A Study to Evaluate the Safety and Immunogenicity of Ad5-vector Based Vaccine Against Coronavirus Variants in Adults (≥18 Years) Immunized With 2 Doses of mRNA Vaccines Plus One Dose of Booster AZD1222 Vaccine

A Multicenter, Randomized, and Observer-blind Clinical Trial to Evaluate the Safety and Immunogenicity of Ad5-based COVID-19 Vaccine Against Coronavirus Variants in Adults (≥ 18 Years) Who Have Been Immunized With 2 Doses of mRNA Vaccines Plus One Dose of Booster AZD1222 Vaccine

Subjects who have completed the primary mRNA vaccine immunizations and the 1st booster AZD1222 immunization for more than 6 months will be randomized to receive a 2nd booster dose of Ad5-nCoV/O, Ad5-nCoV/O-IH or mRNA-based COVID-19 vaccine in a ratio of 2:2:1.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19
• Intervention / Treatment: Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector); Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation; Biological: mRNA-based COVID-19 vaccine

Detailed Description

This is a multicenter, randomized, observer-blind, and parallel-controlled clinical study to evaluate the immune responses and safety profiles in adults (≥ 18 years) receiving investigational products (intramuscular injection or nebulized inhalation) ≥ 180 days after the immunization of 2 doses of BNT162b2 vaccines plus one dose of booster AZD1222 vaccine. This study will enroll about 30% participants aged 60 years and above.

Subjects who have completed the primary mRNA vaccine immunizations and the 1st booster AZD1222 immunization for more than 6 months will be randomized to receive a 2nd booster dose of Ad5-nCoV/O, Ad5-nCoV/O-IH or mRNA-based COVID-19 vaccine in a ratio of 2:2:1.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ruijie Wang; Phone Number: (022)58213600; Email: ruijie.wang@cansinotech.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants aged 18 years and above at the time of screening.
2. Received the 1st booster vaccination at least 180 days earlier.
3. Agree to attend all visits and sign the written informed consent form.

Exclusion Criteria:

