Evaluation of the Safety and Immunogenicity of SII Vaccine Constructs Based on the SARS-CoV-2 (COVID-19) Variant in Adults

Novavax

Overview

This is a randomized, observer-blinded, Phase 1/2 study with an open-label group to evaluate the safety and immunogenicity of 3 novel SARS-CoV-2 variant vaccine constructs adjuvanted with Matrix-M1 adjuvant. Investigational products will include a monovalent SII SARS-CoV-2 B.1.351 (Beta) variant vaccine (SII B.1.351), a bivalent SII vaccine containing antigen for both the ancestral strain and B.1.351 (Beta) variant of SARS-CoV-2 (SII Bivalent), and a monovalent SII SARS-CoV-2 B.1.617.2 (Delta) variant vaccine (SII B.1.617.2).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Conditions

Covid19

Interventions

SII B.1.351BIOLOGICAL

Intramuscular (deltoid) injections of 3 μg SII B.1.351 and 50 μg Matrix-M1 Adjuvant, 1 or 2 doses:1 on Day 0 and ± 1 on Day 21.

SII B.1.351BIOLOGICAL

Intramuscular (deltoid) injections of 5 μg SII B.1.351 and 50 μg Matrix-M1 Adjuvant, 1 or 2 doses:1 on Day 0 and ± 1 on Day 21.

SII BivalentBIOLOGICAL

Intramuscular (deltoid) injections of 6 μg SII Bivalent and 50 μg Matrix-M1 Adjuvant, 2 doses: 1 on Day 0 and 1 on Day 21.

Eligibility

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

Medical Language ↔ Plain English

Inclusion Criteria: 1. Adults 18 to 64 years of age, inclusive, 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 \[defined as amenorrhea at least 12 consecutive months\]) 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 at least 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 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 first vaccination. 5. Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study. For previously vaccinated Participants (Groups C, D and H): 6. Documented receipt of 2 doses of the investigational Novavax vaccine with Matrix-M1 adjuvant (NVX-CoV2373) administered approximately 21 days apart or 2 doses of a TGA-authorized/approved COVID-19 vaccine administered at least 60 days prior to first study vaccination. Exclusion Criteria: If an individual meets any of the following criteria, he or she is ineligible for this study: 1. History of laboratory-confirmed (by PCR or serology to SARS-CoV-2) COVID-19 infection at any time prior to randomization/enrollment. 2. Previous receipt of any investigational or authorized/approved vaccine, prophylactic or therapeutic agent for the prevention or treatment of SARS-CoV-2 infection, except for previously vaccinated participants. 3. Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to first study vaccination. 4. Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 30 days prior to the first study vaccination. 5. Any known allergies to products contained in the investigational product. 6. Any history of anaphylaxis to any prior vaccine. 7. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy. 8. Chronic administration (defined as \> 14 continuous days) of immunosuppressants, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination. 9. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination. 10. 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). 11. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study. 12. 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. 13. 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). 14. Study team member or immediate family member of any study team member (inclusive of Sponsor, CRO, and study site personnel involved in the conduct or planning of the study).

Locations (4)

Australian Clinical Research Network (ACRN)

Maroubra, New South Wales, Australia

Holdsworth House Medical Practice - Sydney

Sydney, New South Wales, Australia

University Hospital Geelong-Barwon Health

Geelong, Victoria, Australia

Emeritus Research

Melbourne, Victoria, Australia

Outcomes

Primary Outcomes

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMT

(MN50) geometric mean titers (GMTs) to the SARS-CoV-2 B.1.351 (Beta) variant at Day 14 (one-dose regimen; Groups C and D) and Day 35 (two-dose regimen; Groups A and B);

Time frame: Day 14 and Day 35

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs

Seroconversion rates (SCRs) or seroresponse rates (SRRs) (proportion of participants who achieve ≥ 4-fold increase from baseline) in MN50 titer concentrations to the SARS-CoV-2 B.1.351 (Beta) variant following their last vaccination.

Time frame: Day 14 and Day 35

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as GMT

Neutralizing antibody MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variant at Day 14 (one-dose regimen; Group H) and Day 35 (two-dose regimen; Group G);

Time frame: Day 14 and Day 35

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/SRRs

SCRs/SRRs (proportion of participants who achieve ≥ 4-fold increase from baseline) in MN50 titer concentrations to the SARS-CoV-2 Delta variant following their last vaccination.

Time frame: Day 14 and Day 35

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 each vaccination

Time frame: Day 0 to Day 7

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

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

Time frame: Day 0 to Day 28

Data from ClinicalTrials.gov

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Secondary Outcomes

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated patients

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) variants and to the ancestral SARS-CoV-2 strain at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) variants and to the ancestral SARS-CoV-2 strain at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in previously vaccinated patients

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) variants and to the ancestral SARS-CoV-2 strain at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in participants seronegative at baseline.

MN50 GMTs to the SARS-CoV-2 B.1.351 (Beta) variants and to the ancestral SARS-CoV-2 strain at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in participants seronegative at baseline

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variants and to the ancestral SARS-CoV-2 strain at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in previously vaccinated participants

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variants and to the ancestral SARS-CoV-2 strain at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/ SRRs in participants seronegative at baseline

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variants and to the ancestral SARS-CoV-2 strain at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta)expressed as SCRs/ SRRs in previously vaccinated participants

MN50 GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variants and to the ancestral SARS-CoV-2 strain at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated participants

IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.351 (Beta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline

IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.351 (Beta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

IgG geometric mean concentrations (GMCs) to the B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein in participants seronegative at baseline

IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

IgG geometric mean concentrations (GMCs) to the B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein in previously vaccinated participants

IgG geometric mean concentrations (GMCs) to the SARS-CoV-2 B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in previously vaccinated participants

GMTs to the SARS-CoV-2 B.1.351 (Beta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as GMFR in participants seronegative at baseline

GMTs to the SARS-CoV-2 B.1.351 (Beta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in previously vaccinated participants

GMTs to the SARS-CoV-2 B.1.351 (Beta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.351 (Beta) expressed as SCRs/SRRs in participants seronegative at baseline

GMTs to the SARS-CoV-2 B.1.351 (Beta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein at Days 0, 14, and 189 at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in participants seronegative at baseline

GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein and at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as GMFR in previously vaccinated participants

GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein and at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189

Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as SCRs/SRRs in participants seronegative at baseline

GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein and at Days 0, 21, 35, and 217 in participants seronegative at baseline.

Time frame: Day 0 to Day 217

Human Angiotensin-Converting Enzyme 2 (hACE2) receptor binding inhibition assay GMT to the SARS-CoV-2 B.1.617.2 (Delta) expressed as SCRs/SRRs in previously vaccinated participants

GMTs to the SARS-CoV-2 B.1.617.2 (Delta) variant S proteins and to the ancestral SARS-CoV-2 strain S protein and at Days 0, 14, and 189 in previously vaccinated individuals

Time frame: Day 0 to Day 189