COVID-19, SARS CoV 2 Infection
Conditions
Keywords
Coronavirus
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.
Interventions
DRUGNVX-CoV2515
Intramuscular (deltoid) injection of co-formulated Omicron BA.1 SARS-CoV-2 rS vaccine with Matrix-M adjuvant (0.5 mL).
DRUGNVX-Cov2373
Intramuscular (deltoid) injection of co-formulated prototype SARS-CoV-2 rS vaccine with Matrix-M adjuvant(0.5 mL).
DRUGNVX-CoV2373 + NVX-CoV2515
Intramuscular (deltoid) injection of 5 µg total (2.5 µg NVX-CoV2373 + 2.5 µg NVX-CoV2515) with 50 µg Matrix-M adjuvant.
DRUGNVX-CoV2540
Intramuscular (deltoid) injection of co-formulated prototype SARS-CoV-2 rS vaccine with Matrix-M adjuvant(0.5 mL).
DRUGNVX-CoV2373 + NVX-CoV2540
Intramuscular (deltoid) injection of 5 µg total (2.5 µg NVX-CoV2373 + 2.5 µg NVX-CoV2515) with 50 µg Matrix-M adjuvant.
Sponsors
Novavax
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
Part 1 Inclusion Criteria: To be included in this study, each individual must satisfy all the following criteria: 1. Adults ≥ 18 and ≤ 64 years of age at screening. 2. Willing and able to give informed consent prior to study enrollment and to comply with study procedures. 3. 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. 4. 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. 5. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. 6. 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: 1. Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clinical trial COVID- 19 vaccines. 2. Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to study vaccination. 3. 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. 4. Any known allergies to products contained in the investigational product. 5. Any history of anaphylaxis to any prior vaccine. 6. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy. 7. Chronic administration (defined as \> 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study vaccination. 8. 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. 9. 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). 10. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of the study. 11. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance. 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). Part 2 Inclusion Criteria: To be included in this study, each individual must satisfy all of the following criteria: 1. Adults and adolescents ≥ 18 years of age at screening. 2. Willing and able to give informed consent prior to study enrollment and to comply with study procedures. 3. 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. 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. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. 6. Have previously received ≥ 3 doses of the Moderna and/or Pfizer-BioNTech monovalent and/or bivalent COVID-19 vaccines with the last dose having been given ≥ 90 days previously prior to first study booster.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: MN50 geometric mean titers (GMTs) to the Omicron BA.1 subvariant expressed as GMTs | 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) | 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. |
| Part 2: Neutralizing Antibody (NAb) GMTs to the Omicron BA.5 subvariant expressed as GMTs | 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 | 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 | Day 28 | NAb GMTs to the ancestral (Wuhan) strain, assessed at Day 28 following initial study vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Immunoglobulin G (IgG) antibody levels to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combinations received. |
| 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 | IgG antibody levels to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
| 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 | IgG antibody levels to the ancestral (Wuhan) and Omicron BA.5 viruses at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
| 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 | hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
| 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 | hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. Derived/calculated endpoints based on these data will include GMFR. |
| 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 | hACE2 receptor binding inhibition assay to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. Derived/calculated endpoints based on these data will include SRRs. |
| Part 1: MN50 GMTs to the to the ancestral (Wuhan) virus expressed as GMT | Day 14 | MN50 GMTs to the ancestral (Wuhan) virus, assessed at Day 14 following initial study vaccination and analyzed by previous vaccine combination received. |
| Part 1: MN50 GMTs to the to the ancestral (Wuhan) virus expressed as GMFR | Day 14 | MN50 GMFRs to the ancestral (Wuhan) virus at Day 14, from baseline (Day 0) and analyzed by previous vaccine combination received. |
