A Trial of a Next Generation COVID-19 Vaccine Delivered by Inhaled Aerosol

Phase 2

Not yet recruiting

• Conditions: COVID-19 Infection
• Interventions: Other: Control; Biological: ChAd-triCoV/Mac

• Registration Number: NCT06381739
• Lead Sponsor: McMaster University

Brief Summary

The goal of this clinical trial is to study the safety of a new inhaled vaccine to prevent COVID infection and learn about the immune responses that are made in the lungs and the blood after vaccination. Participants will be randomized (like the toss of a coin) to receive the experimental vaccine or a placebo (a look-alike solution that contains no vaccine).

To be in the study participants will have to have already had three doses of a messenger ribonucleic acid (mRNA) COVID vaccine and be generally healthy. Participants are given a single dose of the vaccine by breathing in a fine mist that goes directly into the lungs.

During follow-up participants will:

* visit the clinic for checkups and blood tests at 2, 4 and 8 weeks after vaccination

* report their symptoms for 24 weeks after getting the vaccine.

In some participants, the researchers will collect cells from the lung 4 weeks after vaccination (a test known as a bronchoscopy).

Detailed Description

The global impact of the coronavirus disease 2019 (COVID-19) pandemic remains profound; COVID-19 continues to be one of the leading causes of death and hospitalization due to infectious disease, disproportionately affecting the elderly and immunocompromised. The continuous evolution of the virus has significantly challenged the effectiveness of first-generation and updated vaccination strategies. These variants of concern (VOCs) can evade neutralizing antibodies.

Adequate and early lung mucosal immunity is critical for control of infection but current vaccines fail to induce robust mucosal immunity in the lungs, a major reason for the high rates of break-through infections. The respiratory mucosal route of immunization, however, can induce protective respiratory mucosal immunity consisting of trained innate immunity (via memory airway macrophages), mucosal antibodies, and tissue-resident memory CD4+/CD8+ T cells.

A phase 1 study has been completed using a recombinant chimpanzee adenovirus (ChAd) vector, ChAd-CoV3/Mac in 23 healthy volunteers and has shown that the vaccine can be safely administered by aerosol and that immune responses against COVID-19 develop in the lung and T-cells and neutralizing antibodies are generated in the blood.

The purpose of this placebo-controlled Phase 2 trial is to determine if this new COVID-19 vaccine, ChAd-triCoV/Mac, is safe to give by aerosol to people who have been vaccinated with at least three doses of a COVID mRNA vaccine and evaluate the immune responses generated. Specifically, the researchers want to see if T cell responses and antibody responses to the COVID virus proteins develop in the blood after receiving the vaccine.

There is a lack of surrogate immune markers for vaccine-induced protection against antibody-evading VOCs of SARS-CoV-2. However, given the now recognized importance of respiratory mucosal T cell immunity in anti-SARS-CoV-2 host defense, this study will allow for a correlation of mucosal T cell immunity with the T cells in blood to help predict vaccine efficacy, and inform the design of phase 3 efficacy studies.

Study Timeline

• Study First Submitted: 2024-04-23
• Study First Submitted QC: 2024-04-23
• Study First Posted: 2024-04-24
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-20
• Last Update Posted: 2024-11-21
• Study Start: 2025-01
• Primary Completion: 2026-07
• Study Completion: 2027-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Control	Placebo
ChAd-triCoV/Mac	ChAd-triCoV/Mac	ChAd-triCoV/Mac

Primary Outcome Measures

Name	Time	Method
Antigen specific T cell responses in bronchoalveolar lavage (BAL).	4 weeks	Percentage of cytokine positive T cells in the BAL
Any grade 3, 4, or 5 adverse events that are possibly or probably related to study vaccine.	24 weeks	Frequency, incidence and nature of adverse events
Antigen specific T cell responses in blood.	2 weeks	Percentage of cytokine positive T cells in the blood

Secondary Outcome Measures

Name	Time	Method
Tissue-resident memory surface marker expression airway T cells	4 weeks	Percentage CD103+CD8+ specific cells
CD4 and CD8 T cell responses specific for the spike (S1), nucleoprotein (N) and polymerase (POL) SARS-CoV-2 antigens expressed by the vaccine, including those expressing memory T cell markers, in the peripheral blood.	4 and 8 weeks	Percentage of cytokine positive T cells in the blood to specific antigens
Confirmed COVID infection by reverse transcriptase polymerase chain reaction (RT-PCR)	24 weeks	Positive RT-PCR test
Neutralizing and total antibody levels in BAL and blood	2, 4 and 8 weeks	Anti-receptor binding domain (RBD) IgG and IgA endpoint titre; percent neutralization (surrogate virus neutralization test \[sVNT\])
Any adverse events, including grade 1 or 2 or where relationship to vaccine/placebo administration or study procedures is judged not related or unlikely.	24 weeks	Frequency, incidence and nature of any adverse events

Trial Locations

Locations (1)

Health Sciences Centre; 🇨🇦 Hamilton, Ontario, Canada