Evaluation of the Safety and Immunogenicity of a SARS-CoV-2 rS Nanoparticle Vaccine With/Without Matrix-M Adjuvant
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
1 other identifier
interventional
1,419
2 countries
18
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 covid19
Started May 2020
Longer than P75 for phase_1 covid19
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 24, 2020
CompletedFirst Posted
Study publicly available on registry
April 30, 2020
CompletedStudy Start
First participant enrolled
May 25, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2022
CompletedApril 10, 2023
April 1, 2023
2 years
April 24, 2020
April 6, 2023
Conditions
Outcome Measures
Primary Outcomes (11)
Participants with Solicited Adverse Events (AEs) - Phase 1
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.
28 days
Safety Laboratory Values (Serum Chemistry, Hematology) - Phase 1
Safety laboratory values (serum chemistry, hematology) by FDA toxicity scoring (absolute and change from baseline where identified) at 7 days after each vaccination.
28 days
Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs) - Phase 1
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 21.
21 days
Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs) - Phase 1
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.
35 days
Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs) - Phase 1
Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs through Day 35.
35 days
Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs) - Phase 1
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.
35 days
Serum IgG Antibody Levels Expressed as GMEUs - Phase 2
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.
Day 35
Serum IgG Antibody Levels Expressed as GMFRs - Phase 2
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.
Day 35
Serum IgG Antibody Levels Expressed as SCRs - Phase 2
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.
Day 35
Participants with Solicited Adverse Events (AEs) - Phase 2
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.
28 days
Participants with Unsolicited AEs - Phase 2
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.
35 days
Secondary Outcomes (43)
Participants with Unsolicited AEs - Phase 1
49 days
Participants with Abnormal Vital Signs - Phase 1
21 days
Changes from Baseline in Body Temperature - Phase 1
189 days
Changes from Baseline in Blood Pressure - Phase 1
189 days
Changes from Baseline in Pulse Rate - Phase 1
189 days
- +38 more secondary outcomes
Study Arms (12)
Placebo - Phase 1
PLACEBO COMPARATOR2 doses of Placebo (Saline), 1 dose each on Days 0 and 21.
SARS-CoV-2 rS - 25 μg without Matrix-M - Phase 1
EXPERIMENTAL2 doses of SARS-CoV-2 rS - 25 μg, 1 dose each on Days 0 and 21.
SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M - Phase 1
EXPERIMENTAL2 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.
SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M - Phase 1
EXPERIMENTAL2 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.
SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M then Placebo - Phase 1
EXPERIMENTAL1 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.
Placebo - Phase 2
PLACEBO COMPARATOR3 doses of Placebo (Saline), 1 dose each on Days 0, 21, and 189.
SARS-CoV-2 rS - 5/5 μg + 50 μg Matrix-M - Phase 2
EXPERIMENTAL2 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.
SARS-CoV-2 rS - Alternating 5/5 μg + 50 μg Matrix-M - Phase 2
EXPERIMENTAL1 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.
SARS-CoV-2 rS - 25/25 μg + 50 μg Matrix-M - Phase 2
EXPERIMENTAL2 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.
SARS-CoV-2 rS - 25 μg + 50 μg Matrix-M - Phase 2
EXPERIMENTAL1 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.
SARS-CoV-2 rS - 5/5/5 μg + 50 μg Matrix-M - Phase 2
EXPERIMENTAL3 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.
SARS-CoV-2 rS - 5 μg + 50 μg Matrix-M - Phase 2
EXPERIMENTAL1 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.
Interventions
Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS (0.6 mL) on Days 0 and 21.
Alternating intramuscular (deltoid) injections of SARS-CoV-2 rS mixed with Matrix-M adjuvant (0.6 mL) on Days 0 and 21.
Alternating intramuscular (deltoid) injections of placebo (0.6 mL) on Days 0 and 21.
Intramuscular (deltoid) injections of placebo (0.5 mL).
Intramuscular (deltoid) injection of SARS-CoV-2 rS mixed with Matrix-M adjuvant (0.6 mL) on Day 0.
Intramuscular injection of placebo (0.6 mL) in alternate deltoid on Day 21.
Intramuscular (deltoid) injections of SARS-CoV-2 rS co-formulated with Matrix-M adjuvant (0.5 mL).
