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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
15,185
Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Days 0 and 21.
Alternating intramuscular (deltoid) injections of placebo (0.5 mL) on Days 0 and 21.
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.
Belfast Health and Social Care Trust (BHSCT) (Site UK011)
Belfast, Antrim, United Kingdom
Synexus Midlands Clinical Research Centre (Site UK024)
Edgbaston, Birmingham, United Kingdom
The Royal Cornwall Hospitals NHS Trust (Site UK036)
Truro, Cornwall, United Kingdom
Royal Devon and Exeter Hospital (Site UK013)
Exeter, Devon, United Kingdom
"Maidstone Hospital - Central Research and Development Office Above Breast Care Centre - 1st Floor" (Site UK028)
Maidstone, Kent, United Kingdom
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.
Time frame: From Day 28 to Day 386
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.
Time frame: From Day 28 to Day 386
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.
Time frame: From Day 28 to Day 386
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.
Time frame: From Day 28 to Day 386
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.
Time frame: From Day 28 to Day 386
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.
Time frame: From Day 28 to Day 386
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.
Time frame: From Day 28 to Day 386
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.
Time frame: Day 0 to Day 35
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.
Time frame: 386 days
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.
Time frame: 386 days
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.
Time frame: 386 days
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.
Time frame: 28 days
Participants with All MAAEs Through Day 35
Number of participants with all MAAEs through Day 35 by MedDRA classification and relationship to study vaccination.
Time frame: 35 days
Participants with Unsolicited AEs Through Day 49
Number of participants with unsolicited AEs through Day 49 by MedDRA classification and relationship to study vaccination.
Time frame: 49 days
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Queen Elizabeth University Hospital (Site UK008)
Glasgow, Lanarkshire, United Kingdom
Blackpool Teaching Hospitals (Site UK010)
Blackpool, Lancashire, United Kingdom
Salford Hospital (Site UK030)
Oldham, Lancashire, United Kingdom
Synexus Merseyside Clinical Research Centre (Site UK026)
Waterloo, Liverpool, United Kingdom
Royal Free (Site UK012)
Hampstead, London, United Kingdom
...and 23 more locations