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COVID-19Phase 1NCT05094609

Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 Vaccines Delivered by Aerosol

A Phase 1 study testing Ad5-triCoV/Mac and ChAd-triCoV/Mac in people with COVID-19 and SARS-CoV2 Infection, run by McMaster University at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
COVID-19, SARS-CoV2 Infection
What is being tested?
Ad5-triCoV/Mac and ChAd-triCoV/Mac
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteCanada
Study dates
3 Jan 2022to 31 Jan 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • History of severe reaction to a previous COVID vaccination (including hives, difficulty breathing, angioedema, high fever, seizure).
  • History of venous or arterial thrombosis with thrombocytopenia following any vaccination.
  • History of cerebral venous thrombosis with thrombocytopenia.
  • History of heparin induced thrombocytopenia.
  • History of myocarditis or pericarditis.
  • History of Bell's Palsy.
  • History of hospitalization with an admitting diagnosis of primary COVID infection.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • McMaster University Medical Centre

    Hamilton, Ontario, L8N 3Z5

Other trials in Canada

About this study

Official title: 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

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.

Read the detailed description

This is a phase 1, dose-escalating study to evaluate the safety and immunogenicity of a single dose of either Ad5-triCoV/Mac, a replication deficient human adenovirus vector, or ChAd-triCoV/Mac, a replication deficient chimpanzee adenovirus 68 vector, delivered to the respiratory tract by aerosol, in healthy volunteers who have received at least three doses of an mRNA COVID-19 vaccine. Both vectors have been engineered to express the spike, nucleocapsid and RNA polymerase proteins.

Up to 36 healthy volunteers will be enrolled in this dose escalation study. The first cohort (n=6) will receive Ad5-triCoV/Mac (n=3) or ChAd-triCoV/Mac (n=3) at the lowest dose of 10e5 TCID50, administered using the AeroNeb Solo Vibrating Mesh Nebulizer. Assuming no safety concerns, participants will then be administered Ad5-triCoV/Mac (n=3) or ChAd-triCoV/Mac (n=3) at a dose of 10e6. Assuming no safety signals we will move to vaccinate at the next dose level of 1x10e7 TCID50. Decisions about dose escalation will be made independently for each vaccine based on safety and immunogenicity profile. If the immunogenicity endpoints are not reached, in the absence of a safety signal, at the 10e7 dose level, we will move to the next dose level of 3x10e7 TCID50 and enrol three participants/vaccine group. Similarly, if all of the immunogenicity endpoints in the BAL are not met at 3x10e7, and in the absence of any safety signal, we will further escalate to 6x10e7, then 1x10e8 TCID50 and enrol three participants/vaccine group, if required. Once safety has been shown in participants without a history of COVID, we will proceed to enrol participants with a history of COVID infection to receive ChAd-triCoV/Mac, beginning with a dose of 3x10e7 (n=3) and, in the absence of any safety signal, escalating to 6x10e7 and, if required, 1x10e8 and, once the optimal dose has been determined based on immunogenicity outcomes, continue to enrol participants at this dose level to complete enrolment of the cohort (n=6).

Antibody and specific T cell responses will be measured in lung from bronchoalveolar lavage fluid collected at bronchoscopy at baseline and at 4 weeks following vaccination and in blood at several time points up to week 48 following vaccination.

Safety endpoints will include the nature of any adverse events, their severity and the probability of a relationship to study procedures and administration of vaccine.

Being tested
Ad5-triCoV/Mac, ChAd-triCoV/Mac
Keywords
COVID-19, SARS-CoV-2, Aerosol, Adenovirus, Chimpanzee, Immunogenicity, Inhalation, Vaccine, Vaccination
Medical subject headings
COVID-19, Adenoviridae Infections, Respiratory Aspiration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ad5-triCoV/MacBiological

    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/MacBiological

    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).

