A 2-Part, Phase 1/2, Randomized, Observer-Blinded Study To Evaluate The Safety And Immunogenicity Of A SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Or Without MATRIX-M Adjuvant In Healthy Subjects
Latest Information Update: 08 Jun 2023
At a glance
- Drugs NVX CoV 2373 (Primary) ; Matrix M
- Indications COVID 2019 infections
- Focus Adverse reactions; First in man; Pharmacodynamics; Registrational
- Sponsors Novavax
- 02 Jun 2023 Results(n=1283) assessing Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373 published in the Vaccine
- 12 May 2023 Results published in the Journal of Infectious Diseases
- 01 Nov 2022 Results(n= 1282) of a secondary analysis assessing the immunogenicity and safety of a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine published in The Lancet Infectious Diseases
Most Recent Events
Trial Overview
Purpose
2019nCoV-101 is a 2-part, randomized, observer-blinded, placebo-controlled, Phase 1/2 trial. Part 1 (Phase 1) of the study is designed to evaluate the safety and immunogenicity of SARS-CoV-2 rS nanoparticle vaccine with or without Matrix-M adjuvant in 131 healthy participants ≥ 18 to 59 (inclusive) years of age at 2 sites in Australia. An interim analysis of Part 1 safety and immunogenicity will be performed prior to optional expansion to Part 2. Part 2 (Phase 2) of the study is designed to evaluate the immunogenicity, safety, and preliminary efficacy of a single construct of SARS-CoV-2 rS nanoparticle vaccine with Matrix-M adjuvant in up to 1,500 healthy participants ≥ 18 to 84 (inclusive) years of age at up to 40 sites across Australia and/or the United States.
Comments
According to an Novavax media release, based on positive recommendation of CHMP the European Commission (EC) has approved the expanded conditional marketing authorization (CMA) of Nuvaxovid™ (NVX-CoV2373) COVID-19 vaccine in the European Union (EU) as a homologous and heterologous booster for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for adults aged 18 and older.
According to a Novavax media release, the Australian Therapeutic Goods Administration (TGA) has granted provisional registration of Nuvaxovid (NVX-CoV2373) COVID-19 vaccine as a booster in individuals aged 18 and over, based on data from this trial.
According to a Novavax media release, Takeda received manufacturing and marketing approval from the Japan Ministry of Health, Labour and Welfare for its Nuvaxovid Intramuscular Injection for primary and booster immunization in individuals aged 18 and older.
Primary Endpoints
Participants with Solicited Adverse Events (AEs) - Phase 1
description: Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0, 21) by severity score, duration, and peak intensity.
time_frame: 28 days
Safety Laboratory Values (Serum Chemistry, Hematology) - Phase 1
description: Safety laboratory values (serum chemistry, hematology) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
time_frame: 28 days
Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs) - Phase 1
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs through Day 35.
time_frame: 35 days
Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs) - Phase 1
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs through Day 35.
time_frame: 35 days
Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs) - Phase 1
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs through Day 35. SCR is the proportion of participants with ≥4-fold rises in ELISA units.
time_frame: 35 days
Serum IgG Antibody Levels Expressed as GMEUs - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
time_frame: Day 35
primary_outcome
Serum IgG Antibody Levels Expressed as GMFRs - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
time_frame: Day 35
Serum IgG Antibody Levels Expressed as SCRs - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (≥4-fold rises) for the two-dose regimens by dose at Day 35 regardless of baseline immune status and stratified by baseline immune status.
time_frame: Day 35
Participants with Solicited Adverse Events (AEs) - Phase 2
description: Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0 and 21) by severity score, duration, and peak intensity.
time_frame: 28 days
Participants with Solicited Adverse Events (AEs) - Phase 2
description: Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0 and 21) by severity score, duration, and peak intensity. Unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all medically attended adverse events [MAAEs]) through the 35 days by Medical Dictionary for Regulatory Activities (MedDRA) classification, severity score, and relatedness.
time_frame: 28 days
Participants with Solicited Adverse Events (AEs) - Phase 2
description: Percentage of participants with solicited AEs (local, systemic) for 7 days following each primary vaccination (Days 0 and 21) by severity score, duration, and peak intensity. Unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all medically attended adverse events [MAAEs]) through the 35 days by Medical Dictionary for Regulatory Activities (MedDRA) classification, severity score, and relatedness.
time_frame: 28 days
Participants with Unsolicited AEs - Phase 2
description: Percentage of participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all medically attended adverse events [MAAEs]) through the 35 days by Medical Dictionary of Regulatory Activities (MedDRA) classification, severity score, and relatedness.
time_frame: 35 days
Other Endpoints
Participants with Unsolicited AEs - Phase 1
description: Percentage of participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, all MAAEs) through the first 49 days by MedDRA classification, severity score, and relatedness.
time_frame: 49 days
Participants with Abnormal Vital Signs - Phase 1
description: Percentage of participants with vital sign abnormalities on the day of vaccination by severity scoring immediately following vaccination.
time_frame: 21 days
Changes from Baseline in Body Temperature - Phase 1
description: Mean changes from baseline in body temperature by treatment group and visit.
time_frame: 189 days
Changes from Baseline in Blood Pressure - Phase 1
description: Mean changes from baseline in blood pressure by treatment group and visit.
time_frame: 189 days
Changes from Baseline in Pulse Rate - Phase 1
description: Mean changes from baseline in pulse rate by treatment group and visit.
time_frame: 189 days
Participants with MAAEs - Phase 1
description: Percentage of participants with MAAEs, defined as AEs that lead to an unscheduled visit to a healthcare practitioner, through Day 105 by MedDRA classification, severity score, and relatedness.
time_frame: 105 days
Participants with Related MAAEs; Serious Adverse Events (SAEs); and Adverse Events of Special Interest (AESI) - Phase 1
description: Percentage of participants with MAAEs assessed as related to study vaccine, SAEs, and AESIs until the end of the study (EOS) by MedDRA classification and severity score. All SAEs and AESI, defined as potential immune-mediated medical conditions or AEs relevant to COVID-19, by MedDRA classification, severity score, and relatedness.
time_frame: 386 days
Assessment of Serum IgG Antibody Levels Expressed as GMTs at Multiple Time Points - Phase 1
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at multiple time points through Day 189.
time_frame: 189 days
Assessment of Serum IgG Antibody Levels Expressed as GMFRs at Multiple Time Points - Phase 1
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at multiple time points through Day 189.
time_frame: 189 days
Assessment of Serum IgG Antibody Levels Expressed as SCRs at Multiple Time Points - Phase 1
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (proportion of participants with ≥2-fold and ≥4-fold rises in antibody levels) at multiple time points through Day 189.
time_frame: 189 days
Assessment of Serum IgG Antibody Levels Expressed by Seroresponse Rates (SRRs) at Multiple Time Points - Phase 1
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SRRs (proportion of participants with rises in ELISA units exceeding the 95th percentile of placebo participants) at multiple time points through Day 189.
