Phase 3 Boosting Study for the SARS-CoV-2 rS Variant Vaccines

Novavax1,340 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,340

Conditions

COVID-19 SARS CoV 2 Infection

Interventions

NVX-CoV2515DRUG

Intramuscular (deltoid) injection of co-formulated Omicron BA.1 SARS-CoV-2 rS vaccine with Matrix-M adjuvant (0.5 mL).

NVX-Cov2373DRUG

Intramuscular (deltoid) injection of co-formulated prototype SARS-CoV-2 rS vaccine with Matrix-M adjuvant(0.5 mL).

NVX-CoV2373 + NVX-CoV2515DRUG

Intramuscular (deltoid) injection of 5 µg total (2.5 µg NVX-CoV2373 + 2.5 µg NVX-CoV2515) with 50 µg Matrix-M adjuvant.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 YearsHealthy volunteers:

Medical Language ↔ Plain English

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. 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 first study vaccination. 3. Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccination which may be received \> 14 days prior to first 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 first study vaccination. 8. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to 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 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). 10. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study. 11. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the first 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). 14. Participants with a history of myocarditis or pericarditis

Locations (19)

Paratus Clinical Research Canberra

Bruce, Australian Capital Territory, Australia

Paratus Clinical Research Western Sydney

Outcomes

Primary Outcomes

Part 1: MN50 geometric mean titers (GMTs) to the Omicron BA.1 subvariant expressed as GMTs

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.

Time frame: Day 14

Part 1: MN50 titer concentrations to the Omicron BA.1 subvariant vaccine expressed as seroresponse rates (SRRs)

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.

Time frame: Day 14

Part 2: Neutralizing Antibody (NAb) GMTs to the Omicron BA.5 subvariant expressed as GMTs

Neutralizing antibody (NAb) GMTs to the Omicron BA.5 subvariant, assessed at Day 28 following initial study vaccination.

Time frame: Day 28

Part 2: Neutralizing Antibody (NAb) titers to the Omicron BA.5 subvariant expressed as SRRs

SRRs in NAb titer concentrations to the Omicron BA.5 subvariant, assessed at Day 28 following initial study vaccination

Time frame: Day 28

Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) strain expressed as GMTs

NAb GMTs to the ancestral (Wuhan) strain, assessed at Day 28 following initial study vaccination.

Time frame: Day 28

Secondary Outcomes

Part 1: MN50 geometric mean titers (GMTs) to the ancestral (Wuhan),and Omicron BA.1 viruses expressed as GMT

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.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Intramuscular (deltoid) injection of co-formulated prototype SARS-CoV-2 rS vaccine with Matrix-M adjuvant(0.5 mL).

NVX-CoV2373 + NVX-CoV2540DRUG

Intramuscular (deltoid) injection of 5 µg total (2.5 µg NVX-CoV2373 + 2.5 µg NVX-CoV2515) with 50 µg Matrix-M adjuvant.

Blacktown, New South Wales, Australia

Emeritus Research

Botany, New South Wales, Australia

Northern Beaches Clinical Research

Brookvale, New South Wales, Australia

Paratus Clinical Research Central Coast

Kanwal, New South Wales, Australia

Australian Clinical Research Network (ACRN)

Maroubra, New South Wales, Australia

AIM Centre (Hunter Diabetes Centre)

Merewether, New South Wales, Australia

Novatrials

Newcastle, New South Wales, Australia

Holdsworth House Medical Practice

Sydney, New South Whales, Australia

Paratus Clinical Research Brisbane

Albion, Queensland, Australia

...and 9 more locations

Time frame: Day 0 to Day 240

Part 1: MN50 titer concentrations to the ancestral (Wuhan), and Omicron BA.1 viruses expressed as GMFR

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.

Time frame: Day 7 to Day 240

Part 1: MN50 titer concentrations to the ancestral (Wuhan), and Omicron BA.1 viruses expressed as SRRs

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.

Time frame: 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

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.

Time frame: 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

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.

Time frame: 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

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.

Time frame: 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

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.

Time frame: 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

Time frame: 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

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.

Time frame: Day 0 to Day 240

Part 1: MN50 GMTs to the to the ancestral (Wuhan) virus expressed as GMT

MN50 GMTs to the ancestral (Wuhan) virus, assessed at Day 14 following initial study vaccination and analyzed by previous vaccine combination received.

Time frame: Day 14

Part 1: MN50 GMTs to the to the ancestral (Wuhan) virus expressed as GMFR

MN50 GMFRs to the ancestral (Wuhan) virus at Day 14, from baseline (Day 0) and analyzed by previous vaccine combination received.

Time frame: Day 14

Part 1: SRRs in MN50 titer concentrations to the ancestral (Wuhan) virus expressed as SRRs

SRR in MN50 titer concentrations to the ancestral (Wuhan) virus, assessed at Day 14 following initial study vaccination.

Time frame: Day 14

Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as GMT

MN50 GMTs to the Omicron BA.1 subvariant virus, assessed at Day 14 following initial study vaccination and analyzed by previous vaccine combination received.

Time frame: Day 14

Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as GMFR

MN50 GMFRs to the Omicron BA.1 subvariant virus at Day 14, from baseline (Day 0) and analyzed by previous vaccine combination received.

Time frame: Day 14

Part 1: MN50 GMTs to the Omicron BA.1 subvariant virus expressed as SRR

SRR in MN50 titer concentrations to the Omicron BA.1 variant virus, assessed at Day 14 following initial study vaccination.

Time frame: Day 14

Part 1 and Part 2: Incidence of solicited local and systemic Adverse Events (AEs)

Incidence, duration, and severity of solicited local and systemic AEs for 7 days following vaccination.

Time frame: Day 7

Part 1 and Part 2 : Incidence of unsolicited AEs

Incidence, duration, severity, and relationship of unsolicited AEs through 28 days after vaccination.

Time frame: 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)

Incidence and relationship of MAAEs, AESIs (predefined list), and SAEs throughout the study

Time frame: 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

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.

Time frame: 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

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.

Time frame: Day 0 to Day 240

Part 1: GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as SRR

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.

Time frame: Day 0 to Day 240

Part 1: GMTs to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 S proteins expressed as GMFR

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.

Time frame: Day 0 to Day 240

Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as GMTs

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).

Time frame: Day 0 to Day 270

Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as GMFRs

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).

Time frame: Day 0 to Day 270

Part 2: Neutralizing Antibody (NAb) titers to the ancestral (Wuhan) and Omicron BA.5 strains expressed as SRRs

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).

Time frame: Day 0 to Day 270

Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as GMTs

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).

Time frame: Day 0 to Day 270

Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as GMFRs

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).

Time frame: Day 0 to Day 270

Part 2: IgG GMEUs antibody levels to the ancestral (Wuhan) and Omicron BA.5 S proteins expressed as SRRs

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).

Time frame: 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

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).

Time frame: 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

Time frame: 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

Time frame: Day 0 to Day 270