Study groups in NCT05094609
Study groupRoleWhat they receive
Aerosol Ad5-triCoV/Mac dose level 10e5ExperimentalSingle dose by inhalation of 10e5 Ad5-tri-CoV/Mac
Receives: Biological: Ad5-triCoV/Mac
Aerosol ChAd-tri-CoV/Mac dose level 10e5ExperimentalSingle dose by inhalation of 10e5 ChAd-triCoV/Mac
Receives: Biological: ChAd-triCoV/Mac
Aerosol Ad5-triCoV/Mac dose level 10e6ExperimentalSingle dose by inhalation of 10e6 Ad5-triCoV/Mac
Receives: Biological: Ad5-triCoV/Mac
Aerosol ChAd-triCoV/Mac dose level 10e6ExperimentalSingle dose by inhalation of 10e6 ChAd-triCoV/Mac
Receives: Biological: ChAd-triCoV/Mac
Aerosol Ad5-triCoV/Mac dose level 10e7ExperimentalSingle dose by inhalation of 10e7 Ad5-triCoV/Mac
Receives: Biological: Ad5-triCoV/Mac
Aerosol ChAd-triCoV/Mac dose level 10e7ExperimentalSingle dose by inhalation of 10e7 ChAd-triCoV/Mac
Receives: Biological: ChAd-triCoV/Mac
Aerosol Ad5-triCoV/Mac dose level 3x10e7ExperimentalSingle dose by inhalation of 3x10e7 Ad5-triCoV/Mac
Receives: Biological: Ad5-triCoV/Mac
Aerosol ChAd-triCoV/Mac dose level 6x10e7ExperimentalSingle dose by inhalation of 6x10e7 ChAd-triCoV/Mac
Receives: Biological: ChAd-triCoV/Mac
Aerosol ChAd-triCoV/Mac dose level 1x10e8ExperimentalSingle dose by inhalation of 1x10e8 ChAd-triCoV/Mac
Receives: Biological: ChAd-triCoV/Mac
ChAd-triCoV/Mac at a dose level of 3x10e7ExperimentalSingle dose by inhalation of 3x10e7 Ad5-triCoV/Mac
Receives: Biological: ChAd-triCoV/Mac

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Over 48 weeks post vaccination

  2. 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

    Measured: Over 48 weeks post vaccination

Secondary outcomes (4)

  1. Immunogenicity of Ad5-triCoV/Mac administered by aerosol

    Change from baseline in: 1) spike-specific and anti-RBD antibodies including neutralizing antibodies both in the blood and airways; 2) spike/N/POL-specific CD4 and CD8 T cells in the airways (BAL fluid) four weeks post vaccination and 3) spike/N/POL-specific CD4 and CD8 T cells in the blood up to the last timepoint of examination.

    Measured: Over 48 weeks post vaccination

  2. Immunogenicity of ChAd-triCoV/Mac administered by aerosol

    Change from baseline in: 1) spike-specific and anti-RBD antibodies including neutralizing antibodies both in the blood and airways; 2) spike/N/POL-specific CD4 and CD8 T cells in the airways (BAL fluid) four weeks post vaccination and 3) spike/N/POL-specific CD4 and CD8 T cells in the blood up to the last timepoint of examination.

    Measured: Over 48 weeks post vaccination

  3. Immune response to Ad5-triCoV/Mac and ChAd-triCoV/Mac correlated with pre-existing adenovirus antibodies

    Change from baseline in: 1) spike-specific and anti-RBD antibodies including neutralizing antibodies both in the blood and airways; 2) spike/N/POL-specific CD4 and CD8 T cells in the airways (BAL fluid) four weeks post vaccination and 3) spike/N/POL-specific CD4 and CD8 T cells in the blood up to the last timepoint of examination, correlated with baseline Ad5 antibodies

    Measured: Over 48 weeks

  4. Correlation of antibodies measured in saliva with antibodies measured in BAL fluid and blood

    Change from baseline in spike-specific and anti-RBD antibodies including neutralizing antibodies both in the blood and airways the airway (BAL fluid), correlated with antibodies measured in saliva

    Measured: Over 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2021
  2. Study start3 Jan 2022
  3. Primary completion15 Jan 2025
  4. Study completion31 Jan 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Dose escalation: Assuming no safety signal, the dose for each vaccine (Ad5-triCoV/Mac and ChAd-triCoV/Mac) will be escalated from a dose of 10e5 TCID50/dose (n=3/vaccine group), to a dose of 10e6 (n=3/vaccine group) and then further increased for each vaccine group to 1x10e7 (n=3 per group) and 3x10e7 (n=3 per group) assuming no safety signal. Based on poor immune responses to Ad5-triCoV/Mac the dose of Ad5-triCoV/Mac will not be further escalated. Since immunogenicity endpoints were not met at 3x10e7 for ChAd-triCoV/Mac and there was no safety signal, the dose will be further escalated to 6x10e7 and 1x10e8 (n=3 per dose level). Participants with a history of COVID infection will be enrolled to receive ChAd-triCoV/Mac, beginning with a dose of 3x10e7 (n=3) and, in the absence of any safety signal, escalated to 6x10e7 and, if required, 1x10e8 and, once the optimal dose has been determined, participants enrolled at this dose level to complete enrolment of the cohort (n=6).
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05094609
Sponsor's protocol ID
M010
Status last verified
Jul 2025
First submitted
25 Oct 2021
Last updated
17 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: On request, individual patient data that underlie the results in a publication will be made to other researchers

Publications

  • 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.

    PubMed 40603330

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ad5-triCoV/Mac and ChAd-triCoV/Mac in people with COVID-19 and SARS-CoV2 Infection, run by McMaster University at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants reporting adverse events and severity of adverse events following Ad5-triCoV/Mac vaccination (time frame: Over 48 weeks post vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05094609, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2025.

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