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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04611802
Recruitment Status : Active, not recruiting
First Posted : November 2, 2020
Last Update Posted : August 5, 2022
Sponsor:
Collaborator:
Department of Health and Human Services
Information provided by (Responsible Party):
Novavax

Brief 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 previously fully vaccinated and subsequently boosted with a third dose (first booster)

Condition or disease Intervention/treatment Phase
SARS-CoV Infection Covid19 Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Initial Vaccination Period) Other: Placebo (Initial Vaccination Period) Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Crossover Vaccination period) Other: Placebo (Crossover Vaccination period) Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Booster Vaccination) Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant (Second Booster Vaccination) Phase 3

Detailed 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 a booster dose in the Booster Amendment of the study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33000 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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)
Actual Study Start Date : December 27, 2020
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023


Arm Intervention/treatment
Experimental: 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 in Initial Vaccination Period. One dose of 5 μg SARS-CoV-2 rS + 50 μg Matrix-M1 adjuvant (co-formulated) on Day 0 or Day 21 in Crossover Vaccination Period. One dose of 5 μg SARS-CoV-2 rS + 50 μg Matrix-M1 adjuvant (co-formulated) on Day 0 Booster Vaccination Period.One dose of 5 μg SARS-CoV-2 rS + 50 μg Matrix-M1 adjuvant (co-formulated) on Day 0 Second Booster Vaccination Period.
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 Name: NVX-CoV2373

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 Name: NVX-CoV2373

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
Other Name: NVX-CoV2373

Biological: 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
Other Name: NVX-CoV2373

Placebo Comparator: Placebo
2 doses of Placebo (Saline), 1 dose each on Days 0 and 21. One dose of Placebo (Saline) on Day 0 or Day 21 in Crossover 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.
Other Name: Sodium chloride 0.9% (BP, sterile)

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
Other Name: Sodium chloride 0.9% (BP, sterile)




Primary Outcome Measures :
  1. Adult Main Study and Pediatric Expansion: Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19) [ Time Frame: Day 28 to Day 750 ]
    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.

  2. Pediatric Expansion: Reactogenicity Incidence and Severity [ Time Frame: Day 0 to Day 27 ]
    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).

  3. Pediatric Expansion: Incidence and Severity of Medically Attended Adverse Events (MAAEs) Through Day 49 [ Time Frame: Day 0 to 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).

  4. Pediatric Expansion: Incidence and Severity of Unsolicited Adverse Events (AEs) Through Day 49 [ Time Frame: Day 0 to 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).

  5. Pediatric Expansion: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points [ Time Frame: Day 90 to Day 750 ]
    Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through specified time points approximately every 3 and 6 months.

  6. Pediatric Expansion: Incidence and Severity of Serious Adverse Events (SAEs) Through Specified Time Points [ Time Frame: Day 90 to Day 750 ]
    Number of participants with mild, moderate, or severe SAEs attributed to study vaccine through specified time points approximately every 3 and 6 months.

  7. Pediatric Expansion: Incidence and Severity of Adverse Events of Special Interest (AESIs) Through Specified Time Points [ Time Frame: Day 90 to Day 750 ]
    Number of participants with mild, moderate, or severe AESIs attributed to study vaccine through specified time points approximately every 3 and 6 months.

  8. Pediatric Expansion: Incidence and Severity of SAEs Attributed to Study Vaccine Through Specified Time Points until Month 24 [ Time Frame: Day 90 to Day 750 ]
    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.

  9. Pediatric Expansion: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points until Month 24 [ Time Frame: Day 90 to Day 750 ]
    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.

  10. Pediatric Expansion: Incidence and Severity of AESIs Attributed to Study Vaccine Through Specified Time Points until Month 24 [ Time Frame: Day 90 to Day 750 ]
    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.

  11. Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specified Time Points [ Time Frame: Day 35 ]
    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.

  12. Pediatric Expansion: Deaths Due to Any Cause [ Time Frame: Day 0 to Day 750 ]
    Number of participants who died during the study due to any cause.


Secondary Outcome Measures :
  1. Adult Main Study and Pediatric Expansion: Participants with Symptomatic Moderate or Severe COVID-19 [ Time Frame: Day 28 to Day 750 ]
    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.

  2. Adult Main Study and Pediatric Expansion: Participants with Any Symptomatic COVID-19 [ Time Frame: Day 28 to Day 750 ]
    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.

  3. Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as Geometric Mean Titers (GMTs) [ Time Frame: Day 0 to Day 750 ]
    Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0, 35 and at specified time points through EoS.

  4. Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as Geometric Mean Fold Rises (GMFRs) [ Time Frame: Day 0 to Day 750 ]
    Neutralizing antibody activity as detected by MN as expressed as GMFRs at Days 0, 35 and at specified time points through EoS.

  5. Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs [ Time Frame: Day 0 to Day 750 ]
    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.