time_frame: 189 days
Angiotensin-Converting Enzyme 2 (ACE2) Receptor Binding Inhibition Assay Expressed as GMTs - Phase 1
description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at multiple time points through Day 189.
time_frame: 189 days
ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs - Phase 1
description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at multiple time points through Day 189.
time_frame: 189 days
ACE2 Receptor Binding Inhibition Assay Expressed as SCRs - Phase 1
description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at multiple time points through Day 189.
time_frame: 189 days
ACE2 Receptor Binding Inhibition Assay Expressed as SRRs - Phase 1
description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at multiple time points through Day 189.
time_frame: 189 days
Neutralizing Antibody Activity Expressed as GMTs - Phase 1
description: Neutralizing antibody activity as detected by microneutralization assay (MN) expressed as GMTs at multiple time points through Day 49.
time_frame: 49 days
Neutralizing Antibody Activity Expressed as GMFRs - Phase 1
description: Neutralizing antibody activity as detected by MN expressed as GMFRs at multiple time points through Day 49.
time_frame: 49 days
Neutralizing Antibody Activity Expressed as SCRs - Phase 1
description: Neutralizing antibody activity as detected by MN expressed as SCRs at multiple time points through Day 49.
time_frame: 49 days
Neutralizing Antibody Activity Expressed as SRRs - Phase 1
description: Neutralizing antibody activity as detected by MN expressed as SRRs at multiple time points through Day 49.
time_frame: 49 days
Assessment of Cell-Mediated (T helper 1 [Th1]/T helper 2 [Th2]) Pathways - Phase 1
description: Cell-mediated (Th1/Th2) pathways as measured by whole blood (flow cytometry) and/or in vitro peripheral blood mononuclear cell (PBMC) stimulation (eg, enzyme-linked immunospot [ELISpot], cytokine staining) with SARS-CoV-2 rS protein(s) through Day 28.
time_frame: 28 days
Assessment of Serum IgG Antibody Levels Expressed as GMTs - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs for the single-dose regimens compared to the two-dose regimens and to placebo through Day 35 regardless of baseline immune status and stratified by baseline immune status.
time_frame: 35 days
Assessment of Serum IgG Antibody Levels Expressed as GMFRs - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs for the single-dose regimens compared to the two-dose regimens and to placebo through Day 35 regardless of baseline immune status and stratified by baseline immune status.
time_frame: 35 days
Assessment of Serum IgG Antibody Levels Expressed as SCRs (≥ 4-fold change) - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (≥ 4-fold change) for the single-dose regimens compared to the two-dose regimens and to placebo through Day 35 regardless of baseline immune status and stratified by baseline immune status.
time_frame: 35 days
Assessment of Serum IgG Antibody Levels Expressed as GMEUs at Multiple Time Points - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at multiple time points through Day 357 for the single-dose regimens compared to the two-dose regimens and to placebo, stratified by baseline immune response.
time_frame: 357 days
Assessment of Serum IgG Antibody Levels Expressed as GMFRs at Multiple Time Points - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at multiple time points through Day 357 for the single-dose regimens compared to the two-dose regimens and to placebo, stratified by baseline immune response.
time_frame: 357 days
Assessment of Serum IgG Antibody Levels Expressed as SCRs (≥ 4-fold change) at Multiple Time Points - Phase 2
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs (≥ 4-fold change) at multiple time points through Day 357 for the single-dose regimens compared to the two-dose regimens and to placebo, stratified by baseline immune response.
time_frame: 357 days
ACE2 Receptor Binding Inhibition Assay Expressed as GMTs - Phase 2
description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at multiple time points through Day 357 for the single-dose regimens compared to the two-dose regimens and to placebo.
time_frame: 357 days
ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs - Phase 2
description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at multiple time points through Day 357 for the single-dose regimens compared to the two-dose regimens and to placebo.
time_frame: 357 days
ACE2 Receptor Binding Inhibition Assay Expressed as SCRs - Phase 2
description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs (≥ 4-fold change) at multiple time points through Day 357 for the single-dose regimens compared to the two-dose regimens and to placebo.
time_frame: 357 days
Neutralizing Antibody Activity Expressed as GMTs - Phase 2
description: Neutralizing antibody activity as detected by MN expressed as GMTs at Days 35, 217, and 357 relative to baseline in a subset of subjects by absolute titers and change from baseline.
time_frame: 357 days
Neutralizing Antibody Activity Expressed as GMFRs - Phase 2
description: Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 35, 217 and 357 relative to baseline in a subset of subjects by absolute titers and change from baseline.
time_frame: 357 days
Neutralizing Antibody Activity Expressed as SCRs (≥ 4-fold change) - Phase 2
description: Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4-fold change) at Days 35, 217, and 357 relative to baseline in a subset of subjects by absolute titers and change from baseline.
time_frame: 357 days
Assessment of Serum IgG Antibody Levels Expressed as GMTs - Phase 2 Boost
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 189, 217, and 357 for all treatment groups and additionally at Day 371 and Day 546 for treatment groups B and C for boosting assessment with either placebo or active boost.
time_frame: 546 days
Assessment of Serum IgG Antibody Levels Expressed as GMFRs - Phase 2 Boost
description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 189, 217, and 357 for all treatment groups and additionally at Day 371 and Day 546 for treatment groups B and C for boosting assessment with either placebo or active boost.
time_frame: 546 days
Participants with MAAEs - Phase 2
description: All MAAEs, defined as AEs that lead to an unscheduled visit to a healthcare practitioner, through Day 217 by MedDRA classification, severity score, and relatedness.
time_frame: 217 days
Participants with Related MAAEs; SAEs; and AESIs - Phase 2
description: Percentage of participants with MAAEs assessed as related to study vaccine, SAEs, and AESIs until the end of the study (EOS) by MedDRA classification and severity score. All SAEs and AESI, defined as potential immune-mediated medical conditions or AEs relevant to COVID-19, by MedDRA classification, severity score, and relatedness.
time_frame: 357 days
Participants with Abnormal Vital Signs - Phase 2
description: Percentage of participants with vital sign abnormalities on the day of vaccination by severity scoring immediately following vaccination. Descriptive statistics (mean, standard deviation, change from baseline) by treatment group, by visit.
time_frame: 21 days
Changes from Baseline in Body Temperature - Phase 2
description: Mean changes from baseline in body temperature by treatment group and visit.
time_frame: 189 days
Changes from Baseline in Blood Pressure - Phase 2
description: Mean changes from baseline in blood pressure by treatment group and visit.
time_frame: 189 days
Changes from Baseline in Pulse Rate - Phase 2
description: Mean changes from baseline in pulse rate by treatment group and visit.
