A Multi-Part, Phase 3, Randomized, Observer Blinded Study to Evaluate the Safety and Immunogenicity of Omicron Subvariant and Bivalent SARS-CoV-2 rS Vaccines in Adults Previously Vaccinated With Other COVID-19 Vaccines
Overview
- Phase
- Phase 3
- Intervention
- NVX-CoV2515
- Conditions
- COVID-19
- Sponsor
- Novavax
- Enrollment
- 1340
- Locations
- 18
- Primary Endpoint
- Part 2: Neutralizing Antibody (NAb) GMTs to the Omicron BA.5 subvariant expressed as GMTs
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Multi-Part, Phase 3, randomized, observer-blinded study to evaluate the safety and immunogenicity of booster doses of Omicron subvariant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant (r) spike (S) protein nanoparticle vaccines (SARS-CoV-2 rS) adjuvanted with Matrix-M™ adjuvant (NVX-CoV2515 [BA.1] and NVX-CoV2540 [BA.5]) and bivalent (NVX-CoV2373 [prototype] + Omicron subvariant) SARS-CoV-2 rS vaccines (NVX-CoV2373 + NVX CoV2515 and NVX CoV2373 + NVX CoV2540) in previously vaccinated adults 18 years of age and older.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be included in this study, each individual must satisfy all the following criteria:
- •Adults ≥ 18 and ≤ 64 years of age at screening.
- •Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
- •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 and through the end of the study.
- •Is medically stable, as determined by the investigator (based on a 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 vaccination.
- •Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.
- •Have previously received 2 doses of the Moderna and/or Pfizer-BioNTech COVID-19 prototype vaccines with the last dose having been given ≥ 180 days prior to study vaccination or 3 doses of the Moderna and/or Pfizer-BioNTech COVID-19 prototype vaccines with the last dose having been given ≥ 90 days previously prior to the study vaccination.
Exclusion Criteria
- •If an individual meets any of the following criteria, he or she is ineligible for this study:
- •Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clinical trial COVID- 19 vaccines.
- •Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to study vaccination.
- •Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccination which may be received \> 14 days prior to study vaccination, or rabies vaccine which may be given if medically indicated.
- •Any known allergies to products contained in the investigational product.
- •Any history of anaphylaxis to any prior vaccine.
- •Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
- •Chronic administration (defined as \> 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study vaccination.
- •Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to the first study vaccination, except for rabies immunoglobulin which may be given if medically indicated.
- •Active cancer (malignancy) on therapy within 3 years prior to 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).
Arms & Interventions
Group A (NVX-CoV2515 )
1 intramuscular (IM) injection of NVX-CoV2515 of 0.5 mL injection volume on Day 0.
Intervention: NVX-CoV2515
Group B (NVX-CoV2373 )
1 intramuscular (IM) injection of NVX-CoV2373 of 0.5 mL injection volume on Day 0.
Intervention: NVX-Cov2373
Group C (NVX-CoV2515 )
1 intramuscular (IM) injection of NVX-CoV2515 of 0.5 mL injection volume on Day 0.
Intervention: NVX-CoV2515
Group D (NVX-CoV2373)
1 intramuscular (IM) injection of NVX-CoV2373 of 0.5 mL injection volume on Day 0.
Intervention: NVX-Cov2373
Group E (BA.1 Bivalent Vaccine)
1 intramuscular (IM) injection of Bivalent Vaccine (NVX-CoV2373 + NVX-CoV2515) of 0.5 mL injection volume on Day 0.
Intervention: NVX-CoV2373 + NVX-CoV2515
Group F (NVX-CoV2540)
2 intramuscular (IM) injections of NVX-CoV2373 of 0.5 mL injection volume on Day 0 and on Day 90.
Intervention: NVX-CoV2540
Group G (NVX-CoV2373)
2 intramuscular (IM) injections of NVX-CoV2373 of 0.5 mL injection volume on Day 0 and on Day 90.
Intervention: NVX-Cov2373
Group H (NVX-CoV2373 + NVX-CoV2540)
2 intramuscular (IM) injections of NVX-CoV2373 of 0.5 mL injection volume on Day 0 and on Day 90.
Intervention: NVX-CoV2373 + NVX-CoV2540
Outcomes
Primary Outcomes
Part 2: Neutralizing Antibody (NAb) GMTs to the Omicron BA.5 subvariant expressed as GMTs
Time Frame: Day 28
Neutralizing antibody (NAb) GMTs to the Omicron BA.5 subvariant, assessed at Day 28 following initial study vaccination.
