Clinical trial NCT05303584: Heterologous Boost Immunization with Ad5-nCoV After Three-dose Priming with an Inactivated SARS-CoV-2 Vaccine
Official title: Immunogenicity and Safety of the Heterologous Prime-boost Immunization with an Adenovirus Type-5 Vector-based COVID-19 Vaccine (Ad5-nCoV) After Three-dose Priming with an Inactivated COVID-19 Vaccine in Adults Aged 18 Years and Above: a Randomized, Open-label, Parallel-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID-19
Keywords: SARS-CoV-2
Ad5-nCoV
Inactivated Vaccine
Safety
Immunogenicity
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
First posted: 2022-03-31
Enrollment: 362
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse reactions within 28 days after the booster dose
timeFrame: Within 28 days the booster dose
measure: GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.
timeFrame: On day 28 after the booster dose
Secondary outcomes:
measure: Geometric Mean Fold Increase (GMI) and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.
timeFrame: On day 28 after the boost vaccination
measure: GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 14, month 3 and 6 after the booster dose.
timeFrame: On day 14, month 3 and 6 after the booster dose
measure: 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.
timeFrame: On day 14, day 28 and month 3 and 6 after the booster dose
measure: Incidence of adverse reactions within 30 minutes after the booster dose.
timeFrame: Within 30 minutes after the booster dose
measure: Incidence of adverse reactions within 14 days after the booster dose.
timeFrame: Within 14 days after the booster dose
measure: Incidence of adverse events within 28 days after the booster dose.
timeFrame: Within 28 days after the booster dose
measure: Incidence of serious adverse events (SAE) until 6 months after the booster dose.
timeFrame: Within 6 months after the booster dose
Other outcomes:
measure: GMT, GMI and seroconversion of neutralizing antibodies against VOC/VOI of SARS-CoV-2 virus on day 28 after the booster dose.
timeFrame: On day 28 after the booster dose
measure: 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.
timeFrame: On day 14 after the booster vaccination
measure: 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.
timeFrame: On day 28 after the booster dose
measure: 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).
timeFrame: On day 28 after the booster dose
measure: The levels of anti-SARS-CoV-2 N protein binding IgG on day 14 after the booster dose.
timeFrame: On day 14 after the booster dose
measure: 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）
timeFrame: On day 0 before the booster dose
Locations:
city: Nanjing
country: China
facility: Jiangsu Provincial Center for Diseases Control and Prevention
state: Jiangsu
Study officials:
affiliation: Jiangsu Provincial Center for Diseases Control and Prevention
name: Jingxin Li, PhD
role: PRINCIPAL_INVESTIGATOR
References: