A Study to Evaluate the Efficacy, Immune Response, and Safety of a COVID-19 Vaccine in Adults ≥ 18 Years With a Pediatric Expansion in Adolescents (12 to<18 Years) at Risk for SARS-CoV-2

Covid19 Clinical Trial

Official title:

A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in Adult Participants ≥ 18 Years With a Pediatric Expansion in Adolescents (12 to < 18 Years)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04611802
• Other study ID #: 2019nCoV-301
• Status: Completed
• Phase: Phase 3
• Start date: December 27, 2020
• Est. completion date: December 15, 2023

Study information

• Verified date: November 2023
• Source: Novavax
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 3, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in adult participants and adolescent participants. Additionally providing a Booster Dose to fully vaccinated participants. A substudy is to be conducted at selected sites to evaluate the safety and immunogenicity of a fourth dose (second booster) of NVX-CoV2373 in adults and adolescents, previously fully vaccinated and subsequently boosted with a third dose (first booster)

Description:

This is a Phase 3, randomized, observer-blinded, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of SARS-CoV-2 rS with Matrix-M1 adjuvant in adult participants ≥ 18 years of age (Adult Main Study) and adolescent participants 12 to <18 years (Pediatric Expansion). Additionally, a Booster Amendment will allow for the evaluation of a booster dose of SARS-CoV-2 rS with Matrix-M1 adjuvant in participants who completed the primary series of active vaccine in the Adult Main Study or Pediatric Expansion, as well as in participants who previously completed the primary series of an authorized/approved COVID-19 vaccine. Additionally, a sub-study conducted at specific sites will allow for the evaluation of a second booster dose of SARS-CoV-2 rS with Matrix-M1 adjuvant in participants who completed the primary series of active vaccine in the Adult Main Study and Pediatric Expansion as well as a booster dose in the Booster Amendment of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33000
• Est. completion date: December 15, 2023
• Est. primary completion date: April 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

Adult Participants :

Each participant in the Adult Main Study and/or the Booster Amendment must meet all of the

following criteria to be enrolled in this study:

1. Adults = 18 years of age at screening who, by virtue of age, race, ethnicity or life circumstances, are considered at substantial risk of exposure to and infection with SARS CoV-2.

2. Willing and able to give informed consent prior to study enrollment and to comply with study procedures.

3. Participants of childbearing potential (defined as any participant 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]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through 3 months after the last vaccination OR agree to consistently use a medically acceptable method of contraception from at least 28 days prior to enrollment and through 3 months after the last vaccination.

4. Is medically stable, as determined by the investigator (based on review of health status, vital signs [to include body temperature], medical history, and targeted physical examination [to include body weight]). Vital signs must be within medically acceptable ranges prior to the first vaccination.

5. Agree to not participate in any other SARS-CoV-2 prevention trial during the study follow-up.

6. For the Booster Amendment only, active participants who received a full dose regimen of active vaccine (SARS-CoV-2 rS with Matrix-M1 adjuvant) or any authorized/approved COVID-19 vaccine are eligible for participation. Such participants must demonstrate receipt by producing valid documentation of vaccination at the booster visit. Pediatric Participants : Each participant in the Pediatric Expansion and/or the Booster Amendment must meet all of

the following criteria to be enrolled in this study:

1. Pediatric participants 12 to < 18 years of age at screening, determined to be healthy or medically stable by the investigator (based on review of health status, vital signs [to include body temperature], medical history, and targeted physical examination [to include body weight]). Vital signs must be within medically acceptable ranges prior to the first vaccination.

2. Participant and parent(s)/caregiver(s) or legally acceptable representative willing and able to give informed consent and assent, as required, prior to study enrollment and to comply with study procedures.

3. 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] must agree to be heterosexually inactive from at least 28 days prior to enrollment and through 3 months after the last vaccination OR agree to consistently use a medically acceptable method of contraception from at least 28 days prior to enrollment and through 3 months after the last vaccination.

4. Agree to not participate in another SARS-CoV-2 prevention trial during the study follow-up.

5. For the Booster Amendment only, active participants who received a full dose regimen of active vaccine (SARS-CoV-2 rS with Matrix-M1 adjuvant) or any authorized/approved COVID-19 vaccine are eligible for participation. Such participants must demonstrate receipt by producing valid documentation of vaccination. Site-Specific Sub Study: Each participant in the Substudy must meet all of the following criteria to be enrolled in

this study:

1. Be an active, enrolled participant in the 2019nCoV-301 study.

2. Adults 18 years of age or older or adolescents 12 to < 18 years of age at initial screening for the parent study.

3. Willing and able to give informed consent prior to substudy enrollment and to comply with extra study procedures.

4. Documented receipt of the 2 doses of the primary series of NVX-CoV2373 and the booster (third dose) of NVX-CoV2373 in the parent protocol. The booster dose must have been administered at least 6 months prior to entering the substudy.

5. Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile or postmenopausal) must agree to be heterosexually inactive from at least 28 days prior to entering and through the end of the substudy OR agree to consistently use a medically acceptable method of contraception for the 28 days of follow-up for the substudy.

6. Is medically stable, as determined by the investigator (based on review of health status, vital signs (to include body temperature) and targeted physical examination (if medically indicated by reported symptoms). Vital signs must be within medically acceptable ranges prior to administration of study vaccination.

7. Agree to not participate in any other non-NVX-CoV2373 study during the substudy. Note: For participants who develop COVID-19, anti-SARS-CoV-2 therapy (approved, authorized or investigational) is permitted. Exclusion Criteria: Adult and adolescent participants meeting any of the following criteria will be excluded

from the study:

1. Unstable acute or chronic illness. Criteria for unstable medical conditions include:

1. Substantive changes in chronic prescribed medication (change in class or significant change in dose) in the past 2 months.

2. Currently undergoing workup of undiagnosed illness that could lead to diagnosis of a new condition. Note: Well-controlled human immunodeficiency virus [HIV] with undetectable HIV RNA [< 50 copies/mL] and CD4 count > 200 cells/µL for at least 1 year, documented within the last 6 months, is NOT considered an unstable chronic illness. Participant's or parent's/caregiver's verbal report will suffice as documentation.

2. Participation in research involving an investigational product (drug/biologic/device) administered within 45 days prior to first study vaccination.

3. History of a previous laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-19. A previous diagnosis of COVID-19 during participation in this trial is not exclusionary for the Booster Amendment.

4. Received any vaccine within 4 days prior to first study vaccination or planned receipt of any vaccine before Day 49 (i.e., 28 days after second vaccination), except for influenza vaccination, which may be received = 4 days prior to or = 7 days after either study vaccination. Rabies vaccine, at any time it is medically indicated, is not exclusionary. Prior receipt of another approved or authorized COVID-19 vaccine prior to booster injection is not exclusionary in the Booster Amendment. Such participants must provide documentation of vaccine and date(s) of administration.

5. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) or therapy that causes clinically significant immunosuppression. NOTE: Stable endocrine disorders (eg, thyroiditis, pancreatitis, including stable diabetes mellitus) are NOT excluded.

6. Chronic administration (defined as > 14 continuous days) of immunosuppressant or systemic glucocorticoids causing clinically significant immunocompromise, within 90 days prior to first study vaccination and/or third (booster) vaccination. NOTE: An immunosuppressant dose of glucocorticoid is defined as a systemic dose = 20 mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids is permitted. Topical tacrolimus and ocular cyclosporin are permitted.

7. Received immunoglobulin or blood-derived products, within 90 days prior to first study vaccination and/or third (booster) vaccination.

8. Active cancer (malignancy) on chemotherapy that is judged to cause clinically significant immunocompromise within 1 year prior to first study vaccination (with the exception of malignancy cured via excision, at the discretion of the investigator). This criterion is not applicable to participants diagnosed during participation in this trial who accept participation in the Booster Amendment.

9. Any known allergies to products contained in the investigational product.

10. Participants who are breastfeeding, pregnant, or who plan to become pregnant within 3 months following last study vaccination.

11. 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.

12. Study team member or first-degree relative of any study team member (inclusive of Sponsor, and study site personnel involved in the study).

13. Current participation in any other COVID-19 prevention clinical trial.

14. Adult participants who have not received a full dose of any authorized/approved COVID-19 vaccine and are unable to provide valid documentation of vaccination will be excluded from the Booster Amendment. Adult and adolescent participants meeting any of the following criteria will be excluded

from the substudy:

1. History of laboratory-confirmed (by PCR or other antigen testing) COVID-19 infection = 4 months prior to entering the substudy.

2. Known to be clinically significantly immunocompromised.

3. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to entering substudy.

4. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of substudy.

5. History of confirmed myocarditis and/or pericarditis since enrollment to the parent study.

6. Any condition that, in the opinion of the investigator, might pose a health risk to the participant, interfere with protocol compliance or interfere with evaluation of the trial vaccine.

7. Study team member or immediate family member of any study team member (inclusive of Sponsor, CRO, and study site personnel involved in the conduct or planning of the substudy).

Related Conditions & MeSH terms

• COVID-19
• Covid19
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Biological:
• SARS-CoV-2 rS/Matrix-M1 Adjuvant (Initial Vaccination Period)
Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Days 0 and 21 in Initial Vaccination Period.

Other:
• Placebo (Initial Vaccination Period)
Alternating intramuscular (deltoid) injections of placebo (0.5 mL) on Days 0 and 21 in Initial Vaccination Period.

