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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 : December 1, 2021
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 ≥ 18 years of age (Adult Main Study) and a Pediatric Expansion.

In the Adult Main Study, participants will be stratified by age group, and enrollment will occur concurrently within the 2 age strata, 18 to ≤ 64 years and ≥ 65 years.

In the Pediatric Expansion, adolescent participants 12 to < 18 years of age will be enrolled without further stratification.


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) Phase 3

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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

Resource links provided by the National Library of Medicine


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.
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

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 Month 12 [ Time Frame: Day 0 to Day 375 ]
    Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through Month 12.

  6. Pediatric Expansion: Incidence and Severity of Serious Adverse Events (SAEs) Through Month 12 [ Time Frame: Day 0 to Day 375 ]
    Number of participants with mild, moderate, or severe SAEs through Month 12.

  7. Pediatric Expansion: Incidence and Severity of Adverse Events of Special Interest (AESIs) Through Month 12 [ Time Frame: Day 0 to Day 375 ]
    Number of participants with mild, moderate, or severe AESIs through Month 12.

  8. Pediatric Expansion: Incidence and Severity of SAEs from Month 12 to Month 24 [ Time Frame: Day 360 to Day 750 ]
    Number of participants with mild, moderate, or severe SAEs from Month 12 to Month 24.

  9. Pediatric Expansion: Incidence and Severity of MAAEs Attributed to Study Vaccine from Month 12 to Month 24 [ Time Frame: Day 360 to Day 750 ]
    Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine from Month 12 to Month 24.

  10. Pediatric Expansion: Incidence and Severity of AESIs from Month 12 to Month 24 [ Time Frame: Day 360 to Day 750 ]
    Number of participants with mild, moderate, or severe AESIs attributed to study vaccine from Month 12 to Month 24.

  11. Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specific Time Points [ Time Frame: Day 0 to Day 750 ]
    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 105 ]
    Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0, 35 and Month 3.

  4. Adult Main Study and Pediatric Expansion: Neutralizing Antibody Activity Expressed as Geometric Mean Fold Rises (GMFRs) [ Time Frame: Day 0 to Day 105 ]
    Neutralizing antibody activity as detected by MN as expressed as GMFRs at Days 0, 35 and Month 3.

  5. Adult Main Study and Pediatric Expansion: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs [ Time Frame: Day 0 to Day 105 ]
    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 Month 3.

  6. Adult Main Study and Pediatric Expansion: Serum IgG Antibody Levels Expressed as GMFRs [ Time Frame: Day 0 to Day 105 ]
    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 Month 3.

  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 105 ]
    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 Month 3.

  8. Adult Main Study and Pediatric Expansion: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs [ Time Frame: Day 0 to Day 105 ]
    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 Month 3.

  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 Month 12 [ Time Frame: Day 0 to Day 375 ]
    Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through Month 12.

  20. Adult Main Study: Incidence and Severity of Serious Adverse Events (SAEs) Through Month 12 [ Time Frame: Day 0 to Day 375 ]
    Number of participants with mild, moderate, or severe SAEs through Month 12.

  21. Adult Main Study: Incidence and Severity of Adverse Events of Special Interest (AESIs) Through Month 12 [ Time Frame: Day 0 to Day 375 ]
    Number of participants with mild, moderate, or severe AESIs through Month 12.

  22. Adult Main Study: Incidence and Severity of SAEs from Month 12 to Month 24 [ Time Frame: Day 360 to Day 750 ]
    Number of participants with mild, moderate, or severe SAEs from Month 12 to Month 24.

  23. Adult Main Study: Incidence and Severity of MAAEs Attributed to Study Vaccine from Month 12 to Month 24 [ Time Frame: Day 360 to Day 750 ]
    Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine from Month 12 to Month 24.

  24. Adult Main Study: Incidence and Severity of AESIs from Month 12 to Month 24 [ Time Frame: Day 360 to Day 750 ]
    Number of participants with mild, moderate, or severe AESIs attributed to study vaccine from Month 12 to Month 24.

  25. Adult Main Study and Pediatric Expansion: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specific 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 Months 3, 6, 12, 18 and 24 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.



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.


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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 Main 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 [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 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.

Pediatric Expansion:

  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

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 a diagnosis of a new condition.
  2. Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to the first study vaccination.
  3. History of a previous laboratory-confirmed diagnosis of SARS-CoV-2 infection or COVID-19.
  4. Received influenza vaccination or any other adult vaccine within 4 days prior to or within 7 days after either study vaccination. Received any vaccine within 4 days prior to first study vaccination or planned receipt of any vaccine before Day 49 (ie, 28 days after second vaccination).
  5. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
  6. Chronic administration (defined as > 14 continuous days) of immunosuppressants, systemic glucocorticoids, or other immune-modifying drugs causing clinically significant immunocompromise, within 90 days prior to first study vaccination.
  7. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination.
  8. Active cancer (malignancy) on therapy 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 Adult Main Study with 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.

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
Show Show 156 study locations
Sponsors and Collaborators
Novavax
Department of Health and Human Services
Investigators
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Study Director: Clinical Development Novavax, Inc.
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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: December 1, 2021
Last Verified: November 2021
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
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
Vaccines
Immunologic Factors
Physiological Effects of Drugs