- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05007275
A Study to Determine Safety and Immunogenicity of the Candidate COVID-19 Vaccine AZD1222 Delivered by Aerosol in Healthy Adult Volunteers (COVAXAER01)
A Phase I Study to Determine Safety and Immunogenicity of the Candidate COVID-19 Vaccine AZD1222 Delivered by Aerosol in Healthy Adult Volunteers
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a Phase I, open label non-randomised dose escalation study in healthy adults aged 30-55 years recruited in the UK. AZD1222 will be administered by inhalation via vibrating mesh nebuliser. The study will assess safety and immunogenicity of AZD1222 with blood and respiratory tract samples. The dose evaluation will be conducted in a single centre supervised by the Chief Investigator and senior clinician experienced in first-in human studies in a cohort of 30 individuals. Approximately 14 days before vaccination, participants will undergo bronchoscopy to sample their lower airways, obtaining bronchoalveolar lavage (BAL), bronchial lining fluid and bronchial tissue. This will be repeated at day +21 and day +182 post-vaccination.
The dose escalation cohort will proceed through low (1x10^9), medium (5x10^9) and high (1x10^10 vp) dose as follows: The first participant will receive the low dose and be invited to enter information on local and systemic reactions into a diary that evening and daily thereafter for 6 days. At 48 hours post-vaccination, the team will call the first participant and go through their diary. If the reactions are Grade 1-2 or transient Grade 3 that resolved within 24 hours, two further participants will receive the same dose. At 48 hours post-vaccination, the team will call participants 2 and 3 to go through their diaries.
Provided there are no safety concerns, the fourth participant can proceed to receive the medium dose. The steps above will be repeated in order to escalate to the highest dose (1x 10^10 vp). Provided there are no safety concerns outlined, a further 6 participants will be vaccinated at the maximum tolerated dose - a total of 9 individuals vaccinated with the maximum tolerated dose. The DSMB chair will review safety data before each dose escalation and the full DSMB will periodically assess safety data every 4-8 weeks and/or as required.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Chris Chiu, PhD
- Phone Number: +44 20 3313 2301
- Email: c.chiu@imperial.ac.uk
Study Contact Backup
- Name: Nana-Marie Lemm
- Email: n.lemm19@imperial.ac.uk
Study Locations
-
-
-
London, United Kingdom
- Imperial College London
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Healthy adults aged 30-55 years.
- Able and willing (in the Investigator's opinion) to comply with all study requirements.
- Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner and access all medical records when relevant to study procedures.
- For females only, willingness to practice continuous highly effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening, bronchoscopy and vaccination.
- Agreement to refrain from blood donation during the course of the study.
- Provide written informed consent.
- Have had a complete COVID-19 vaccination course (as one or two intramuscular injections depending on the authorisation schedule) with the last injection at least 30 days before enrolment
- Sero-suitable i.e. with evidence of SARS-CoV-2 vaccine-induced antibody responses but no evidence of previous SARS-CoV-2 infection by an authorised serology test. Those with indeterminate levels and no history of laboratory-confirmed SARS-CoV-2 infection may be included or excluded at the PI's discretion on a case-by-case basis.
Exclusion Criteria:
- History of laboratory-confirmed SARS-CoV-2 infection.
- Acute upper respiratory infection (URI or sinusitis) in the past 6 weeks
- Prior receipt of any vaccine within ≤30 days prior to enrolment or planned receipt of any vaccine within 30 days after the study vaccination
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
- Inhaled bronchodilator or steroid use within the last 12 months
- Intranasal steroid use within the last 6 months
- Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids.
- Any autoimmune conditions, except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease not requiring immunosuppressive or immunomodulatory therapy.
- History of allergic disease or reactions likely to be exacerbated by any component of the AZD1222 vaccine.
- Any history of angioedema.
- Any history of anaphylaxis.
- Pregnancy, lactation or willingness/intention to become pregnant during the study.
