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
Overview
- Phase
- Phase 3
- Intervention
- SARS-CoV-2 rS/Matrix M1-Adjuvant
- Conditions
- SARS-CoV-2 Infection
- Sponsor
- Novavax
- Enrollment
- 15185
- Locations
- 33
- Primary Endpoint
- Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19)
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief 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. 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.
Investigators
Eligibility Criteria
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
- •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.
Arms & Interventions
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.
Intervention: SARS-CoV-2 rS/Matrix M1-Adjuvant
Cohort 1: Placebo
2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.
Intervention: Placebo
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.
Intervention: SARS-CoV-2 rS/Matrix M1-Adjuvant
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.
Intervention: Licensed seasonal influenza vaccine
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.
Intervention: Placebo
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.
Intervention: Licensed seasonal influenza vaccine
Outcomes
Primary Outcomes
Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19)
Time Frame: From Day 28 to Day 386
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.
Secondary Outcomes
- Participants with Symptomatic Severe COVID-19(From Day 28 to Day 386)
- Participants with Unsolicited AEs Through Day 49(49 days)
- Participants with Adverse Events of Special Interest (AESIs)(386 days)
- Participants with Symptomatic Moderate or Severe COVID-19(From Day 28 to Day 386)
- Participants with Serious Adverse Events (SAEs)(386 days)
- Participants with Solicited Local and Systemic Adverse Events (AEs)(28 days)
- Participants with All MAAEs Through Day 35(35 days)
- Participants with COVID-19 requiring Hospitalization, Intensive Care Unit (ICU), or Mechanical Ventilation(From Day 28 to Day 386)
- Participants with Symptomatic Mild COVID-19(From Day 28 to Day 386)
- Serum IgG Antibody Levels at Multiple Time Points Expressed as Geometric Mean ELISA Units (GMEUs)(Day 0 to Day 35)
- Participants with Symptomatic Mild, Moderate, or Severe COVID-19 Regardless of Baseline Serostatus(From Day 28 to Day 386)
- Participants with Asymptomatic or Symptomatic COVID-19(From Day 28 to Day 386)
- Participants with Medically Attended Adverse Events (MAAEs) Related to Study Vaccination(386 days)