A Study of a Candidate COVID-19 Vaccine (COV001)

Coronavirus Clinical Trial

Official title:

A Phase I/II Study to Determine Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19 in UK Healthy Adult Volunteers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04324606
• Other study ID #: COV001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 23, 2020
• Est. completion date: March 31, 2024

Study information

• Verified date: July 2023
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A phase I/II single-blinded, randomised, multi-centre study to determine efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in UK healthy adult volunteers aged 18-55 years. The vaccine will be administered intramuscularly (IM) into the deltoid region of the arm

Description:

There will be 4 study groups and it is anticipated that a total of 1090 volunteers will be enrolled. Volunteers will participate in the study for approximately 12 months from last vaccination visit (approximately 15 months from enrolment for participants receiving 2 doses)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1090
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria

The volunteer must satisfy all the following criteria to be eligible for the study:

• Healthy adults aged 18-55 years.

• Able and willing (in the Investigator's opinion) to comply with all study requirements (participants must not rely on public transport or taxis).

• 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 effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination.

• Agreement to refrain from blood donation during the course of the study.

• Provide written informed consent.

Exclusion Criteria

The volunteer may not enter the study if any of the following apply:

• Planned receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination .with the exception of the licensed seasonal influenza vaccination and the licensed pneumococcal vaccine. Participants will be encouraged to receive this vaccination at least 7 days before or after their study vaccine.

• Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines).

• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.

• 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 or short-term oral steroids (course lasting <14 days) .

• 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 ChAdOx1 nCoV-19 or MenACWY vaccines.

• 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.

• Any other serious chronic illness requiring hospital specialist supervision.

• Chronic respiratory diseases, including mild asthma (resolved childhood asthma is allowed)

• 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.

• Any clinically significant abnormal finding on screening biochemistry, haematology blood tests or urinalysis.

• 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.

• History of laboratory confirmed COVID-19.

• New onset of fever or a cough or shortness of breath or anosmia/ageusia since February 2020. Should a reliable test become available, this exclusion criteria will be replaced with seropositivity for SARS-CoV-2 before enrolment.

• Those who have been at high risk of exposure before enrolment, including but not limited to: close contacts of confirmed COVID-19 cases, anyone who had to self-isolate as a result of a symptomatic household member, frontline healthcare professionals working in A&E, ICU and other higher risk areas. Should a reliable test become available, this exclusion criteria will be replaced with seropositivity for SARS-CoV-2 before enrolment.

• Living in the same household as any vulnerable groups at risk of severe COVID-19 disease (as per Public Health England guidance)

Additional exclusion criteria (subset of participants receiving Paracetamol in group 4 only)

• History of allergic disease or reactions likely to be exacerbated by Paracetamol

Re-vaccination exclusion criteria:

The following AEs associated with any vaccine, or identified on or before the day of vaccination constitute absolute contraindications to further administration of an IMP to the volunteer in question. If any of these events occur during the study, the subject will not be eligible to receive a booster dose and will be followed up by the clinical team or their GP until resolution or stabilisation of the event:

• Anaphylactic reaction following administration of vaccine

• Pregnancy. An exception to this will be prior to receipt of a booster dose at extra visit B. If a pregnant woman has discussed vaccination with their usual clinician (e.g. GP) and chooses to receive a COVID-19 vaccination, this may be administered by the trial team as part of extra visit B or as part of the provision of treatment to controls

• Any AE that in the opinion of the Investigator may affect the safety of the participant or the interpretation of the study results

Related Conditions & MeSH terms

• Coronavirus
• Coronavirus Infections
• COVID-19

Intervention

Biological:
• ChAdOx1 nCoV-19
A single dose of 5x10^10vp of ChAdOx1 nCoV-19
• MenACWY
Standard single dose of MenACWY vaccine delivered intramuscularly
• ChAdOx1 nCoV-19 full boost
A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 5x10^10vp of ChAdOx1 nCoV-19
• ChAdOx1 nCoV-19 half boost
A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 2.5x10^10vp of ChAdOx1 nCoV-19
• MenACWY boost
A standard dose of MenACWY followed by a boost dose of MenACWY

Drug:
• Paracetamol
1g every 6 hours for 24 hours

Biological:
• ChAdOx1 nCoV-19 0.5mL boost
A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp)
• ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)
A dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) 9 months after receiving a single or double dose of 5x10^10vp of ChAdOx1 nCoV-19
• ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine two (LVT)
A dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) 9 months after receiving a single or double dose of MenACWY, then a boost 4-12 weeks later

Locations

Country	Name	City	State
United Kingdom	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	St Georges University Hospital NHS Foundation Trust	London
United Kingdom	CCVTM, University of Oxford, Churchill Hospital	Oxford
United Kingdom	John Radcliffe Hospital	Oxford
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton	Hampshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through Virus neutralising antibody assays	Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus	6 months
Other	Assess safety, reactogenicity, immunogenicity and efficacy endpoints, for participants receiving prophylactic paracetamol	All safety, reactogenicity, immunogenicity and efficacy endpoints	6 months
Other	Assess immunogenicity of ChAdOx1 nCoV-19 given as homologous prime-boost	Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) post boost	6 months
Other	Compare viral shedding on stool samples of SARS-CoV-2 PCR or NAAT positive individuals	Differences in viral shedding on stool between vaccine and comparator arms at 7 days and beyond post SARS-CoV-2 PCR or NAAT positivity	6 months
Other	Assess immunogenicity of a delayed three dose ChAdOx1 nCoV-19 schedule	Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) post boost	Blood samples drawn at LV14, LV28 and LV182
Other	assess immunological correlates of protection in relation to occurrence of COVID-19 disease in ChAdOx1 nCoV-19 recipients	Immunological endpoints (antibody & cellular responses to SARS-COV2 spike protein) and COVID-19 disease endpoints (SARS-COV2 PCR positivity plus symptoms) in ChAdOx1 nCoV-19 recipients	Throughout the study, average of 18 months
Primary	Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19: Number of virologically confirmed (PCR positive) symptomatic cases	Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19	6 months
Primary	Assess the safety of the candidate vaccine ChAdOx1 nCoV: Occurrence of serious adverse events (SAEs)	Occurrence of serious adverse events (SAEs) throughout the study until a cutoff date of 1st July 2021 or 6 months post late vaccination visit, whichever is latest	Throughout the study, average of 18 months
Secondary	Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited local reactogenicity signs and symptoms	Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination	7 days following vaccination
Secondary	Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited systemic reactogenicity signs and symptoms	Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination	7 days following vaccination
Secondary	Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of unsolicited adverse events (AEs)	Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination (7 days following vaccination for groups 1c, 1d, 5a & 5b)	7 or 28 days following vaccination
Secondary	Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV through standard blood tests	Change from baseline for safety laboratory measures (haematology and biochemistry blood results)	6 months
Secondary	Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV by measuring the number of disease enhancement episodes	Occurrence of disease enhancement episodes	6 months
Secondary	Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by hospital admissions	Number of hospital admissions associated with COVID-19	6 months
Secondary	Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by ICU admissions	Number of intensive care unit admissions associated with COVID-19	6 months
Secondary	Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by COVID-19 related deaths	Number of deaths associated with COVID-19	6 months
Secondary	Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19	Occurrence of severe COVID-19 disease (defined according to clinical severity scales)	6 months
Secondary	Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates	Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study	6 months
Secondary	Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays	Interferon-gamma (IFN-?) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein	6 months
Secondary	Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19	Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)	6 months