeding or positive in pregnancy test on day of enrollment, or is planning to be pregnant during the next 6 months. Any acute fever disease or infections. Have a medical history of SARS. Have serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension and not well-controlled. Major chronic illness, such as asthma, diabetes, or thyroid disease, and not well-controlled. Hereditary angioneurotic edema or acquired angioneurotic edema. Urticaria in last one year. Asplenia or functional asplenia. Platelet disorder or other bleeding disorder may cause injection contraindication. Faint at the sight of blood or needles. Prior administration of immunodepressant or corticosteroids, antianaphylactics treatment, cytotoxic treatment in last 6 months. Prior administration of blood products in last 4 months. Prior administration of other research medicines in last 1 month. Prior administration of attenuated vaccine in last 1 month. Prior administration of subunit vaccine or inactivated vaccine in last 14 days. Being treated for tuberculosis. Any condition that in the opinion of the investigators may interfere with the evaluation of study objectives. Exclusion criteria for subsequent doses: Patients with severe allergic reactions after the previous dose of vaccination; Patients with serious adverse events causally related to the previous dose of vaccination.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose vaccine (18-59 years) & Two dose regimen<br>two doses of low-dose Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 21. | Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Two dose regimen<br>* 18-59 years group, two doses of low-dose (20µg/0.5ml) Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 21.<br>|
| Experimental: Low-dose vaccine (18-59 years) & Three dose regimen<br>three doses of low-dose Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 14, 28. | Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Three dose regimen<br>* 18-59 years group, three doses of low-dose (20µg/0.5ml) Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 14, 28.<br>|
| Experimental: High-dose vaccine (18-59 years) & Two dose regimen<br>two doses of high-dose Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 21. | Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Two dose regimen<br>* 18-59 years group, two doses of high-dose (40µg/1.0ml) Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 21.<br>|
| Experimental: High-dose vaccine (18-59 years) & Three dose regimen<br>three doses of high-dose Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 14, 28. | Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Three dose regimen<br>* 18-59 years group, three doses of high-dose (40µg/1.0ml) Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 14, 28.<br>|
| Experimental: Low-dose vaccine (60-85 years) & Two dose regimen<br>two doses of low-dose Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 21. | Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Two dose regimen<br>* 60-85 years group, two doses of low-dose (20µg/0.5ml) Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 21.<br>|
| Experimental: Low-dose vaccine (60-85 years) & Three dose regimen<br>three doses of low-dose Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 14, 28. | Biological: Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Three dose regimen<br>* 60-85 years group, three doses of low-dose (20µg/0.5ml) Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 14, 28.<br>|
| Experimental: High-dose vaccine (60-85 years) & Two dose regimen<br>two doses of high-dose Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 21. | Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Two dose regimen<br>* 60-85 years group, two doses of high-dose (40µg/1.0ml) Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 21.<br>|
| Experimental: High-dose vaccine (60-85 years) & Three dose regimen<br>three doses of high-dose Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 14, 28. | Biological: High-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Three dose regimen<br>* 60-85 years group, three doses of high-dose (40µg/1.0ml) Recombinant COVID-19 vaccine (Sf9 cells) at the schedule of day 0, 14, 28.<br>|
| Placebo Comparator: Low-dose placebo (18-59 years) & Two dose regimen<br>two doses of placebo at the schedule of day 0, 21. | Biological: Low-dose placebo (18-59 years) & Two dose regimen<br>* 18-59 years group, two doses of placebo(0.5ml) at the schedule of day 0, 21.<br>|