time_frame: 189 days
Participants with SARS-CoV-2 Positivity - Phase 2
description: Percentage of participants with SARS-CoV-2 positivity as diagnosed by qualitative polymerase chain reaction (PCR) following COVID-19 symptoms assessment from Day 28 through 6 months with severity classification, overall and by age strata (18-59, 60-84 years).
time_frame: 161 days
Assessment of SARS-CoV-2 by Qualitative PCR - Phase 2
description: Assessment of SARS-CoV-2 by qualitative PCR based on routine screening by self- collection (nasal mid-turbinate or saliva) from Day 28 through 6 months without symptomatology to further describe epidemiologic evolution of the pandemic and potential effect of vaccination.
time_frame: 161 days
Assessment of Cell-Mediated (Th1/Th2) Pathways - Phase 2
description: Assessment of cell-mediated (Th1/Th2) pathways as measured by whole blood (flow cytometry) and/or in vitro PBMC stimulation (eg, ELISpot, cytokine staining) with SARS-CoV-2 rS protein(s) through Day 28.
time_frame: 28 days [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| COVID 2019 infections | prevention | - |
Biomarker
| NCT Number | Biomarker Name | Biomarker Function |
|---|---|---|
| NCT04368988 | ACE2 | Outcome Measure |
| serine racemase | Outcome Measure | |
| seryl-tRNA synthetase | Eligibility Criteria |
Subjects
- Subject Type patients
-
Number
Planned: 1631
Actual: 1419
- Sex male & female
- Age Group 18-84 years; adult; elderly
Patient Inclusion Criteria
Inclusion Criteria (Part 1): - Healthy adult males or females between 18 and 59 years of age, inclusive, at screening. Healthy status will be determined by the investigator based on medical history, clinical laboratory results, vital sign measurements, and physical examination at screening. - The participant has a body mass index 17 to 35 kg/m2, inclusive, at screening. - Willing and able to give informed consent prior to study enrollment and comply with study procedures. - Female participants of childbearing potential (defined as any female 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 or documented plasma follicle-stimulating hormone (FSH) level ≥40 mIU/mL]) must agree to be heterosexually inactive from at least 21 days prior to enrollment and through 6 months after the last vaccination OR agree to consistently use any of the described methods of contraception from at least 21 days prior to enrollment and through 6 months after the last vaccination.
Patient Exclusion Criteria
(Part 1): - Any ongoing, symptomatic acute or chronic illness requiring medical or surgical care, inclusive of changes in medication in the past 2 months indicating that chronic illness/disease is not stable (at the discretion of the investigator). This includes any current workup of undiagnosed illness that could lead to a new condition. - Chronic disease inclusive of: a) hypertension uncontrolled for age according to the Eighth Joint National Committee (JNC 8) guidelines; b) congestive heart failure by New York Heart Association (NYHA) functional classification of greater or equal to II; c) chronic obstructive pulmonary disease by Global Initiative for Obstructive Lung Disease (GOLD) classification of greater or equal to 2; d) recent (within 6 months prior to first study vaccination) exacerbation of coronary artery disease as manifested by cardiac intervention, addition of new cardiac medications for control of symptoms, or unstable angina; e) asthma (diagnosed by spirometry showing reversibility of disease and must meet at least the Step 1 classification with current prescription/use of medications to control symptoms); f) diabetes requiring use of medicine (insulin or oral) or not controlled with diet. - Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination. - History of a confirmed diagnosis of SARS or COVID-19 disease (confirmed by a specific test for each disease) or known exposure to a SARS-CoV-2 positive confirmed close contact (eg, family member, housemate, daycare provider, aged parent requiring care), at the discretion of the investigator. - Currently working in an occupation with a high risk of exposure to SARS-CoV-2 (eg, healthcare worker, emergency response personnel). - Currently taking any product (investigational or off-label) for prevention of COVID-19 disease. - Positive rapid test for SARS-CoV-2 (either ELISA IgG or PCR) at screening or prior to first vaccination. Testing may be repeated during the screening period if exposure to SARS-CoV-2 is suspected, at the discretion of the investigator. - Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 4 weeks prior to first study vaccination. - Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital). - Chronic administration (defined as more than 14 continuous days) of immunosuppressant, systemic glucocorticosteroids, or other immune-modifying drugs within 90 days prior to first study vaccination; or anticipation of the need for immunosuppressive treatment within 6 months after last vaccination. - Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days prior to first study vaccination. - Any acute illness concurrent or within 14 days prior to first study vaccination (medical history and/or physical examination) or documented temperature of >38°C during this period. This includes respiratory or constitutional symptoms consistent with SARS-CoV-2 (COVID-19) exposure (ie, cough, sore throat, difficulty breathing). - Known disturbance of coagulation (iatrogenic or congenital). - Evidence of Hepatitis B or C or HIV by laboratory testing. - A positive test result for drugs of abuse (except a positive test result associated with prescription medication that has been reviewed and approved by the investigator) or alcohol at screening. - Any neurological disease or history of significant neurological disorder (eg, meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré syndrome [genetic/congenital or acquired]). - Active cancer (malignancy) within 5 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma, at the discretion of the investigator) - Vital sign (blood pressure, pulse, temperature) abnormalities of toxicity grade >1. - Clinical laboratory abnormalities of toxicity grade >1 for selected serum chemistry and hematology parameters - Any known allergies to products contained in the investigational product or latex allergy. - Women who are pregnant, breastfeeding or who plan to become pregnant during the study. - History of alcohol abuse or drug addiction within 1 year prior to the first study vaccination. - Any 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 deemed likely to impair the quality of safety reporting). - Study team member or first-degree relative of any study team member (inclusive of sponsor, PPD, and site personnel involved in the study). Inclusion Criteria (Part 2): - Healthy adult males or females between 18 and 84 years of age, inclusive, at screening who are of legal adult age in their local jurisdiction. Healthy status will be determined by the investigator based on medical history, clinical laboratory results, vital sign measurements, and physical examination at screening. - The participant has a body mass index 17 to 35 kg/m2, inclusive, at screening. - Willing and able to give informed consent prior to study enrollment and comply with study procedures. - Female participants of childbearing potential (defined as any female 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 or documented plasma FSH level ≥40 mIU/mL]) must agree to be heterosexually inactive from at least 21 days prior to enrollment and through 6 months after the last vaccination OR agree to consistently use any of the following methods of contraception from at least 21 days prior to enrollment and through 6 months after the last vaccination. Exclusion Criteria (Part 2): - Participants who are having any current workup of undiagnosed illness within the last 8 weeks, which is either participant-reported or has been clinician-assessed, that could lead to a new condition diagnosis. - Participation in research involving an investigational product (drug/biologic/device) within 45 days prior to first study vaccination. - History of a confirmed diagnosis of SARS or history of a confirmed diagnosis of COVID-19 disease resulting in medical intervention. - Received influenza vaccination within 14 days prior to first study vaccination, or any other vaccine within 4 weeks prior to first study vaccination. - Have clinically significant chronic cardiovascular, endocrine, gastrointestinal/ hepatic, renal, neurological, respiratory, or other medical disorders not excluded by other exclusion criteria, that are assessed by the Investigator as being clinically unstable within the prior 4 weeks evidenced by: a) hospitalization for the condition, including day surgical interventions, b) new significant organ function deterioration, c) needing addition of new treatments or major dose adjustments of current treatments. - Diabetes mellitus requiring insulin therapy (either type 1 or type 2 diabetes mellitus). - Chronic obstructive pulmonary disease with a history of an acute exacerbation of any severity in the prior year. - Any history of congestive heart failure. - Any history of chronic kidney disease (the presence of impaired or reduced kidney function lasting at least 3 months). Clinical validation of potential cases of chronic kidney disease should be conducted. - Evidence of unstable coronary artery disease as manifested by cardiac intervention, addition of new cardiac medications for control of symptoms, or unstable angina in the past 3 months. - History of chronic neurological disorders that have required prior specialist physician review for diagnosis and management (such as multiple sclerosis, dementia, transient ischemic attacks, Parkinson's disease, degenerative neurological conditions, neuropathy, and epilepsy) or a history of stroke or previous neurological disorder within 12 months with residual symptoms. Participants with a history of migraine or chronic headaches or nerve root compression that have been stable on treatment for the last 4 weeks are not excluded. - Any autoimmune or immunodeficiency disease/condition (iatrogenic or congenital). - Chronic administration (defined as more than 14 continuous days) of immunosuppressants, systemic glucocorticosteroids reaching an immunosuppressive dose, or other immune-modifying drugs within 90 days prior to first study vaccination. - Received immunoglobulin, blood-derived products, or other immunosuppressant drugs within 90 days prior to first study vaccination. - Known disturbance of coagulation (iatrogenic or congenital). - Active cancer (malignancy) within 5 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma, at the discretion of the investigator). - Any known allergies to products contained in the investigational product or latex allergy. - Women who are breastfeeding or who plan to become pregnant during the study. - History of alcohol abuse or drug addiction within one year prior to the first study vaccination. - Any condition that, in the opinion of the investigator, would pose a health risk to the subject if enrolled or could interfere with evaluation of the study vaccine or interpretation of study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting). - Study team member or first-degree relative of any study team member (inclusive of sponsor, PPD, and site personnel involved in the study).
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04368988 | ClinicalTrials.gov: US National Institutes of Health |
| 2019nCoV101 | - |
Organisations
- Sponsors Novavax
- Affiliations Novavax; Takeda
Trial Dates
-
Initiation Dates
Planned : 15 May 2020
Actual : 25 May 2020
-
Primary Completion Dates
Planned : 21 May 2022
Actual : 01 Jun 2022
-
End Dates
Planned : 21 May 2022
Actual : 01 Jun 2022
Other Details
- Design double-blind; multicentre; parallel; prospective; randomised
- Phase of Trial Phase I/II
- Location Australia; USA
- Focus Adverse reactions; First in man; Pharmacodynamics; Registrational
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| Matrix M | Intramuscular | Injection |
| NVX CoV 2373Primary Drug | Intramuscular | Injection |
SARS-CoV-2 rS - 25 μg without Matrix-M - Phase 1
2 doses of SARS-CoV-2 rS - 25 μg, 1 dose each on Days 0 and 21.
Biological: SARS-CoV-2 rS - Phase 1 (Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS (0.6 mL) on Days 0 and 21.)
SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M - Phase 1
2 doses of SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M (mixed together for each injection), 1 dose each on Days 0 and 21.
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 1 (Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS mixed with Matrix-M adjuvant (0.6 mL) on Days 0 and 21.) Other Name: NVX-CoV2373
SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M - Phase 1
2 doses of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M (mixed together for each injection), 1 dose each on Days 0 and 21.
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 1 (Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS mixed with Matrix-M adjuvant (0.6 mL) on Days 0 and 21.) Other Name: NVX-CoV2373
Placebo - Phase 1
2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.
Other: Normal saline solution (NSS), Placebo - Phase 1 (Alternating intramuscular (deltoid) injections of placebo (0.6 mL) on Days 0 and 21.) Other Name: Sodium chloride solution for injection, 0.9%
Placebo - Phase 2
3 doses of Placebo (Saline), 1 dose each on Days 0, 21, and 189.
Other: Normal saline solution (NSS), Placebo - Phase 2 (Intramuscular (deltoid) injections of placebo (0.5 mL).) Other Name: Sodium chloride solution for injection, 0.9%
SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M - Phase 2
1 dose of SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M (co-formulated) on Day 0 then 2 doses of Placebo, 1 dose each on Days 21 and 189.
Other: Normal saline solution (NSS), Placebo - Phase 2 (Intramuscular (deltoid) injections of placebo (0.5 mL).) Other Name: Sodium chloride solution for injection, 0.9%
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 2 (Intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL).) Other Name: NVX-CoV2373
SARS-CoV-2 rS - 25/25 μg + 50 μg Matrix-M - Phase 2
2 doses of SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M (co-formulated), 1 dose each on Days 0 and 21, followed by 1 dose of Placebo on Day 189.
Other: Normal saline solution (NSS), Placebo - Phase 2 (Intramuscular (deltoid) injections of placebo (0.5 mL).) Other Name: Sodium chloride solution for injection, 0.9%
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 2 (Intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL).) Other Name: NVX-CoV2373
SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M - Phase 2
1 dose of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M (co-formulated) on Day 0 then 2 doses of Placebo, 1 dose each on Days 21 and 189.
Other: Normal saline solution (NSS), Placebo - Phase 2 (Intramuscular (deltoid) injections of placebo (0.5 mL).) Other Name: Sodium chloride solution for injection, 0.9%
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 2 (Intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL).) Other Name: NVX-CoV2373
SARS-CoV-2 rS - 5/5 μg + 50 μg Matrix-M - Phase 2
2 doses of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M (co-formulated), 1 dose each on Days 0 and 21, followed by 1 dose of Placebo on Day 189.
Other: Normal saline solution (NSS), Placebo - Phase 2 (Intramuscular (deltoid) injections of placebo (0.5 mL).) Other Name: Sodium chloride solution for injection, 0.9%
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 2 (Intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL).) Other Name: NVX-CoV2373
SARS-CoV-2 rS - Alternating 5/5 μg + 50 μg Matrix-M - Phase 2
1 dose of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M (co-formulated) on Day 0 then 1 dose of Placebo on Day 21 followed by 1 dose of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M (co-formulated) on Day 189.
Other: Normal saline solution (NSS), Placebo - Phase 2 (Intramuscular (deltoid) injections of placebo (0.5 mL).) Other Name: Sodium chloride solution for injection, 0.9%
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 2 (Intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL).) Other Name: NVX-CoV2373
SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M then Placebo - Phase 1
1 dose of SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M (mixed together for injection), on Day 0 followed by 1 dose of Placebo on Day 21.
