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

Phase 2

Active, not recruiting

• Conditions: COVID-19
• Interventions: Biological: 1 Nebulized inhalation for booster groups; Biological: 2 Nebulized inhalation for booster groups; Biological: 6 Intramuscular injection for booster groups; Biological: 5 Intramuscular injection for booster groups; Biological: 11 Nebulized inhalation for booster groups; Biological: 9 Intramuscular injection for booster groups; Biological: 10 Intramuscular injection for booster groups; Biological: 16 Intramuscular injection for booster groups; Biological: 21 Nebulized inhalation for primary groups; Biological: 7 Intramuscular injection for booster groups; Biological: 3 Nebulized inhalation for booster groups; Biological: 8 Intramuscular injection for booster groups; Biological: 4 Nebulized inhalation for booster groups; Biological: 12 Nebulized inhalation for booster groups; Biological: 17 Intramuscular injection for booster groups; Biological: 19 Intramuscular injection for booster groups; Biological: 22 Nebulized inhalation for primary groups; Biological: 20 Intramuscular injection 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: 18 Intramuscular injection for booster groups; Biological: 24 Nebulized inhalation for primary groups; Biological: 23 Nebulized inhalation for primary groups

• Registration Number: NCT05330871
• Lead Sponsor: Seventh Medical Center of PLA General Hospital

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.

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 Timeline

• Study First Submitted: 2022-04-14
• Study First Submitted QC: 2022-04-14
• Study First Posted: 2022-04-15
• Study Start: 2022-04-17
• Primary Completion: 2022-06-30
• Status Verified: 2023-03
• Last Update Submitted: 2023-04-12
• Last Update Posted: 2023-04-13
• Study Completion: 2023-05-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 410

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).

Exclusion criteria for second dose:

• Newly emerged situations that meet the first-dose exclusion criteria.
• Vaccine related SAE post first dose vaccination.
• Serious allergic reactions post first dose vaccination.
• Other reasons in the opinion of the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1. Adolescent booster sentinel group	1 Nebulized inhalation for booster groups	1 dose of 0.1ml Ad5-nCoV-IH
2. Adolescent booster safety group to receive Ad5-nCoV-IH	2 Nebulized inhalation for booster groups	1 dose of 0.1ml Ad5-nCoV-IH
6. Adolescent booster immuno-persistency group to receive Ad5-nCoV-IM	6 Intramuscular injection for booster groups	1 dose of 0.3ml Ad5-nCoV-IM
5. Adolescent booster safety group to receive Ad5-nCoV-IM	5 Intramuscular injection for booster groups	1 dose of 0.3ml Ad5-nCoV-IM
11. Children booster sentinel group to receive Ad5-nCoV-IH	11 Nebulized inhalation for booster groups	1 dose of 0.1ml Ad5-nCoV-IH
9. Adolescent booster immunopersistency group to receive ICV	9 Intramuscular injection for booster groups	1 dose of 0.5ml ICV
10. Adolescent booster cellular immunity group to receive ICV	10 Intramuscular injection for booster groups	1 dose of 0.5ml ICV
16. Children booster immuno-persistency group to receive Ad5-nCoV-IM	16 Intramuscular injection for booster groups	1 dose of 0.3ml Ad5-nCoV-IM
21. Adolescent primary sentinel group	21 Nebulized inhalation for primary groups	2 doses of 0.1ml Ad5-nCoV-IH, 56 days interval
7. Adolescent booster cellular immunity group to receive Ad5-nCoV-IM	7 Intramuscular injection for booster groups	1 dose of 0.3ml Ad5-nCoV-IM
3. Adolescent booster immuno-persistency group to receive Ad5-nCoV-IH	3 Nebulized inhalation for booster groups	1 dose of 0.1ml Ad5-nCoV-IH
8. Adolesent booster safety group to receive ICV	8 Intramuscular injection for booster groups	1 dose of 0.5ml ICV
4. Adolescent booster cellular immunity group to receive Ad5-nCoV-IH	4 Nebulized inhalation for booster groups	1 dose of 0.1ml Ad5-nCoV-IH
12. Children booster safety group to receive Ad5-nCoV-IH	12 Nebulized inhalation for booster groups	1 dose of 0.1ml Ad5-nCoV-IH
17. Children booster cellular immunity group to receive Ad5-nCoV-IM	17 Intramuscular injection for booster groups	1 dose of 0.3ml Ad5-nCoV-IM
19. Children booster immuno-persistency group to receive ICV	19 Intramuscular injection for booster groups	1 dose of 0.5ml ICV
22. Adolescent primary group	22 Nebulized inhalation for primary groups	2 doses of 0.1ml Ad5-nCoV-IH, 56 days interval
20. Children booster cellular immunity group to receive ICV	20 Intramuscular injection for booster groups	1 dose of 0.5ml ICV
13. Children booster immuno-persistency group to receive Ad5-nCoV-IH	13 Nebulized inhalation for booster groups	1 dose of 0.1ml Ad5-nCoV-IH
14. Children booster cellular immunity group to receive Ad5-nCoV-IH	14 Nebulized inhalation for booster groups	1 dose of 0.1ml Ad5-nCoV-IH
15. Children booster safety group to receive Ad5-nCoV-IM	15 Intramuscular injection for booster groups	1 dose of 0.3ml Ad5-nCoV-IM
18. Children booster safety group to receive ICV	18 Intramuscular injection for booster groups	1 dose of 0.5ml ICV
24. Children primary group	24 Nebulized inhalation for primary groups	2 doses of 0.1ml Ad5-nCoV-IH, 56 days interval
23. Children primary sentinel group	23 Nebulized inhalation for primary groups	2 doses of 0.1ml Ad5-nCoV-IH, 56 days interval

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Immunogenicity of anti SARS-CoV-2 neutralizing antibody	Post vaccination	GMI of anti SARS-CoV-2 neutralizing 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
Changes in laboratory indicators in sentinel groups and safety groups	4 days post each vaccination	Changes in platelet counts
Immunogenicity of anti Ad5 vector antibody	Day 0 before vaccination	Stratified analysis of baseline level of anti Ad5 vector antibody
Incidence of Serious Adverse Event	First dose vaccination to 12 months post last vaccination]	Incidence of SAE
Incidence of adverse event/adverse reaction	0-28 days post each vaccination	Incidence of AE/AR
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

Trial Locations

Locations (1)

CDC of of Luxi County, Xiangxi Tujia and Miao Autonomous Prefecture, Hunan Province; 🇨🇳 Xiangxi, Hunan, China