Clinical trial NCT04833101: Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine
Official title: Safety and Immunogenicity of a Heterologous Immunization of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine Against COVID-19 in Chinese Healthy Population
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID-19
Keywords: SARS-CoV-2 Vaccine
Recombinant Ad5 Vector
Subunit Vaccine
Safety
Immunogenicity
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
First posted: 2021-04-06
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a randomized, observer-blind, placebo-controlled study, for evaluation of safety and immunogenicity of heterologous prime-boost immunization of recombinant COVID-19 vaccine (adenovirus type-5 vector) and RBD-based protein subunit vaccine (ZF2001) against COVID-19 in Chinese healthy population. 120 healthy subjects aged over 18 years of age who have been vaccinated with recombinant adenovirus type-5 vectored vaccine will be recruited in this study. Of them, 60 subjects will be enrolled in the "0-28 days" regimen and other 60 will be enrolled in "0-56 days" regimen. Subjects, 30 of them are 18-59 years old and 30 are 60 years old and above in each regimen will be randomly vaccinated with the second dose of subunit vaccine(ZF2001) against COVID-19 or a commercial influenza vaccine in a ratio of 2:1. They will then be vaccinated with the third dose of ZF2001 on month 4 after the second dose. The occurrence of adverse events within 28 days and serious adverse events within 6 months after the last vaccination will be observed. In addition, blood samples will be collected on day 0 before the second vaccination, day 14, 28 after the second vaccination and day 14, month 6 after third vaccination to test serum antibody levels and to profile the immune cells' subgroups and germlines. Each subject will remain in this study for approximately 12 months.


Eligibility criteria: Inclusion Criteria:

* The subjects ≥ 18 years old who has completed one dose of recombinant Ad5 vectored COVID-19 vaccine.
* The subjects 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 can 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 these products immunization.

Exclusion Criteria:

* have a 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 smoothly controlled, such as asthma, diabetes, thyroid disease
* Congenital or acquired angioedema / neuroedema.
* have the history of urticaria 1 year before receiving the trial vaccine.
* have asplenia or functional asplenia.
* have thrombocytopenia or other coagulation disorders (which may cause contraindications for intramuscular injection).
* 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 trial vaccines.
* have received another investigational product within one month before injection of trial vaccine.
* have received attenuated vaccine within 1 month before injection of trial vaccine except the recombinant Ad5 vectored COVID-19 vaccine.
* have received subunit or inactivated vaccine within 14 days before the vaccination with trial vaccine.
* 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 solicited adverse events within 7 days after vaccination.
timeFrame: Within 7 days after vaccination
measure: GMT of neutralizing antibodies against live SARS-CoV-2 virus at Day 14 after the booster vaccination.
timeFrame: At Day 14 after the booster vaccination
Secondary outcomes:
measure: Incidence of adverse reactions within 28 days after vaccination.
timeFrame: Within 28 days after vaccination
measure: Incidence of adverse events within 28 days after vaccination.
timeFrame: Within 28 days after vaccination.
measure: Incidence of unsolicited AE within 28 days after vaccination.
timeFrame: Within 28 days after vaccination.
measure: Incidence of serious adverse events(SAE) from the first dose to the 6 months after completing the last dose of vaccination.
timeFrame: From the first dose to the 6 months after completing the last dose of vaccination.
measure: GMT of binding antibodies against SARS-CoV-2 S and RBD protein measured by ELISA at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.
timeFrame: at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.
measure: Proportion of the participants with at least a four-fold increase of the binding antibodies against SARS-CoV-2 S and RBD protein at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.
timeFrame: at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.
measure: Fold increase of binding antibodies against SARS-CoV-2 S and RBD protein at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.
timeFrame: at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.
measure: GMT of neutralizing antibodies against live SARS-CoV-2 virus at day 28 after the second vaccination, and day 14, month 6 after the third vaccination
timeFrame: at day 28 after the second vaccination, and day 14, month 6 after the third vaccination
measure: Proportion of the participants with at least a four-fold increase of neutralizing antibodies against live SARS-CoV-2 virus at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.
timeFrame: at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.
measure: Fold increase of neutralizing antibodies against live SARS-CoV-2 virus at day 14, day 28 after the second vaccination and day 14, month 6 after the third vaccination.
timeFrame: at day 14, day 28 after the second vaccination and day 14, month 6 after the third vaccination.
Other outcomes:
measure: Types of binding antibodies IgG against SARS-CoV-2 S protein at day 14, day 28 after the second vaccination and day 14, month 6 after the third vaccination.
timeFrame: at day 14, day 28 after the second vaccination and day 14, month 6 after the third vaccination.
measure: Cross neutralizing of the antibodies to variants of SARS-CoV-2 measured by pseudovirus neutralization test at Day 28 after the booster vaccination.
timeFrame: At Day 28 after the booster vaccination.
measure: The immune cells' subgroups and germlines at Day 28 after vaccination.
timeFrame: At Day 28 after vaccination.
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: Jing-Xin Li, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jin P, Guo X, Chen W, Ma S, Pan H, Dai L, Du P, Wang L, Jin L, Chen Y, Shi F, Liu J, Xu X, Zhang Y, Gao GF, Chen C, Feng J, Li J, Zhu F. Safety and immunogenicity of heterologous boost immunization with an adenovirus type-5-vectored and protein-subunit-based COVID-19 vaccine (Convidecia/ZF2001): A randomized, observer-blinded, placebo-controlled trial. PLoS Med. 2022 May 26;19(5):e1003953. doi: 10.1371/journal.pmed.1003953. eCollection 2022 May.