COVID-19
Conditions
Keywords
SARS-CoV-2, Ad5-nCoV, Inactivated Vaccine, Safety, Immunogenicity
Brief summary
This is an open-label, randomized, parallel-controlled clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost immunization with an aerosolized (Ad5-nCoV-IH) or intramuscular (Ad5-nCoV-IM) Ad5-nCoV after three-dose priming with an inactivated COVID-19 vaccine (CoronaVac) in adults aged 18 years and above. A total of 360 subjects will be included. Approximately 210 subjects who have completed three doses of CoronaVac more than 6 months ago in the prior clinical trial and other 150 eligible subjects will be recruited and randomized respectively in a ratio of 1:1:1 to receive a booster dose of Ad5-nCoV-IH or Ad5-nCoV-IM or ICV. The occurrence of adverse reactions within 28 days and serious adverse events within 6 months after vaccination will be observed in all participants. In addition, blood and saliva samples will be collected from all participants on the day 0 before and 14, 28 days and 3, 6 months after the booster vaccination. Each subject will remain in this study for approximately 6 months.
Interventions
BIOLOGICALAd5-nCoV-IH
The orally aerosolized Ad5-nCoV is a replication defective Ad5 vectored COVID-19 vaccine expressing the full-length spike gene of wide-type SARS-CoV-2, Wuhan-Hu-1. The Ad5-nCoV vaccine was supplied in 1.5mL/vial, at a concentration of 1.0 × 1011 viral particles per mL as a liquid formulation. 0.1 ml of Ad5-nCoV vaccine will be aerosolized by using Continuous Vapouring System. Then, the aerosolized droplets will be poured into a disposable suction cup and be inhaled by participants through mouth.
BIOLOGICALAd5-nCoV-IM
The Ad5-nCoV is a replication defective Ad5 vectored COVID-19 vaccine expressing the full-length spike gene of wide-type SARS-CoV-2, Wuhan-Hu-1. It was supplied in 1·5mL/vial, at a concentration of 1.0 × 1011 viral particles per mL as a liquid formulation. Participants will be administrated 0.5ml（5×1010VP）of Ad5-nCoV vaccine intramuscularly.
BIOLOGICALCoronaVac
CoronaVac is an inactivated whole-virion vaccine with aluminium hydroxide as the adjuvant, prepared with a novel coronavirus (CZ02 strain) inoculated in African green monkey kidney cells (Vero cells). One dose of CoronaVac contains 3 μg of SARS-CoV-2 virion in a 0.5 mL aqueous suspension for injection with 0.45 mg/mL of aluminium.
Sponsors
Jiangsu Province Centers for Disease Control and Prevention
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Health subjects aged ≥18 years * The subject can provide with informed consent and sign informed consent form (ICF). * The subjects are able to and willing to comply with the requirements of the clinical trial program and could complete the 6-month follow-up of the study. * Participants who have received three-dose of inactivated SARS-CoV-2 vaccine more than 6 months ago.
