A Strain Change Study for SARS-CoV-2 rS Vaccines (COVID-19)

A Phase 3 Open-Label, Single-Arm Study to Evaluate the Safety and Immunogenicity of a JN.1 Subvariant SARS CoV-2 rS Vaccine

The present study aims to investigate the safety and immunogenicity of the Novavax JN.1 subvariant vaccine SARS-CoV-2 rS adjuvanted with Matrix-M (NVX CoV2705) in previously vaccinated adults. A descriptive comparison will be made with participants who received the prior authorized vaccine NVX-CoV2601 in an earlier study (2019nCoV-313).

Study Overview

• Status: Completed
• Conditions: Severe Acute Respiratory Syndrome Coronavirus 2 Infection
• Intervention / Treatment: Biological: NVX-CoV2705 Vaccine

Detailed Description

This is a Phase 3, open-label, single arm study to evaluate the safety and immunogenicity of a single dose of a JN.1 subvariant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant (r) spike (S) protein nanoparticle vaccine (SARS-CoV-2 rS) adjuvanted with Matrix-M™ (NVX CoV2705) in previously vaccinated adults.

Approximately 60 participants will be enrolled to receive a single dose of NVX CoV2705 on Day 0 and remain on study for immunogenicity until Day 28 and safety data collection up to 180 days post-vaccination.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85044
      • Foothills Research Center - CCT Research
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adults ≥ 18 years of age at time of study vaccination.
2. Previously vaccinated with ≥ 3 doses of an authorized/approved COVID-19 vaccine with the last dose administered ≥ 6 months prior to study vaccination.
3. Willing and able to give informed consent prior to study enrollment and to comply with study procedures.

4. Female 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 ≥ 12 consecutive months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of the study OR agree to consistently use a medically acceptable method of contraception listed below from ≥ 28 days prior to enrollment and through the end of the study.

   1. Condoms (male or female) with spermicide (if acceptable in country)
   2. Diaphragm with spermicide
   3. Cervical cap with spermicide
   4. Intrauterine device
   5. Oral or patch contraceptives
   6. Norplant®, Depo-Provera®, or other in country regulatory approved contraceptive method that is designed to protect against pregnancy
   7. Abstinence, as a form of contraception, is acceptable if in line with the participant's lifestyle
5. 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 study vaccination. Blood pressure must be ≤ 160/100 mmHg; any participant who is otherwise eligible with a blood pressure of ≥ 160/100 mmHg may be retested onsite several times over a 3-hour interval to achieve a lower blood pressure.
6. Agrees not to participate in any research involving receipt of investigational products (drug/biologic/device) including other SARS-CoV-2 prevention or treatment trials for the duration of the study.

Exclusion Criteria:

1. Current participation in research involving receipt of investigational products (drug/biologic/device).
2. Received any other vaccine within 28 days prior to study vaccination or plans to receive any other vac-cine within 28 days after study vaccination. Influenza vaccines can be administered up to 14 days before study vaccination.
3. Any known history of allergies to products contained in the investigational product in the participant's lifetime.
4. Any known history of anaphylaxis to any prior vaccine in the participant's lifetime.
5. Known history of myocarditis or pericarditis in the participant's lifetime.
6. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to study vaccination that, in the opinion of the investigator, might interfere with protocol compliance.
7. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) that requires the use of immune modulators.
8. Chronic administration (defined as > 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study vaccination (Day 0). Persons with human immunodeficiency virus are excluded
9. Received any prohibited medication, immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to study vaccination (Day 0).
10. Active cancer (malignancy) on chemotherapy within 3 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the investigator).
11. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study.
12. 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 study vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
13. 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).
14. Temperature of > 38°C (oral measurement) or respiratory symptoms in the past 3 days (ie, cough, sore throat, difficulty breathing) leading up to Day 0.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NVX-CoV2705 vaccine (5 µg ); NVX-CoV2705 COVID-19 vaccine will contain rS antigen from the JN.1 subvariant of SARS-CoV-2	Biological: NVX-CoV2705 Vaccine; All injections will be administered in a 0.5 mL injection volume at an antigenic dose of 5 µg with 50 µg Matrix-M adjuvant at each injection.; Other Names: SARS-CoV-2 rS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, duration, and severity of solicited local and systemic adverse events (AEs)	Incidence, duration, and severity of solicited local and systemic adverse events (AEs) for 7 days following vaccination.	Day 7[ following 1st vaccination]
Incidence, severity, and relationship of any unsolicited AEs	Incidence, severity, and relationship of any unsolicited AEs through 28 days after vaccination.	Day 28
Incidence and severity of treatment-related MAAEs, adverse events of special interest and serious adverse events interest (AESIs; predefined list, including PIMMCs, myocarditis and/or pericarditis), and serious adverse events (SAEs)	Incidence and severity of treatment-related MAAEs, adverse events of special interest and serious adverse events interest (AESIs; predefined list, including PIMMCs, myocarditis and/or pericarditis), and serious adverse events (SAEs) through day 180 or end of study (EoS).	Day 180 or end of study (EoS).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pseudovirus neutralization titers for the JN.1 subvariant expressed as GMTs	Pseudo virus neutralization antibody responses induced by NVX CoV2705 for the JN.1 subvariant at Day 28 following study vaccination.	Day 0 to Day 28
Pseudovirus neutralization antibody responses against the JN.1 subvariant Expressed as GMFR	Pseudovirus neutralization antibody responses of ID50 titers for the JN.1 subvariant of time points (Day 28) from Baseline	Day 0 to Day 28
Pseudovirus neutralization antibody responses against the JN.1 subvariant Expressed as SRRs	Pseudovirus neutralization antibody responses of ID50 titers for the JN.1 subvariant of time points (Day 28) from Baseline	Day 28
Anti-S IgG antibody responses for the JN.1 subvariant Expressed as (GMEU)	immunoglobulin G (IgG) antibody responses for the JN.1 subvariant at relevant time points (Days 0 and 28).	Day-0 (baseline) to Day 28.
Anti-S IgG antibody responses for the JN.1 subvariant Expressed as GMFR	immunoglobulin G (IgG) antibody responses for the JN.1 subvariant at relevant time points (Days 0 and 28).	Frame: Day 0 and Day-28
Anti-S IgG antibody responses for the JN.1 subvariant Expressed as SRRs	Immunoglobulin G (IgG) antibody responses for the JN.1 subvariant at relevant time points (Days 0 and 28).	Frame: Day 0 and Day 28

Collaborators and Investigators

• Sponsor: Novavax

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2024
• Primary Completion (Actual): October 15, 2024
• Study Completion (Actual): April 17, 2025

Study Registration Dates

• First Submitted: May 8, 2024
• First Submitted That Met QC Criteria: May 8, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Actual): July 18, 2025
• Last Update Submitted That Met QC Criteria: July 16, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: coronavirus 2 (SARS-CoV-2)
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coronavirus Infections; Severe Acute Respiratory Syndrome
• Other Study ID Numbers: 2019nCoV-315

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No