Evaluate the Safety and Immunogenicity of Ad5 COVID-19 Vaccines for Booster Use in Children Aged 6-17 Years.

Sponsor

Seventh Medical Center of PLA General Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05330871

Collaborator

(none)

410

Enrollment

Arms

15.5

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a single center, open-label, parallel controlled, and randomized Phase II clinical trial to evaluate the safety and immunogenicity of two types of Recombinant Novel Corona Virus Vaccine (Adenovirus type 5 vector) in population aged 6-17 years who have been previously immunized with 2 doses of inactivated COVID-19 vaccine. This is to evaluate the safety and immunogenicity of different heterologous prime-boost regimen in this population.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Biological: 1 Nebulized inhalation for booster groups Biological: 2 Nebulized inhalation for booster groups Biological: 3 Nebulized inhalation for booster groups Biological: 4 Nebulized inhalation for booster groups Biological: 5 Intramuscular injection for booster groups Biological: 6 Intramuscular injection for booster groups Biological: 7 Intramuscular injection for booster groups Biological: 8 Intramuscular injection for booster groups Biological: 9 Intramuscular injection for booster groups Biological: 10 Intramuscular injection for booster groups Biological: 11 Nebulized inhalation for booster groups Biological: 12 Nebulized inhalation for booster groups Biological: 13 Nebulized inhalation for booster groups Biological: 14 Nebulized inhalation for booster groups Biological: 15 Intramuscular injection for booster groups Biological: 16 Intramuscular injection for booster groups Biological: 17 Intramuscular injection for booster groups Biological: 18 Intramuscular injection for booster groups Biological: 19 Intramuscular injection for booster groups Biological: 20 Intramuscular injection for booster groups Biological: 21 Nebulized inhalation for primary groups Biological: 22 Nebulized inhalation for primary groups Biological: 23 Nebulized inhalation for primary groups Biological: 24 Nebulized inhalation for primary groups	Phase 2

Detailed Description

Participants will be randomized into two age groups: children aged 6-12 years and adolescents aged 13-17 years. Subjects who have previously been immunized with 2 doses of inactivated COVID-19 vaccine will be randomized into the booster dose groups to receive either 1 dose of 0.1ml inhaled Ad5- nCoV-IH, 1 dose of 0.3ml intramuscular Ad5-nCoV-IM or 1 dose of 0.5ml intramuscular inactivated vaccine ICV as activecomparator in a ratio of 3:1:1. Participants who have not received any COVID-19 vaccine previously will be randomized into 2 primary dose age groups: children aged 6-12 years and adolescents aged 13-17 years to receive 2 doses of 0.1ml inhaled Ad5-nCoVIH. The first 5 subjects of each age group will enter the sentinel group to receive Ad5-nCoV-IH and monitor for safety before the rest of the enrollment process.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

410 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Single Center, Open-label, Parallel Controlled, Randomized Phase II Study to Evaluate the Safety and Immunogenicity of Ad5-nCoV-IM, Ad5-nCoV-IH or Inactivated COVID-19 Vaccine in Population 6 to 17 Years of Age

Anticipated Study Start Date :

Apr 15, 2022

Anticipated Primary Completion Date :

Mar 30, 2023

Anticipated Study Completion Date :

