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Heterologous Boost Immunization With Ad5-nCoV After Three-dose Priming With an Inactivated SARS-CoV-2 Vaccine

Primary Purpose

COVID-19

Status
Active
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Ad5-nCoV-IH
Ad5-nCoV-IM
CoronaVac
Sponsored by
Jiangsu Province Centers for Disease Control and Prevention
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for COVID-19 focused on measuring SARS-CoV-2, Ad5-nCoV, Inactivated Vaccine, Safety, Immunogenicity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Jiangsu Provincial Center for Diseases Control and Prevention

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group A

Group B

Group C

Arm Description

Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive a booster dose of aerosolized Ad5-nCoV after three-dose priming with ICV

Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive a booster dose of intramuscular Ad5-nCoV after three-dose priming with CoronaVac

Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive homologous fourth dose of CoronaVac.

Outcomes

Primary Outcome Measures

Incidence of adverse reactions within 28 days after the booster dose
Incidence of adverse reactions within 28 days after the booster dose.
GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.
GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.

Secondary Outcome Measures

Geometric Mean Fold Increase (GMI) and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.
GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose in immunogenicity cohort.
GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 14, month 3 and 6 after the booster dose.
GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus as compared to baseline on day 14, month 3 and 6 after the booster dose.
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.
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.
Incidence of adverse reactions within 30 minutes after the booster dose.
Incidence of adverse reactions within 30 minutes after the booster dose.
Incidence of adverse reactions within 14 days after the booster dose.
Incidence of adverse reactions within 14 days after the booster dose.
Incidence of adverse events within 28 days after the booster dose.
Incidence of adverse events within 28 days after the booster dose.
Incidence of serious adverse events (SAE) until 6 months after the booster dose.
Incidence of SAE until 6 months after booster vaccination.

Full Information

First Posted
March 22, 2022
Last Updated
August 12, 2022
Sponsor
Jiangsu Province Centers for Disease Control and Prevention
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1. Study Identification

Unique Protocol Identification Number
NCT05303584
Brief Title
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

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 23, 2022 (Actual)
Primary Completion Date
June 20, 2022 (Actual)
Study Completion Date
March 20, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu Province Centers for Disease Control and Prevention

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
SARS-CoV-2, Ad5-nCoV, Inactivated Vaccine, Safety, Immunogenicity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
360 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group A
Arm Type
Experimental
Arm Description
Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive a booster dose of aerosolized Ad5-nCoV after three-dose priming with ICV
Arm Title
Group B
Arm Type
Experimental
Arm Description
Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive a booster dose of intramuscular Ad5-nCoV after three-dose priming with CoronaVac
Arm Title
Group C
Arm Type
Experimental
Arm Description
Approximately 70 subjects recruited from the prior clinical trial and newly enrolled 50 subjects will receive homologous fourth dose of CoronaVac.
Intervention Type
Biological
Intervention Name(s)
Ad5-nCoV-IH
Other Intervention Name(s)
aerosolized Ad5-nCoV, Convidecia
Intervention Description
The orally aerosolized Ad5-nCoV is a replication defective Ad5 vectored COVID-19 vaccine expressing the full-length spike gene of wide-type SARS-CoV-2, Wuhan-Hu-1. The Ad5-nCoV vaccine was supplied in 1.5mL/vial, at a concentration of 1.0 × 1011 viral particles per mL as a liquid formulation. 0.1 ml of Ad5-nCoV vaccine will be aerosolized by using Continuous Vapouring System. Then, the aerosolized droplets will be poured into a disposable suction cup and be inhaled by participants through mouth.
Intervention Type
Biological
Intervention Name(s)
Ad5-nCoV-IM
Other Intervention Name(s)
intramuscular Ad5-nCoV
Intervention Description
The Ad5-nCoV is a replication defective Ad5 vectored COVID-19 vaccine expressing the full-length spike gene of wide-type SARS-CoV-2, Wuhan-Hu-1. It was supplied in 1·5mL/vial, at a concentration of 1.0 × 1011 viral particles per mL as a liquid formulation. Participants will be administrated 0.5ml（5×1010VP）of Ad5-nCoV vaccine intramuscularly.
Intervention Type
Biological
Intervention Name(s)
CoronaVac
Intervention Description
CoronaVac is an inactivated whole-virion vaccine with aluminium hydroxide as the adjuvant, prepared with a novel coronavirus (CZ02 strain) inoculated in African green monkey kidney cells (Vero cells). One dose of CoronaVac contains 3 μg of SARS-CoV-2 virion in a 0.5 mL aqueous suspension for injection with 0.45 mg/mL of aluminium.
Primary Outcome Measure Information:
Title
Incidence of adverse reactions within 28 days after the booster dose
Description
Incidence of adverse reactions within 28 days after the booster dose.
Time Frame
Within 28 days the booster dose
Title
GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.
Description
GMT of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.
Time Frame
On day 28 after the booster dose
Secondary Outcome Measure Information:
Title
Geometric Mean Fold Increase (GMI) and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose.
Description
GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 28 after the booster dose in immunogenicity cohort.
Time Frame
On day 28 after the boost vaccination
Title
GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus on day 14, month 3 and 6 after the booster dose.
Description
GMT, GMI and seroconversion of neutralizing antibodies against live SARS-CoV-2 virus as compared to baseline on day 14, month 3 and 6 after the booster dose.
Time Frame
On day 14, month 3 and 6 after the booster dose
Title
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.
Description
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.
Time Frame
On day 14, day 28 and month 3 and 6 after the booster dose
Title
Incidence of adverse reactions within 30 minutes after the booster dose.
Description
Incidence of adverse reactions within 30 minutes after the booster dose.
Time Frame
Within 30 minutes after the booster dose
Title
Incidence of adverse reactions within 14 days after the booster dose.
Description
Incidence of adverse reactions within 14 days after the booster dose.
Time Frame
Within 14 days after the booster dose
Title
Incidence of adverse events within 28 days after the booster dose.
Description
Incidence of adverse events within 28 days after the booster dose.
Time Frame
Within 28 days after the booster dose
Title
Incidence of serious adverse events (SAE) until 6 months after the booster dose.
Description
Incidence of SAE until 6 months after booster vaccination.
Time Frame
Within 6 months after the booster dose
Other Pre-specified Outcome Measures:
Title
GMT, GMI and seroconversion of neutralizing antibodies against VOC/VOI of SARS-CoV-2 virus on day 28 after the booster dose.
Description
GMT, GMI and seroconversion of neutralizing antibodies against VOC/VOI of SARS-CoV-2 virus on day 28 after the booster dose.
Time Frame
On day 28 after the booster dose
Title
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.
Description
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.
Time Frame
On day 14 after the booster vaccination
Title
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.
Description
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.
Time Frame
On day 28 after the booster dose
Title
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).
Description
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).
Time Frame
On day 28 after the booster dose
Title
The levels of anti-SARS-CoV-2 N protein binding IgG on day 14 after the booster dose.
Description
The levels of anti-SARS-CoV-2 N protein binding IgG on day 14 after the booster dose.
Time Frame
On day 14 after the booster dose
Title
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）
Description
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）
Time Frame
On day 0 before the booster dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jingxin Li, PhD
Organizational Affiliation
Jiangsu Provincial Center for Diseases Control and Prevention
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jiangsu Provincial Center for Diseases Control and Prevention
City
Nanjing
State/Province
Jiangsu
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Heterologous Boost Immunization With Ad5-nCoV After Three-dose Priming With an Inactivated SARS-CoV-2 Vaccine

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