COVID-19Phase 3NCT05875701
Phase 3 Study of Novavax Vaccine(s) as Booster Dose After mRNA Vaccines
A Phase 3 study testing NVX-CoV2373 and SARS-CoV-2 rS antigen/Matrix-M Adjuvant in people with COVID-19, run by Novavax at 5 sites in United States.
Trial summary
This is an open-label Phase 3 study evaluating the immunogenicity and safety of Novavax vaccine(s) with Matrix-M™ adjuvant (ancestral strain NVX-CoV2373 and an alternative strain and/or multivalent Novavax vaccine) as booster doses following a series of primary and booster doses of authorized/approved mRNA vaccines… Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- COVID-19
- What is being tested?
- NVX-CoV2373 and SARS-CoV-2 rS antigen/Matrix-M Adjuvant
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 147 participants
- Where
- 5 sitesUnited States
- Study dates
- 28 Mar 2023to 11 Nov 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- To be included in this study, each individual must satisfy all the following criteria:
- Adults 18 to 49 years (inclusive) of age at the time of vaccination in Study 307 who received two or three doses of mRNA prior to enrollment in Study 307, then one dose of ancestral strain NVX-CoV2373 in Study 307.
- Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
- Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of study (EOS) visit OR agree to consistently use a medically acceptable method of contraception from at least 28 days prior to enrollment and through the EOS visit.
- Is medically stable, as determined by the investigator (based on review of health status, vital signs [to include body temperature], medical history, and physical examination [to include body weight]). Vital signs must be within medically acceptable ranges prior to the study vaccination.
- Agree to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. Note: For participants who become hospitalized with COVID-19, participation in investigational treatment studies is permitted.
- Documented receipt of COVID-19 vaccines. The most recent dose of NVX-CoV2373 must have been administered at least 180 days prior to vaccination in this study.
Who cannot join
- Participants meeting any of the following criteria will be excluded from the study.
- Received any additional COVID-19 vaccine booster after the Day 1 dose of NVX-CoV2373 administered during participation in Study 307.
- History of laboratory-confirmed (by polymerase chain reaction [PCR] or rapid antigen test) COVID-19 infection ≤ 4 months prior to Day 1.
- Current participation in research involving receipt of an investigational product (drug/biologic/device).
- Any known allergies or history of anaphylaxis to the active substance or any of the other ingredients contained in the investigational product.
- Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) or therapy that causes clinically significant immunosuppression.
Show all 14Show fewer
- Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccine which may be received > 4 days prior to study vaccine, or rabies vaccine, which may be received at any time if medically indicated.
- Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to study vaccination, except for rabies immunoglobulin which may be given if medically indicated.
- Active cancer (malignancy) on chemotherapy that is judged to cause significant immunocompromise within 1 year prior to first study vaccination (with the exception of malignancy cured via excision, at the discretion of the investigator).
- Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the EOS visit.
- Suspected or known history of alcohol abuse or drug addiction within 3 months prior to the study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
- Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
- Study team member or immediate family member of any study team member (inclusive of Sponsor, clinical research organization [CRO], and study site personnel involved in the conduct or planning of the study).
- Participants with a history of myocarditis or pericarditis.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Benchmark Research
Austin, Texas, 78705
Tekton Research
Austin, Texas, 78747
Benchmark Research
Fort Worth, Texas, 76135
Research Your Health
Plano, Texas, 75093
Tekton Research
San Antonio, Texas, 78229
About this study
Official title: A Phase 3 Study to Evaluate the Immunogenicity and Safety of Novavax COVID-19 Vaccine(s) as Second or Subsequent Booster After mRNA Vaccines in Individuals 18 to 49 Years of Age
This is an open-label Phase 3 study evaluating the immunogenicity and safety of Novavax vaccine(s) with Matrix-M™ adjuvant (ancestral strain NVX-CoV2373 and an alternative strain and/or multivalent Novavax vaccine) as booster doses following a series of primary and booster doses of authorized/approved mRNA vaccines followed by a single booster dose of NVX-CoV2373 in the Novavax 2019nCoV-307 study (NCT05463068).
