Prevention of COVID-19 caused by SARS-CoV-2 MedDRA version: 23.1 Level: LLT Classification code 10084465 Term: COVID-19 vaccination System Organ Class: 100000004865
Conditions
Interventions
Product Name: SARS-CoV-2 rS with Matrix-M1™ Adjuvant
Product Code: NVX-CoV2373
Pharmaceutical Form: Solution for injection
INN or Proposed INN: SARS-CoV-2 recombinant spike protein (SARS-CoV-2 rS) Dru
Sponsors
Novavax, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult males or females aged 18 to 84 years (inclusive) at screening. 2. Able and willing (in the investigator’s opinion) to comply with all study requirements. 3. 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. 4. Willing and able to give informed consent prior to study enrolment. 5. Female participants of childbearing potential (defined as any female who has experienced menarche and who is NOT surgically sterile [i.e., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months or > 1 documented plasma follicle-stimulating hormone level = 40 mIU/mL]) must agree to be heterosexually inactive from at least 28 days prior to enrolment and through 3 months after the last study vaccination OR agree to consistently use any of the following methods of contraception from at least 28 days prior to enrolment and through 3 months after the last study vaccination: a. Condoms (male or female) b. Diaphragm with spermicide c. Cervical cap with spermicide d. Intrauterine device e. Oral or patch contraceptives f. Norplant®, Depo-Provera®, or other in country regulatory-approved contraceptive method that is designed to protect against pregnancy g. Abstinence, as a form of contraception, is acceptable if in line with the participant’s lifestyle (Other approaches to abstinence are not acceptable) NOTE: Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. 6. Room air oxygen saturation >95% at Screening/Day 0 Seasonal Influenza Vaccine Co-Administration Sub-Study Only 7. Participant should not have received a current season influenza vaccine, have no contraindication to the specific vaccine to be administered in the study, and no prior history of allergy or severe reaction to seasonal influenza vaccines. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3750
Exclusion criteria
Exclusion criteria: 1. Participation in COVID-19 prophylactic drug trials for the duration of the study. 2. Future participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus for the duration of the study. 3. Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination. 4. History of laboratory-confirmed (by PCR or serology to SARS-CoV-2) COVID-19 infection at any time prior to randomisation. 5. Administration of immunoglobulins and/or any blood products within the 3 months preceding the planned administration of the study vaccine candidate. 6. 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 are not exclusionary. HIV-positive participants receiving highly active antiretroviral therapy and a history within 6 months of screening of viral load 300 cells/mm3 would be eligible. 7. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccines. 8. Any history of anaphylaxis to any prior vaccine. 9. Pregnancy, lactation or willingness/intention to become pregnant within 3 months following the last study vaccination. 10. Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ, at the discretion of the investigator). 11. Bleeding disorder (e.g., factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. 12. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e., warfarin) or novel oral anticoagulants/anti-platelet agents. (NOTE: The use of = 325 mg of aspirin per day as prophylaxis is permitted) 13. Suspected or known current alcohol or drug dependency. 14. Study team member or first-degree relative of any study team member (inclusive of sponsor, contract research organisation (CRO), and site personnel involved in the study). 15. Participants who are having any current workup of undiagnosed illness within the last 8 weeks that is either participant-reported or has been clinician-assessed, which could lead to a new condition or diagnosis. 16. Received any live vaccine within 4 weeks or any vaccine (excluding influenza) within 2 weeks prior to first study vaccination or any licensed influenza vaccine within 1 week prior to first study vaccination or plans to receive any vaccine from these time periods until 28 days after second study vaccination. NOTE: In addition, a licensed seasonal influenza vaccine may be given 7 days after dose 1 and dose 2 but should not be given within 7 days of dose 2. 17. Have clinically significant chronic cardiovascular, endocrine, gastrointestinal, hepatic (including hepatitis B and C), renal, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of SARS-CoV-2 rS with Matrix-M1 adjuvant in the prevention of virologically confirmed (by polymerase chain reaction [PCR]) to SARS-CoV-2, symptomatic COVID-19, when given as a 2-dose vaccination regimen, as compared to placebo, in serologically negative (to SARS-CoV-2) adult participants.;Secondary Objective: To demonstrate efficacy of the study drug in prevention of virologically confirmed, symptomatic COVID-19, versus placebo, regardless of serostatus at baseline. To assess efficacy of the study drug on: - SARS-CoV-2 seropositive participants requiring specific medical interventions. - mild COVID-19 symptoms. - occurrence of asymptomatic or undetected infections with SARSCoV-2. In a subset of participants, evaluate the immunogenicity of study drug. To evaluate safety in terms of: - SAEs and MAAEs related to study vaccination during entire study. - AESI, which encompasses PIMMCs and AESIs relevant to COVID-19 including possible vaccine-enhanced disease, at any time after the first dose. - All MAAEs for 14 days after second vaccination and unsolicited AEs for 21 days after first and 28 days after second study vaccinations. In a subset, to evaluate safety and reactogenicity in terms of solicited local and systemic AEs for 7 days after each vaccination.;Primary end point(s): First occurrence of virologically confirmed (by PCR to SARS-CoV-2), symptomatic mild, moderate or severe COVID-19 with onset at least 7 days after second study vaccination (e.g., Day 28) in serologically negative (to SARS-CoV-2) adult participants at baseline until the endpoint-driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints. ;Timepoint(s) of evaluation of this end point: This will be an event-driven study for the assessment of vaccine efficacy (VE) and will end when a sufficient number of events have been observed, yet all participants will be followed for the entire study duration for safety | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary endpoint is: - First occurrence of virologically confirmed (by PCR to SARS-CoV-2), symptomatic moderate or severe COVID-19 with onset at least 7 days after second study vaccination (e.g., Day 28) in serologically negative (to SARS-CoV-2) adult participants at baseline until the endpoint-driven efficacy analysis is triggered by the occurrence of a prespecified number of blinded endpoints. The other secondary endpoints are: - First occurrence of virologically confirmed (by PCR to SARS-CoV-2), symptomatic mild, moderate or severe COVID-19, with onset at least 7 days after second study vaccination (e.g., Day 28) in adult participants regardless of their serostatus at baseline. - First occurrence of laboratory-confirmed (by PCR or nucleocapsid (N)protein serology to SARS-CoV-2) symptomatic or asymptomatic COVID19 with onset at least 7 days after second study vaccination (e.g., Day 28) in adult participants regardless of their serostatus at baseline. - First occurrence of COVID-19 requiring hospitalisation, intensive care unit (ICU) admission or mechanical ventilation linked to any virologically confirmed (by PCR to SARS-CoV-2) COVID-19 with onset at least 7 days after second study vaccination (e.g., Day 28) in adult participants regardless of their serostatus at baseline. - First occurrence of virologically confirmed (by PCR to SARS-CoV-2), symptomatic mild COVID-19 (with no progression to moderate or severe COVID-19 during the course of the COVID-19 episode) with onset at least 7 days after second study vaccination (e.g., Day 28) in adult participants, regardless of their serostatus at baseline. - Analysis of antibodies binding to the SARS-CoV-2 spike (S) protein by enzyme-linked immunosorbent assay (ELISA) at Day 0 (baseline) and Day 35 (14 days after second study vaccination). - The occurrence and relationship to study vaccination of SAEs and MAAEs related to study vaccination (in all adult participants) during the entir | — |
Countries
United Kingdom
Contacts
Public ContactLakshmi Kumar
Novavax, Inc.
Outcome results
None listed