| Part 1: SRRs in MN50 titer concentrations to the ancestral (Wuhan) virus expressed as SRRs | Day 14 | SRR in MN50 titer concentrations to the ancestral (Wuhan) virus, assessed at Day 14 following initial study vaccination. |
| Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as GMT | Day 14 | MN50 GMTs to the Omicron BA.1 subvariant virus, assessed at Day 14 following initial study vaccination and analyzed by previous vaccine combination received. |
| Part 1 and Part 2: Incidence of solicited local and systemic Adverse Events (AEs) | Day 7 | Incidence, duration, and severity of solicited local and systemic AEs for 7 days following vaccination. |
| Part 1 and Part 2 : Incidence of unsolicited AEs | Day 28 | Incidence, duration, severity, and relationship of unsolicited AEs through 28 days after vaccination. |
| 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 | Incidence and relationship of MAAEs, AESIs (predefined list), and SAEs throughout the study |
| Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as SRR | Day 14 | SRR in MN50 titer concentrations to the Omicron BA.1 variant virus, assessed at Day 14 following initial study vaccination. |
| 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 | IgG GMCs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
| Part 1: GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR | Day 0 to Day 240 | GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
| Part 1: GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as GMFR | Day 0 to Day 240 | GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
| Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as GMTs | Day 0 to Day 270 | NAb GMTs to the ancestral (Wuhan) and Omicron BA.5 strains at relevant time points (Days 0, 14, 28, 90, 104, 118, and 270) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as GMFRs | Day 0 to Day 270 | NAb GMFR to the ancestral (Wuhan), and Omicron BA.5 strains at relevant time points (Days 14, 28, 104, 118, and 270) from baseline (Day 0 or Day 90) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as SRRs | Day 0 to Day 270 | SRRs in NAb titers to the ancestral (Wuhan) and Omicron BA.5 strains at relevant time points (Days 14, 28, 104, 118, and 270) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as GMTs | Day 0 to Day 270 | IgG GMEUs to the ancestral (Wuhan) and Omicron BA.5 S proteins at relevant time points (Days 0, 14, 28, 90, 104, 118, and 270) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as GMFRs | Day 0 to Day 270 | IgG GMEUs to the ancestral (Wuhan) and Omicron BA.5 S proteins at relevant time points (Days 0, 14, 28, 90, 104, 118, and 270) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as SRRs | Day 0 to Day 270 | IgG GMEUs to the ancestral (Wuhan) and Omicron BA.5 S proteins at relevant time points (Days 0, 14, 28, 90, 104, 118, and 270) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| 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 | hACE2 receptor binding inhibition assay GMTs to the ancestral (Wuhan) and Omicron BA.5 S proteins at relevant time points (Days 0, 14, 28, 90, 104, 118, and 270) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| 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 | hACE2 receptor binding inhibition assay GMTs to the ancestral (Wuhan) and Omicron BA.5 S proteins at relevant time points (Days 0, 14, 28, 90, 104, 118, and 270) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| 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 | hACE2 receptor binding inhibition assay GMTs to the ancestral (Wuhan) and Omicron BA.5 S proteins at relevant time points (Days 0, 14, 28, 90, 104, 118, and 270) and analyzed by age group (overall, 18 to 54, and ≥ 55 years of age). |
| 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 | IgG GMCs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
| Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as GMFR | Day 14 | MN50 GMFRs to the Omicron BA.1 subvariant virus at Day 14, from baseline (Day 0) and analyzed by previous vaccine combination received. |
| Part 1: MN50 geometric mean titers (GMTs) to the ancestral (Wuhan),and Omicron BA.1 viruses expressed as GMT | Day 0 to Day 240 | MN50 GMTs to the ancestral (Wuhan), and Omicron BA.1 viruses at relevant time points (Days 0, 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
| Part 1: MN50 titer concentrations to the ancestral (Wuhan), and Omicron BA.1 viruses expressed as GMFR | Day 7 to Day 240 | MN50 geometric mean fold rise (GMFR) to the ancestral (Wuhan), and Omicron BA.1 viruses at relevant time points (Days 7, 14, 28, and 240) from baseline (Day 0) and analyzed by previous vaccine combination received. |
| Part 1: MN50 titer concentrations to the ancestral (Wuhan), and Omicron BA.1 viruses expressed as SRRs | Day 7 to Day 240 | SRRs in MN50 titer concentrations to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses at relevant time points (Days 7, 14, 28, and 240) and analyzed by previous vaccine combination received. |
Countries
Australia
Outcome results
None listed