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 1 (Intramuscular (deltoid) injection of SARS-CoV-2 rS mixed with Matrix-M adjuvant (0.6 mL) on Day 0.) Other Name: NVX-CoV2373
Other: Normal saline solution (NSS), Placebo, Day 21 - Phase 1 (Intramuscular injection of placebo (0.6 mL) in alternate deltoid on Day 21.) Other Name: Sodium chloride solution for injection, 0.9%
SARS-CoV-2 rS - 5/5/5 μg + 50 μg Matrix-M - Phase 2
3 doses of SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M (co-formulated), 1 dose each on Day 0, Day 21, and Day 189.
Biological: SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 2 (Intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL).) Other Name: NVX-CoV2373
Results
Adverse events
Results from phase II part of phase I/II trial demonstrated that the administration of the booster dose was generally well-tolerated. Local and systemic reactogenicity increased between dose 1, dose 2 and dose 3, with 90% of symptoms rated as mild or moderate after the third dose [2] . Results from the phase I portion of a phase I/II trial showed that that NVX CoV 2373 with the Matrix-M adjuvant was well-tolerated with a reassuring safety profile. The reactogenicity events were generally mild. Tenderness and pain were the most frequent local symptoms reported post Dose 1 and the systemic events were individually less frequent with headache, fatigue and myalgia being reported most commonly and greater reactogenicity was reported, following the second dose, although the majority of symptoms were reported as = Grade 1. The average duration of events was < 2 days. There were no severe/mild (Grade 3) unsolicited adverse events through 28 days after dose 2. Most of the adverse events were mild and deemed not related to vaccination. No serious adverse events (SAEs) were reported. One participant had mild fever that lasted 1 day [3] .
Immunogenicity
Results from phase II trial demonstrated that a single booster dose of NVX-CoV2373, given six months after an initial two-dose regimen, elicited a 4.6-fold increase in functional antibody titers. Additionally, functional ACE-2 binding inhibition antibodies cross-reactive with the Delta (B.1.617.2) variant were more than 6-fold higher than the primary vaccination series. Twenty-eight days following boosting, anti-spike IgG increased approximately 4.6-fold compared to the peak response seen after the second dose (Day 217 GMEU = 200,408 (95% CI: 159,796; 251,342)). This boosted value represents a 3.7 to 4.4-fold increase in anti-spike IgG values that were associated with protection in Novavax' PREVENT-19 and UK phase III clinical studies. Wild-type neutralization responses increased approximately 4.3-fold compared to the peak response seen after Dose 2 (IC50 neutralization titers = 6,231 (95% CI: 4,738; 8,195)). This boosted value represents a 4.6 to 5.5-fold increase over the neutralization response associated with protection in the PREVENT-19 and UK phase III clinical trials. Older participants (aged 60-84) showed a 5.4-fold increase in antibody responses, while younger participants (aged 18-59) showed a 3.7-fold increase. Very high levels of functional antibodies to the Alpha (B.1.1.7), Beta (B.1.351) and Delta variants were induced by boosting with NVX-CoV2373, with a 6.6-fold higher Delta variant-specific response when compared to the Delta response observed with the primary vaccination series [2] . Results from the phase I portion of a phase I/II trial showed that that NVX CoV 2373 induced neutralization titers in all the volunteers. Both 5 µg and 25 µg adjuvanted doses generated peak geometric mean titer (GMT) greater than 1:3,300 (5 µg adjuvanted dose group peak GMT: 3,906 (95% CI: 2,556; 5,970). Post administration of a single dose of vaccine, all the volunteers developed anti-spike IgG antibodies, and many also developed wild-type virus neutralizing antibody responses. However after the second dose, all (100%) the volunteers developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID-19 disease. Also, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional. The adjuvant was dose-sparing, with the lower 5 µg dose of NVX-CoV2373 performing comparably with the 25 µg dose. In a subset of vounteers, and NVX CoV 2373 induced antigen-specific polyfunctional CD4+ T cell responses with a strong bias toward the Th1 phenotype (IFN-g, IL-2, and TNF-a) [3] .
Publications
-
Novavax. Novavax Announces COVID-19 Vaccine Booster Data Demonstrating Four-Fold Increase in Neutralizing Antibody Levels Versus Peak Responses After Primary Vaccination. Media-Rel 2021;.
Media Release -
Novavax. Novavax Announces Positive Phase 1 Data for its COVID-19 Vaccine Candidate. Media-Rel 2020;.
Media Release -
Alves K, Plested JS, Galbiati S, Chau G, Cloney-Clark S, Zhu M, et al. Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373. . Vaccine 2023;.
PubMed | CrossRef Fulltext -
Mallory RM, Formica N, Pfeiffer S, Wilkinson B, Marcheschi A, Albert G, et al. Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial. Lancet-Infect-Dis 2022;22(11):1565-1576.
PubMed | CrossRef Fulltext -
Formica N, Mallory R, Albert G, Robinson M, Plested JS, Cho I, et al. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: A phase 2 randomized placebo-controlled trial. PLOS-Med 2021;18(10):e1003769.
PubMed | CrossRef Fulltext -
Novavax. Novavax Announces Publication of Phase 1 Data for COVID-19 Vaccine Candidate in The New England Journal of Medicine. Media-Rel 2020;.
Media Release -
Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. . N-Engl-J-Med 2020;.
PubMed | CrossRef Fulltext -
Fries L, Formica N, Mallory RM, Zhou H, Plested JS, Kalkeri R, et al. Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 SARS-CoV-2 Primary Vaccination. . J-Infect-Dis 2023;.