Biological:
• SARS-CoV-2 rS/Matrix-M1 Adjuvant (Crossover Vaccination period)
In Crossover Vaccination period, one dose of intramuscular (deltoid) injection of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Day 0 or Day 21

Other:
• Placebo (Crossover Vaccination period)
In Crossover Vaccination period, one dose of intramuscular (deltoid) injection of placebo (0.5 mL) on Day 0 or Day 21

Biological:
• SARS-CoV-2 rS/Matrix-M1 Adjuvant (Booster Vaccination)
In Booster Vaccination period, one dose of intramuscular (deltoid) injection of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Day 0
• SARS-CoV-2 rS/Matrix-M1 Adjuvant (Second Booster Vaccination)
In Second Booster Vaccination period, one dose of intramuscular (deltoid) injection of SARS-CoV-2 rS co-formulated with Matrix-M1 adjuvant (0.5 mL) on Day 0

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Salud Publica (INSP) - Cuernavaca - Centro de Investigacion en Salud Poblacional (CISP) (Adult Site)	Cuernavaca	Morelos
Mexico	PanAmerican Clinical Research Mexico S.A de C.V (Adult Site)	Guadalajara	Jalisco
Mexico	PanAmerican Clinical Research Mexico (Adult Site)	Juriquilla	Queretaro
Mexico	Unidad de Atencion Medica e Investigacion en Salud (UNAMIS) (Adult Site)	Merida	Yucatan
Mexico	CAIMED Investigacion en Salud S.A de C.V (Adult Site)	Mexico City
Mexico	Caimed Investigacion en Salud S.A. de C.V. (Adult Site)	Mexico City
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Adult Site)	Mexico City
Mexico	FAICIC S. DE R.L. DE C.V. (Adult Site)	Veracruz
Puerto Rico	Ponce Medical School Foundation Inc. / CAIMED Cneter (Pediatric & Adult Site)	Ponce
Puerto Rico	University of Puerto Rico Medical Sciences Campus Maternal Infant Studies Center (Adult Site)	San Juan
United States	Synexus Clinical Research, US, Inc. (Adult Site)	Akron	Ohio
United States	Anaheim Clinical Trials (Adult Site)	Anaheim	California
United States	Synexus Clinical Research US, Inc. (Adult Site)	Anderson	South Carolina
United States	VA Ann Arbor Healthcare System (Adult Site)	Ann Arbor	Michigan
United States	Atlanta - Morehouse School of Medicine (Adult Site)	Atlanta	Georgia
United States	Atlanta Center for Medical Research (Adult Site)	Atlanta	Georgia
United States	Emory University Hospital (Adult Site)	Atlanta	Georgia
United States	Synexus Clinical Research US, Inc. (Adult Site)	Atlanta	Georgia
United States	University of Colorado Clinical and Translational Research Centers (Pediatric & Adult Site)	Aurora	Colorado
United States	Benchmark Research (Pediatric & Adult Site)	Austin	Texas
United States	c/o The Pediatric Center of Frederick LLC (Adult & Pediatric Site)	Baltimore	Maryland
United States	Advanced Clinical Research - Rancho Paseo (Pediatric & Adult Site)	Banning	California
United States	Kentucky Pediatric/Adult Research (Pediatric Site)	Bardstown	Kentucky
United States	Meridian Clinical Research Baton Rouge (Pediatric Site)	Baton Rouge	Louisiana
United States	Meridian Clinical Research, LLC (Adult Site)	Baton Rouge	Louisiana
United States	Coast Clinical Research, LLC (Pediatric Site)	Bellflower	California
United States	Meridian Clinical Research (Pediatric Site)	Binghamton	New York
United States	Accel Research Sites (Adult Site)	Birmingham	Alabama
United States	Alabama Clinical Therapeutics, Llc (Pediatric Site)	Birmingham	Alabama
United States	Central Research Associates, Inc (Pediatric Site)	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center (Adult Site)	Boston	Massachusetts
United States	Accellacare of Bristol (Pediatric & Adult Site)	Bristol	Tennessee
United States	Tekton Research, Inc. (Pediatric Site)	Chamblee	Georgia
United States	NC TraCS Institute - CTRC; University of North Carolina at Chapel Hill (Pediatric & Adult Site)	Chapel Hill	North Carolina
United States	Medical University of South Carolina, SCTR Research Nexus (Adult Site)	Charleston	South Carolina
United States	The Charlotte-Mecklenburg Hospital Authority d/b/a Atrium Health (Pediatric & Adult Site)	Charlotte	North Carolina
United States	Pediatric Research of Charlottesville, LLC (Pediatric Site)	Charlottesville	Virginia
United States	WR Clinsearch, LLC (Pediatric & Adult Site)	Chattanooga	Tennessee
United States	MultiCare Institute for Research & Innovation (Adult Site)	Cheney	Washington
United States	Cedar Crosse Research Center (Adult Site)	Chicago	Illinois
United States	Synexus Clinical Research US, Inc (Adult Site)	Chicago	Illinois
United States	Velocity Clinical Research (Pediatric & Adult Site)	Chula Vista	California
United States	Sterling Research Group, Ltd (Pediatric & Adult Site)	Cincinnati	Ohio
United States	Sterling Research Group, Ltd. (Adult Site)	Cincinnati	Ohio