Read the detailed description
This Phase 3 study investigates the immunogenicity and safety of Novavax's NVX-CoV2373 vaccine (including its Matrix-M adjuvant) as an additional booster dose for adults aged 18 to 49. Participants must have already received both their primary mRNA vaccine series and at least one booster dose of the same type. All participants were previously enrolled in Study 307 (NCT05463068), where they received either their primary mRNA vaccines with or without an additional mRNA booster, followed by a single NVX-CoV2373 booster.
The study involves up to 300 volunteers who will receive a single dose of the Novavax vaccine (5 micrograms of recombinant spike protein antigen and 50 micrograms of Matrix-M adjuvant) on Day 1.
- Conditions
- COVID-19
- Being tested
- NVX-CoV2373, SARS-CoV-2 rS antigen/Matrix-M Adjuvant
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NVX-CoV2373Biological
Also called SARS-CoV-2 rS/Matrix-M Adjuvant
1 intramuscular (IM) injection of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5 mL) given on Day 1
SARS-CoV-2 rS antigen/Matrix-M AdjuvantBiological
Also called Updated Novavax COVID-19 vaccine
1 intramuscular (IM) injection of 5 µg SARS-CoV-2 rS antigen+ 50 µg Matrix-M1 adjuvant (0.5 mL) given on Day 1
| Study group | Role | What they receive |
|---|---|---|
| NVX CoV2373 (Ancestral strain) | Experimental | 1dose of NVX-COV2373 on Day 1 Receives: Biological: NVX-CoV2373 |
| Updated COVID-19 Vaccine | Experimental | 1dose of updated COVID-19 vaccine on Day 1 Receives: Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neutralizing Antibody (Nab) for SARS-CoV-2 Wildtype Virus (Wuhan) Responses Expressed as Geometric Mean Titers (GMT)
Neutralizing Antibody responses to ancestral strain Novavax vaccine (NVX-CoV2373) for the participants in the ancestral strain NVX-2373 group and NVX-CoV2540 group at Day 29
Measured: Day 28
Secondary outcomes (10)
Neutralizing Antibody (Nab) for SARS-CoV-2 Wildtype Virus (Wuhan) Responses Expressed as Seroconversion Rate (SCR)
Neutralizing Antibody responses to ancestral strain Novavax vaccine (NVX-CoV2373) for the participants in the ancestral strain NVX-2373 group and NVX-CoV2540 group at Day 28
Measured: Day 28
Serum Immunoglobulin G (IgG) ELISA Units to SARS-CoV-2 Spike Protein (Wuhan) Expressed as Geometric Mean ELISA Unit (GMEU)
Serum Immunoglobulin G (IgG) ELISA Units to SARS-CoV-2 Spike Protein (Wuhan) in Ancestral strain NVX-CoV2373 group and updated NVX Vaccine group at Day 28
Measured: Day 28
Serum Immunoglobulin G (IgG) ELISA Units to SARS-CoV-2 Spike Protein (Wuhan) Expressed as SCR
Serum Immunoglobulin G (IgG) ELISA Units to SARS-CoV-2 Spike Protein (Wuhan) in Ancestral strain NVX-CoV2373 group and updated NVX Vaccine group at Day 28
Measured: Day 28
Neutralizing Antibody Responses (Post-Booster) Expressed as GMT
Post Booster Neutralizing Antibody responses GMTs compared with post-first booster results from Study 307
Measured: Day 0 and Day 28 of Study 307 and Study 312 (approximately 1 year from Day 0 of Study 307 and Day 0 of Study 312)
Serum IgG Antibody Levels (Post-Booster) Expressed as GMEU
Post Booster Serum IgG antibody levels expressed GMEUs compared with post-first booster results from Study 307
Measured: Day 0 and Day 28 of Study 307 and Study 312 (approximately 1 year from Day 0 of Study 307 and Day 0 of Study 312)
Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as SCR
hACE2 Receptor Binding Inhibition Assay the SARS-CoV-2 ancestral strain spike protein expressed as SCR at Day 28
Measured: Day 28
Number of Participants Reported Solicited Local and Systemic Adverse Events (AEs)
Number of participants reported Solicited Local and Systemic Adverse Events (AEs) in the 7 days following study vaccination.
Measured: Day 7
Number of Participants Reported With Medically Attended Adverse Events (MAAEs)
Number of participants reported with Medically Attended Adverse Events (MAAEs) through Day 180 after the vaccine dose.
Measured: Day 180
Number of Participants Reported With Serious Adverse Events (SAEs)
Number of participants reported with Serious Adverse Events (SAEs) through Day 180 after the vaccine dose
Measured: Day 1 to Day 180
Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as SCR
hACE2 Receptor Binding Inhibition Assay to the NVX-CoV2540(Updated COVID-19 Vaccine) expressed as SCR at Day 28
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2023
- Study start28 Mar 2023
- Primary completion11 Nov 2023
- Study completion11 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novavax
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Development, Study director, Novavax, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05875701
- Sponsor's protocol ID
- 2019nCoV-312
- Status last verified
- Jun 2025
- First submitted
- 16 May 2023
- Last updated
- 26 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Study to Evaluate the Immunogenicity and Safety of Novavax COVID-19 Vaccine(s) as Second or Subsequent Booster After mRNA Vaccines in Individuals 18 to 49 Years of Age
- ClinicalTrials.gov ID
- NCT05875701
- Acronym / sponsor ID
- 2019nCoV-312
- Conditions
- COVID-19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- NovavaxIndustry (pharma, biotech, devices)
- Study start
- 28 Mar 2023 (actual)
- Primary completion
- 11 Nov 2023 (actual)
- Study completion
- 11 Nov 2023 (actual)
- First posted
- 25 May 2023 (actual)
- Results
- Posted 26 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label Phase 3 study evaluating the immunogenicity and safety of Novavax vaccine(s) with Matrix-M™ adjuvant (ancestral strain NVX-CoV2373 and an alternative strain and/or multivalent Novavax vaccine) as booster doses following a series of primary and booster doses of authorized/approved mRNA vaccines followed by a single booster dose of NVX-CoV2373 in the Novavax 2019nCoV-307 study (NCT05463068).
Detailed description
This Phase 3 study investigates the immunogenicity and safety of Novavax's NVX-CoV2373 vaccine (including its Matrix-M adjuvant) as an additional booster dose for adults aged 18 to 49. Participants must have already received both their primary mRNA vaccine series and at least one booster dose of the same type. All participants were previously enrolled in Study 307 (NCT05463068), where they received either their primary mRNA vaccines with or without an additional mRNA booster, followed by a single NVX-CoV2373 booster.
The study involves up to 300 volunteers who will receive a single dose of the Novavax vaccine (5 micrograms of recombinant spike protein antigen and 50 micrograms of Matrix-M adjuvant) on Day 1.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NVX CoV2373 (Ancestral strain) | Experimental | Biological: NVX-CoV23731dose of NVX-COV2373 on Day 1 |
| Updated COVID-19 Vaccine | Experimental | Biological: SARS-CoV-2 rS antigen/Matrix-M Adjuvant1dose of updated COVID-19 vaccine on Day 1 |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Adults 18 to 49 years (inclusive) of age at the time of vaccination in Study 307 who received two or three doses of mRNA prior to enrollment in Study 307, then one dose of ancestral strain NVX-CoV2373 in Study 307.
- Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
- Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea at least 12 consecutive months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of study (EOS) visit OR agree to consistently use a medically acceptable method of contraception from at least 28 days prior to enrollment and through the EOS visit.
- Is medically stable, as determined by the investigator (based on review of health status, vital signs [to include body temperature], medical history, and physical examination [to include body weight]). Vital signs must be within medically acceptable ranges prior to the study vaccination.
- Agree to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. Note: For participants who become hospitalized with COVID-19, participation in investigational treatment studies is permitted.
Key exclusion criteria (14 listed)
- Participants meeting any of the following criteria will be excluded from the study.
- Received any additional COVID-19 vaccine booster after the Day 1 dose of NVX-CoV2373 administered during participation in Study 307.
- History of laboratory-confirmed (by polymerase chain reaction [PCR] or rapid antigen test) COVID-19 infection ≤ 4 months prior to Day 1.
- Current participation in research involving receipt of an investigational product (drug/biologic/device).
- Any known allergies or history of anaphylaxis to the active substance or any of the other ingredients contained in the investigational product.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NVX-CoV2373Also: SARS-CoV-2 rS/Matrix-M Adjuvant1 intramuscular (IM) injection of 5 µg SARS-CoV-2 rS + 50 µg Matrix-M1 adjuvant (0.5 mL) given on Day 1 | Biological | NVX CoV2373 (Ancestral strain) |
| SARS-CoV-2 rS antigen/Matrix-M AdjuvantAlso: Updated Novavax COVID-19 vaccine1 intramuscular (IM) injection of 5 µg SARS-CoV-2 rS antigen+ 50 µg Matrix-M1 adjuvant (0.5 mL) given on Day 1 | Biological | Updated COVID-19 Vaccine |
Primary outcome
Neutralizing Antibody (Nab) for SARS-CoV-2 Wildtype Virus (Wuhan) Responses Expressed as Geometric Mean Titers (GMT)
Time frame: Day 28
Neutralizing Antibody responses to ancestral strain Novavax vaccine (NVX-CoV2373) for the participants in the ancestral strain NVX-2373 group and NVX-CoV2540 group at Day 29
10 secondary outcomes
Neutralizing Antibody (Nab) for SARS-CoV-2 Wildtype Virus (Wuhan) Responses Expressed as Seroconversion Rate (SCR)
Time frame: Day 28
Serum Immunoglobulin G (IgG) ELISA Units to SARS-CoV-2 Spike Protein (Wuhan) Expressed as Geometric Mean ELISA Unit (GMEU)
Time frame: Day 28
Serum Immunoglobulin G (IgG) ELISA Units to SARS-CoV-2 Spike Protein (Wuhan) Expressed as SCR
Time frame: Day 28
Neutralizing Antibody Responses (Post-Booster) Expressed as GMT
Time frame: Day 0 and Day 28 of Study 307 and Study 312 (approximately 1 year from Day 0 of Study 307 and Day 0 of Study 312)
Serum IgG Antibody Levels (Post-Booster) Expressed as GMEU
Time frame: Day 0 and Day 28 of Study 307 and Study 312 (approximately 1 year from Day 0 of Study 307 and Day 0 of Study 312)
Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as SCR
Time frame: Day 28
Number of Participants Reported Solicited Local and Systemic Adverse Events (AEs)
Time frame: Day 7
Number of Participants Reported With Medically Attended Adverse Events (MAAEs)
Time frame: Day 180
Number of Participants Reported With Serious Adverse Events (SAEs)
Time frame: Day 1 to Day 180
Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as SCR
Time frame: Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Development study director
Novavax, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NVX-CoV2373 and SARS-CoV-2 rS antigen/Matrix-M Adjuvant in people with COVID-19, run by Novavax at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neutralizing Antibody (Nab) for SARS-CoV-2 Wildtype Virus (Wuhan) Responses Expressed as Geometric Mean Titers (GMT) (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025; AzTrials last refreshed its copy on 7 Nov 2026.