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +33 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novavaxlead
- Coalition for Epidemic Preparedness Innovationscollaborator
Study Sites (18)
Meridian Clinical Research-(Savannah Georgia) - Platinum - PPDS - Phase 2
Savannah, Georgia, 31406, United States
Advanced Clinical Research - Meridian - ERN-PPDS - Phase 2
Meridian, Idaho, 83642, United States
Alliance for Multispecialty Research, LLC - Phase 2
Newton, Kansas, 67114, United States
Alliance for Multispecialty Research, LLC - Phase 2
Wichita, Kansas, 67207, United States
Central Kentucky Research Associates Inc - Phase 2
Lexington, Kentucky, 40509, United States
Meridian Clinical Research-(Rockville Maryland) - Platinum - PPDS - Phase 2
Rockville, Maryland, 20854, United States
Synexus Clinical Research US, Inc. - Cincinnati - Phase 2
Cincinnati, Ohio, 45236, United States
Rapid Medical Research Inc - ERN-PPDS - Phase 2
Cleveland, Ohio, 44122, United States
Paratus Clinical Research - Canberra - Phase 2
Bruce, Australian Capital Territory, 2617, Australia
Paratus Clinical Research - Western Sydney - Phase 2
Blacktown, New South Wales, 2148, Australia
Paratus Clinical Research - Central Coast - Phase 2
Kanwal, New South Wales, 2259, Australia
Australian Clinical Research Network - Phase 2
Maroubra, New South Wales, 2035, Australia
Scientia Clinical Research Limited - Phase 2
Randwick, New South Wales, 2031, Australia
Q Pharm Pty Limited - Phase 1
Herston, Queensland, 4006, Australia
University of the Sunshine Coast, Health Hub Morayfield - Phase 2
Morayfield, Queensland, 4506, Australia
University of the Sunshine Coast - Phase 2
Sippy Downs, Queensland, 4556, Australia
Barwon Health - Phase 2
Geelong, Victoria, 3220, Australia
Center for Clinical Studies - Phase 1 and Phase 2
Melbourne, Victoria, 3181, Australia
Related Publications (8)
Bangaru S, Jackson AM, Copps J, Fernandez-Quintero ML, Torres JL, Richey ST, Nogal B, Sewall LM, Torrents de la Pena A, Rehman A, Guebre-Xabier M, Girard B, Das R, Corbett-Helaire KS, Seder RA, Graham BS, Edwards DK, Patel N, Smith G, Ward AB. Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines. Cell Rep. 2025 Jul 22;44(7):115986. doi: 10.1016/j.celrep.2025.115986. Epub 2025 Jul 8.
PMID: 40632654DERIVEDAlves K, Plested JS, Galbiati S, Chau G, Cloney-Clark S, Zhu M, Kalkeri R, Patel N, Smith K, Marcheschi A, Pfeiffer S, McFall H, Smith G, Glenn GM, Dubovsky F, Mallory RM; Novavax 2019nCoV-101 Study Group. Immunogenicity and safety of a fourth homologous dose of NVX-CoV2373. Vaccine. 2023 Jun 29;41(29):4280-4286. doi: 10.1016/j.vaccine.2023.05.051. Epub 2023 Jun 2.
PMID: 37271706DERIVEDFries L, Formica N, Mallory RM, Zhou H, Plested JS, Kalkeri R, Moldovan I, Patel N, Albert G, Robinson M, Cho I, Chau G, Dubovsky F, Glenn GM; 2019nCoV-101 Study Group. Strong CD4+ T-Cell Responses to Ancestral and Variant Spike Proteins Are Established by NVX-CoV2373 Severe Acute Respiratory Syndrome Coronavirus 2 Primary Vaccination. J Infect Dis. 2023 Sep 15;228(6):734-741. doi: 10.1093/infdis/jiad163.
PMID: 37210741DERIVEDMallory RM, Formica N, Pfeiffer S, Wilkinson B, Marcheschi A, Albert G, McFall H, Robinson M, Plested JS, Zhu M, Cloney-Clark S, Zhou B, Chau G, Robertson A, Maciejewski S, Hammond HL, Baracco L, Logue J, Frieman MB, Smith G, Patel N, Glenn GM; Novavax 2019nCoV101 Study Group. 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 Nov;22(11):1565-1576. doi: 10.1016/S1473-3099(22)00420-0. Epub 2022 Aug 10.
PMID: 35963274DERIVEDFormica N, Mallory R, Albert G, Robinson M, Plested JS, Cho I, Robertson A, Dubovsky F, Glenn GM; 2019nCoV-101 Study Group. 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 Oct 1;18(10):e1003769. doi: 10.1371/journal.pmed.1003769. eCollection 2021 Oct.
PMID: 34597298DERIVEDTian JH, Patel N, Haupt R, Zhou H, Weston S, Hammond H, Logue J, Portnoff AD, Norton J, Guebre-Xabier M, Zhou B, Jacobson K, Maciejewski S, Khatoon R, Wisniewska M, Moffitt W, Kluepfel-Stahl S, Ekechukwu B, Papin J, Boddapati S, Jason Wong C, Piedra PA, Frieman MB, Massare MJ, Fries L, Bengtsson KL, Stertman L, Ellingsworth L, Glenn G, Smith G. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021 Jan 14;12(1):372. doi: 10.1038/s41467-020-20653-8.
PMID: 33446655DERIVEDGuebre-Xabier M, Patel N, Tian JH, Zhou B, Maciejewski S, Lam K, Portnoff AD, Massare MJ, Frieman MB, Piedra PA, Ellingsworth L, Glenn G, Smith G. NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge. Vaccine. 2020 Nov 25;38(50):7892-7896. doi: 10.1016/j.vaccine.2020.10.064. Epub 2020 Oct 23.
PMID: 33139139DERIVEDKeech C, Albert G, Cho I, Robertson A, Reed P, Neal S, Plested JS, Zhu M, Cloney-Clark S, Zhou H, Smith G, Patel N, Frieman MB, Haupt RE, Logue J, McGrath M, Weston S, Piedra PA, Desai C, Callahan K, Lewis M, Price-Abbott P, Formica N, Shinde V, Fries L, Lickliter JD, Griffin P, Wilkinson B, Glenn GM. Phase 1-2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N Engl J Med. 2020 Dec 10;383(24):2320-2332. doi: 10.1056/NEJMoa2026920. Epub 2020 Sep 2.
PMID: 32877576DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Development
Novavax
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 24, 2020
First Posted
April 30, 2020
Study Start
May 25, 2020
Primary Completion
June 1, 2022
Study Completion
June 1, 2022
Last Updated
April 10, 2023
Record last verified: 2023-04
Data Sharing
- IPD Sharing
- Will not share