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

NCT05372588 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 2019nCoV- 311
• Study Type: interventional
• Target: 1,340
• Locations: 1 country
• Sites: 19

Brief Summary

This is a Multi-Part, Phase 3, randomized, observer-blinded study to evaluate the safety and immunogenicity of booster doses of Omicron subvariant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant (r) spike (S) protein nanoparticle vaccines (SARS-CoV-2 rS) adjuvanted with Matrix-M™ adjuvant (NVX-CoV2515 \[BA.1\] and NVX-CoV2540 \[BA.5\]) and bivalent (NVX-CoV2373 \[prototype\] + Omicron subvariant) SARS-CoV-2 rS vaccines (NVX-CoV2373 + NVX CoV2515 and NVX CoV2373 + NVX CoV2540) in previously vaccinated adults 18 years of age and older.

Conditions

COVID-19; SARS CoV 2 Infection

Keywords

Coronavirus

Outcome Measures

Primary Outcomes (5)

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

  Microneutralization \[MN\] geometric mean titers (GMTs) with an inhibitory concentration of 50% (MN50) to the Omicron BA.1 subvariant, assessed at Day 14 following initial study vaccination and analyzed by previous vaccine combination received.

  Day 14

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

  Seroresponse rates (SRRs) (proportion of participants who achieve ≥ 4-fold increase from baseline \[Day 0\]) in MN50 titer concentrations to the Omicron BA.1 subvariant, assessed at Day 14 following initial study vaccination and analyzed by previous vaccine combination received.

  Day 14

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

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

  Day 28

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

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

  Day 28

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

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

  Day 28

Secondary Outcomes (31)

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

  Day 0 to Day 240

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

  Day 7 to Day 240

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

  Day 7 to Day 240

• Part 1: Immunoglobulin G (IgG) antibody levels to the ancestral (Wuhan), Omicron BA.1 and Omicron BA.5 viruses expressed as GMT

  Day 0 to Day 240

• Part 1:IgG antibody levels to the ancestral (Wuhan), Omicron BA.1, and Omicron BA.5 viruses expressed as GMFR

  Day 0 to Day 240

Study Arms (8)

Group A (NVX-CoV2515 )

EXPERIMENTAL

1 intramuscular (IM) injection of NVX-CoV2515 of 0.5 mL injection volume on Day 0.

Drug: NVX-CoV2515

Group B (NVX-CoV2373 )

EXPERIMENTAL

1 intramuscular (IM) injection of NVX-CoV2373 of 0.5 mL injection volume on Day 0.

Drug: NVX-Cov2373

Group C (NVX-CoV2515 )

EXPERIMENTAL

1 intramuscular (IM) injection of NVX-CoV2515 of 0.5 mL injection volume on Day 0.

Drug: NVX-CoV2515

Group D (NVX-CoV2373)

EXPERIMENTAL

1 intramuscular (IM) injection of NVX-CoV2373 of 0.5 mL injection volume on Day 0.

Drug: NVX-Cov2373

Group E (BA.1 Bivalent Vaccine)

EXPERIMENTAL

1 intramuscular (IM) injection of Bivalent Vaccine (NVX-CoV2373 + NVX-CoV2515) of 0.5 mL injection volume on Day 0.

Drug: NVX-CoV2373 + NVX-CoV2515

Group F (NVX-CoV2540)

EXPERIMENTAL

2 intramuscular (IM) injections of NVX-CoV2373 of 0.5 mL injection volume on Day 0 and on Day 90.

Drug: NVX-CoV2540

Group G (NVX-CoV2373)

EXPERIMENTAL

2 intramuscular (IM) injections of NVX-CoV2373 of 0.5 mL injection volume on Day 0 and on Day 90.

Drug: NVX-Cov2373

Group H (NVX-CoV2373 + NVX-CoV2540)

EXPERIMENTAL

2 intramuscular (IM) injections of NVX-CoV2373 of 0.5 mL injection volume on Day 0 and on Day 90.

Drug: NVX-CoV2373 + NVX-CoV2540

Interventions

NVX-CoV2515 DRUG

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

Also known as: Omicron BA.1 SARS-CoV-2 rS /Matrix-M Adjuvant

Group A (NVX-CoV2515 ); Group C (NVX-CoV2515 )

NVX-Cov2373 DRUG

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

Also known as: SARS-CoV-2 rS/Matrix-M Adjuvant

Group B (NVX-CoV2373 ); Group D (NVX-CoV2373); Group G (NVX-CoV2373)

NVX-CoV2373 + NVX-CoV2515 DRUG

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

Also known as: Prototype/BA.1 Bivalent Vaccine

Group E (BA.1 Bivalent Vaccine)

NVX-CoV2540 DRUG

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

Also known as: Omicron BA.5 SARS-CoV-2 rS /Matrix-M Adjuvant

Group F (NVX-CoV2540)