| Placebo Comparator: Low-dose placebo (18-59 years) & Three dose regimen<br>three doses of placebo at the schedule of day 0, 14, 28. | Biological: Low-dose placebo (18-59 years) & Three dose regimen<br>* 18-59 years group, three doses of placebo(0.5ml) at the schedule of day 0, 14, 28.<br>|
| Placebo Comparator: High-dose placebo (18-59 years) & Two dose regimen<br>two doses of placebo at the schedule of day 0, 21. | Biological: High-dose placebo (18-59 years) & Two dose regimen<br>* 18-59 years group, two doses of placebo(1.0ml) at the schedule of day 0, 21.<br>|
| Placebo Comparator: High-dose placebo (18-59 years) & Three dose regimen<br>three doses of placebo at the schedule of day 0, 14, 28. | Biological: High-dose placebo (18-59 years) & Three dose regimen<br>* 18-59 years group, three doses of placebo(1.0ml) at the schedule of day 0, 14, 28.<br>|
| Placebo Comparator: Low-dose placebo (60-85 years) & Two dose regimen<br>two doses of placebo at the schedule of day 0, 21. | Biological: Low-dose placebo (60-85 years) & Two dose regimen<br>* 60-85 years group, two doses of placebo(0.5ml) at the schedule of day 0, 21.<br>|
| Placebo Comparator: Low-dose placebo (60-85 years) & Three dose regimen<br>three doses of placebo at the schedule of day 0, 14, 28. | Biological: Low-dose placebo (60-85 years) & Three dose regimen<br>* 60-85 years group, three doses of placebo(0.5ml) at the schedule of day 0, 14, 28.<br>|
| Placebo Comparator: High-dose placebo (60-85 years) & Two dose regimen<br>two doses of placebo at the schedule of day 0, 21. | Biological: High-dose placebo (60-85 years) & Two dose regimen<br>* 60-85 years group, two doses of placebo(1.0ml) at the schedule of day 0, 21.<br>|
| Placebo Comparator: High-dose placebo (60-85 years) & Three dose regimen<br>three doses of placebo at the schedule of day 0, 14, 28. | Biological: High-dose placebo (60-85 years) & Three dose regimen<br>* 60-85 years group, three doses of placebo(1.0ml) at the schedule of day 0, 14, 28.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean (GMT) of specific antibody | Geometric mean (GMT) of specific antibody against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike protein Receptor-binding domain(S-RBD) protein (ELISA) | 1 months after immunization in each study group | 
| The incidence of adverse reaction (AR) | The incidence of adverse reaction (AR) | 0 to 7 days after vaccination in each study group | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of adverse events (AE) | The incidence of adverse events (AE) | 0 to 28 days after vaccination in each study group | 
| The incidence of severe adverse events (SAE) | The incidence of severe adverse events (SAE) | 0 to 28 days after vaccination in each study group | 
| The incidence of serious adverse events | The incidence of serious adverse events | 6 months after vaccination in each study group | 
| Geometric mean (GMT) of anti-SARS-CoV-2-specific neutralizing antibodies | Geometric mean (GMT) of anti-SARS-CoV-2-specific neutralizing antibodies (euvirus and pseudovirus-neutralizing assays) | 1 months after immunization in each study group | 
| The positive conversion rate of S-RBD protein-specific antibody | The positive conversion rate of S-RBD protein-specific antibody (ELISA) against SARS-CoV-2 | 14 days, 30 days after immunization in each study group | 
| Geometric mean fold increase (GMI) of S-RBD protein-specific antibody | Geometric mean fold increase (GMI) of S-RBD protein-specific antibody (ELISA) against SARS-CoV-2 | 14 days, 30 days after immunization in each study group | 
| Geometric mean (GMT) of anti-SARS-CoV-2-specific neutralizing antibodies | Geometric mean (GMT) of anti-SARS-CoV-2-specific neutralizing antibodies (euvirus and pseudovirus-neutralizing assays) | 14 days after immunization in each study group | 
| The positive conversion rate of anti-SARS-CoV-2 specific neutralizing antibody | The positive conversion rate of anti-SARS-CoV-2 specific neutralizing antibody (euvirus and pseudovirus neutralization test) | 14 days, 30 days after immunization in each study group | 
| Geometric mean fold increase (GMI) of anti-SARS-CoV-2 specific neutralizing antibodies | Geometric mean fold increase (GMI) of anti-SARS-CoV-2 specific neutralizing antibodies (eucivirus and pseudovirus neutralization assays) | 14 days, 30 days after immunization in each study group | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Immunogenicity, COVID-19 Vaccine, Recombinant vaccine