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SARS-CoV-2 InfectionPhase 3NCT04583995

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

A Phase 3 study testing SARS-CoV-2 rS/Matrix M1-Adjuvant and Licensed seasonal influenza vaccine in people with SARS-CoV-2 Infection and COVID-19, run by Novavax at 33 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 84 yearsHealthy volunteers can take part
Conditions the study is for
SARS-CoV-2 Infection, COVID-19
What is being tested?
SARS-CoV-2 rS/Matrix M1-Adjuvant and Licensed seasonal influenza vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
15,185 participants
Where
33 sitesUnited Kingdom
Study dates
28 Sep 2020to 29 Mar 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 84 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Have clinically significant chronic cardiovascular, endocrine (hormones), gastrointestinal, hepatic (including hepatitis B and C), renal (kidney), neurological, respiratory, psychiatric or other medical disorders not excluded by other exclusion criteria, that are assessed by the investigator as being clinically unstable within the prior 4 weeks as evidenced by: a) Hospitalisation for the condition, including day surgical interventions; b) New significant organ function deterioration; or c) Needing addition of new treatments or major dose adjustments of current treatments (mild or moderate well-controlled comorbidities are allowed).
  • 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.
  • Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

United Kingdom33 sites

  • Aberdeen Royal Infirmary (Site UK007), Foresterhill

    Aberdeen, AB25 2ZN

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

    Belfast, Antrim, BT9 7AB

  • Blackpool Teaching Hospitals (Site UK010)

    Blackpool, Lancashire, FY3 8NR

  • Bradford Teaching Hospitals NHS Trust (Site UK018)

    Bradford, BD9 6RJ

  • Synexus Wales Clinical Research Centre (Site UK025)

    Cardiff, CF15 9SS

  • Synexus Lancashire Clinical Research Centre (Site UK022)

    Chorley, PR7 7 NA

  • Colchester Hospital (Site UK034)

    Colchester, CO4 5JL

  • Lakeside Healthcare, Lakeside Surgery (Site UK005)

    Corby, Northants, NN17 2UR

  • Synexus Midlands Clinical Research Centre (Site UK024)

    Edgbaston, Birmingham, B15 2 SQ

  • Royal Devon and Exeter Hospital (Site UK013)

    Exeter, Devon, EX2 5DW

  • Queen Elizabeth University Hospital (Site UK008)

    Glasgow, Lanarkshire, G51 4TF

  • AES - Glasgow (Site UK033)

    Glasgow, G20 0SP

  • Royal Free (Site UK012)

    Hampstead, London, NW3 2QG

  • University Hartlepool Hospital (Site UK021)

    Hartlepool, TS24 9AH

  • Synexus Hexham Clinical Research Centre (Site UK023)

    Hexham, NE46 1QJ

  • Royal Lancaster Infirmary (Site UK029)

    Lancaster, LA1 4RP

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

    Leeds, LS9 7TF

  • St. Thomas' Hospital (Site UK020)

    London, SE1 7EH

  • Chelsea & Westminster NHS Foundation Trust (Site UK006)

    London, SW10 9NH

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

    Maidstone, Kent, ME16 9QQ

  • AES - Synexus Manchester (Site UK032)

    Manchester, M15 6SE

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

    Norwich, NR4 7UY

  • Salford Hospital (Site UK030)

    Oldham, Lancashire, OL1 2JH

  • Warneford Hospital (Site UK016)

    Oxford, Oxfordshire, OX3 7JX

  • Wansford and Kingscliffe Practice (Site UK035)

    Peterborough, PE8 6PL

  • AES - Synexus Thames Valley (Site UK031)

    Reading, RG2 0TG

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

    Southampton, SO16 6YD

  • Midlands Partnership NHS Foundation Trust Headquarters (Site UK017)

    Stafford, ST16 3SR

  • Stockport NHS Foundation Trust (Site UK009)

    Stockport, SK2 7JE

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

    Tooting, London, SW17 0QT

  • The Royal Cornwall Hospitals NHS Trust (Site UK036)

    Truro, Cornwall, TR1 3LJ

  • Synexus Merseyside Clinical Research Centre (Site UK026)

    Waterloo, Liverpool, L22 0LG

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

    Wrexham, North Wales, LL13 7YP

Other trials in United Kingdom

About this study

Official title: A Phase 3, Randomised, Observer-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in Adult Participants 18-84 Years of Age in the United Kingdom

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.

Being tested
SARS-CoV-2 rS/Matrix M1-Adjuvant, Placebo, Licensed seasonal influenza vaccine
Keywords
Coronavirus
Medical subject headings
COVID-19, Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SARS-CoV-2 rS/Matrix M1-AdjuvantBiological

    Also called NVX-CoV2373

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

  • PlaceboOther

    Also called Sodium chloride 0.9% (BP, sterile)

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

  • Licensed seasonal influenza vaccineBiological

    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.

Study groups in NCT04583995
Study groupRoleWhat they receive
Cohort 1: SARS-CoV-2 rS/Matrix-M1 AdjuvantExperimental2 doses of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (co-formulated), 1 dose each on Days 0 and 21.
Receives: Biological: SARS-CoV-2 rS/Matrix M1-Adjuvant
Cohort 1: PlaceboPlacebo comparator2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.
Receives: Other: Placebo
Cohort 2: SARS-CoV-2 rS/Matrix-M1 Adjuvant Plus Licensed Seasonal Flu VaccineExperimental2 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.
Receives: Biological: SARS-CoV-2 rS/Matrix M1-Adjuvant; Biological: Licensed seasonal influenza vaccine
Cohort 2: Placebo Plus Licensed Seasonal Flu VaccinePlacebo comparator2 doses of Placebo (Saline), 1 dose each on Days 0 and 21. 1 dose of licensed seasonal flu vaccine on Day 0.
Receives: Other: Placebo; Biological: Licensed seasonal influenza vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19)

    Number of participants, testing serologically negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, with first occurrence of positive (+) polymerase chain reaction (PCR)-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 with onset from Day 28 through the length of the study.

    Measured: From Day 28 to Day 386

Secondary outcomes (13)

  1. Participants with Symptomatic Moderate or Severe COVID-19

    Number of participants, testing serologically negative for SARS-CoV-2 at baseline with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic moderate or severe COVID-19 with onset from Day 28 through the length of the study.

    Measured: From Day 28 to Day 386

  2. Participants with Symptomatic Severe COVID-19

    Number of participants, testing serologically negative for SARS-CoV-2 at baseline with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic severe COVID-19 with onset from Day 28 through the length of the study.

    Measured: From Day 28 to Day 386

  3. Participants with Symptomatic Mild, Moderate, or Severe COVID-19 Regardless of Baseline Serostatus

    Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 assessed from Day 28 through the length of the study.

    Measured: From Day 28 to Day 386

  4. Participants with Asymptomatic or Symptomatic COVID-19

    Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, or nucleocapsid protein serologically confirmed, SARS-CoV-2 illness with asymptomatic or symptomatic COVID-19 with onset from Day 28 through the length of the study.

    Measured: From Day 28 to Day 386

  5. Participants with COVID-19 requiring Hospitalization, Intensive Care Unit (ICU), or Mechanical Ventilation

    Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with COVID-19 with onset from Day 28 through the length of the study.

    Measured: From Day 28 to Day 386

  6. Participants with Symptomatic Mild COVID-19

    Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic mild COVID-19 (with no progression to moderate or severe COVID-19 during the course of the COVID-19 episode) with onset from Day 28 through the length of the study.

    Measured: From Day 28 to Day 386

  7. Serum IgG Antibody Levels at Multiple Time Points Expressed as Geometric Mean ELISA Units (GMEUs)

    Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMEUs at Day 0 and Day 35.

    Measured: Day 0 to Day 35

  8. Participants with Serious Adverse Events (SAEs)

    Number of participants with SAEs through the length of the study by Medical Dictionary for Regulatory Activities (MedDRA) classification and relationship to study vaccination.

    Measured: 386 days

  9. Participants with Medically Attended Adverse Events (MAAEs) Related to Study Vaccination

    Number of participants with MAAEs related to study vaccination through the length of the study by MedDRA classification.

    Measured: 386 days

  10. Participants with Adverse Events of Special Interest (AESIs)

    Number of participants with AESIs, which include potential immune-mediated medical conditions (PIMMCs) and AESIs relevant to COVID-19 such as possible vaccine-enhanced disease by MedDRA classification through the length of the study.

    Measured: 386 days

  11. Participants with Solicited Local and Systemic Adverse Events (AEs)

    Number of participants with solicited local and systemic AEs for 7 days after each study vaccination.

    Measured: 28 days

  12. Participants with All MAAEs Through Day 35

    Number of participants with all MAAEs through Day 35 by MedDRA classification and relationship to study vaccination.

    Measured: 35 days

  13. Participants with Unsolicited AEs Through Day 49

    Number of participants with unsolicited AEs through Day 49 by MedDRA classification and relationship to study vaccination.

    Measured: 49 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2020
  2. Study start28 Sep 2020
  3. Primary completion29 Mar 2022
  4. Study completion29 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
15,185 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04583995
Sponsor's protocol ID
2019nCoV-302
Status last verified
May 2025
First submitted
9 Oct 2020
Last updated
8 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34800364

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing SARS-CoV-2 rS/Matrix M1-Adjuvant and Licensed seasonal influenza vaccine in people with SARS-CoV-2 Infection and COVID-19, run by Novavax at 33 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19) (time frame: From Day 28 to Day 386). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04583995, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2025; AzTrials last refreshed its copy on 29 Oct 2026.

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