United States	Synexus Clinical Research US, Inc. (Adult Site)	Cincinnati	Ohio
United States	Dr. Shelly David Senders MD Inc. dba Senders Pediatrics (Pediatric Site)	Cleveland	Ohio
United States	Velocity Clinical Research (Pediatric & Adult Site)	Cleveland	Ohio
United States	Lynn Institute of the Rockies (Adult Site)	Colorado Springs	Colorado
United States	The Curators of University of Missouri (Adult Site)	Columbia	Missouri
United States	Aventiv Research Inc (Pediatric Site)	Columbus	Ohio
United States	Columbus Regional Research Institute (Adult Site)	Columbus	Georgia
United States	Stony Brook Responder Vaccine Program (Adult Site)	Commack	New York
United States	University Clinical Research-Deland, LLC dba Accel Research Sites (Pediatric & Adult Site)	DeLand	Florida
United States	Wayne State University/ Children's Hospital of Michigan (Adult Site)	Detroit	Michigan
United States	Premier Health Research Center, Llc (Pediatric Site)	Downey	California
United States	M3-Emerging Medical Research, LLC (Pediatric & Adult Site)	Durham	North Carolina
United States	American Indian Clinical Trials Research Network (Pediatric & Adult Site)	Eagle Butte	South Dakota
United States	Synexus USA (Adult Site)	Evansville	Indiana
United States	Providea Health Partners LLC (Adult Site)	Evergreen Park	Illinois
United States	Carolina Institute for Clinical Research (Adult Site)	Fayetteville	North Carolina
United States	Carolina Institute for Clinical Research (Adult Site)	Fayetteville	North Carolina
United States	Womack Army Medical Center (Adult Site)	Fort Bragg	North Carolina
United States	Benchmark Research (Pediatric & Adult Site)	Fort Worth	Texas
United States	Ventavia Research Group, LLC (Pediatric Site)	Fort Worth	Texas
United States	SIMED Health, LLC / SIMED Research (Adult Site)	Gainesville	Florida
United States	MedPharmics, LLC-Biloxi (Pediatric & Adult Site)	Gulfport	Mississippi
United States	M D Clinical (Adult Site)	Hallandale Beach	Florida
United States	Synexus Clinical Research US, Inc. (Adult Site)	Henderson	Nevada
United States	Baylor College of Medicine (Adult Site)	Houston	Texas
United States	DM Clinical Research - Pediatric Healthcare of NW Houston, P.A. (Pediatric Site)	Houston	Texas
United States	Texas Center for Drug Development, Inc (Pediatric & Adult Site)	Houston	Texas
United States	Ventavia Research Group, LLC (Pediatric Site)	Houston	Texas
United States	The University of Iowa Hospitals & Clinics (Adult Site)	Iowa City	Iowa
United States	Jacksonville Center for Clinical Research (Pediatric & Adult Site)	Jacksonville	Florida
United States	Holston Medical Group (Pediatric Site)	Kingsport	Tennessee
United States	Accellacare US Inc., d/b/a Accellacare of Knoxville (Adult Site)	Knoxville	Tennessee
United States	eStudySite - Corporate Offices (Adult Site)	La Mesa	California
United States	Paradigm Clinical Research Centers, Inc (Pediatric Site)	La Mesa	California
United States	Meridien Research/Accel Research (Pediatric & Adult site)	Lakeland	Florida
United States	Clinical Research Center of Nevada (Pediatric Site)	Las Vegas	Nevada
United States	Clinical Research Consortium (Adult Site)	Las Vegas	Nevada
United States	Wee Care Pediatrics (Pediatric Site)	Layton	Utah
United States	The University Of Texas Medical Branch (Utmb) (Pediatric Site)	League City	Texas
United States	Johnson County Clin-Trials, Inc. (Pediatric & Adult Site)	Lenexa	Kansas
United States	Lynn Institute of the Ozarks (Adult Site)	Little Rock	Arkansas
United States	Preferred Research Partners, Inc. (Adult Site)	Little Rock	Arkansas
United States	WR-PRI, LLC (Adult Site)	Los Alamitos	California
United States	National Research Institute (Pediatric & Adult Site)	Los Angeles	California
United States	Brownsboro Park Pediatrics (Pediatric Site)	Louisville	Kentucky
United States	Centex Studies, Inc (Adult Site)	McAllen	Texas
United States	Velocity Clinical Research (Pediatric & Adult Site)	Medford	Oregon
United States	Clinical Neurosciecne Solutions, Inc. dba CNS Healthcare (Pediatric & Adult Site)	Memphis	Tennessee
United States	Advanced Clinical Research (Pediatric & Adult Site)	Meridian	Idaho
United States	Med Pharmics, LLC (Pediatric & Adult Site)	Metairie	Louisiana
United States	Acevedo Clinical Research Associates (Pediatric Site)	Miami	Florida
United States	Miami Veterans Affairs Medical Center (Adult Site)	Miami	Florida
United States	Suncoast Research Associates, LLC (Adult Site)	Miami	Florida
United States	Suncoast Research Associates, LLC (Adult Site)	Miami	Florida
United States	University of Minnesota (Adult Site)	Minneapolis	Minnesota