  6. Adult Main Study and Pediatric Expansion: Serum IgG Antibody Levels Expressed as GMFRs [ Time Frame: Day 0 to Day 750 ]
    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.

  7. Adult Main Study and Pediatric Expansion: Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as GMTs [ Time Frame: Day 0 to Day 750 ]
    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.

  8. Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs [ Time Frame: Day 0 to Day 750 ]
    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.

  9. Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs at Later Time Points [ Time Frame: Day 165 to Day 750 ]
    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.

  10. Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMFRs at Later Time Points [ Time Frame: Day 165 to Day 750 ]
    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.

  11. Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMTs at Later Time Points [ Time Frame: Day 165 to Day 750 ]
    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.

  12. Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs at Later Time Points [ Time Frame: Day 165 to Day 750 ]
    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.

  13. Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as GMTs at Later Time Points [ Time Frame: Day 165 to Day 750 ]
    Neutralizing antibody activity as detected by MN as expressed as GMTs at Months 6, 12, 18, and 24.

  14. Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as GMFRs at Later Time Points [ Time Frame: Day 165 to Day 750 ]
    Neutralizing antibody activity as detected by MN as expressed as GMFRs at Months 6, 12, 18, and 24.

  15. Adult Main Study and Pediatric Expansion: Description of Course, Treatment and Severity of COVID-19 [ Time Frame: Day 28 to Day 750 ]
    Description of course, treatment and severity of COVID-19 reported after a PCR-confirmed case via the Endpoint Form.

  16. Adult Main Study: Reactogenicity Incidence and Severity [ Time Frame: Day 0 to Day 27 ]
    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).

  17. Adult Main Study: Incidence and Severity of Medically Attended Adverse Events (MAAEs) Through Day 49 [ Time Frame: Day 0 to 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).

  18. Adult Main Study: Incidence and Severity of Unsolicited Adverse Events (AEs) Through Day 49 [ Time Frame: Day 0 to 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).

  19. Adult Main Study: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points [ Time Frame: Day 90 to Day 750 ]
    Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through specified time points approximately every 3 months.

  20. Adult Main Study: Incidence and Severity of Serious Adverse Events (SAEs) Attributed to Study Vaccine Through Specified Time Points [ Time Frame: Day 90 to Day 750 ]
    Number of participants with mild, moderate, or severe SAEs attributed to study vaccine through specified time points approximately every 3 months.

  21. Adult Main Study: Incidence and Severity of Adverse Events of Special Interest (AESIs) Attributed to Study Vaccine Through Specified Time Points [ Time Frame: Day 90 to Day 750 ]
    Number of participants with mild, moderate, or severe AESIs attributed to study vaccine through specified time points approximately every 3 months.

  22. Adult Main Study: Incidence and Severity of SAEs Attributed to Study Vaccine Through Specified Time Points until Month 24 [ Time Frame: Day 90 to Day 750 ]
    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.

  23. Adult Main Study: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Specified Time Points until Month 24 [ Time Frame: Day 360 to Day 750 ]
    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.

  24. Adult Main Study: Incidence and Severity of AESIs Attributed to Study Vaccine Through Specified Time Points until Month 24 [ Time Frame: Day 360 to Day 750 ]
    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.

  25. Adult Main Study and Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specified Time Points [ Time Frame: Day 0 to Day 750 ]
    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.

  26. Adult Main Study and Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Any Time Point [ Time Frame: Day 0 to Day 750 ]
    Number of participants with antibodies to SARS-CoV-2 NP, regardless of whether the infection was symptomatic.

  27. Adult Main Study: IgG antibodies to SARS-CoV-2 rS at Day 35 After First Crossover Vaccination [ Time Frame: Day 35 after the 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.

  28. Adult Main Study : Deaths Due to Any Cause [ Time Frame: Day 0 to Day 750 ]
    Number of participants who died during the study due to any cause.

  29. 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" [ Time Frame: Day 28 to Day 750 ]
    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.


Other Outcome Measures:
  1. Booster Amendment: Participants with symptomatic mild, moderate or severe COVID-19 [ Time Frame: Day 0 to Day 7 ]
    First episode of PCR-positive mild, moderate, or severe COVID-19 occurring ≥ 7 days after the third (booster) vaccine dose.

  2. Booster Amendment: Participants with PCR positive moderate-to-severe COVID-19 [ Time Frame: Day 0 to Day 7 ]
    First episode of PCR-positive moderate-to-severe COVID-19 occurring ≥ 7 days after the third (booster) vaccine dose.

  3. Booster Amendment: Participants with PCR positive COVID-19 due to a variant not considered "variant of interest/concern" [ Time Frame: Day 0 to Day 7 ]
    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

  4. Booster Amendment: Participants with PCR positive COVID-19 due to a 'variant of concern/interest" [ Time Frame: Day 0 to Day 7 ]
    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.