PubMed | CrossRef Fulltext
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
| Amber Leah | Paratus Clinical Research - Canberra - Phase 2 | Australia |
|
Arianna Mahfoud
+61283470645 adrianna@acrn.com.au
show details
|
Australian Clinical Research Network - Phase 2 | Australia |
|
Ashlee Innes
+61484007388 ashlee.innes@paratusclinical.com
show details
|
Paratus Clinical Research - Canberra - Phase 2 | Australia |
|
Audra Weslowski
208-377-8653 aweslowski@velocityclinical.com
show details
|
Advanced Clinical Research - Meridian - ERN-PPDS - Phase 2 | USA |
|
Biljana Georgievska
61 3 8593 9817 B.Georgievska@nucleusnetwork.com.au
show details
|
Center for Clinical Studies - Phase 1 and Phase 2, Q Pharm Pty Limited - Phase 1 and Phase 2 | Australia |
| Charlotte Lemech | Scientia Clinical Research Limited - Phase 2 | Australia |
|
Courtney Heisey
816-835-3481 cheisey@mcrmed.com
show details
|
Meridian Clinical Research-(Rockville Maryland) - Platinum - PPDS - Phase 2 | USA |
| Eugene Athan | Barwon Health - Phase 2 | Australia |
| Fiona Napier-Flood | Paratus Clinical Research - Western Sydney - Phase 2 | Australia |
|
Gemma Blunt
+61286088668 gemma.blunt@paratusclinical.com
show details
|
Paratus Clinical Research - Western Sydney - Phase 2 | Australia |
| Ira Berger | Meridian Clinical Research-(Rockville Maryland) - Platinum - PPDS - Phase 2 | USA |
| Jason Lickliter | Center for Clinical Studies - Phase 1 and Phase 2 | Australia |
|
Jeanne Blevins
513-247-5594 jeanne.blevins@synexus-us.com
show details
|
Synexus Clinical Research US, Inc. - Cincinnati - Phase 2 | USA |
| Joshua Kim | Paratus Clinical Research - Central Coast - Phase 2 | Australia |
|
Joy Soper
859-264-8799 joy.soper@amrllc.com
show details
|
Central Kentucky Research Associates Inc - Phase 2 | USA |
|
Justin Phillips
316-283-7403 justin.phillips@amrllc.com
show details
|
Alliance for Multipsecialty Research, LLC - Phase 2 | USA |
|
Kathryn Ellis
+61342152878 kathryc@barwonhealth.org.au
show details
|
Barwon Health - Phase 2 | Australia |
|
Lisa Hoagland
216-682-0320 242 lisa.hoagland@rapidmedicalresearch.com
show details
|
Rapid Medical Research Inc - ERN-PPDS - Phase 2 | USA |
|
Lisa Nelson
610438008816 lisa.nelson@scientiaclinicalresearch.com.au
show details
|
Scientia Clinical Research Limited - Phase 2 | Australia |
| Mark Adams | Central Kentucky Research Associates Inc - Phase 2 | USA |
| Mark Arya | Australian Clinical Research Network - Phase 2 | Australia |
| Mark Turner | Advanced Clinical Research - Meridian - ERN-PPDS - Phase 2 | USA |
| Mary Beth Manning | Rapid Medical Research Inc - ERN-PPDS - Phase 2 | USA |
|
Meenakshi (Kavya) Natesan
316-689-6645 kavya.natesan@amrllc.com
show details
|
Alliance for Multispecialty Research, LLC - Phase 2 | USA |
|
Monica Harris
+61243479185 monica.harris@paratusclinical.com
show details
|
Paratus Clinical Research - Central Coast - Phase 2 | Australia |
| Paul Bradley | Meridian Clinical Research-(Savannah Georgia) - Platinum - PPDS - Phase 2 | USA |
| Paul Griffin | Q Pharm Pty Limited - Phase 1 and Phase 2 | Australia |
| Paul Nugent | Synexus Clinical Research US, Inc. - Cincinnati - Phase 2 | USA |
| Richard Glover, II | Alliance for Multipsecialty Research, LLC - Phase 2 | USA |
|
Sarah Piplica
+61754431033 spiplica@usc.edu.au
show details
|
University of the Sunshine Coast - Phase 2, University of the Sunshine Coast, Health Hub Morayfield - Phase 2 | Australia |
| Scott Kitchener | University of the Sunshine Coast, Health Hub Morayfield - Phase 2 | Australia |
|
Stephanie Ailey
405-227-7047 sailey@mcrmed.com
show details
|
Meridian Clinical Research-(Savannah Georgia) - Platinum - PPDS - Phase 2 | USA |
| Susan Thackwray | University of the Sunshine Coast - Phase 2 | Australia |
| Terry Klein | Alliance for Multispecialty Research, LLC - Phase 2 | USA |
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| Advanced Clinical Research - Meridian - ERN-PPDS - Phase 2 | Meridian, Idaho | USA |
| Alliance for Multipsecialty Research, LLC - Phase 2 | Newton, Kansas | USA |
| Alliance for Multispecialty Research, LLC - Phase 2 | Wichita, Kansas | USA |
| Australian Clinical Research Network - Phase 2 | Maroubra, New South Wales | Australia |
| Barwon Health - Phase 2 | Geelong, Victoria | Australia |
| Center for Clinical Studies - Phase 1 and Phase 2 | Melbourne, Victoria | Australia |
| Central Kentucky Research Associates Inc - Phase 2 | Lexington, Kentucky | USA |
| Coalition for Epidemic Preparedness Innovations (CEPI) |
-
|
-
|
| Meridian Clinical Research-(Rockville Maryland) - Platinum - PPDS - Phase 2 | Rockville, Maryland | USA |
| Meridian Clinical Research-(Savannah Georgia) - Platinum - PPDS - Phase 2 | Savannah, Georgia | USA |
| Novavax |
-
|
-
|
| Paratus Clinical Research - Canberra - Phase 2 | Bruce, Australian Capital Territory | Australia |
| Paratus Clinical Research - Central Coast - Phase 2 | Kanwal, New South Wales | Australia |
| Paratus Clinical Research - Western Sydney - Phase 2 | Blacktown, New South Wales | Australia |
| Q Pharm Pty Limited - Phase 1 and Phase 2 | Herston, Queensland | Australia |
| Rapid Medical Research Inc - ERN-PPDS - Phase 2 | Cleveland, Ohio | USA |
| Scientia Clinical Research Limited - Phase 2 | Randwick, New South Wales | Australia |
| Synexus Clinical Research US, Inc. - Cincinnati - Phase 2 | Cincinnati, Ohio | USA |
| University of the Sunshine Coast - Phase 2 | Sippy Downs, Queensland | Australia |
| University of the Sunshine Coast, Health Hub Morayfield - Phase 2 | Morayfield, Queensland | Australia |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 02 Jun 2023 | Results | Results(n=1283) assessing Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373 published in the Vaccine Updated 08 Jun 2023 |
| 12 May 2023 | Results | Results published in the Journal of Infectious Diseases Updated 24 May 2023 |
| 01 Nov 2022 | Results | Results(n= 1282) of a secondary analysis assessing the immunogenicity and safety of a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine published in The Lancet Infectious Diseases Updated 14 Nov 2022 |
| 12 Sep 2022 | Other trial event | According to an Novavax media release, based on positive recommendation of CHMP the European Commission (EC) has approved the expanded conditional marketing authorization (CMA) of Nuvaxovid™ (NVX-CoV2373) COVID-19 vaccine in the European Union (EU) as a homologous and heterologous booster for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for adults aged 18 and older. Updated 14 Sep 2022 |
| 01 Sep 2022 | Other trial event | According to an Novavax media release, based on results from two Phase 2 trials conducted in Australia and South Africa, and the UK-sponsored COV-BOOST trial, The CHMP has recommended for expanded conditional marketing authorization (CMA) in the European Union (EU) as a homologous and heterologous booster for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for adults aged 18 and older. Updated 05 Sep 2022 |
| 18 Jul 2022 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 18 Jul 2022 |
| 12 Jul 2022 | Status change - completed | Status changed from active, no longer recruiting to completed. Updated 18 Jul 2022 |
| 13 Jun 2022 | Other trial event | According to a Novavax media release, the Australian Therapeutic Goods Administration (TGA) has granted provisional registration of Nuvaxovid (NVX-CoV2373) COVID-19 vaccine as a booster in individuals aged 18 and over, based on data from this trial. Updated 16 Jun 2022 |
| 19 Apr 2022 | Other trial event | According to a Novavax media release, Takeda received manufacturing and marketing approval from the Japan Ministry of Health, Labour and Welfare for its Nuvaxovid Intramuscular Injection for primary and booster immunization in individuals aged 18 and older. Updated 21 Apr 2022 |
| 01 Oct 2021 | Results | Results (n=1288) reporting safety and immunogenicity, assessing 1- or 2-dose regimens for 2 antigen dose levels from phase 2 portion of this trial published in the PLOS Medicine Updated 27 Oct 2021 |