Exclusion criteria
* Have the medical history or family history of convulsion, epilepsy, encephalopathy and psychosis. * Be allergic to any component of the research vaccines, or used to have a history of hypersensitivity or serious reactions to vaccination. * Vaccine-related SAE occurred after previous vaccination with COVID-19 vaccine. * Women with positive urine pregnancy test or in lactation. * Have acute febrile diseases or infectious diseases or have a history of SARS. * Axillary temperature\>37.0℃ * Have serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension that cannot be controlled by medication (systolic blood pressure ≥180mmHg and/or diastolic blood pressure ≥110mmHg when measured in the field) * Have severe chronic diseases or condition is not stable, such as asthma, diabetes, thyroid disease * Congenital or acquired angioedema / neuroedema. * Have the history of urticaria 1 year before. * Have asplenia or functional asplenia. * Patients with chronic obstructive pulmonary disease, pulmonary fibrosis and other pulmonary abnormalities. * Have history of SARS-CoV-2 infection or COVID-19. * Have symptoms of upper respiratory tract infection. * Have traveled to medium or high risk areas or traveled abroad in the past 21 days, and epidemiologically contacted with SARS-CoV-2. * Any medical, psychological, social, or other conditions that, in the investigator's judgment, are inconsistent with the protocol or affect the subject's informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse reactions within 28 days after the booster dose | Within 28 days the booster dose | Incidence of adverse reactions within 28 days after the booster dose. |
| GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose. | On day 28 after the booster dose | GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 14, month 3 and 6 after the booster dose. | On day 14, month 3 and 6 after the booster dose | GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus as compared to baseline on day 14, month 3 and 6 after the booster dose. |
| Geometric Mean Fold Increase (GMI) and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose. | On day 28 after the boost vaccination | GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose in immunogenicity cohort. |
| Geometric mean concentration (GMC), GMI and seroconversion of anti-SARS-CoV-2 NP-specific, RBD-specific and NTD-specific IgG measured by ELISA on day 14, day 28 and month 3 and 6 after the booster dose. | On day 14, day 28 and month 3 and 6 after the booster dose | Geometric mean concentration (GMC), GMI and seroconversion of anti-SARS-CoV-2 NP-specific, RBD-specific and NTD-specific IgG measured by ELISA on day 14, day 28 and month 3 and 6 after the booster dose. |
| Incidence of adverse reactions within 30 minutes after the booster dose. | Within 30 minutes after the booster dose | Incidence of adverse reactions within 30 minutes after the booster dose. |
| Incidence of adverse reactions within 14 days after the booster dose. | Within 14 days after the booster dose | Incidence of adverse reactions within 14 days after the booster dose. |
| Incidence of adverse events within 28 days after the booster dose. | Within 28 days after the booster dose | Incidence of adverse events within 28 days after the booster dose. |
| Incidence of serious adverse events (SAE) until 6 months after the booster dose. | Within 6 months after the booster dose | Incidence of SAE until 6 months after booster vaccination. |
Other
| Measure | Time frame | Description |
|---|---|---|
| GMT and GMI of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose stratified by age (aged 18-59 years and over 60 years). | On day 28 after the booster dose | GMT and GMI of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose stratified by age (aged 18-59 years and over 60 years). |
| The levels of anti-SARS-CoV-2 N protein binding IgG on day 14 after the booster dose. | On day 14 after the booster dose | The levels of anti-SARS-CoV-2 N protein binding IgG on day 14 after the booster dose. |
| The GMT of neutralizing antibodies against the Ad5 before vaccination and any exploratory analyses of other indicators stratified by pre-existing anti-Ad5 NAb titres at baseline（>1:200，≤1:200） | On day 0 before the booster dose | The GMT of neutralizing antibodies against the Ad5 before vaccination and any exploratory analyses of other indicators stratified by pre-existing anti-Ad5 NAb titres at baseline（\>1:200，≤1:200） |
| The levels of anti-SARS-CoV-2 RBD-specific binding IgA in saliva on day 14, day 28 and month 3 and 6 after the booster dose. | On day 28 after the booster dose | The levels of anti-SARS-CoV-2 RBD-specific binding IgA in saliva on day 14, day 28 and month 3 and 6 after the booster dose. |
| GMT, GMI and seroconversion of neutralizing antibodies against VOC/VOI of SARS-CoV-2 virus on day 28 after the booster dose. | On day 28 after the booster dose | GMT, GMI and seroconversion of neutralizing antibodies against VOC/VOI of SARS-CoV-2 virus on day 28 after the booster dose. |
| The levels of IFN-γ、TNF-α、IL-2 secreted by specific T cells stimulated with a peptide pool covering the full-length spike glycoprotein on day 14 after the booster vaccination. | On day 14 after the booster vaccination | The levels of IFN-γ、TNF-α、IL-2 secreted by specific T cells stimulated with a peptide pool covering the full-length spike glycoprotein on day 14 after the booster vaccination. |
Countries
China
Outcome results
None listed