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
- History of serious psychiatric condition likely to affect participation in the study (e.g. ongoing severe depression, history of admission to an in-patient psychiatric facility, recent suicidal ideation, history of suicide attempt, bipolar disorder, personality disorder, alcohol and drug dependency, severe eating disorder, psychosis, use of mood stabilisers or antipsychotic medication).
- Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
- History of frequent nose bleeds
- Any other serious chronic illness requiring hospital specialist supervision.
- Chronic respiratory diseases, including mild asthma (resolved childhood asthma is allowed)
- Smoking (includes any inhaled product, such as cigarettes and vapes) in the past 6 months OR >5 pack-year lifetime history.
- Chronic cardiovascular disease (including hypertension), gastrointestinal disease, liver disease (except Gilberts Syndrome), renal disease, endocrine disorder (including diabetes) and neurological illness (excluding migraine)
- Seriously overweight (BMI≥40 Kg/m2) or underweight (BMI≤18 Kg/m2)
- Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week.
- Suspected or known injecting drug abuse in the 5 years preceding enrolment.
- Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 3 months
- Any clinically significant abnormal finding on screening biochemistry or haematology blood tests. Grade 1 abnormalities are permissible at investigator discretion.
- Clinically relevant abnormality on chest X-ray
- Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
- A history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome or vaccine-induced thrombosis with thrombocytopenia
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single arm, dose escalation
Experimental: Healthy Volunteers Biological/Vaccine: AZD1222 (1x10^9 vp, 5x10^9 vp and 1x10^10 vp)
|
A single dose of 1x 10^9 vp AZD1222
A single dose of 5x 10^9 vp AZD1222
A single dose of 1x10^10 vp AZD1222
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess the safety, tolerability and reactogenicity profile of the candidate vaccine AZD1222 delivered by aerosol
Time Frame: Day 0-7
|
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination, measured with self-reported symptoms recorded using vaccination diaries.
|
Day 0-7
|
To assess the safety, tolerability and reactogenicity profile of the candidate vaccine AZD1222 delivered by aerosol
Time Frame: Day 0-7
|
Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination, measured with self-reported symptoms recorded using vaccination diaries.
|
Day 0-7
|
To assess the safety, tolerability and reactogenicity profile of the candidate vaccine AZD1222 delivered by aerosol
Time Frame: Day 0-28
|
Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination, measured with self-reported symptoms recorded using vaccination diaries and/or AEs reported post 7 days recorded in CRFs by study team.
|
Day 0-28
|
To assess the safety, tolerability and reactogenicity profile of the candidate vaccine AZD1222 delivered by aerosol
Time Frame: Screening to Day 28
|
Change from baseline for safety laboratory measures, determined by blood samples drawn at enrolment (before vaccination), Day 3, 7 and 28.
|
Screening to Day 28
|
To assess the safety, tolerability and reactogenicity profile of the candidate vaccine AZD1222 delivered by aerosol
Time Frame: Screening to Day 364
|
Occurence of SAEs reported throughout the study.
|
Screening to Day 364
|
To assess the safety, tolerability and reactogenicity profile of the candidate vaccine AZD1222 delivered by aerosol
Time Frame: Screening to Day 364
|
Occurence of SAEs of special interest reported throughout the study.
