Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines

Study Overview
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Brief Summary
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This is an open-label Phase 3 study evaluating the immunogenicity and safety of Novavax vaccine(s) with Matrix-M™ adjuvant (ancestral strain NVX-CoV2373 and an alternative strain and/or multivalent Novavax vaccine) as booster doses following a series of primary and booster doses of authorized/approved mRNA vaccines followed by a single booster dose of NVX-CoV2373 in the Novavax 2019nCoV-307 study (Study 307).

Official Title
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A Phase 3 Study to Evaluate the Immunogenicity and Safety of Novavax COVID-19 Vaccine(s) as Second or Subsequent Booster After mRNA Vaccines in Individuals 18 to 49 Years of Age

Conditions
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COVID-19

Intervention / Treatment
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* Biological: NVX-CoV2373
* Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be included in this study, each individual must satisfy all the following criteria: Adults 18 to 49 years (inclusive) of age at the time of vaccination in Study 307 who received two or three doses of mRNA prior to enrollment in Study 307, then one dose of ancestral strain NVX-CoV2373 in Study 307. Willing and able to give informed consent prior to study enrollment and to comply with study procedures. Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of study (EOS) visit OR agree to consistently use a medically acceptable method of contraception from at least 28 days prior to enrollment and through the EOS visit. Is medically stable, as determined by the investigator (based on review of health status, vital signs [to include body temperature], medical history, and physical examination [to include body weight]). Vital signs must be within medically acceptable ranges prior to the study vaccination. Agree to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. Note: For participants who become hospitalized with COVID-19, participation in investigational treatment studies is permitted. Documented receipt of COVID-19 vaccines. The most recent dose of NVX-CoV2373 must have been administered at least 180 days prior to vaccination in this study. Exclusion Criteria: Participants meeting any of the following criteria will be excluded from the study. Received any additional COVID-19 vaccine booster after the Day 1 dose of NVX-CoV2373 administered during participation in Study 307. History of laboratory-confirmed (by polymerase chain reaction [PCR] or rapid antigen test) COVID-19 infection ≤ 4 months prior to Day 1. Current participation in research involving receipt of an investigational product (drug/biologic/device). Any known allergies or history of anaphylaxis to the active substance or any of the other ingredients contained in the investigational product. Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) or therapy that causes clinically significant immunosuppression. Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccine which may be received > 4 days prior to study vaccine, or rabies vaccine, which may be received at any time if medically indicated. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to study vaccination, except for rabies immunoglobulin which may be given if medically indicated. Active cancer (malignancy) on chemotherapy that is judged to cause significant immunocompromise within 1 year prior to first study vaccination (with the exception of malignancy cured via excision, at the discretion of the investigator). Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the EOS visit. Suspected or known history of alcohol abuse or drug addiction within 3 months prior to the study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting). Study team member or immediate family member of any study team member (inclusive of Sponsor, clinical research organization [CRO], and study site personnel involved in the conduct or planning of the study). Participants with a history of myocarditis or pericarditis.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NVX CoV2373 (Ancestral strain)<br>1dose of NVX-COV2373 on Day 1 | Biological: NVX-CoV2373<br>* 1 intramuscular (IM) injection of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5 mL) given on Day 1<br>* Other names: SARS-CoV-2 rS/Matrix-M Adjuvant;|
| Experimental: Updated COVID-19 Vaccine<br>1dose of updated COVID-19 vaccine on Day 1 | Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant<br>* 1 intramuscular (IM) injection of 5 µg SARS-CoV-2 rS antigen+ 50 µg Matrix-M1 adjuvant (0.5 mL) given on Day 1<br>* Other names: Updated Novavax COVID-19 vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing Antibody (Nab) responses expressed as Geometric Mean Titers | Neutralizing Antibody responses GMTs to ancestral strain Novavax vaccine (NVX-CoV2373) at Day 29 | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nab Antibody responses expressed as Seroconversion Rate (SCR) | Proportion of participants who achieve seroconversion (≥ 4-fold increase from baseline) in neutralization antibody titers to the ancestral strain Novavax Vaccine (NVX-CoV2373) at Day 29 | Day 29 | 
| Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMEU | IgG antibody levels to the SARS-CoV-2 ancestral strain spike protein as detected by enzyme-linked immunosorbent assay (ELISA) expressed as (GMEU/mL) at Day 29 | Day 29 | 
| Serum IgG Antibody levels expressed as SCR | Proportion of participants who achieve seroconversion (≥ 4-fold increase from baseline) in IgG concentration to the ancestral strain spike protein at Day 29 | Day 29 | 
| Neutralizing Antibody responses (Post-Booster) expressed as GMT | Post Booster Neutralizing Antibody responses GMTs compared with post-first booster results from Study 307 | Day to Day 181 | 
| Serum IgG Antibody Levels (Post-Booster) Expressed as GMEU | Post Booster Serum IgG antibody levels expressed GMEUs compared with post-first booster results from Study 307 | Day to Day 181 | 
| Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as Seroresponse (SPR) | hACE2 Receptor Binding Inhibition Assay the SARS-CoV-2 ancestral strain spike protein expressed as SPR at Day 29 | Day 29 | 
| Incidence and Severity of Solicited Adverse Events (AEs) | Incidence, duration, and severity of solicited adverse reactions in the 7 days following study vaccination. | Day 7 | 
| Incidence and Severity of Medically Attended Adverse Events (MAAEs) | Incidence, duration, severity and of MAAEs through Day 180 after the vaccine dose. | Day 1 to Day 180 | 
| Incidence and Severity of Adverse Events Special Interests (AESIs) | Incidence, duration, severity and of AESIs (including myocarditis and/or pericarditis) through Day 180 after the vaccine dose. | Day 1 to Day 180 | 
| Incidence and Relationship of Serious Adverse Events (SAEs) | Incidence and Relationship of SAEs through Day 180 after the vaccine dose | Day 1 to Day 180 |