Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Determine Safety and Immunogenicity of the Candidate COVID-19 Vaccine AZD1222 Delivered by Aerosol in Healthy Adult Volunteers (COVAXAER01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05007275
Recruitment Status : Recruiting
First Posted : August 16, 2021
Last Update Posted : March 28, 2022
Sponsor:
Collaborators:
University of Oxford
AstraZeneca
Information provided by (Responsible Party):
Imperial College London

Brief Summary:
This study will test the COVID-19 vaccine candidate AZD1222 to investigate its safety, tolerability and capability of boosting immune responses both in the blood and the lung when administered to the respiratory tract, in volunteers previously vaccinated by intramuscular COVID-19 vaccination. Using standardised methods, we will measure immune responses in the blood, nose and lower airway and compare with data from ongoing clinical trials of intramuscular vaccination. Thus, we will show the effect of the delivery method and provide the critical information required to begin further clinical trials to show the efficacy of this needle-free vaccination strategy for booster vaccination.

Condition or disease Intervention/treatment Phase
Covid19 SARS-CoV-2 Infection Biological: 1x10^9 vp AZD1222 Biological: 5x10^9 vp AZD1222 Biological: 1x10^10 vp AZD1222 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model 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.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase I Study to Determine Safety and Immunogenicity of the Candidate COVID-19 Vaccine AZD1222 Delivered by Aerosol in Healthy Adult Volunteers
Actual Study Start Date : October 10, 2021
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

Drug Information available for: AZD-1222

Arm Intervention/treatment
Experimental: Single arm, dose escalation
Experimental: Healthy Volunteers Biological/Vaccine: AZD1222 (1x10^9 vp, 5x10^9 vp and 1x10^10 vp)
Biological: 1x10^9 vp AZD1222
A single dose of 1x 10^9 vp AZD1222

Biological: 5x10^9 vp AZD1222
A single dose of 5x 10^9 vp AZD1222

Biological: 1x10^10 vp AZD1222
A single dose of 1x10^10 vp AZD1222




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. 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

  2. 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


Other Outcome Measures:
  1. 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

  2. To explore the immunology of participants [ Time Frame: Screening to Day 364 ]
    Cell analysis by flow cytometry assays on blood and BAL

  3. 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

  4. 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

  5. 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

  6. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   30 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05007275


Contacts
Layout table for location contacts
Contact: Chris Chiu, PhD +44 20 3313 2301 c.chiu@imperial.ac.uk
Contact: Nana-Marie Lemm n.lemm19@imperial.ac.uk

Locations
Layout table for location information
United Kingdom
Imperial College London Recruiting
London, United Kingdom
Contact: Christopher Chiu, PhD    +44(0)20 383 2301    c.chiu@imperial.ac.uk   
Contact: Lydia Taylor, BSc    +44(0)7872 850 212    lydia.taylor@imperial.ac.uk   
Sponsors and Collaborators
Imperial College London
University of Oxford
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: Chris Chiu, PhD Imperial College London
Layout table for additonal information
Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT05007275    
Other Study ID Numbers: 20HH6296
First Posted: August 16, 2021    Key Record Dates
Last Update Posted: March 28, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: Data will become available approximately 6 months from the last patient's last visit and remain available indefinitely.
Access Criteria: According to study protocol.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Imperial College London:
Vaccine
Vaccination
COVID-19
SARS-CoV-2
Pandemic
Immune system
Immune response
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases