Aerosolized Adenovirus COVID-19 Vaccines for COVID-19

Overseen By Zhou Xing, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: McMaster University

Must not be taking: Immunosuppressants, Inhaled steroids

Disqualifiers: Respiratory diseases, Smoking, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and immune response of two new COVID-19 vaccines administered by inhalation, Ad5-triCoV/Mac and ChAd-triCoV/Mac. These vaccines aim to enhance immunity in individuals already vaccinated with at least three doses of mRNA COVID-19 vaccines. Participants will assist researchers in evaluating the effectiveness of these inhaled vaccines in the lungs and blood. Ideal candidates for this trial are healthy individuals who have not had COVID-19, or had it six months or more ago, and have completed their mRNA vaccine series. As a Phase 1 trial, this research seeks to understand how these new inhaled vaccines function in people, offering participants the chance to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or treatments for respiratory diseases, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that both the Ad5-triCoV/Mac and ChAd-triCoV/Mac vaccines were well tolerated. Most side effects were mild and short-lived, with common issues including headaches, tiredness, vomiting, and muscle aches. Participants received these vaccines by inhaling a mist, a method known to be safe. Although this trial is in an early stage with limited safety information, early data appears promising for both vaccines. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these aerosolized adenovirus COVID-19 vaccines because they offer a new delivery method: inhalation. Unlike traditional COVID-19 vaccines, which are typically injected, these treatments are inhaled, potentially making them easier to administer and more acceptable to people who dislike needles. Additionally, using adenovirus vectors like Ad5 and ChAd can trigger a robust immune response, providing a unique mechanism compared to other vaccines. This novel approach could improve vaccine accessibility and effectiveness, especially in settings where injections are less feasible.

What evidence suggests that this trial's treatments could be effective for COVID-19?

Research has shown that both the Ad5-triCoV/Mac and ChAd-triCoV/Mac vaccines, studied in this trial, are promising in creating strong immune responses. Participants will receive one of these vaccines via inhalation, a method studies have found can boost immunity in the lungs, where COVID-19 usually attacks first. This approach is important because it could help stop the virus from spreading in the body. Specifically, the ChAd-triCoV/Mac vaccine has triggered a strong T cell response, which is key for long-lasting immunity. Early findings also suggest that these vaccines are safe and well-tolerated in people. These results are encouraging for developing effective COVID-19 vaccines delivered through the lungs. ^{1 5 6 7 8}

Who Is on the Research Team?

Fiona M Smaill, MD

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

Healthy adults aged 18-65 who've had at least three mRNA COVID-19 vaccine doses can join this trial. They must not be pregnant, agree to use contraception, have no history of severe COVID or certain respiratory diseases, and cannot be current smokers or recent ex-smokers.

Inclusion Criteria

I am not pregnant and will use two forms of birth control during the study.

I have received three doses of an mRNA COVID vaccine over 3 months ago.

I have never had COVID or had it over 6 months ago with proof.

Exclusion Criteria

I've had blood clots and low platelet counts after a vaccination.

I have never received an experimental adenovirus vaccine through inhalation.

You have breathing tests that show significant abnormalities, such as low lung capacity or difficulty moving air in and out of your lungs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of either Ad5-triCoV/Mac or ChAd-triCoV/Mac vaccine via inhaled aerosol, with dose escalation based on safety and immunogenicity

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and immunogenicity, with assessments at multiple time points including 48-72 hours post-vaccination and up to 48 weeks

48 weeks

Multiple visits (in-person and virtual)

Extension

Potential continuation of monitoring or additional dosing based on immunogenicity outcomes

As required

What Are the Treatments Tested in This Trial?

Interventions

• Ad5-triCoV/Mac
• ChAd-triCoV/Mac

Trial Overview The trial is testing two experimental adenovirus-based COVID-19 vaccines delivered by aerosol: Ad5-triCoV/Mac and ChAd-triCoV/Mac. It aims to assess safety and immune responses in the blood and lungs after administration.

How Is the Trial Designed?

Group I: ChAd-triCoV/Mac at a dose level of 3x10e7 Experimental Treatment 1 Intervention

Single dose by inhalation of 3x10e7 Ad5-triCoV/Mac

Group II: Aerosol ChAd-triCoV/Mac dose level 6x10e7 Experimental Treatment 1 Intervention

Single dose by inhalation of 6x10e7 ChAd-triCoV/Mac

Group III: Aerosol ChAd-triCoV/Mac dose level 1x10e8 Experimental Treatment 2 Interventions

Single dose by inhalation of 1x10e8 ChAd-triCoV/Mac

Group IV: Aerosol ChAd-triCoV/Mac dose level 10e7 Experimental Treatment 1 Intervention

Single dose by inhalation of 10e7 ChAd-triCoV/Mac

Group V: Aerosol ChAd-triCoV/Mac dose level 10e6 Experimental Treatment 1 Intervention

Single dose by inhalation of 10e6 ChAd-triCoV/Mac

Group VI: Aerosol ChAd-tri-CoV/Mac dose level 10e5 Experimental Treatment 1 Intervention

Single dose by inhalation of 10e5 ChAd-triCoV/Mac

Group VII: Aerosol Ad5-triCoV/Mac dose level 3x10e7 Experimental Treatment 1 Intervention

Single dose by inhalation of 3x10e7 Ad5-triCoV/Mac

Group VIII: Aerosol Ad5-triCoV/Mac dose level 10e7 Experimental Treatment 1 Intervention

Single dose by inhalation of 10e7 Ad5-triCoV/Mac

Group IX: Aerosol Ad5-triCoV/Mac dose level 10e6 Experimental Treatment 1 Intervention

Single dose by inhalation of 10e6 Ad5-triCoV/Mac

Group X: Aerosol Ad5-triCoV/Mac dose level 10e5 Experimental Treatment 1 Intervention

Single dose by inhalation of 10e5 Ad5-tri-CoV/Mac

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05094609

Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 ... 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 ...

2. nature.com nature.com/articles/s41467-025-60726-0

Induction of lung mucosal immunity by a next-generation ... We report an open-label, multi-arm phase 1 study (NCT05094609) to evaluate a multi-antigenic COVID-19 vaccine delivered once via inhaled aerosol to the lung.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10172971/

Adenoviral-vectored next-generation respiratory mucosal ... Recent studies have shown that AdV vaccines against TB and COVID-19 are safe and well-tolerated in humans when delivered via inhaled aerosol 24 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X25008990

Review Mucosal COVID-19 vaccines in clinical development The ability of these vaccines to induce mucosal immune responses in the upper respiratory tract may allow efficient prevention of infection and ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05094609/phase-1-trial-of-chad68-and-ad5-adenovirus-covid-19-vaccines-delivered-by-aerosol

Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 ... 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12223143/

Induction of lung mucosal immunity by a next-generation ... Both vaccines were well tolerated, and adverse events were mild and of short duration in most cases (Tables 2 and 3 and Fig. 1b).

7. synapse.patsnap.com synapse.patsnap.com/drug/d60f166c2e5c4876bd674f029b480bf9

Ad5-triCoV/Mac(CIHR) - Drug Targets, Indications, Patents 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.

8. ctv.veeva.com ctv.veeva.com/study/phase-1-trial-of-chad68-and-ad5-adenovirus-covid-19-vaccines-delivered-by-aerosol

Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 ... 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 ...