Part 2: Neutralizing Antibody (NAb) titers to the Omicron BA.5 subvariant expressed as SRRs
Time Frame: Day 28
SRRs in NAb titer concentrations to the Omicron BA.5 subvariant, assessed at Day 28 following initial study vaccination
Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) strain expressed as GMTs
Time Frame: Day 28
NAb GMTs to the ancestral (Wuhan) strain, assessed at Day 28 following initial study vaccination.
Part 1: MN50 geometric mean titers (GMTs) to the Omicron BA.1 subvariant expressed as GMTs
Time Frame: Day 14
Microneutralization \[MN\] geometric mean titers (GMTs) with an inhibitory concentration of 50% (MN50) to the Omicron BA.1 subvariant, assessed at Day 14 following initial study vaccination and analyzed by previous vaccine combination received.
Part 1: MN50 titer concentrations to the Omicron BA.1 subvariant vaccine expressed as seroresponse rates (SRRs)
Time Frame: Day 14
Seroresponse rates (SRRs) (proportion of participants who achieve ≥ 4-fold increase from baseline \[Day 0\]) in MN50 titer concentrations to the Omicron BA.1 subvariant, assessed at Day 14 following initial study vaccination and analyzed by previous vaccine combination received.
Secondary Outcomes
- Part 1: MN50 geometric mean titers (GMTs) to the ancestral (Wuhan),and Omicron BA.1 viruses expressed as GMT(Day 0 to Day 240)
- Part 1: MN50 titer concentrations to the ancestral (Wuhan), and Omicron BA.1 viruses expressed as GMFR(Day 7 to Day 240)
- Part 1: MN50 titer concentrations to the ancestral (Wuhan), and Omicron BA.1 viruses expressed as SRRs(Day 7 to Day 240)
- Part 1: Immunoglobulin G (IgG) antibody levels to the ancestral (Wuhan), Omicron BA.1 and Omicron BA.5 viruses expressed as GMT(Day 0 to Day 240)
- Part 1:IgG antibody levels to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR(Day 0 to Day 240)
- Part 1: IgG antibody levels to the ancestral (Wuhan), Omicron BA.1 and Omicron BA.5 viruses expressed as SRRs(Day 0 to Day 240)
- Part 1: 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(Day 0 to Day 240)
- Part 1: hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR(Day 0 to Day 240)
- Part 1: hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR(Day 0 to Day 240)
- Part 1: MN50 GMTs to the to the ancestral (Wuhan) virus expressed as GMT(Day 14)
- Part 1: MN50 GMTs to the to the ancestral (Wuhan) virus expressed as GMFR(Day 14)
- Part 1: SRRs in MN50 titer concentrations to the ancestral (Wuhan) virus expressed as SRRs(Day 14)
- Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as GMT(Day 14)
- Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as GMFR(Day 14)
- Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as SRR(Day 14)
- Part 1 and Part 2: Incidence of solicited local and systemic Adverse Events (AEs)(Day 7)
- Part 1 and Part 2 : Incidence of unsolicited AEs(Day 28)
- Part 1 and Part 2 :Incidence and relationship of Medically Attended Adverse Event(s) (MAAEs), Adverse event(s) of Special Interest (AESIs), and Serious Adverse Event(s) (SAEs)(Day 0 to Day 270)
- Part 1: IgG Geometric Mean Concentrations (GMCs) to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as GMFR(Day 0 to Day 240)
- Part 1: IgG GMCs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR(Day 0 to Day 240)
- Part 1: GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR(Day 0 to Day 240)
- Part 1: GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as GMFR(Day 0 to Day 240)
- Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as GMTs(Day 0 to Day 270)
- Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as GMFRs(Day 0 to Day 270)
- Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as SRRs(Day 0 to Day 270)
- Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as GMTs(Day 0 to Day 270)
- Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as GMFRs(Day 0 to Day 270)
- Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as SRRs(Day 0 to Day 270)
- Part 2:hACE2 receptor binding inhibition assay to the ancestral (Wuhan),and Omicron BA.5 S proteins expressed as GMTs(Day 0 to Day 270)
- Part 2:hACE2 receptor binding inhibition assay to the ancestral (Wuhan), and Omicron BA.5 S proteins expressed as GMFRs(Day 0 to Day 270)
- Part 2:hACE2 receptor binding inhibition assay to the ancestral (Wuhan), and Omicron BA.5 S proteins expressed as SRRs(Day 0 to Day 270)