United States	Clinical and Translational Research Center at Meharry Medical College (Adult Site)	Nashville	Tennessee
United States	Clinical Research Associates (Pediatric Site)	Nashville	Tennessee
United States	Weill Cornell Chelsea CRS (Adult Site)	New York	New York
United States	Health Research of Hampton Roads, Inc (Pediatric & Adult Site)	Newport News	Virginia
United States	Alliance for Multispecialty Research (AMR) (Pediatric Site)	Newton	Kansas
United States	Meridian Clinical Research (Adult & Pediatric Site)	Norfolk	Nebraska
United States	Coastal Carolina Research Center (Pediatric Site)	North Charleston	South Carolina
United States	Lynn Health Science Institute (Pediatric & Adult Site)	Oklahoma City	Oklahoma
United States	Medical Research International (Adult Site)	Oklahoma City	Oklahoma
United States	Meridian Clinical Research Associates, LLC (Pediatric & Adult Site)	Omaha	Nebraska
United States	University Of Nebraska Medical Center (Pediatric & Adult Site)	Omaha	Nebraska
United States	Orange County Research Institute (Pediatric Site)	Ontario	California
United States	Clinical Neuroscience Solutions Inc (Pediatric & Adult Site)	Orlando	Florida
United States	Headlands Research Orlando (Adult Site)	Orlando	Florida
United States	Foothills Research Center-CCT Research (Pediatric Site)	Phoenix	Arizona
United States	The Pain Center of Arizona (Adult Site)	Phoenix	Arizona
United States	Synexus Clinical Research US, Inc (Adult Site)	Pinellas Park	Florida
United States	Preferred Primary Care Physicians, Inc. (Pediatric Site)	Pittsburgh	Pennsylvania
United States	Research Your Health (Pediatric & Adult site)	Plano	Texas
United States	Empire Clinical Research (Pediatric & Adult Site)	Pomona	California
United States	The Miriam Hospital (TMH) (Adult Site)	Providence	Rhode Island
United States	M3 Wake Research, Inc (Adult Site)	Raleigh	North Carolina
United States	Synexus Clinical Research US, Inc. (Adult Site)	Richfield	Minnesota
United States	Rochester Clinical Research (Pediatric & Adult Site)	Rochester	New York
United States	PMG Research of Rocky Mount, LLC (Adult Site)	Rocky Mount	North Carolina
United States	Benchmark Research (Pediatric & Adult Site)	Sacramento	California
United States	University of California Davis Health (Pediatric & Adult Site)	Sacramento	California
United States	Sundance Clinical Research, LLC (Pediatric & Adult Site)	Saint Louis	Missouri
United States	Wake Forest Health Network - Pediatrics - Ford, Simpson, Lively & Rice (Pediatric Site)	Salem	North Carolina
United States	AES San Antonio (Adult Site)	San Antonio	Texas
United States	Tekton Research, Inc. (Pediatric Site)	San Antonio	Texas
United States	University of Texas Health Science Center San Antonio (Adult Site)	San Antonio	Texas
United States	California Research Foundation (Pediatric & Adult Site)	San Diego	California
United States	University of Washington VTEU (Adult Site)	Seattle	Washington
United States	Willis-Knighton Physician Network (Adult Site)	Shreveport	Louisiana
United States	Meridian Clinical Research (Adult Site)	Sioux City	Iowa
United States	Spartanburg Medical Research (Pediatric Site)	Spartanburg	South Carolina
United States	Asclepes Research Centers (Adult & Pediatric Site)	Spring Hill	Florida
United States	Clinical Research Atlanta (Adult Site)	Stockbridge	Georgia
United States	Wee Care Pediatrics (Pediatric Site)	Syracuse	Utah
United States	Office Of John S. Curran MD (Adult Site)	Tampa	Florida
United States	Tampa Heart & Cardiovascular Center (Adult Site)	Tampa	Florida
United States	Alliance for Multispecialty Research, LLC (Adult Site)	Tempe	Arizona
United States	Synexus Clinical Research US, Inc. (Adult Site)	The Villages	Florida
United States	DM Clinical Research (Pediatric & Adult Site)	Tomball	Texas
United States	Buynak Clinical Research, P.C. (Pediatric & Adult Site)	Valparaiso	Indiana
United States	Synexus Clinical Research US, Inc. (Adult Site)	Vista	California
United States	Omega Medical Research, Providence (Pediatric & Adult Site)	Warwick	Rhode Island
United States	Howard University Hospital Howard/ University College of Medicine (Adult Site)	Washington	District of Columbia
United States	Meridian Clinical Research (Pediatric Site)	Washington	District of Columbia
United States	Advanced Clinical Research (Adult Site)	West Jordan	Utah
United States	Comprehensive Clinical Trials, Llc (Pediatric & Adult site)	West Palm Beach	Florida
United States	AMR Wichita East (Formerly Heartland Research Associates) (Pediatric SIte)	Wichita	Kansas
United States	PMG Research of Wilmington, LLC (Adult Site)	Wilmington	North Carolina
United States	Dignity Health Medical Foundation - Woodland (Adult Site)	Woodland	California

