Clinical trial NCT05204589: Heterologous Boost Immunization with an Aerosolised Ad5-nCoV After Two-dose Priming with an Inactivated SARS-CoV-2 Vaccine
Official title: Heterologous Prime-boost Immunization with an Aerosolised Adenovirus Type-5 Vector-based COVID-19 Vaccine (Ad5-nCoV) After Two-dose Priming with an Inactivated SARS-CoV-2 Vaccine in Adults Aged 18 Years and Above: a Multicenter, Open-label, Partially Parallel-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: COVID-19
Keywords: SARS-CoV-2
Aerosolised COVID-19 vaccine
Recombinant Ad5 Vector
Inactivated Vaccine
Safety
Immunogenicity
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
Collaborators: name: Anhui Provincial Center for Disease Control and Prevention
name: Shandong Province Centers for Disease Control and Prevention
name: Hunan Provincial Center for Disease Control and Prevention
name: Yunnan Center for Disease Control and Prevention
name: Chongqing Center for Disease Control and Prevention
First posted: 2022-01-24
Enrollment: 10285
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 a multicenter, open-label, partially radomized, parallel-controlled clinical trial to evaluate the safety and immunogenicity of heterologous prime-boost immunization with an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV-IH) after two-dose priming with an inactivated SARS-CoV-2 vaccine (ICV) in adults aged 18 years and above. 10420 healthy subjects aged over or equal to 18 years whom have received two doses of ICV before 6 months or more, will be recruited from six provinces in China in this study.Of them, 10000 eligible participants in an open cohort will receive a booster dose of Ad5-nCoV-IH to evaluate the safety profile. Another 420 participants were involved in immunogenicity cohort and randomized in a ratio of 1:1 to receive a boost of Ad5-nCoV-IH or ICV. The ICV homologous to the priming series will be supplied as the booster. 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 in immunogenicity cohort on the day 0 before and 14, 28 and month 3 and 6 after the booster vaccination. Each subject will remain in this study for approximately 6 months.


Eligibility criteria: Inclusion Criteria:

* Health subjects aged ≥18 years.
* Have received two-dose inactivated SARS-CoV-2 vaccine before 6 months or more.
* 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.

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.
* Women with positive urine pregnancy test.
* Have acute febrile diseases and infectious diseases.
* Axillary temperature\>37.0℃.
* Have serious cardiovascular disease, 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 in progress cannot be smoothly controlled, such as asthma, diabetes, thyroid disease.
* Congenital or acquired angioedema / neuroedema.
* Have the history of urticaria 1 year before receiving the investigational vaccine.
* 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 in immunogenicity cohort.
timeFrame: On day 28 after the booster dose
Secondary outcomes:
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) till the 6 months after the booster dose.
timeFrame: Within 6 months after the booster dose
measure: Fold increase 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, Fold increase 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: GMT, fold increase and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus at month 3, 6, and 12 after the booster dose.
timeFrame: At month 3, 6, and 12 after the boost vaccination.
measure: Geometric mean concentration (GMC), fold increase and seroconversion of binding IgG against S protein of SARS-CoV-2 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: GMT of neutralizing antibodies against live SARS-CoV-2 virus in participants with pre-existing anti-Ad5 antibody titers>1:200 or ≤1:200 at baseline.
timeFrame: On day 28 after the booster dose
measure: GMT, fold increase 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、IL-4、IL-5、IL-13 secreted by specific T cells on day 14 after the booster vaccination.
timeFrame: On day 14 after the booster vaccination
Other outcomes:
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: Fengcai Zhu, Prof
role: PRINCIPAL_INVESTIGATOR
References: