A Study Looking at the Effectiveness, Immune Response, and Safety of a COVID-19 Vaccine in Adults in the United Kingdom

NCT ID: NCT04583995

Last Updated: 2025-05-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

15185 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-28

Study Completion Date

2022-03-29

Brief Summary

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This is a study to evaluate the efficacy, immune response, and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in adults aged 18-84 years in the United Kingdom. A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in the study population. Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections over the course of the study. Approximately 15,000 participants will take part in the study. The first approximately 400 participants who meet additional criteria will receive a flu vaccine, in addition to the SARS-CoV-2 rS vaccine or placebo, as part of a sub-study.

An effort will be made to enroll a target of at least 25% of participants who are ≥ 65 years of age, as well as prioritizing other groups that are most affected by COVID-19, including racial and ethnic minorities.

Unblinding of treatment assignment may occur in order to allow a participant to make an informed decision regarding receipt of an already approved or deployed SARS-CoV-2 vaccine. Participants who choose to receive an approved or deployed SARS-CoV-2 vaccine as per UK government guidance will be encouraged to remain in the study for scheduled safety assessments.

Detailed Description

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Conditions

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SARS-CoV-2 Infection COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cohort 1: SARS-CoV-2 rS/Matrix-M1 Adjuvant

2 doses of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (co-formulated), 1 dose each on Days 0 and 21.

Group Type EXPERIMENTAL

SARS-CoV-2 rS/Matrix M1-Adjuvant

Intervention Type BIOLOGICAL

Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Days 0 and 21.

Cohort 1: Placebo

2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Alternating intramuscular (deltoid) injections of placebo (0.5 mL) on Days 0 and 21.

Cohort 2: SARS-CoV-2 rS/Matrix-M1 Adjuvant Plus Licensed Seasonal Flu Vaccine

2 doses of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (co-formulated), 1 dose each on Days 0 and 21. 1 dose of licensed seasonal flu vaccine on Day 0.

Group Type EXPERIMENTAL

SARS-CoV-2 rS/Matrix M1-Adjuvant

Intervention Type BIOLOGICAL

Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Days 0 and 21.

Licensed seasonal influenza vaccine

Intervention Type BIOLOGICAL

Single intramuscular injection of licensed seasonal flu vaccine, administered ideally in opposite deltoid to SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo injection on Day 0.

Cohort 2: Placebo Plus Licensed Seasonal Flu Vaccine

2 doses of Placebo (Saline), 1 dose each on Days 0 and 21. 1 dose of licensed seasonal flu vaccine on Day 0.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Alternating intramuscular (deltoid) injections of placebo (0.5 mL) on Days 0 and 21.

Licensed seasonal influenza vaccine

Intervention Type BIOLOGICAL

Single intramuscular injection of licensed seasonal flu vaccine, administered ideally in opposite deltoid to SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo injection on Day 0.

Interventions

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SARS-CoV-2 rS/Matrix M1-Adjuvant

Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Days 0 and 21.

Intervention Type BIOLOGICAL

Placebo

Alternating intramuscular (deltoid) injections of placebo (0.5 mL) on Days 0 and 21.

Intervention Type OTHER

Licensed seasonal influenza vaccine

Single intramuscular injection of licensed seasonal flu vaccine, administered ideally in opposite deltoid to SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo injection on Day 0.

Intervention Type BIOLOGICAL

Other Intervention Names

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NVX-CoV2373 Sodium chloride 0.9% (BP, sterile)

Eligibility Criteria

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Inclusion Criteria

* Able and willing to comply with all study requirements.
* Willing to allow investigators to discuss medical history with their General Practitioner and access all relevant medical records.
* Willing and able to give informed consent.
* Women of child-bearing potential must agree not to have sexual intercourse with men, or must consistently use an agreed method of contraception, from at least 28 days prior to enrolment in the study, through 3 months after the last vaccination.
* Room air oxygen saturation \> 95% at Screening/Day 0.
* Seasonal Flu Vaccine Co-Administration Sub-Study only: Participant should not have received a current season flu vaccine, should have no reason why the specific sub-study flu vaccine cannot be administered, and should not have any prior history of allergy or severe reaction to seasonal flu vaccines.

Exclusion Criteria

* Participation in other COVID-19 vaccine or preventative drug trials for the duration of the study.
* Future participation in any blood tests for the duration of the study where participants are informed of their levels of COVID-19 antibodies or antigens.
* Participation in any trial involving an investigational drug, biologic or device within 45 days prior to the first study vaccination.
* History of laboratory-confirmed COVID-19 infection any time prior to first study vaccination.
* Receipt of any immunoglobulins and/or any blood products within 3 months prior to planned administration of study vaccine.
* Any confirmed or suspected immunosuppressive or immunodeficient state. Chronic administration (defined as more than 14 continuous days) of immunosuppressant medication within the past 3 months, except topical steroids or short-term oral steroids (course lasting ≤ 14 days). Note: An immunosuppressant dose of glucocorticoid is defined as a systemic dose ≥ 10 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted if other chronic disease conditions do not exclude a participant from the study.
* History of allergic disease or reactions likely to be made worse by any component of the study vaccines.
* History of anaphylaxis to any prior vaccine.
* Pregnancy, breast-feeding or willingness/intention to become pregnant within 3 months following the last study vaccination.
* Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ.
* Bleeding disorder, or prior history of significant bleeding or bruising following intramuscular injections or venepuncture (e.g. to draw blood for tests).
* Continuous use of anticoagulants or anti-platelet agents. Note: The preventative use of ≤ 325 mg of aspirin per day is permitted.
* Suspected or known current alcohol or drug dependency.
* Study team member or first-degree relative of any study team member (inclusive of sponsor, contract research organization (CRO), and site personnel involved in the study).
* Participants having any current workup of undiagnosed illness within 8 weeks prior to start of study which could lead to new condition or diagnosis.
* Received any live vaccine within 4 weeks or any vaccine (excluding flu) within 2 weeks prior to first study vaccination; or any licensed flu vaccine within 1 week prior to first study vaccination or plans to receive any vaccine from these time periods until 28 days after the second study vaccination.
* History of chronic neurological disorders that have required prior specialist physician review for diagnosis and management (such as multiple sclerosis, dementia, transient ischemic attacks, Parkinson's disease, degenerative neurological conditions, and neuropathy) or a history of stroke or previous neurological disorder within 12 months with residual symptoms. Participants with a history of migraine or chronic headaches or nerve root compression that have been stable on treatment for the last 4 weeks are not excluded.
* Any autoimmune disease/condition (iatrogenic or congenital).
* Any other significant disease, disorder or finding that, in the opinion of the investigator, 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.
* Participant requires the use of continuous oxygen therapy or any oxygen therapy while awake or is anticipated to require daytime oxygen therapy during the course of the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

84 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Novavax

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Development

Role: STUDY_DIRECTOR

Novavax, Inc.

Paul T Heath, MB BS FRACP FRCPCH

Role: PRINCIPAL_INVESTIGATOR

Vaccine Institute, St Georges, University of London

Locations

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Belfast Health and Social Care Trust (BHSCT) (Site UK011)

Belfast, Antrim, United Kingdom

Site Status

Synexus Midlands Clinical Research Centre (Site UK024)

Edgbaston, Birmingham, United Kingdom

Site Status

The Royal Cornwall Hospitals NHS Trust (Site UK036)

Truro, Cornwall, United Kingdom

Site Status

Royal Devon and Exeter Hospital (Site UK013)

Exeter, Devon, United Kingdom

Site Status

"Maidstone Hospital - Central Research and Development Office Above Breast Care Centre - 1st Floor" (Site UK028)

Maidstone, Kent, United Kingdom

Site Status

Queen Elizabeth University Hospital (Site UK008)

Glasgow, Lanarkshire, United Kingdom

Site Status

Blackpool Teaching Hospitals (Site UK010)

Blackpool, Lancashire, United Kingdom

Site Status

Salford Hospital (Site UK030)

Oldham, Lancashire, United Kingdom

Site Status

Synexus Merseyside Clinical Research Centre (Site UK026)

Waterloo, Liverpool, United Kingdom

Site Status

Royal Free (Site UK012)

Hampstead, London, United Kingdom

Site Status

St. George's University Hospitals NHS Foundation Trust Clinical Research Facility (Site UK001)

Tooting, London, United Kingdom

Site Status

North Wales Clinical Research Centre (NWCRC) (Site UK027)

Wrexham, North Wales, United Kingdom

Site Status

Lakeside Healthcare, Lakeside Surgery (Site UK005)

Corby, Northants, United Kingdom

Site Status

Warneford Hospital (Site UK016)

Oxford, Oxfordshire, United Kingdom

Site Status

Aberdeen Royal Infirmary (Site UK007), Foresterhill

Aberdeen, , United Kingdom

Site Status

Bradford Teaching Hospitals NHS Trust (Site UK018)

Bradford, , United Kingdom

Site Status

Synexus Wales Clinical Research Centre (Site UK025)

Cardiff, , United Kingdom

Site Status

Synexus Lancashire Clinical Research Centre (Site UK022)

Chorley, , United Kingdom

Site Status

Colchester Hospital (Site UK034)

Colchester, , United Kingdom

Site Status

AES - Glasgow (Site UK033)

Glasgow, , United Kingdom

Site Status

University Hartlepool Hospital (Site UK021)

Hartlepool, , United Kingdom

Site Status

Synexus Hexham Clinical Research Centre (Site UK023)

Hexham, , United Kingdom

Site Status

Royal Lancaster Infirmary (Site UK029)

Lancaster, , United Kingdom

Site Status

Research & Innovation Centre, St. James's University Hospital (Site UK019)

Leeds, , United Kingdom

Site Status

St. Thomas' Hospital (Site UK020)

London, , United Kingdom

Site Status

Chelsea & Westminster NHS Foundation Trust (Site UK006)

London, , United Kingdom

Site Status

AES - Synexus Manchester (Site UK032)

Manchester, , United Kingdom

Site Status

Norfolk and Norwich University Hospital NHS Foundation Trust, Norfolk and Norwich University Hospital (Site UK015)

Norwich, , United Kingdom

Site Status

Wansford and Kingscliffe Practice (Site UK035)

Peterborough, , United Kingdom

Site Status

AES - Synexus Thames Valley (Site UK031)

Reading, , United Kingdom

Site Status

University Hospital Southampton NHS Foundation Trust (UHS) (Site UK014)

Southampton, , United Kingdom

Site Status

Midlands Partnership NHS Foundation Trust Headquarters (Site UK017)

Stafford, , United Kingdom

Site Status

Stockport NHS Foundation Trust (Site UK009)

Stockport, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Toback S, Galiza E, Cosgrove C, Galloway J, Goodman AL, Swift PA, Rajaram S, Graves-Jones A, Edelman J, Burns F, Minassian AM, Cho I, Kumar L, Plested JS, Rivers EJ, Robertson A, Dubovsky F, Glenn G, Heath PT; 2019nCoV-302 Study Group. Safety, immunogenicity, and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory substudy of a randomised, observer-blinded, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022 Feb;10(2):167-179. doi: 10.1016/S2213-2600(21)00409-4. Epub 2021 Nov 17.

Reference Type DERIVED
PMID: 34800364 (View on PubMed)

Related Links

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http://www.CDC.gov/coronavirus/2019-nCoV/index.html

CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website

https://www.hra.nhs.uk/covid-19-research/

NHS Health Research Authority: COVID-19 Research

Other Identifiers

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2019nCoV-302

Identifier Type: -

Identifier Source: org_study_id

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