| 05 Aug 2021 | Other trial event | According to a Novavax media release,Complete data from the study will be submitted to a peer review publication and posted to a preprint server. Updated 16 Aug 2021 |
| 05 Aug 2021 | Results | Preliminary results published in the Novavax Media Release Updated 16 Aug 2021 |
| 26 Jul 2021 | Biomarker Update | Biomarkers information updated Updated 17 Sep 2021 |
| 23 Jul 2021 | Completion date | Planned End Date changed from 30 Oct 2021 to 21 May 2022. Updated 28 Jul 2021 |
| 23 Jul 2021 | Other trial event | Planned primary completion date changed from 1 Dec 2020 to 21 May 2022. Updated 28 Jul 2021 |
| 15 Jul 2021 | Completion date | Planned End Date changed from 18 Nov 2021 to 30 Oct 2021. Updated 26 Jul 2021 |
| 30 Nov 2020 | Other trial event | According to a Novavax media release, additional clinical data are expected to be unblinded in Q1 2021. Updated 10 Dec 2020 |
| 09 Nov 2020 | Results | According to a Novavax media release, favorable preliminary reactogenicity data presented during the CDC Advisory Committee on Immunization Practices meeting. Updated 20 Nov 2020 |
| 27 Oct 2020 | Other trial event | According to a Novavax media release, it will present data from its ongoing Phase 1/2 clinical trial, including new Phase 2 reactogenicity data, on Friday, October 30 during the United States (U.S.) Center for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices' (ACIP) meeting between 10:00 am and 12:30 am ET on Friday, October 30. Updated 04 Nov 2020 |
| 08 Oct 2020 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 12 Oct 2020 |
| 25 Sep 2020 | Other trial event | According to an Endo International media release, interim data from this study is expected before the end of 2020. Updated 28 Sep 2020 |
| 08 Sep 2020 | Other trial event | Planned number of patients changed from 1500 to 1631. Updated 11 Sep 2020 |
| 08 Sep 2020 | Completion date | Planned End Date changed from 31 Jul 2021 to 18 Nov 2021. Updated 11 Sep 2020 |
| 08 Sep 2020 | Other trial event | Planned primary completion date changed from 31 Dec 2020 to 1 Dec 2020. Updated 11 Sep 2020 |
| 02 Sep 2020 | Results | Results (n=83) published in the New England Journal of Medicine Updated 08 Sep 2020 |
| 02 Sep 2020 | Results | According to a Novavax media release, results from phase 1 portion were published in The New England Journal of Medicine. Updated 04 Sep 2020 |
| 02 Sep 2020 | Results | Results presented in the Novavax Media Release. Updated 04 Sep 2020 |
| 24 Aug 2020 | Other trial event | According to a Novavax media release, interim data from this study is anticipated in the fourth quarter of this year. Updated 25 Aug 2020 |
| 24 Aug 2020 | Other trial event | Planned number of patients changed from 131 to 1500, according to a Novavax media release. Updated 25 Aug 2020 |
| 24 Aug 2020 | Other trial event | According to a Novavax media release, the first volunteers have been enrolled in the Phase 2 portion of this study. The Phase 2 clinical trial expands on the age range of the Phase 1 portion by including older adults 60-84 years of age as approximately 50 percent of the trial population. Updated 25 Aug 2020 |
| 17 Aug 2020 | Other trial event | According to a Novavax media release, Phase 2 clinical trials will begin in August Updated 20 Aug 2020 |
| 17 Aug 2020 | Other trial event | According to a Novavax media release, data from phase 1 portion have been submitted to the U.S. Food and Drug Administration (FDA) and an independent safety monitoring committee.The company intends to initiate the Phase 2 portion of this trial in the U.S. and Australia in the near future. This trial will include approximately 1,500 subjects and will include older adults. Updated 20 Aug 2020 |
| 04 Aug 2020 | Other trial event | According to a Novavax media release, Conference call to be held and Detailed data slides will be posted on novavax.com. Updated 06 Aug 2020 |
| 04 Aug 2020 | Other trial event | According to a Novavax media release, data have been submitted for peer-review to a scientific journal and to an online preprint server at medRxiv.org. Updated 06 Aug 2020 |
| 04 Aug 2020 | Results | Results from phase I portion presented in the Novavax Media Release. Updated 06 Aug 2020 |
| 23 Jul 2020 | Other trial event | According to a Novavax media release, the company will announce phase I data consisting preliminary immunogenicity and safety results, during the first week of August and phase 2 portion to assess immunity, safety, and COVID-19 disease reduction is expected to begin shortly thereafter. Updated 28 Jul 2020 |
| 25 May 2020 | Other trial event | According to a Novavax media release, first patient has been enrolled in this study. Updated 26 May 2020 |
| 11 May 2020 | Other trial event | According to a Novavax media release, the Coalition for Epidemic Preparedness Innovations (CEPI) will invest up to $384 million of additional funding, on top of $4 million it invested in March, to advance clinical development of NVX-CoV2373. Updated 21 May 2020 |
| 11 May 2020 | Other trial event | According to a Novavax media release, phase I portion of this trial is starting this month in Australia and the Phase 2 portion conducted in multiple countries following successful Phase 1 top-line results that are expected in July. Updated 21 May 2020 |
| 11 May 2020 | Other trial event | According to a Novavax media release, recruitment for this trial began in May 2020. Updated 14 May 2020 |
| 11 May 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting, according to a Novavax media release. Updated 14 May 2020 |
| 08 May 2020 | Other trial event | New source identified and integrated (ClinicalTrial.gov: NCT04368988) Updated 08 May 2020 |
| 28 Apr 2020 | Other trial event | According to a 360 Biolabs media release, Novavax has selected Australian speciality laboratory 360biolabs, to conduct sample analysis for this clinical trial of its SARS-CoV-2 recombinant spike protein nanoparticle vaccine, NVX-CoV2373. Updated 20 Jul 2020 |
| 28 Apr 2020 | Status change - not yet recruiting | Status changed from planning to not yet recruiting. Updated 08 May 2020 |
| 16 Apr 2020 | Other trial event | According to a Novavax media release, Nucleus (multi-site phase I clinical trials provider) is due to commence Phase 1 testing for the NVX-CoV2373, at its Melbourne and Brisbane clinics within the coming weeks. Updated 17 Apr 2020 |
| 08 Apr 2020 | Other trial event | According to a Novavax media release, the company has planned to initiate this trial ahead of schedule in mid-May and expects preliminary immunogenicity and safety results to be available in July 2020. Updated 15 Apr 2020 |
| 11 Mar 2020 | Other trial event | According to a Novavax media release, the company began efforts to develop a novel vaccine to protect against COVID-19 in January.Initiation of Phase I clinical testing is expected in May or June 2020 (late spring of 2020).The company expects to utilize its proprietary Matrix-M adjuvant with its COVID-19 vaccine candidate to enhance immune responses. Updated 18 Mar 2020 |
| 11 Mar 2020 | Other trial event | According to a Novavax media release, the company recently announced that the Coalition for Epidemic Preparedness Innovations (CEPI) awarded an initial funding of $4 million to support its effort to develop a COVID-19 vaccine. CEPI and Novavax are having ongoing discussions on additional funding from CEPI to address Novavax costs through Phase 1. Updated 18 Mar 2020 |
| 02 Mar 2020 | New trial record | New trial record Updated 02 Mar 2020 |
| 26 Feb 2020 | Other trial event | According to a Novavax media release, this study will begin by the end of Spring 2020. Updated 02 Mar 2020 |
Table of Contents
References
-
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
Novavax. Novavax Announces COVID-19 Vaccine Booster Data Demonstrating Four-Fold Increase in Neutralizing Antibody Levels Versus Peak Responses After Primary Vaccination. Media-Rel 2021;.