Sponsors (2)

Lead Sponsor	Collaborator
Novavax	Department of Health and Human Services

Countries where clinical trial is conducted

United States,  Mexico,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Booster Amendment: Participants with symptomatic mild, moderate or severe COVID-19	First episode of PCR-positive mild, moderate, or severe COVID-19 occurring = 7 days after the third (booster) vaccine dose.	Day 0 to Day 7
Other	Booster Amendment: Participants with PCR positive moderate-to-severe COVID-19	First episode of PCR-positive moderate-to-severe COVID-19 occurring = 7 days after the third (booster) vaccine dose.	Day 0 to Day 7
Other	Booster Amendment: Participants with PCR positive COVID-19 due to a variant not considered "variant of interest/concern"	First episode of PCR-positive COVID-19 occurring =7 days after the third (booster) vaccine dose and shown by gene sequencing to represent a variant not considered as a "variant of concern/interest" according to the CDC Variants Classification	Day 0 to Day 7
Other	Booster Amendment: Participants with PCR positive COVID-19 due to a 'variant of concern/interest"	First episode of PCR-positive COVID-19 occurring =7 days after the third (booster) vaccine dose, and shown by gene sequencing to represent a "variant of concern/interest" according to the CDC Variants Classification.	Day 0 to Day 7
Other	Booster Amendment: Neutralizing antibody activity expressed as GMT	Neutralizing antibody titers from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMT.	Day 0 to Day 28
Other	Booster Amendment: Neutralizing antibody activity expressed as GMFR	Neutralizing antibody titers from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMFR.	Day 0 to Day 28
Other	Booster Amendment: Serum IgG antibody levels expressed as GMT	Serum levels of IgG to SARS-CoV-2 S protein from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMT.	Day 0 to Day 28
Other	Booster Amendment: Serum IgG antibody levels expressed as GMFR	Serum levels of IgG to SARS-CoV-2 S protein from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMFR.	Day 0 to Day 28
Other	Booster Amendment: hACE2 receptor binding inhibition assay expressed as GMT	hACE2 inhibition titers from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMT.	Day 0 to Day 28
Other	Booster Amendment: hACE2 receptor binding inhibition assay expressed as GMFR	hACE2 inhibition titers from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMFR.	Day 0 to Day 28
Other	Booster Amendment: Incidence and severity of unsolicited AE's	Incidence and severity of unsolicited AEs through 28 days after the third (booster) vaccine dose.	Day 0 to Day 28
Other	Booster Amendment: Incidence and severity of MAAE's, SAE's and AESI's	Incidence and severity of MAAEs attributed to study vaccine, SAEs and AESIs through EoS.	Day 0 to Day 720
Other	Booster Amendment: Description of course, treatment and severity of COVID-19	Description of course, treatment and severity of COVID-19 reported after a PCR-confirmed case occurring =7 days after the third (booster) vaccine dose via the Endpoint Form.	Day 0 to Day 7
Other	Booster Amendment: Reactogenicity Incidence and Severity	Reactogenicity incidence and severity (mild, moderate or severe) recorded by all participants on their electronic patient-reported outcome diary application (eDiary) on days of the third (booster) vaccination and subsequent 6 days.	Day0 to Day 7
Other	Booster Amendment: Deaths Due to Any Cause	Number of participants who died during the study due to any cause.	Day 0 to Day 720
Other	Site Specific Sub Study: Serum IgG to the SARS-CoV-2 spike protein expressed as GMEU	IgG geometric mean ELISA unit concentrations (EU/ml) to the SARS-CoV-2 spike protein at Day 28 following the second booster dose.	Day 28
Other	Site Specific Sub Study: Serum IgG antibody expressed as GMFR	IgG Geometric Mean Fold Rises (GMFR) at Day 28 post second booster dose relative to Day 28 post-first booster dose.	Day 28
Other	Site Specific Sub Study: Serum IgG to the SARS-CoV-2 spike protein expressed as SPR	Proportion of participants who achieve seroresponse (= 4-fold increase from pre-second booster baseline) in IgG ELISA unit concentrations to the SARS-CoV-2 spike protein at Day 28 post second booster dose.	Day 28
Other	Site Specific Sub Study: hACE2 Receptor Binding Inhibition Assay Expressed as GMTs	hACE2 inhibition assay titers (GMTs) at Day 28 post second booster dose.	Day 28
Other	Site Specific Sub Study: hACE2 Receptor Binding Inhibition Assay Expressed as GMFR	hACE2 GMFR at Day 28 post second booster dose relative to Day 28 post-first booster dose.	Day 28
Other	Site Specific Sub Study: hACE2 Receptor Binding Inhibition Assay Expressed as SPR	Proportion of participants who achieve seroresponse (= 4-fold increase from pre-second booster baseline) in hACE2 inhibition assay titers at Day 28 post-second booster dose.Incidence, severity, and duration of solicited adverse events for the 7 days period following the second booster dose.	Day 28
Other	Site Specific Sub Study: Microneutralization assay (MN) titers to the SARS-CoV-2 wild type virus expressed as GMTs	MN50 geometric mean titers to the SARS-CoV-2 wild-type virus at Day 28 post second booster dose.	Day 28
