Study on Heterologous Prime-boost of Recombinant COVID-19 Vaccine (Ad5 Vector) and RBD-based Protein Subunit Vaccine

NCT04833101 | Completed Phase 4 DMC

• 1 other identifier: JSVCT115
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Keywords

SARS-CoV-2 Vaccine; Recombinant Ad5 Vector; Subunit Vaccine; Safety; Immunogenicity

Outcome Measures

Primary Outcomes (2)

• Incidence of solicited adverse events within 7 days after vaccination.

  Incidence of solicited adverse events within 7 days after vaccination.

  Within 7 days after vaccination

• GMT of neutralizing antibodies against live SARS-CoV-2 virus at Day 14 after the booster vaccination.

  GMT of neutralizing antibodies against live SARS-CoV-2 virus at Day 14 after the booster vaccination.

  At Day 14 after the booster vaccination

Secondary Outcomes (10)

• Incidence of adverse reactions within 28 days after vaccination.

  Within 28 days after vaccination

• Incidence of adverse events within 28 days after vaccination.

  Within 28 days after vaccination.

• Incidence of unsolicited AE within 28 days after vaccination.

  Within 28 days after vaccination.

• Incidence of serious adverse events(SAE) from the first dose to the 6 months after completing the last dose of vaccination.

  From the first dose to the 6 months after completing the last dose of vaccination.

• 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.

  at day 14, day 28 after the second vaccination, and day 14, month 6 after the third vaccination.

Other Outcomes (3)

• 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.

  at day 14, day 28 after the second vaccination and day 14, month 6 after the third vaccination.

• Cross neutralizing of the antibodies to variants of SARS-CoV-2 measured by pseudovirus neutralization test at Day 28 after the booster vaccination.

  At Day 28 after the booster vaccination.

• The immune cells' subgroups and germlines at Day 28 after vaccination.

  At Day 28 after vaccination.

Study Arms (4)

"0-28 days" vaccine group

EXPERIMENTAL

One dose of recombinant Ad5 vectored COVID-19 vaccine on day 0, the second dose of subunit vaccine (ZF2001) against COVID-19 on day 28, and a third of subunit vaccine (ZF2001) against COVID-19 on month 4.

Biological: recombinant Ad5 vectored COVID-19 vaccine; Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19

"0-28 days" placebo group

PLACEBO COMPARATOR

One dose of recombinant Ad5 vectored COVID-19 vaccine on day 0, the second dose of a commercial influenza vaccine on day 28, a third of subunit vaccine (ZF2001) against COVID-19 on month 4.

Biological: recombinant Ad5 vectored COVID-19 vaccine; Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19; Biological: trivalent split influenza vaccine

"0-56 days" vaccine group

EXPERIMENTAL

One dose of recombinant Ad5 vectored COVID-19 vaccine on day 0, the second dose of subunit vaccine (ZF2001) against COVID-19 on day 56, a third of subunit vaccine (ZF2001) against COVID-19 on month 4.

Biological: recombinant Ad5 vectored COVID-19 vaccine; Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19

"0-56 days" placebo group

PLACEBO COMPARATOR

One dose of recombinant Ad5 vectored COVID-19 vaccine on day 0, the second dose of a commercial influenza vaccine on day 56, a third of subunit vaccine (ZF2001) against COVID-19 on month 4.

Biological: recombinant Ad5 vectored COVID-19 vaccine; Biological: RBD-based protein subunit vaccine (ZF2001) against COVID-19; Biological: trivalent split influenza vaccine

Interventions

recombinant Ad5 vectored COVID-19 vaccine BIOLOGICAL

This vaccine contains 5×10\^10 virus particles of recombinant replication defective human type-5 adenovirus expressing SARS-CoV-2 S protein, which is produced by CanSino Biologics Inc. It is a liquid dosage form, 0.5 ml / bottle.

Also known as: Ad5-nCoV

"0-28 days" placebo group; "0-28 days" vaccine group; "0-56 days" placebo group; "0-56 days" vaccine group

RBD-based protein subunit vaccine (ZF2001) against COVID-19 BIOLOGICAL

This is a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19, made by using CHO cell, 25μg/dose, produced by Anhui Zhifei Longcom Biopharmaceutical Co.,Ltd.

Also known as: ZF2001 vaccine

"0-28 days" placebo group; "0-28 days" vaccine group; "0-56 days" placebo group; "0-56 days" vaccine group

trivalent split influenza vaccine BIOLOGICAL

This vaccine contains 15 μ g H1NI, 15 μ g H3N2 and 15 μ g B-series hemagglutinin, produced by Dalian Aleph Biomedical Co., Ltd.It is a liquid dosage form, 0.5 ml / bottle.

"0-28 days" placebo group; "0-56 days" placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu Province Centers for Disease Control and Prevention: lead

Study Sites (1)

Jiangsu Provincial Center for Diseases Control and Prevention

Nanjing, Jiangsu, China

Location

Related Publications (1)

• 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.

  PMID: 35617368 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Ad5-nCoV vaccine; ZF2001 COVID-19 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jing-Xin Li, PhD

  Jiangsu Provincial Center for Diseases Control and Prevention

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2021
• First Posted: April 6, 2021
• Study Start: April 7, 2021
• Primary Completion: September 18, 2021
• Study Completion: March 4, 2022
• Last Updated: April 6, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: 1 month to 1 year after the completion of the study
• Access Criteria: Researchers who provide a scientifically sound proposal will be allowed access to the individual participant data.These proposals will be reviewed and approved by the sponsor, investigator, and collaborators on the basis of scientific merit. To gain access, data requesters will need to sign a data access agreement.

Locations

CN (1)