|
Screening to Day 364
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess cellular and humoral immunogenicity of AZD1222
Time Frame: Screening to Day 364
|
Interferon-gamma (IFN-y) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein in blood
|
Screening to Day 364
|
To assess cellular and humoral immunogenicity of AZD1222
Time Frame: Screening to Day 364
|
Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) in blood
|
Screening to Day 364
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To explore the immunology of participants
Time Frame: Screening to Day 364
|
Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus in blood
|
Screening to Day 364
|
To explore the immunology of participants
Time Frame: Screening to Day 364
|
Cell analysis by flow cytometry assays on blood and BAL
|
Screening to Day 364
|
To explore the immunology of participants
Time Frame: Screening to Day 364
|
Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein in bronchoalveolar lavage
|
Screening to Day 364
|
To explore the immunology of participants
Time Frame: Screening to Day 364
|
Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) in respiratory lining fluid and saliva
|
Screening to Day 364
|
To assess changes in commensal organisms in response to vaccination
Time Frame: Screening to Day 364
|
Quantify S protein expression in bronchial mucosa following vaccine administration using confocal microscopy
|
Screening to Day 364
|
Analyse immunology to assess changes in commensal organisms in response to vaccination
Time Frame: Screening to Day 364
|
Analysis of microbiota in nasopharyngeal and/or stool samples
|
Screening to Day 364
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Chris Chiu, PhD, Imperial College London
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20HH6296
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
The expectation is that after analysis the data from this study will be widely distributed in the medical and scientific community. Facilitated with presentations at local, national and international meetings, the hope is to publish widely in the medical literature. In addition, there is an excellent media department at Imperial College that will publicise research that has public interest when it is published.
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Data from the study may also be used as part of a thesis for a PhD or MD.
All data will be anonymised and aggregated or pseudonymised; no identifying participant information will be published.
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Covid19
-
Anavasi DiagnosticsNot yet recruiting
-
Ain Shams UniversityRecruiting
-
Israel Institute for Biological Research (IIBR)Completed
-
Colgate PalmoliveCompleted
-
Christian von BuchwaldCompleted
-
Luye Pharma Group Ltd.Shandong Boan Biotechnology Co., LtdActive, not recruiting
-
University of ZurichLabor Speiz; Swiss Armed Forces; Universitätsspital ZürichEnrolling by invitation
-
Alexandria UniversityCompleted
Clinical Trials on 1x10^9 vp AZD1222
-
International AIDS Vaccine InitiativeBeth Israel Deaconess Medical Center; University of RochesterCompleted
-
Merck Sharp & Dohme LLCNational Institute of Allergy and Infectious Diseases (NIAID); HIV Vaccine...Completed
-
Merck Sharp & Dohme LLCCompleted
-
AerasCrucell Holland BVCompletedTuberculosisSouth Africa
-
Ilya PharmaEuropean CommissionRecruitingDiabetic Foot Ulcer | Wound Heal | Wound Healing Disorder | Wound Healing Delayed | Wound Healing Disturbance of | Diabetic Foot Ulcer MixedSweden
-
PATHCompleted
-
H. Lee Moffitt Cancer Center and Research InstituteNational Cancer Institute (NCI); Astex Pharmaceuticals, Inc.CompletedUnspecified Adult Solid Tumor, Protocol SpecificUnited States
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingRecurrent Adult Burkitt Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Post-Transplant Lymphoproliferative Disorder | Recurrent Chronic Lymphocytic Leukemia | Recurrent Follicular Lymphoma and other conditionsUnited States
-
M.D. Anderson Cancer CenterWithdrawnMalignant Glioma | Medulloblastoma | Anaplastic Ependymoma | Recurrent Malignant Glioma | Recurrent Medulloblastoma | Atypical Teratoid/Rhabdoid Tumor | Primitive Neuroectodermal Tumor | Choroid Plexus Carcinoma | Recurrent Atypical Teratoid/Rhabdoid Tumor | Malignant Brain Neoplasm | Central Nervous System... and other conditionsUnited States
-
M.D. Anderson Cancer CenterRecruitingRefractory Malignant Solid Neoplasm | Recurrent Malignant Solid Neoplasm | Recurrent Neuroblastoma | Recurrent Rhabdomyosarcoma | Refractory Neuroblastoma | Refractory Rhabdomyosarcoma | Desmoplastic Small Round Cell Tumor | Recurrent Malignant Peripheral Nerve Sheath Tumor | Ewing Sarcoma/Peripheral... and other conditionsUnited States