Other	Site Specific Sub Study: Microneutralization assay (MN) titers to the SARS-CoV-2 wild type virus expressed as GMFR	MN50 GMFR at Day 28 post second booster dose relative to Day 28 post-first booster dose.	Day 28
Other	Site Specific Sub Study: Microneutralization assay (MN) titers to the SARS-CoV-2 wild type virus expressed as SPR	Proportion of participants who achieve seroresponse (= 4-fold increase from pre-second booster baseline) in MN50 titers concentrations to the wild-type virus at Day 28 post second booster dose.	Day 28
Primary	Adult Main Study and Pediatric Expansion: Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19)	Number of participants with first occurrence of positive (+) polymerase chain reaction (PCR)-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.	Day 28 to Day 750
Primary	Pediatric Expansion: Reactogenicity Incidence and Severity	Reactogenicity incidence and severity (mild, moderate or severe) recorded by all participants on their electronic patient-reported outcome diary application (eDiary) on days of vaccination and subsequent 6 days (total 7 days after each vaccine injection).	Day 0 to Day 27
Primary	Pediatric Expansion: Incidence and Severity of Medically Attended Adverse Events (MAAEs) Through Day 49	Number of participants with mild, moderate, or severe MAAEs through Day 49 i.e. 28 days after second injection of each set of vaccinations (initial and crossover).	Day 0 to Day 49
Primary	Pediatric Expansion: Incidence and Severity of Unsolicited Adverse Events (AEs) Through Day 49	Number of participants with mild, moderate, or severe AEs through Day 49 i.e. 28 days after second injection of each set of vaccinations (initial and crossover).	Day 0 to Day 49
Primary	Pediatric Expansion: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points	Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through specified time points approximately every 3 and 6 months.	Day 90 to Day 750
Primary	Pediatric Expansion: Incidence and Severity of Serious Adverse Events (SAEs) Through Specified Time Points	Number of participants with mild, moderate, or severe SAEs attributed to study vaccine through specified time points approximately every 3 and 6 months.	Day 90 to Day 750
Primary	Pediatric Expansion: Incidence and Severity of Adverse Events of Special Interest (AESIs) Through Specified Time Points	Number of participants with mild, moderate, or severe AESIs attributed to study vaccine through specified time points approximately every 3 and 6 months.	Day 90 to Day 750
Primary	Pediatric Expansion: Incidence and Severity of SAEs Attributed to Study Vaccine Through Specified Time Points until Month 24	Number of participants with mild, moderate, or severe SAEs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.	Day 90 to Day 750
Primary	Pediatric Expansion: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points until Month 24	Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.	Day 90 to Day 750
Primary	Pediatric Expansion: Incidence and Severity of AESIs Attributed to Study Vaccine Through Specified Time Points until Month 24	Number of participants with mild, moderate, or severe AESIs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.	Day 90 to Day 750
Primary	Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specified Time Points	Number of participants with antibodies to SARS-CoV-2 NP at Day 35 to determine natural infection and to determine the incidence of asymptomatic infection acquired during study follow-up.	Day 35
Primary	Pediatric Expansion: Deaths Due to Any Cause	Number of participants who died during the study due to any cause.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Participants with Symptomatic Moderate or Severe COVID-19	Number of participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with symptomatic moderate or severe COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.	Day 28 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Participants with Any Symptomatic COVID-19	Number of participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with any symptomatic COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.	Day 28 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as Geometric Mean Titers (GMTs)	Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0, 35 and at specified time points through EoS.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as Geometric Mean Fold Rises (GMFRs)	Neutralizing antibody activity as detected by MN as expressed as GMFRs at Days 0, 35 and at specified time points through EoS.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs	Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs at Days 0, 35 and at specified time points through EoS.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Serum IgG Antibody Levels Expressed as GMFRs	Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0, 35 and at specified time points through EoS.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as GMTs	Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMTs at Days 0, 35 and at specified time points through EoS.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs	Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMFRs at Days 0, 35 and at specified time points through EoS.