Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 Vaccines Delivered by Aerosol
Phase 1, Open Label Study to Evaluate the Safety and Immunogenicity of ChAd68 and AdHu5 Vector-based Trivalent COVID-19 Vaccines Delivered Via Inhaled Aerosol
1 other identifier
interventional
36
1 country
1
Brief Summary
This is a phase 1 study in healthy volunteers who have received at least three doses of an mRNA COVID-19 vaccine, to evaluate the safety and immune responses that develop in the blood and lungs following the administration by aerosol of either Ad5-triCoV/Mac or ChAd-triCoV/Mac, new experimental adenovirus-based vaccines expressing SARS-CoV-2 spike, nucleocapsid and RNA polymerase proteins.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 covid19
Started Jan 2022
Longer than P75 for phase_1 covid19
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 25, 2021
CompletedFirst Posted
Study publicly available on registry
October 26, 2021
CompletedStudy Start
First participant enrolled
January 3, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 15, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2025
CompletedJuly 17, 2025
July 1, 2025
3 years
October 25, 2021
July 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of participants reporting adverse events and severity of adverse events following Ad5-triCoV/Mac vaccination
Adverse events will be assessed according to the CTCAE Expanded Common Toxicity Criteria at 48-72 hours after vaccination, and at weeks 2, 4, 8, 12,16, 24, 32, 40 and 48
Over 48 weeks post vaccination
Number of participants reporting adverse events and severity of adverse events following ChAd-triCoV/Mac vaccination
Adverse events will be assessed according to the CTCAE Expanded Common Toxicity Criteria at 48-72 hours after vaccination, and at weeks 2, 4, 8, 12,16, 24, 32, 40 and 48
Over 48 weeks post vaccination
Secondary Outcomes (4)
Immunogenicity of Ad5-triCoV/Mac administered by aerosol
Over 48 weeks post vaccination
Immunogenicity of ChAd-triCoV/Mac administered by aerosol
Over 48 weeks post vaccination
Immune response to Ad5-triCoV/Mac and ChAd-triCoV/Mac correlated with pre-existing adenovirus antibodies
Over 48 weeks
Correlation of antibodies measured in saliva with antibodies measured in BAL fluid and blood
Over 12 weeks
Study Arms (10)
Aerosol Ad5-triCoV/Mac dose level 10e5
EXPERIMENTALSingle dose by inhalation of 10e5 Ad5-tri-CoV/Mac
Aerosol ChAd-tri-CoV/Mac dose level 10e5
EXPERIMENTALSingle dose by inhalation of 10e5 ChAd-triCoV/Mac
Aerosol Ad5-triCoV/Mac dose level 10e6
EXPERIMENTALSingle dose by inhalation of 10e6 Ad5-triCoV/Mac
Aerosol ChAd-triCoV/Mac dose level 10e6
EXPERIMENTALSingle dose by inhalation of 10e6 ChAd-triCoV/Mac
Aerosol Ad5-triCoV/Mac dose level 10e7
EXPERIMENTALSingle dose by inhalation of 10e7 Ad5-triCoV/Mac
Aerosol ChAd-triCoV/Mac dose level 10e7
EXPERIMENTALSingle dose by inhalation of 10e7 ChAd-triCoV/Mac
Aerosol Ad5-triCoV/Mac dose level 3x10e7
EXPERIMENTALSingle dose by inhalation of 3x10e7 Ad5-triCoV/Mac
Aerosol ChAd-triCoV/Mac dose level 6x10e7
EXPERIMENTALSingle dose by inhalation of 6x10e7 ChAd-triCoV/Mac
Aerosol ChAd-triCoV/Mac dose level 1x10e8
EXPERIMENTALSingle dose by inhalation of 1x10e8 ChAd-triCoV/Mac
ChAd-triCoV/Mac at a dose level of 3x10e7
EXPERIMENTALSingle dose by inhalation of 3x10e7 Ad5-triCoV/Mac
Interventions
Ad5-triCoV/Mac is a recombinant type 5 human adenovirus vector which has been engineered to express our trivalent SARS-CoV-2 transgene cassette under the control of an MCMV promoter, and is followed by an SV40 polyA signal. The adenovirus construct is E1 and E3 deleted.This trivalent transgene cassette consists of the S1 region of SARS-CoV-2 spike protein (aa 47-716), full-length SARS-CoV-2 nucleoprotein (N) fused to a highly conserved portion of the SARS-CoV-2 polymerase (RdRp or POL).