Media Release -
Novavax. Novavax Announces Positive Phase 1 Data for its COVID-19 Vaccine Candidate. Media-Rel 2020;.
Media Release -
Novavax. Novavax to commence COVID-19 vaccine trial with Nucleus Network. Media-Rel 2020;.
Media Release -
Novavax. Novavax Initiates Phase 1/2 Clinical Trial of COVID-19 Vaccine. Media-Rel 2020;.
Media Release -
Alves K, Plested JS, Galbiati S, Chau G, Cloney-Clark S, Zhu M, et al. Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373. . Vaccine 2023;.
PubMed | CrossRef Fulltext -
Novavax. Novavax Reports Third Quarter 2020 Financial and Operational Results. Media-Rel 2020;.
Media Release -
Mallory RM, Formica N, Pfeiffer S, Wilkinson B, Marcheschi A, Albert G, et al. Safety and immunogenicity following a homologous booster dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): a secondary analysis of a randomised, placebo-controlled, phase 2 trial. Lancet-Infect-Dis 2022;22(11):1565-1576.
PubMed | CrossRef Fulltext -
Formica N, Mallory R, Albert G, Robinson M, Plested JS, Cho I, et al. Different dose regimens of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373) in younger and older adults: A phase 2 randomized placebo-controlled trial. PLOS-Med 2021;18(10):e1003769.
PubMed | CrossRef Fulltext -
Novavax, FUJIFILM. Novavax and FUJIFILM Diosynth Biotechnologies Initiate Large Scale Manufacturing of COVID-19 Vaccine Candidate. Media-Rel 2020;.
Media Release -
Novavax. Novavax Nuvaxovid(Tm) COVID-19 Vaccine Granted Expanded Conditional Marketing Authorization in the European Union for Use as a Booster for Adults Aged 18 and Older. Media-Rel 2022;.
Media Release -
Novavax. Novavax COVID-19 Vaccine Nuvaxovid(Tm) Provisionally Registered in Australia as a Booster in Individuals Aged 18 and Over. Media-Rel 2022;.
Media Release -
Novavax. Novavax Advances Development of Novel COVID-19 Vaccine. Media-Rel 2020;.
Media Release -
Novavax. Novavax Initiates Efficacy Trial of COVID-19 Vaccine in South Africa. Media-Rel 2020;.
Media Release -
Novavax. Novavax Reports Fourth Quarter and Full Year 2019 Financial Results. Media-Rel 2020;.
Media Release -
Novavax. Novavax Identifies Coronavirus Vaccine Candidate; Accelerates Initiation of First-in-Human Trial to Mid-May. Media-Rel 2020;.
Media Release -
Novavax. Novavax Provides Phase 3 COVID-19 Vaccine Clinical Development Update. Media-Rel 2020;.
Media Release -
Novavax. Novavax Announces Publication of Phase 1 Data for COVID-19 Vaccine Candidate in The New England Journal of Medicine. Media-Rel 2020;.
Media Release -
Novavax. Novavax Initiates Phase 2 Portion of Phase 1/2 Clinical Trial of COVID-19 Vaccine. Media-Rel 2020;.
Media Release -
360 Biolabs. 360biolabs supports the first Australian COVID-19 clinical vaccine trials. Media-Rel 2020;.
Media Release -
Novavax. Novavax Reports First Quarter 2020 Financial Results. Media-Rel 2020;.
Media Release -
Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. . N-Engl-J-Med 2020;.
PubMed | CrossRef Fulltext -
Fries L, Formica N, Mallory RM, Zhou H, Plested JS, Kalkeri R, et al. Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 SARS-CoV-2 Primary Vaccination. . J-Infect-Dis 2023;.
PubMed | CrossRef Fulltext -
Novavax. Novavax Nuvaxovid(Tm) COVID-19 Vaccine Recommended by CHMP for Expanded Conditional Marketing Authorization in the European Union as a Booster for Adults Aged 18 and Older. Media-Rel 2022;.
Media Release -
Novavax. Novavax Announces Approval of Nuvaxovid(Tm) COVID-19 Vaccine for Primary and Booster Immunization in Japan. Media-Rel 2022;.
Media Release -
Endo International. Endo Announces Fill-Finish Manufacturing and Services Agreement for Novavax COVID-19 Vaccine Candidate. Media-Rel 2020;.
Media Release -
Novavax. Novavax to Receive up to $388 Million Funding from CEPI for COVID-19 Vaccine Development and Manufacturing. Media-Rel 2020;.
Media Release -
Takeda. Takeda Announces Approval of Nuvaxovid(Rm) COVID-19 Vaccine for Primary and Booster Immunization in Japan. Media-Rel 2022;.
Media Release -
Novavax. Novavax Announces COVID-19 Vaccine Clinical Development Progress. Media-Rel 2020;.
Media Release
Adis International Ltd. Part of Springer Science+Business Media
© Springer Nature Switzerland AG