  5. Booster Amendment: Neutralizing antibody activity expressed as GMT [ Time Frame: Day 0 to Day 28 ]
    Neutralizing antibody titers from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMT.

  6. Booster Amendment: Neutralizing antibody activity expressed as GMFR [ Time Frame: Day 0 to Day 28 ]
    Neutralizing antibody titers from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMFR.

  7. Booster Amendment: Serum IgG antibody levels expressed as GMT [ Time Frame: Day 0 to Day 28 ]
    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.

  8. Booster Amendment: Serum IgG antibody levels expressed as GMFR [ Time Frame: Day 0 to Day 28 ]
    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.

  9. Booster Amendment: hACE2 receptor binding inhibition assay expressed as GMT [ Time Frame: Day 0 to Day 28 ]
    hACE2 inhibition titers from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMT.

  10. Booster Amendment: hACE2 receptor binding inhibition assay expressed as GMFR [ Time Frame: Day 0 to Day 28 ]
    hACE2 inhibition titers from Immunogenicity Population immediately prior and at 28 days after administration of the third (booster) vaccine dose expressed as GMFR.

  11. Booster Amendment: Incidence and severity of unsolicited AE's [ Time Frame: Day 0 to Day 28 ]
    Incidence and severity of unsolicited AEs through 28 days after the third (booster) vaccine dose.

  12. Booster Amendment: Incidence and severity of MAAE's, SAE's and AESI's [ Time Frame: Day 0 to Day 720 ]
    Incidence and severity of MAAEs attributed to study vaccine, SAEs and AESIs through EoS.

  13. Booster Amendment: Description of course, treatment and severity of COVID-19 [ Time Frame: Day 0 to Day 7 ]
    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.

  14. Booster Amendment: Reactogenicity Incidence and Severity [ Time Frame: Day0 to Day 7 ]
    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.

  15. Booster Amendment: Deaths Due to Any Cause [ Time Frame: Day 0 to Day 720 ]
    Number of participants who died during the study due to any cause.

  16. Site Specific Sub Study: Serum IgG to the SARS-CoV-2 spike protein expressed as GMEU [ Time Frame: Day 28 ]
    IgG geometric mean ELISA unit concentrations (EU/ml) to the SARS-CoV-2 spike protein at Day 28 following the second booster dose.

  17. Site Specific Sub Study: Serum IgG antibody expressed as GMFR [ Time Frame: Day 28 ]
    IgG Geometric Mean Fold Rises (GMFR) at Day 28 post second booster dose relative to Day 28 post-first booster dose.

  18. Site Specific Sub Study: Serum IgG to the SARS-CoV-2 spike protein expressed as SCR [ Time Frame: Day 28 ]
    Proportion of participants who achieve seroconversion (≥ 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.

  19. Site Specific Sub Study: hACE2 Receptor Binding Inhibition Assay Expressed as GMTs [ Time Frame: Day 28 ]
    hACE2 inhibition assay titers (GMTs) at Day 28 post second booster dose.

  20. Site Specific Sub Study: hACE2 Receptor Binding Inhibition Assay Expressed as GMFR [ Time Frame: Day 28 ]
    hACE2 GMFR at Day 28 post second booster dose relative to Day 28 post-first booster dose.

  21. Site Specific Sub Study: hACE2 Receptor Binding Inhibition Assay Expressed as SCR [ Time Frame: Day 28 ]
    Proportion of participants who achieve seroconversion (≥ 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.

  22. Site Specific Sub Study: Microneutralization assay (MN) titers to the SARS-CoV-2 wild type virus expressed as GMTs [ Time Frame: Day 28 ]
    MN50 geometric mean titers to the SARS-CoV-2 wild-type virus at Day 28 post second booster dose.

  23. Site Specific Sub Study: Microneutralization assay (MN) titers to the SARS-CoV-2 wild type virus expressed as GMFR [ Time Frame: Day 28 ]
    MN50 GMFR at Day 28 post second booster dose relative to Day 28 post-first booster dose.

  24. Site Specific Sub Study: Microneutralization assay (MN) titers to the SARS-CoV-2 wild type virus expressed as SCR [ Time Frame: Day 28 ]
    Proportion of participants who achieve seroconversion (≥ 4-fold increase from pre-second booster baseline) in MN50 titers concentrations to the wild-type virus at Day 28 post second booster dose.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

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 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 pediatric 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 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04611802


Locations
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Sponsors and Collaborators
Novavax
Department of Health and Human Services
Investigators
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Study Director: Clinical Development Novavax, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novavax
ClinicalTrials.gov Identifier: NCT04611802    
Other Study ID Numbers: 2019nCoV-301
First Posted: November 2, 2020    Key Record Dates
Last Update Posted: August 5, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novavax:
Coronavirus
Prevent-19
Booster
Additional relevant MeSH terms:
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COVID-19
Severe Acute Respiratory Syndrome
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases