Clinical trial NCT04892459: Study on Sequential Immunization of Inactivated SARS-CoV-2 Vaccine and Recombinant SARS-CoV-2 Vaccine (Ad5 Vector)
Official title: Safety and Immunogenicity of Sequential Immunization of Inactivated SARS-CoV-2 Vaccine and Recombinant SARS-CoV-2 Vaccine (Ad5 Vector) in Chinese Healthy Adults Aged 18-59 Years: a Randomized, Observer-blind, Parallel-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID-19
Keywords: SARS-CoV-2 Vaccine
Sequential immunization
Heterologous prime-boost
Ad5 vectored vaccine
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
Collaborators: name: CanSino Biologics Inc.
First posted: 2021-05-19
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects who have been primed with one dose or two doses of inactive SARS-CoV-2 vaccine will be recruited and randomized at a 1:1 ratio to receive a booster dose of inactive SARS-CoV-2 vaccine or recombinant SARS-CoV-2 Ad5 vectored vaccine
Primary purpose: PREVENTION

Brief summary: This is a randomized, observer-blind, parallel-controlled study, for evaluation of safety and immunogenicity of sequential immunization of a recombinant SARS-CoV-2 vaccine (adenovirus type 5 vector) in Chinese healthy adults aged 18-59 years after the priming vaccination of inactivated vaccine. 300 healthy subjects aged 18-59 years will be recruited in this study. Of them, 200 subjects who have been vaccinated with two dose of inactive SARS-CoV-2 vaccine will be recruited and randomized at a 1:1 ratio to receive a booster dose of inactivated SARS-CoV-2 vaccine or recombinant SARS-CoV-2 Ad5 vectored vaccine at 3\~6 months later. Other 100 subjects who have been vaccinated with one dose of inactivated SARS-CoV-2 vaccine will be recruited and randomized at a 1:1 ratio to receive a booster dose of inactivated SARS-CoV-2 vaccine or recombinant SARS-CoV-2 Ad5 vectored vaccine at 1\~3 months later. The occurrence of adverse events within 28 days and serious adverse events within 6 months after vaccination will be observed. In addition, blood samples will be collected on day 0 before the boosting with ad5 vectored vaccine and on day 14, 28 and month 6 after the boosting. Serum antibody levels, cellular immune responses and the subgroups or germlines of the specific B cells will be analyzed. Each subject will remain in this study for approximately 6 months.


Eligibility criteria: Inclusion Criteria:

* Health subjects aged 18-59 years, who have been completed two-dose regimen of inactive SARS-CoV-2 vaccine in the past 3-6 months, or received one dose of inactive SARS-CoV-2 vaccine in the past 1-3 months.
* 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.
* Axillary temperature ≤ 37.0℃.
* Individuals who are in good health condition at the time of entry into the trial as determined by medical history, physical examination and clinical judgment of the investigator and meet the requirements of immunization.

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, pregnant or breast-feeding, or have a pregnancy plan within six months.
* have acute febrile diseases and infectious diseases.
* have severe chronic diseases or condition in progress cannot be controlled.
* congenital or acquired angioedema / neuroedema
* have the history of urticaria 1 year before receiving the investigational vaccine.
* have asplenia or functional asplenia.
* have thrombocytopenia or other coagulation disorders (which may cause contraindications for intramuscular injection).
* have needle sickness.
* have the history of immunosuppressive therapy, anti-allergy therapy, cytotoxic therapy or inhaled corticosteroids (excluding corticosteroid spray therapy for allergic rhinitis, and acute corticosteroid therapy without dermatitis) over the past 6 months.
* have received blood products within 4 months before injection of investigational vaccines.
* under anti-tuberculosis treatment.
* not be able to follow the protocol, or not be able to understand the informed consent according to the researcher's judgment, due to various medical, psychological, social or other conditions.

Primary outcomes:
measure: Incidence of adverse reactions within 28 days after the booster dose.
timeFrame: Within 28 days after the booster dose
measure: GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 14 after the booster dose.
timeFrame: On day 14 after the booster dose
Secondary outcomes:
measure: Incidence of solicited AE within 14 days after the booster dose
timeFrame: within 14 days after the booster dose
measure: Incidence of unsolicited AE 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: GMT of binding antibodies against SARS-CoV-2 S and N protein on day 14, day 28 and month 6 after the booster dose.
timeFrame: on day 14, day 28 and month 6 after the booster vaccination
measure: GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 and month 6 after the booster dose.
timeFrame: on day 28 and month 6 after the last dose of vaccination
measure: Fold increase of binding antibodies against SARS-CoV-2 S and N protein on day 14, day 28 and month 6 after the booster vaccination.
timeFrame: on day 14, day 28 and month 6 after the booster vaccination
measure: Fold increase of neutralizing antibodies against live SARS-CoV-2 virus on day 14, day 28 and month 6 after the booster vaccination.
timeFrame: on day 14, day 28 and month 6 after the last dose of vaccination
measure: Proportion of the participants with at least a four-fold increase of the binding antibodies against SARS-CoV-2 S and N protein on day 14, day 28 and month 6 after the booster vaccination.
timeFrame: on day 14, day 28 and month 6 after the booster vaccination
measure: Proportion of the participants with at least a four-fold increase of neutralizing antibodies against live SARS-CoV-2 virus on day 14, day 28 and month 6 after the booster vaccination.
timeFrame: on day 14, day 28 and month 6 after the booster vaccination
measure: Specific T cell responses on day 14 after the booster vaccination.
timeFrame: on day 14 after the booster vaccination
Other outcomes:
measure: Types of IgG binding to SARS-CoV-2 S protein on day 14, day 28 and month 6 after the booster vaccination.
timeFrame: on day 14, day 28 and month 6 after the booster vaccination
measure: GMT of neutralizing antibodies against P.1 virants on day 28 after the booster vaccination.
timeFrame: on day 28 after the booster vaccination
measure: GMT of neutralizing antibodies against 501Y.V2 virants on day 28 after the booster vaccination.
timeFrame: on day 28 after the booster vaccination
Locations:
city: Nanjing
country: China
facility: Jiangsu Provincial Center for Disease Control and Prevention
state: Jiangsu
Study officials:
affiliation: Jiangsu Provincial Center for Diseases Control and Prevention
name: Jing-Xin Li, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li J, Hou L, Guo X, Jin P, Wu S, Zhu J, Pan H, Wang X, Song Z, Wan J, Cui L, Li J, Chen Y, Wang X, Jin L, Liu J, Shi F, Xu X, Zhu T, Chen W, Zhu F. Heterologous AD5-nCOV plus CoronaVac versus homologous CoronaVac vaccination: a randomized phase 4 trial. Nat Med. 2022 Feb;28(2):401-409. doi: 10.1038/s41591-021-01677-z. Epub 2022 Jan 27.