1. Have a history of seizures, epilepsy, encephalopathy, psychosis.
2. History of severe anaphylaxis or allergy to any vaccine component.
3. Positive urine pregnancy test result, pregnant, lactating women.
4. Medical history of Guillain-Barré syndrome.
5. Have had asthma attacks within 2 years.
6. Have severe nasal or oral diseases, such as rhinitis (sinusitis), allergic rhinitis, oral ulcer, throat swelling, etc.
7. Bleeding disorder (e.g. protein S or factor deficiency, coagulopathy or platelet disorder).
8. Have chronic systematic infection or chronic obstructive pulmonary disease (COPD), etc.
9. Administration of immunoglobulins and/or any blood products within three months prior to the planned administration of the vaccine candidate.
10. Current diagnosis or receiving treatment for tuberculosis or cancer.
11. History of SARS-CoV-2 infection for less than 3 months.
12. Received or plan to receive any vaccines (licensed or investigational), within 14 days before and after study vaccination.
13. Have an axillary temperature of > 37.0℃.
14. Any other significant diseases, disorders or findings which may significantly increase the risk to the volunteer because of participation in the study, and affect the ability of the volunteer to participate in the study or impair interpretation of the study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ad5-nCoV/O group	Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector); Subjects who have completed the primary mRNA vaccine immunizations and the 1st booster AZD1222 immunization for more than 6 months will be randomized to receive a 2nd booster dose of Ad5-nCoV/O
Experimental: Ad5-nCoV/O-IH group	Biological: Bivalent Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation; Subjects who have completed the primary mRNA vaccine immunizations and the 1st booster AZD1222 immunization for more than 6 months will be randomized to receive a 2nd booster dose of Ad5-nCoV/O-IH
Active Comparator: mRNA-based COVID-19 vaccine group	Biological: mRNA-based COVID-19 vaccine; Subjects who have completed the primary mRNA vaccine immunizations and the 1st booster AZD1222 immunization for more than 6 months will be randomized to receive a 2nd booster dose of mRNA-based COVID-19 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity of Ad5-nCoV/O or Ad5-nCoV/O-IH versus BNT162b2 as the 2nd booster dose.	The geometric mean titers (GMT) of anti-Omicron pseudovirus neutralizing antibody on Day 28 post vaccination in all participants	Day 28 post vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Reactions (ARs)	The incidence of adverse reactions (ARs) within 30 min post vaccination.	within 30 min post vaccination
Incidence of Adverse Reactions (ARs)	The incidence of adverse reactions (ARs) within 14 days post vaccination	within 14 days post vaccination
The incidence of AR and AE	The incidence of ARs/adverse events (AEs) within 28 days post vaccination.	within 28 days post vaccination
Incidence of SAE	The incidence of serious adverse events (SAEs) and adverse events of special interest (AESIs) within 12 months post vaccination.	within 12 months post vaccination
Immunogenicity of pseudovirus neutralizing antibody	The GMT, geometric mean increase fold (GMI) and sero-conversion rate (SCR) of anti-Omicron pseudovirus neutralizing antibody on Day 14 and Day 28 post-vaccination in all participants.	on Day 14 and Day 28 post-vaccination
Immunogenicity of S-RBD IgG antibody	The geometric mean concentration (GMC), GMI and SCR of anti-Omicron S-RBD IgG antibody on Day 14 and Day 28 post-vaccination in all participants.	on Day 14 and Day 28 post-vaccination
Immunogenicity of S-RBD serum IgA antibody	The GMT, GMI, and SCR of anti-Omicron S-RBD serum IgA antibody on Day 14 and Day 28 post-vaccination in all participants.	on Day 14 and Day 28 post-vaccination
Immunogenicity of pseudovirus neutralizing antibody	The GMT, GMI and SCR of anti-Omicron pseudovirus neutralizing antibody on Month 3, Month 6, and Month 12 post-vaccination in participants of the immunogenicity subgroup.	on Month 3, Month 6, and Month 12 post-vaccination
Immunogenicity of S-RBD IgG antibody	The GMC, GMI and SCR of anti-Omicron S-RBD IgG antibody on Month 3, Month 6, and Month 12 post-vaccination in participants of the immunogenicity subgroup.	on Month 3, Month 6, and Month 12 post-vaccination
Immunogenicity of S-RBD serum IgA antibody	The GMC, GMI and SCR of anti-Omicron S-RBD serum IgA antibody on Month 3, Month 6, and Month 12 post-vaccination in participants of the immunogenicity subgroup	on Month 3, Month 6, and Month 12 post-vaccination
Virological confirmed COVID-19 cases	The number of virological confirmed COVID-19 cases occurring from Day 14 post-vaccination in different vaccine groups.	from Day 14 post-vaccination
Virological confirmed severe COVID-19 cases.	The number of virological confirmed severe COVID-19 cases occurring from Day 14 post-vaccination in different vaccine groups.	from Day 14 post-vaccination
Virological confirmed asymptomatic COVID-19 cases	The number of virological confirmed asymptomatic COVID-19 cases occurring from Day 14 post-vaccination in different vaccine groups.	from Day 14 post-vaccination
Immunogenicity of anti-Nucleocapsid antibody	The GMT of anti-Nucleocapsid antibody before vaccination	before vaccination
Immunogenicity of saliva secretory IgA (SIgA)	The GMC, GMI, and SCR of saliva secretory IgA (SIgA) on Day 14 and Day 28 post-vaccination in participants of the immunogenicity subgroup.	on Day 14 and Day 28 post-vaccination
The level and positive rate of interferon γ (IFN-γ)	The level and positive rate of interferon γ (IFN-γ) on Day 14 and Day 28 after the 2nd booster dose.	on Day 14 and Day 28 after the 2nd booster dose
The neutralizing antibody against other VOCs or emerging variant(s).	The neutralizing antibody on Day 28 against VOCs or other emerging variants.	on Day 28

Collaborators and Investigators

• Sponsor: CanSino Biologics Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): November 30, 2022
• Primary Completion (Estimated): March 30, 2023
• Study Completion (Estimated): June 30, 2023

Study Registration Dates

• First Submitted: June 16, 2022
• First Submitted That Met QC Criteria: June 28, 2022
• First Posted (Actual): July 5, 2022

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CTP-AD5NCOV/O-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No