Jul 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1. Adolescent booster sentinel group 1 dose of 0.1ml Ad5-nCoV-IH	Biological: 1 Nebulized inhalation for booster groups Ad5-nCoV-IH, 1 dose 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 2. Adolescent booster safety group to receive Ad5-nCoV-IH 1 dose of 0.1ml Ad5-nCoV-IH	Biological: 2 Nebulized inhalation for booster groups Ad5-nCoV-IH, 1 dose 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 3. Adolescent booster immuno-persistency group to receive Ad5-nCoV-IH 1 dose of 0.1ml Ad5-nCoV-IH	Biological: 3 Nebulized inhalation for booster groups Ad5-nCoV-IH, 1 dose 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 4. Adolescent booster cellular immunity group to receive Ad5-nCoV-IH 1 dose of 0.1ml Ad5-nCoV-IH	Biological: 4 Nebulized inhalation for booster groups Ad5-nCoV-IH, 1 dose 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 5. Adolescent booster safety group to receive Ad5-nCoV-IM 1 dose of 0.3ml Ad5-nCoV-IM	Biological: 5 Intramuscular injection for booster groups Ad5-nCoV-IM, 1 dose 0.3ml Other Names: Recombinant Corona Virus Vaccine (Adenovirus Type 5 Vector)
Experimental: 6. Adolescent booster immuno-persistency group to receive Ad5-nCoV-IM 1 dose of 0.3ml Ad5-nCoV-IM	Biological: 6 Intramuscular injection for booster groups Ad5-nCoV-IM, 1 dose 0.3ml Other Names: Recombinant Corona Virus Vaccine (Adenovirus Type 5 Vector)
Experimental: 7. Adolescent booster cellular immunity group to receive Ad5-nCoV-IM 1 dose of 0.3ml Ad5-nCoV-IM	Biological: 7 Intramuscular injection for booster groups Ad5-nCoV-IM, 1 dose 0.3ml Other Names: Recombinant Corona Virus Vaccine (Adenovirus Type 5 Vector)
Active Comparator: 8. Adolesent booster safety group to receive ICV 1 dose of 0.5ml ICV	Biological: 8 Intramuscular injection for booster groups ICV, 1 dose 0.5ml Other Names: Inactivated COVID-19 Vaccine
Active Comparator: 9. Adolescent booster immunopersistency group to receive ICV 1 dose of 0.5ml ICV	Biological: 9 Intramuscular injection for booster groups ICV, 1 dose 0.5ml Other Names: Inactivated COVID-19 Vaccine
Active Comparator: 10. Adolescent booster cellular immunity group to receive ICV 1 dose of 0.5ml ICV	Biological: 10 Intramuscular injection for booster groups 1 dose 0.5ml Other Names: Inactivated COVID-19 Vaccine
Experimental: 11. Children booster sentinel group to receive Ad5-nCoV-IH 1 dose of 0.1ml Ad5-nCoV-IH	Biological: 11 Nebulized inhalation for booster groups Ad5-nCoV-IH, 1 dose 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 12. Children booster safety group to receive Ad5-nCoV-IH 1 dose of 0.1ml Ad5-nCoV-IH	Biological: 12 Nebulized inhalation for booster groups Ad5-nCoV-IH, 1 dose 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 13. Children booster immuno-persistency group to receive Ad5-nCoV-IH 1 dose of 0.1ml Ad5-nCoV-IH	Biological: 13 Nebulized inhalation for booster groups Ad5-nCoV-IH, 1 dose 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 14. Children booster cellular immunity group to receive Ad5-nCoV-IH 1 dose of 0.1ml Ad5-nCoV-IH	Biological: 14 Nebulized inhalation for booster groups Ad5-nCoV-IH, 1 dose 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 15. Children booster safety group to receive Ad5-nCoV-IM 1 dose of 0.3ml Ad5-nCoV-IM	Biological: 15 Intramuscular injection for booster groups Ad5-nCoV-IM, 1 dose 0.3ml Other Names: Recombinant Corona Virus Vaccine (Adenovirus Type 5 Vector)
Experimental: 16. Children booster immuno-persistency group to receive Ad5-nCoV-IM 1 dose of 0.3ml Ad5-nCoV-IM	Biological: 16 Intramuscular injection for booster groups Ad5-nCoV-IM, 1 dose 0.3ml Other Names: Recombinant Corona Virus Vaccine (Adenovirus Type 5 Vector)
Experimental: 17. Children booster cellular immunity group to receive Ad5-nCoV-IM 1 dose of 0.3ml Ad5-nCoV-IM	Biological: 17 Intramuscular injection for booster groups Ad5-nCoV-IM, 1 dose 0.3ml Other Names: Recombinant Corona Virus Vaccine (Adenovirus Type 5 Vector)
Active Comparator: 18. Children booster safety group to receive ICV 1 dose of 0.5ml ICV	Biological: 18 Intramuscular injection for booster groups ICV, 1 dose 0.5ml Other Names: Inactivated COVID-19 Vaccine
Active Comparator: 19. Children booster immuno-persistency group to receive ICV 1 dose of 0.5ml ICV	Biological: 19 Intramuscular injection for booster groups ICV, 1 dose 0.5ml Other Names: Inactivated COVID-19 Vaccine
Active Comparator: 20. Children booster cellular immunity group to receive ICV 1 dose of 0.5ml ICV	Biological: 20 Intramuscular injection for booster groups ICV, 1 dose 0.5ml Other Names: Inactivated COVID-19 Vaccine
Experimental: 21. Adolescent primary sentinel group 2 doses of 0.1ml Ad5-nCoV-IH, 56 days interval	Biological: 21 Nebulized inhalation for primary groups Ad5-nCoV-IH, 2 doses 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 22. Adolescent primary group 2 doses of 0.1ml Ad5-nCoV-IH, 56 days interval	Biological: 22 Nebulized inhalation for primary groups Ad5-nCoV-IH, 2 doses 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 23. Children primary sentinel group 2 doses of 0.1ml Ad5-nCoV-IH, 56 days interval	Biological: 23 Nebulized inhalation for primary groups Ad5-nCoV-IH, 2 doses 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation
Experimental: 24. Children primary group 2 doses of 0.1ml Ad5-nCoV-IH, 56 days interval	Biological: 24 Nebulized inhalation for primary groups Ad5-nCoV-IH, 2 doses 0.1ml Other Names: Recombinant COVID-19 Vaccine for Inhalation

Outcome Measures

Primary Outcome Measures

Immunogenicity of anti SARS-CoV-2 neutralizing antibody [28 days post vaccination]
GMT of anti SARS-CoV-2 neutralizing antibody
Incidence of adverse reaction (AR) [0-14 days post each vaccination]
Incidence of adverse reaction (AR)

Secondary Outcome Measures

Immunogenicity of anti SARS-CoV-2 S protein IgG antibody [28 days post vaccination]
Seroconversion rate of anti SARS-CoV-2 S protein IgG antibody (4 times fold increase)
Immunogenicity of anti SARS-CoV-2 S protein IgG antibody [28 days post vaccination]
GMC of anti SARS-CoV-2 S protein IgG antibody
Immunogenicity of anti SARS-CoV-2 S protein IgG antibody [28 days post vaccination]
GMI of anti SARS-CoV-2 S protein IgG antibody
Immunogenicity of anti Ad5 vector antibody [Day 0 before vaccination]
Stratified analysis of baseline level of anti Ad5 vector antibody
Immunogenicity of anti SARS-CoV-2 neutralizing antibody [Post vaccination]
Seroconversion rate of anti SARS-CoV-2 neutralizing antibody
Immunogenicity of anti SARS-CoV-2 neutralizing antibody [Post vaccination]
GMI of anti SARS-CoV-2 neutralizing antibody
Incidence of adverse event/adverse reaction [30 minutes post each vaccination]
Incidence of AE/AR
Incidence of adverse event/adverse reaction [0-28 days post each vaccination]
Incidence of AE/AR
Incidence of Serious Adverse Event [First dose vaccination to 12 months post last vaccination]]
Incidence of SAE
Changes in laboratory indicators in sentinel groups and safety groups [4 days post each vaccination]
Changes in WBC counts
Changes in laboratory indicators in sentinel groups and safety groups [4 days post each vaccination]
Changes in lymphocytes counts
Changes in laboratory indicators in sentinel groups and safety groups [4 days post each vaccination]
Changes in platelet counts
Immuno-persistency of anti SARS-CoV-2 S protein IgG antibody [3 months, 6 months and 12 months post vaccination]
GMC of anti SARS-CoV-2 S protein IgG antibody in immuno-persistency and primary groups
Immuno-persistency of anti SARS-CoV-2 S protein IgG antibody [6 months and 12 months post vaccination]
Seroconversion rate of anti SARS-CoV-2 S protein IgG antibody in immuno-persistency and primary groups
Immuno-persistency of anti SARS-CoV-2 S protein IgG antibody [6 months and 12 months post vaccination]
GMI of anti SARS-CoV-2 S protein IgG antibody in immuno-persistency and primary groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Participants aged 6-17 years at the time of enrollment.
Obtain written informed assent from participants and consent from parents, guardians or legal representatives.
Able and willing to complete all the scheduled study procedures during the whole study follow-up period of 12 months.
Have not received any COVID-19 vaccines (for primary groups only).

Exclusion Criteria:

Medical or family history of seizures, epilepsy, encephalopathy, and psychosis disorders.
History of allergies to any ingredient of Ad5-nCoV, history of serious allergic reactions to any vaccine, history of allergies and asthma.
History of vaccine related SAEs after receiving any COVID-19 vaccines.
Positive urine pregnancy test result, females with child bearing potential (have had menarche).
Acute febrile diseases and infectious diseases, medical history of SARS (SARS-CoV-1).
Axillary temperature >37.0#.
Serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension and uncontrollable by medications.
Severe chronic diseases or with advanced stage conditions which cannot be controlled smoothly, such as diabetes, thyroid disease, etc.
Congenital or acquired angioedema/neurological edema.
Urticaria history within 1 year before receiving the study vaccine.
Asplenia or functional aspleenia.
Thrombocytopenia or other coagulation disorders (may cause contraindications for intramuscular injection).
Trypanophobia.
Severe nasal or oral diseases, such as acute rhinitis (sinusitis), allergic rhinitis, oral ulcers, throat redness, and swelling.
Lung function abnormalities such as chronic obstructive pulmonary disease and pulmonary fibrosis.
Abnormal laboratory test indexes that are clinical significant as judged by the investigator (including white blood cell count, lymphocyte count, eosinophils, neutrophils, platelets, hemoglobin, alanine aminotransferase ALT, aspartate aminotransferase AST, total bilirubin , creatinine, activated partial thromboplastin time) (for sentinel and safety groups only).
Respiratory rate ≥ 17 times per minute (for sentinel and safety groups only).
History of receiving immunosuppressant therapy, anti-allergic therapy, cytotoxic therapy, nebulized corticosteroid therapy in the past 6 months (not including corticosteroid spray treatment for allergic rhinitis, and surface corticosteroid treatment for acute non-complicated dermatitis).
Prior administration of blood products in last 4 months.
Received other investigational drugs within 1 month before the study.
Prior administration of live attenuated vaccines within 1 month before the study.
Prior administration of subunit or inactivated vaccines within 14 days before the study.
Current anti-tuberculosis therapy.
Medical history of Covid-19 disease/infection.
History of epidemiological exposure to COVID-19; have traveled to medium or high-risk areas in the past 21 days or have a history of travelling outside the country
Any condition that in the opinion of the investigators may interfere with the participants' compliance or evaluation of study objectives or informed consent (i.e. medical, psychological, social or other conditions, etc).