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

Sponsor

McMaster University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05094609

Collaborator

Canadian Institutes of Health Research (CIHR) (Other)

Enrollment

Location

Arms

20.9

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 1 study in healthy volunteers who have received two 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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 SARS-CoV2 Infection	Biological: Ad5-triCoV/Mac Biological: ChAd-triCoV/Mac	Phase 1

Detailed Description

This is a phase 1 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 two doses of an mRNA COVID-19 vaccine. Both vectors have been engineered to express the spike, nucleocapsid and RNA polymerase proteins.

30 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 a lower dose of 10e5, administered using the AeroNeb Solo Vibrating Mesh Nebulizer. Assuming no safety concerns, the aerosol dose will be increased to 10e6 to complete enrolment [Ad5-triCoV/Mac (n=12) or ChAd-triCoV/Mac (n=12)].

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Dose escalation as follows: 3 participants administered Ad5-triCoV/Mac at the lower dose of 10e5 pfu/dose, then assuming no safety concerns ChAd-triCoV/Mac at 10e5/dose. Assuming no safety concerns the higher dose cohort will then be enrolled, first 3 participants will get Ad5-triCoV/Mac at 10e6 pfu/dose then 3 participants will get ChAd-triCoV/Mac at10e6/dose. Assuming no safety concerns, the investigators will complete enrolment of the study, randomly allocating participants to Ad5-triCoV/Mac (n=9) or ChAd-triCoV/Mac (n=9).Dose escalation as follows:3 participants administered Ad5-triCoV/Mac at the lower dose of 10e5 pfu/dose, then assuming no safety concerns ChAd-triCoV/Mac at 10e5/dose. Assuming no safety concerns the higher dose cohort will then be enrolled, first 3 participants will get Ad5-triCoV/Mac at 10e6 pfu/dose then 3 participants will get ChAd-triCoV/Mac at10e6/dose. Assuming no safety concerns, the investigators will complete enrolment of the study, randomly allocating participants to Ad5-triCoV/Mac (n=9) or ChAd-triCoV/Mac (n=9).

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Jan 3, 2022

Anticipated Primary Completion Date :

Sep 30, 2023

Anticipated Study Completion Date :

Sep 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low dose aerosol Ad5-triCoV/Mac Single dose by inhalation of 10e5 Ad5-tri-CoV/Mac	Biological: Ad5-triCoV/Mac 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).
Experimental: Low dose aerosol ChAd-tri-CoV/Mac Single dose by inhalation of 10e5 ChAd-triCoV/Mac	Biological: ChAd-triCoV/Mac 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).
Experimental: Higher dose aerosol Ad5-triCoV/Mac Single dose by inhalation of 10e6 Ad5-triCoV/Mac	Biological: Ad5-triCoV/Mac 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).
Experimental: Higher dose aerosol ChAd-triCoV/Mac Single dose by inhalation of 10e6 ChAd-triCoV/Mac	Biological: ChAd-triCoV/Mac 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).

Outcome Measures

Primary Outcome Measures

Number of participants reporting adverse events and severity of adverse events following Ad5-triCoV/Mac vaccination [Over 48 weeks post 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
Number of participants reporting adverse events and severity of adverse events following ChAd-triCoV/Mac vaccination [Over 48 weeks post 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

Secondary Outcome Measures

Immunogenicity of Ad5-triCoV/Mac administered by aerosol [Over 48 weeks post vaccination]
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.
Immunogenicity of ChAd-triCoV/Mac administered by aerosol [four weeks after vaccination]
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.
Immune response to Ad5-triCoV/Mac and ChAd-triCoV/Mac correlated with pre-existing adenovirus antibodies [Over 48 weeks]
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
Correlation of antibodies measured in saliva with antibodies measured in BAL fluid and blood [Over 12 weeks]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy human subjects who are between 18 and 65 years of age.
Have completed a COVID vaccine series with 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.

Exclusion Criteria:

History of probable or confirmed diagnosis of COVID-19 infection, based on Ontario Health case definitions.
Subjects who have received any recombinant adenoviral-vectored COVID-19 vaccine, e.g. AstraZeneca COVISHIELD COVID-19 vaccine.
Subjects who have received more than 3 doses of any 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.
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.