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs at Later Time Points	Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Months 6, 12, 18, and 24.	Day 165 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMFRs at Later Time Points	Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Months 6, 12, 18, and 24.	Day 165 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMTs at Later Time Points	Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMTs at Months 6, 12, 18, and 24.	Day 165 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs at Later Time Points	Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMFRs at Months 6, 12, 18, and 24.	Day 165 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as GMTs at Later Time Points	Neutralizing antibody activity as detected by MN as expressed as GMTs at Months 6, 12, 18, and 24.	Day 165 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as GMFRs at Later Time Points	Neutralizing antibody activity as detected by MN as expressed as GMFRs at Months 6, 12, 18, and 24.	Day 165 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Description of Course, Treatment and Severity of COVID-19	Description of course, treatment and severity of COVID-19 reported after a PCR-confirmed case via the Endpoint Form.	Day 28 to Day 750
Secondary	Adult Main Study: Reactogenicity Incidence and Severity	Reactogenicity incidence and severity (mild, moderate or severe) recorded by all participants on their electronic patient-reported outcome diary application (eDiary) on days of vaccination and subsequent 6 days (total 7 days after each vaccine injection).	Day 0 to Day 27
Secondary	Adult Main Study: Incidence and Severity of Medically Attended Adverse Events (MAAEs) Through Day 49	Number of participants with mild, moderate, or severe MAAEs through Day 49 i.e. 28 days after second injection of each set of vaccinations (initial and crossover).	Day 0 to Day 49
Secondary	Adult Main Study: Incidence and Severity of Unsolicited Adverse Events (AEs) Through Day 49	Number of participants with mild, moderate, or severe AEs through Day 49 i.e. 28 days after second injection of each set of vaccinations (initial and crossover).	Day 0 to Day 49
Secondary	Adult Main Study: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points	Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through specified time points approximately every 3 months.	Day 90 to Day 750
Secondary	Adult Main Study: Incidence and Severity of Serious Adverse Events (SAEs) Attributed to Study Vaccine Through Specified Time Points	Number of participants with mild, moderate, or severe SAEs attributed to study vaccine through specified time points approximately every 3 months.	Day 90 to Day 750
Secondary	Adult Main Study: Incidence and Severity of Adverse Events of Special Interest (AESIs) Attributed to Study Vaccine Through Specified Time Points	Number of participants with mild, moderate, or severe AESIs attributed to study vaccine through specified time points approximately every 3 months.	Day 90 to Day 750
Secondary	Adult Main Study: Incidence and Severity of SAEs Attributed to Study Vaccine Through Specified Time Points until Month 24	Number of participants with mild, moderate, or severe SAEs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.	Day 90 to Day 750
Secondary	Adult Main Study: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points until Month 24	Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.	Day 360 to Day 750
Secondary	Adult Main Study: Incidence and Severity of AESIs Attributed to Study Vaccine Through Specified Time Points until Month 24	Number of participants with mild, moderate, or severe AESIs attributed to study vaccine and AESIs through specified time points until Month 24 or the EoS.	Day 360 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specified Time Points	Number of participants with antibodies to SARS-CoV-2 NP at Days 0 and 35, or at specified time points through EoS to determine natural infection and to determine the incidence of asymptomatic infection acquired during study follow-up.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Any Time Point	Number of participants with antibodies to SARS-CoV-2 NP, regardless of whether the infection was symptomatic.	Day 0 to Day 750
Secondary	Adult Main Study: IgG antibodies to SARS-CoV-2 rS at Day 35 After First Crossover Vaccination	The ratio of geometric mean IgG antibody concentrations will be computed at Day 35 for the new manufacturing process versus the old manufacturing process using the data collected from 300 active vaccine recipients 18 to = 64 years of age enrolled at selected study sites.	Day 35 after the first crossover vaccination
Secondary	Adult Main Study : Deaths Due to Any Cause	Number of participants who died during the study due to any cause.	Day 0 to Day 750
Secondary	Adult Main Study and Pediatric Expansion: Participants with 1st episode of positive Polymerase Chain Reaction (PCR) for Coronavirus Disease 2019 (COVID-19) due to a variant not considered as a "variant of concern/interest"	Number of participants with first episode of PCR-positive COVID-19, as defined under the primary endpoint, shown by gene sequencing to represent a variant not considered as a "variant of concern/interest" according to the CDC Variants Classification.	Day 28 to Day 750