This is a Phase 2/3, randomized, double-blind study to evaluate the safety and immunogenicity of different booster dose levels of the monovalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant (r) spike (S) protein nanoparticle (SARS-CoV-2 rS) vaccines with Matrix-M™ adjuvant (NVX-CoV2373 \[prototype Wuhan vaccine with Matrix-M adjuvant\] or NVX-CoV2601 \[Omicron XBB.1.5 subvariant vaccine with Matrix-M adjuvant\]).
The ongoing COVID-19 pandemic has reached a stage where it is necessary to stablish the framework for periodic national vaccination campaigns.The present study aims to investigate the safety and immunogenicity of different booster dose levels of monovalent and bivalent vaccines in adults ≥ 50 years of age who have already been immunized with ≥ 3 doses of a COVID-19 prototype or bivalent licensed mRNA vaccine. The Boosters of investigational products will be administered ≥ 90 days after the participants received their third dose of a COVID-19 prototype or bivalent licensed mRNA vaccine. Approximately 1,980 participants ≥ 50 years of age who have received a regimen of ≥ 3 doses of a coronavirus disease 2019(COVID-19) vaccine (the last vaccine could have been a bivalent licensed mRNA vaccine) will be included in this study. The last COVID-19 vaccine dose should have been administered ≥ 90 days prior to Day 0. Approximately 1,800 participants will be randomly assigned in a 1:2:2:2:2:1 ratio to receive NVX-CoV2373 or NVC-CoV2601 in a double-blinded fashion into 1 of 6 monovalent vaccine groups (vaccine groups A to G). Following completion of enrollment into the 6 monovalent vaccine groups, 180 participants will be enrolled in vaccine group G to receive a bivalent licensed mRNA vaccine in an open-label fashion.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
994
Coformulated prototype SARS-CoV-2 rS vaccine with Matrix-M adjuvant: supplied as a solution for preparation for injection, at a concentration of 10 μg/mL and 100 μg adjuvant per mL, respectively
The vaccination regimen will comprise one IM injection on Day 0 at a dose of 5 µg of antigen with 50 µg Matrix-M adjuvant.
The vaccination regimen will comprise one IM injection on Day 0 at a dose of 5 µg of antigen with 75 µg Matrix-M adjuvant.
Immunogenicity index-Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5
Neutralizing antibody To determine if the combination of antigen and adjuvant levels of NVX-CoV2601 GMTR against the Omicron subvariant XBB.1.5 superior(LB of the 95% CI for GMTR \> 1.0) to that elicited by NVX-CoV2373
Time frame: Day 28
Immunogenicity index-Neutralizing antibody expressed as seroresponse rates (SRRs)against the Omicron subvariant XBB.1.5
Neutralizing antibody SRR against the Omicron XBB.1.5 subvariant elicited by NVXCoV2601 is non-inferior (NI)to the SRR elicited by NVX-CoV2373in participants ≥ 50 years of age previously vaccinated with ≥ 3 doses of a COVID-19 prototype or bivalent licensed mRNA vaccine.
Time frame: Day 28
Neutralizing antibody expressed as geometric mean titer ratio[GMTR ]against the Omicron subvariant XBB.1.5
Neutralizing antibody (GMTR) at relevant time points Days 28 to 180 from baseline (Day 0) and analyzed by dose (5, 10, and 25 µg)
Time frame: Day 28
Immunogenicity index- IgG antibody Anti-S expressed as geometric mean Elisa units GMEUs (EU/mL)
Immunoglobulin G (IgG) antibody Anti-S expressed as geometric mean Elisa units GMEUs (EU/mL) at relevant time points (Days 0 to 180) and analyzed by dose (5, 10, and 25 µg)
Time frame: Day 0 to 180
Immunogenicity index- Neutralizing antibody titers of post-booster by baseline anti-SARS-CoV-2 NP
Neutralizing antibody titers of post-booster by baseline anti-SARS-CoV-2 NP status day-28
Time frame: Day-28
Immunogenicity index- Serum IgG levels to SARS-CoV-2 S protein at Day 28 of post-booster
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The vaccination regimen will comprise one IM injection on Day 0 at a dose of 35 µg of antigen with 50 µg Matrix-M adjuvant.
The vaccination regimen will comprise one IM injection on Day 0 at a dose of 35 µg of antigen with 75 µg Matrix-M adjuvant.
The vaccination regimen will comprise one IM injection on Day 0 at a dose of 50 µg of antigen with 100 µg Matrix-M adjuvant
The bivalent BA.4/5 (or recommended mRNA vaccine at the time of the conduct of this study) Omicron subvariant/prototype licensed mRNA vaccine will be procured and stored per the manufacturer's instructions. For this vaccine group, treatment will be administered open label as a single IM injection
ARS-Birmingham CRU
Birmingham, Alabama, United States
Tucson Neuroscience Research
Tucson, Arizona, United States
Velocity Clinical Research, Banning
Banning, California, United States
Velocity Clinical Research, Chula Vista
Chula Vista, California, United States
Velocity Clinical Research, San Diego
La Mesa, California, United States
Artemis Institute for Clinical Research
Riverside, California, United States
Artemis - San Diego
San Diego, California, United States
WR-MCCR
San Diego, California, United States
Deland CRU
DeLand, Florida, United States
Health Awareness
Jupiter, Florida, United States
...and 40 more locations
Serum IgG levels to SARS-CoV-2 S protein at Day 28 post-booster by baseline anti-SARS-CoV-2 NP status.
Time frame: Day-28
Safety Index-Incidence, duration, and severity of solicited local and systemic AEs expressed as GMT
Incidence, duration, and severity of solicited local and systemic AEs for 7 days following vaccination.
Time frame: 7 days
Safety Index -Incidence and relationship of Medically Attended Adverse Event(s) (MAAEs), Adverse event(s) of Special Interest (AESIs), and Serious Adverse Event(s) (SAEs)
Incidence and relationship of Medically Attended Adverse Event(s) (MAAEs), Adverse event(s) of Special Interest (AESIs), and Serious Adverse Event(s) (SAEs) \[ Time Frame: Day 0 to Day 180 \] Incidence and relationship of MAAEs, AESIs (predefined list), and SAEs throughout the study
Time frame: Day 0 to 180
Safety Index -Incidence, Severity, and relationship of unsolicitated Adverse Event(s) Through 28 days after vaccination by vaccine group p(vaccine groups A to G).
Incidence, Severity, and relationship of unsolicitated Adverse Event(s) Through 28 days after vaccination by vaccine group p(vaccine groups A to G).s the overall safety of single-dose regimens containing NVX-CoV2601, NVX-CoV2373, or mRNA vaccine by vaccine group in participants ≥ 50 years of age previously vaccinated with ≥ 3 doses of a COVID-19 prototype or bivalentlicensed mRNA vaccine.
Time frame: Day 0 to 180
Human angiotensin-converting enzyme 2 (hACE2) receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMTs
hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 0, 28, and 180) and analyzed by dose (5, 10, and 25 µg)
Time frame: Day 0 to 180
hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR
hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 0, 28, and 180) and analyzed by dose (5, 10, and 25 µg).
Time frame: Day 0 to 180
hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR
hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins at relevant time points (Days 0, 28, and 180)and analyzed by previous vaccine combination received. Derived/calculated endpoints based on these data will include SRRs.
Time frame: Day 0 to 180