Safety and Immunogenicity Study of an Inactivated SARS-CoV-2 Vaccine for Preventing Against COVID-19 in People Aged ⩾60 Years

Study Overview
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Brief Summary
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This study is a randomized, double-blinded, and placebo-controlled phase Ib/IIb clinical trial of the Inactivated SARS-CoV-2 Vaccine to evaluate the safety and immunogenicity of the vaccine in healthy people aged ⩾60 Years.

Detailed Description
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This phase Ib/IIb trial is designed to evaluate the safety and immunogenicity of different doses of the Inactivated SARS-CoV-2 Vaccine based upon the randomized, double-blind and placebo-controlled principle. A total of 471 subjects aged ⩾60 years will be enrolled in the study, of which 96 and 375 will be enrolled for phase Ib and phase Ⅱb,respectively. The enrolled subjects in phase Ib receive two doses of low-, medium-, or high-dose of experimental vaccines or placebo at an interval of 28 days, while the enrolled subjects in Phase Ⅱb receive two doses of medium, high-dose experimental vaccines or placebo at an interval of 28 days.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase Ib/IIb Trial of an Inactivated SARS-CoV-2 Vaccine in Healthy People Aged ⩾60 Years

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Low dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule
* Biological: Medium dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule
* Biological: High dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule
* Biological: Placebo on a 0- and 28-day schedule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase Ib: Healthy people aged ⩾60 years (including boundary values), both men and women. Proven legal identity. Participants should understand the contents of the informed consent form, the vaccine in this trial, voluntarily sign the informed consent form, and be capable of using thermometers, scales, and filling in diary cards and contact cards as required. Participants should be able to communicate well with investigators, understand and comply with the requirements of this trial. Axillary temperature ≤37.0 ℃. Phase IIb: Healthy people aged ⩾60 years (including boundary values), both men and women. Proven legal identity. Participants should understand the contents of the informed consent form, the vaccine in this trial, voluntarily sign the informed consent form, and be capable of using thermometers, scales, and filling in diary cards and contact cards as required. Participants should be able to communicate well with investigators, understand and comply with the requirements of this trial. Axillary temperature ≤37.0 ℃. Exclusion Criteria: Phase Ib: Contraindications for vaccination. History of allergy to vaccines or drugs. Immunization with any vaccine within 1 month. Diseases that cannot be controlled by drugs, such as hypertension, diabetes, asthma, etc. Those who developed acute disease within 2 weeks, or had symptoms of fever or upper respiratory tract infection within 7 days. Those who have a hereditary bleeding tendency or coagulation dysfunction, or a history of thrombosis or bleeding disorders. Those who cannot tolerate venipuncture, or have a history of halo needles or halo blood. For any reason, the spleen was removed partially or completely. Those who have undergone surgery within 3 months before signing the informed consent, or those who plan to perform surgery during the trial or within 3 months after the end of the trial (including cosmetic surgery, dental and oral surgery). Those who donated or lost blood (≥200 mL) in the past 3 months, who received blood transfusion or use of blood products, or who planned blood donation during the trial. Receipt of other investigational or unregistered products (drugs, vaccines, biological product or devices) in the past 3 months, or plan to use other investigational or unregistered products during the study. Receipt of immunosuppressive therapy within 6 months before signing the informed consent form, such as long-term systemic glucocorticoid therapy (with systemic glucocorticoid therapy for more than 2 weeks within 6 months, such as prednisone or similar drugs) ), but local administration (such as ointment, eye drops, inhalation, or nasal spray) is allowed. The local administration should not exceed the dosage recommended in the instructions or have any signs of systemic exposure. Those who have took soft drugs (such as marijuana) within 3 months before signing the informed consent form or took hard drugs (such as: cocaine, phencyclidine, etc.) within 1 year before the trial. Those who smoked more than 5 cigarettes per day within 3 months before signing the informed consent form. The weekly drinking volume is greater than 14 units within 3 months before signing the informed consent form (1 unit alcohol approximately equal to 360 mL beer or 45 mL spirits with 40% alcohol content or 150 mL wine). The comprehensive physical examination does not meet the health standards, mainly including: (1) Those with abnormal vital signs with clinical significance. (2) BMI<18 kg/m^2 or> 30 kg/m^2. (3) Abnormal laboratory examination with clinical significance. (4) Those who tested positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B e antigen, hepatitis C virus antibody, or Treponema pallidum antibody (tp-trust). Women who have a positive pregnancy test, or men who have a birth plan or plan to donate sperm from the screening to 12 months after the second vaccination. Positive in drug abuse screening during the screening period (Morphine, Methamphetamine, Ketamine, MDMA and Tetrahydrocannabinolic acid). Positive in alcohol breath test during the screening period. Positive in SARS-CoV-2 nucleic acid screening or antibodies (IgG or IgM) screening. History of severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) or other coronavirus infection (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1). History of contact with confirmed or suspected cases infected with SARS-CoV-2 within 1 month. Any other situations judged by investigators as not suitable for participating in this study. Phase IIb: Contraindications for vaccination. History of allergy to vaccines or drugs. Immunization with any vaccine within 1 month. Diseases that cannot be controlled by drugs, such as hypertension, diabetes, asthma, etc. Those who developed acute disease within 2 weeks, or had symptoms of fever or upper respiratory tract infection within 7 days. Those who have a hereditary bleeding tendency or coagulation dysfunction, or a history of thrombosis or bleeding disorders. For any reason, the spleen was removed partially or completely. Those who have undergone surgery within 3 months before signing the informed consent, or those who plan to perform surgery during the trial or within 3 months after the end of the trial (including cosmetic surgery, dental and oral surgery). Those who donated or lost blood (≥200 mL) in the past 3 months, who received blood transfusion or use of blood products, or who planned blood donation during the trial. Receipt of other investigational or unregistered products (drugs, vaccines, biological product or devices) in the past 3 months, or plan to use other investigational or unregistered products during the study. Receipt of immunosuppressive therapy within 6 months before signing the informed consent form, such as long-term systemic glucocorticoid therapy (with systemic glucocorticoid therapy for more than 2 weeks within 6 months, such as prednisone or similar drugs) ), but local administration (such as ointment, eye drops, inhalation, or nasal spray) is allowed. The local administration should not exceed the dosage recommended in the instructions or have any signs of systemic exposure. Women who have a positive pregnancy test, or men who have a birth plan or plan to donate sperm from the screening to 12 months after the second vaccination. History of severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) or other coronavirus infection (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1). History of contact with confirmed or suspected cases infected with SARS-CoV-2 within 1 month. The comprehensive physical examination does not meet the health standards, mainly including: (1) Those with abnormal vital signs (Pulse <55 beats per minute or> 100 beats per minute at rest, Systolic blood pressure ≥140mmHg or Diastolic blood pressure ≥90mmHg, breathing> 20 beats per minute or <12 beats per minute). (2) Those who tested positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B e antigen, hepatitis C virus antibody, or Treponema pallidum antibody (tp-trust). Positive in SARS-CoV-2 nucleic acid screening or antibodies (IgG or IgM) screening. Any other situations judged by investigators as not suitable for participating in this study.

Ages Eligible for Study
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Minimum Age: 60 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dosage vaccine on a 0- and 28-day schedule<br>Two doses of low dosage Inactivated SARS-CoV-2 Vaccine at the vaccination schedule of day 0, 28 | Biological: Low dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule<br>* Two doses of low dosage(50U/0.5ml) Inactivated SARS-CoV-2 Vaccine at the vaccination schedule of day 0,28<br>|
| Experimental: Medium dosage vaccine on a 0- and 28-day schedule<br>Two doses of medium dosage Inactivated SARS-CoV-2 Vaccine at the vaccination schedule of day 0, 28 | Biological: Medium dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule<br>* Two doses of medium dosage(100U/0.5ml) Inactivated SARS-CoV-2 Vaccine at the vaccination schedule of day 0,28<br>|
| Experimental: High dosage vaccine on a 0- and 28-day schedule<br>Two doses of high dosage Inactivated SARS-CoV-2 Vaccine at the vaccination schedule of day 0, 28 | Biological: High dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule<br>* Two doses of high dosage(150U/0.5ml) Inactivated SARS-CoV-2 Vaccine at the vaccination schedule of day 0,28<br>|
| Placebo Comparator: Placebo on a 0- and 28-day schedule<br>Two doses of placebo at the vaccination schedule of day 0, 28 | Biological: Placebo on a 0- and 28-day schedule<br>* Two doses of placebo at the vaccination schedule of day 0,28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse reactions/events rate | Occurence of adverse reactions/events after vaccination | 7 days after vaccination | 
| Adverse reactions/events rate | Occurence of adverse reactions/events after vaccination | 28 days after vaccination | 
| Seroconversion rate of Neutralizing antibodies against SARS-CoV-2 Phase IIb | Seroconversion rate of neutralizing antibodies against SARS-CoV-2 in serum for Phase IIb with vaccination schedule of day 0, 28 | 28 days after vaccination | 
| Seroconversion rate of IgG antibodies against SARS-CoV-2 Phase IIb | Seroconversion rate of IgG antibodies against SARS-CoV-2 tested by ELISA in serum for Phase IIb with vaccination schedule of day 0, 28 | 28 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious adverse events | Occurence of Serious adverse events after vaccination | 12 months after the second vaccination | 
| Seroconversion rate of Neutralizing antibodies against SARS-CoV-2 Phase Ib | Seroconversion rate of neutralizing antibodies against SARS-CoV-2 in serum for Phase Ib with vaccination schedule of day 0, 28 | 28 days after the second vaccination | 
| Seroconversion rate of IgG antibodies against SARS-CoV-2 Phase Ib | Seroconversion rate of IgG antibodies against SARS-CoV-2 tested by ELISA in serum for Phase Ib with vaccination schedule of day 0, 28 | 28 days after the second vaccination | 
| Level of Neutralizing antibodies against SARS-CoV-2 Phase Ib | Level of neutralizing antibodies against SARS-CoV-2 in serum for Phase Ib with vaccination schedule of day 0, 28 | 7 and 28 days after the second vaccination | 
| Level of IgG antibodies against SARS-CoV-2 Phase Ib | Level of IgG antibodies against SARS-CoV-2 tested by ELISA in serum for Phase Ib with vaccination schedule of day 0, 28 | 7 and 28 days after the second vaccination | 
| Level of Neutralizing antibodies against SARS-CoV-2 Phase IIb | Level of neutralizing antibodies against SARS-CoV-2 in serum for Phase IIb with vaccination schedule of day 0, 28 | 28 days after the second vaccination | 
| Level of IgG antibodies against SARS-CoV-2 Phase IIb | Level of IgG antibodies against SARS-CoV-2 tested by ELISA in serum for Phase IIb with vaccination schedule of day 0, 28 | 28 days after the second vaccination |