ChAd-triCoV/Mac is an E1 and E3 deleted chimpanzee adenovirus serotype 68 where the trivalent SARS-CoV-2 transgene cassette is under the control of an HCMV promoter and is followed by an SV40 polyA signal. The trivalent transgene cassette consists of the S1 region of SARS-CoV-2 spike protein (aa 47-716), full-length SARS-CoV-2 nucleoprotein (N) fused to a highly conserved portion of the SARS-CoV-2 polymerase (RdRp or POL).
Eligibility Criteria
You may qualify if:
- Healthy human subjects who are between 18 and 65 years of age.
- Have completed a COVID vaccine series with at least three doses of a licensed mRNA vaccine at least 3 months prior.
- HIV antibody negative.
- Able to understand and comply with protocol requirements and instructions; able to attend scheduled study visits and complete required investigations.
- For women, negative pregnancy test and for those women of child-bearing potential practising two acceptable forms of contraception for the duration of the study.
- For men, using barrier contraception for the duration of the study.
- No history of COVID infection OR history of documented COVID infection at least 6 months prior, dated from either a self-reported positive rapid antigen test or positive PCR test (self-reported or documented). For participants with a history of COVID infection, anti-nucleocapsid antibodies will be measured prior to enrolment to confirm infection.
You may not qualify if:
- Subjects who have received any recombinant adenoviral-vectored COVID-19 vaccine, e.g. AstraZeneca COVISHIELD COVID-19 vaccine.
- Pregnant or lactating women.
- Subjects who have any acute or chronic illnesses, any relevant findings on physical examination or are receiving any immunosuppressive therapy in the opinion of the investigator likely to affect the immune system including current use of inhaled or nasal steroids.
- Subjects with a history of any bleeding disorder or receiving any drug treatment that in the opinion of the investigator may increase the risk of bleeding.
- Subjects with a history of respiratory diseases requiring regular treatment, e.g. asthma, COPD, interstitial lung diseases, bronchiectasis.
- Current cigarette smokers, current e-cigarette smokers and ex-smokers who have quit less than a year ago, as reported by the subject.
- Subjects with clinically significant abnormal baseline spirometry tests: FEV1\<80% predicted, FVC\<80% predicted, FEV1/FVC\<70%; DLCO\<70% predicted.
- Any health-related condition for which study bronchoscopy is contraindicated.
- Subjects whose baseline laboratory values are outside of the normal range, unless the abnormality is considered not clinically relevant by the investigator. A single repeat test is allowed during the screening period.
- Subjects whose use of alcohol or drugs would, in the opinion of the investigator, interfere with adherence to the study protocol.
- Subjects who are using, or have a history of using, inhaled cocaine, metamphetamine or other inhaled or smoked recreational drugs. Subjects who give a history of smoking marijuana more than a year ago may be enrolled as long as they agree not to smoke marijuana for the duration of the study.
- Failure to provide written consent.
- Known allergy to vaccine components.
- Any abnormality on chest x-ray suggestive of clinically significant respiratory disease.
- Previous receipt of any experimental adenovirus-vector vaccine by the aerosol route.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- McMaster Universitylead
- Canadian Institutes of Health Research (CIHR)collaborator
Study Sites (1)
McMaster University Medical Centre
Hamilton, Ontario, L8N 3Z5, Canada
Related Publications (1)
Jeyanathan M, Afkhami S, D'Agostino MR, Satia I, Fritz DK, Miyasaki K, Ang JC, Zganiacz A, Howie KJ, Swinton M, Aguirre E, Zheng MB, Kazhdan N, Dvorkin-Gheva A, Mbuagbaw L, Medina MFC, Diab N, Brister DL, Gauvreau GM, Lichty BD, Miller MS, Smaill F, Xing Z. Induction of lung mucosal immunity by a next-generation inhaled aerosol COVID-19 vaccine: an open-label, multi-arm phase 1 clinical trial. Nat Commun. 2025 Jul 2;16(1):6000. doi: 10.1038/s41467-025-60726-0.
PMID: 40603330BACKGROUND
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Fiona M Smaill, MD
McMaster University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 25, 2021
First Posted
October 26, 2021
Study Start
January 3, 2022
Primary Completion
January 15, 2025
Study Completion
January 31, 2025
Last Updated
July 17, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- CSR
- Time Frame
- 3 months after publication
- Access Criteria
- Requests will be reviewed by the principal investigator and be judged on the scientific validity of the request and academic qualifications of those requesting access.
On request, individual patient data that underlie the results in a publication will be made to other researchers