NVX-CoV2373 + NVX-CoV2540 DRUG

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

Also known as: Prototype/BA.5 Bivalent Vaccine

Group H (NVX-CoV2373 + NVX-CoV2540)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• To be included in this study, each individual must satisfy all the following criteria:
• Adults ≥ 18 and ≤ 64 years of age at screening.
• Willing and able to give informed consent prior to study enrollment and to comply with study procedures.
• Female participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile \[ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy\] or postmenopausal \[defined as amenorrhea ≥ 12 consecutive months\]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of the study OR agree to consistently use a medically acceptable method of contraception listed below from ≥ 28 days prior to and through the end of the study.
• Is medically stable, as determined by the investigator (based on a review of health status, vital signs \[to include body temperature\], medical history, and targeted physical examination \[to include body weight\]). Vital signs must be within medically acceptable ranges prior to the vaccination.
• Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.
• Have previously received 2 doses of the Moderna and/or Pfizer-BioNTech COVID-19 prototype vaccines with the last dose having been given ≥ 180 days prior to study vaccination or 3 doses of the Moderna and/or Pfizer-BioNTech COVID-19 prototype vaccines with the last dose having been given ≥ 90 days previously prior to the study vaccination.

You may not qualify if:

• If an individual meets any of the following criteria, he or she is ineligible for this study:
• Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clinical trial COVID- 19 vaccines.
• Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to study vaccination.
• Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccination which may be received \> 14 days prior to study vaccination, or rabies vaccine which may be given if medically indicated.
• Any known allergies to products contained in the investigational product.
• Any history of anaphylaxis to any prior vaccine.
• Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
• Chronic administration (defined as \> 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study vaccination.
• Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to the first study vaccination, except for rabies immunoglobulin which may be given if medically indicated.
• Active cancer (malignancy) on therapy within 3 years prior to study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the investigator).
• Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of the study.
• Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
• 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).
• Study team member or immediate family member of any study team member (inclusive of Sponsor, clinical research organization (CRO), and study site personnel involved in the conduct or planning of the study).
• Part 2

Sponsors & Collaborators

• Novavax: lead

Study Sites (19)

Paratus Clinical Research Canberra

Bruce, Australian Capital Territory, 2617, Australia

Location

Paratus Clinical Research Western Sydney

Blacktown, New South Wales, 2148, Australia

Location

Emeritus Research

Botany, New South Wales, 2019, Australia

Location

Northern Beaches Clinical Research

Brookvale, New South Wales, 2100, Australia

Location

Paratus Clinical Research Central Coast

Kanwal, New South Wales, 2291, Australia

Location

Australian Clinical Research Network (ACRN)

Maroubra, New South Wales, 2035, Australia

Location

AIM Centre (Hunter Diabetes Centre)

Merewether, New South Wales, 2291, Australia

Location

Novatrials

Newcastle, New South Wales, 2289, Australia

Location

Holdsworth House Medical Practice

Sydney, New South Whales, 2010, Australia

Location

Paratus Clinical Research Brisbane

Albion, Queensland, 4010, Australia

Location

Core Research Group Pty Ltd

Milton, Queensland, 4064, Australia

Location

Griffith University Clinical Trial Unit

Southport, Queensland, 4222, Australia

Location

Data Health Australia PTY Ltd t/a Austrials

Taringa, Queensland, 4068, Australia

Location

AusTrials Wellers Hill

Wellers Hill, Queensland, 4121, Australia

Location

Clinical Medical and Analytical Excellence (CMAX)

Adelaide, South Australia, 5000, Australia

Location

Eastern Health-Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Emeritus Research

Camberwell, Victoria, 3124, Australia

Location

University Hospital Geelong-Barwon Health

Geelong, Victoria, 3220, Australia

Location

Monash Health -Monash Medical Centre

Melbourne, Victoria, 3168, Australia

Location

Related Publications (2)

• Bennett C, Rivers EJ, Woo W, Bloch M, Cheung K, Griffin P, Mohan R, Deshmukh S, Arya M, Cumming O, Neville AM, Pardey TM, Plested JS, Cloney-Clark S, Zhu M, Kalkeri R, Patel N, Buchanan A, Marcheschi A, Swan J, Smith G, Cho I, Glenn GM, Walker R, Mallory RM. Immunogenicity and Safety of Heterologous Omicron BA.1 and Bivalent SARS-CoV-2 Recombinant Spike Protein Booster Vaccines: A Phase 3 Randomized Clinical Trial. J Infect Dis. 2024 Jul 25;230(1):e4-e16. doi: 10.1093/infdis/jiad508.

  PMID: 39052718 DERIVED

• Bennett C, Woo W, Bloch M, Cheung K, Griffin P, Mohan R, Deshmukh S, Arya M, Cumming O, Neville AM, McCallum Pardey TG, Plested JS, Cloney-Clark S, Zhu M, Kalkeri R, Patel N, Marcheschi A, Swan J, Smith G, Cho I, Glenn GM, Walker R, Mallory RM; Novavax 2019nCoV-311 Study Group. Immunogenicity and safety of a bivalent (omicron BA.5 plus ancestral) SARS-CoV-2 recombinant spike protein vaccine as a heterologous booster dose: interim analysis of a phase 3, non-inferiority, randomised, clinical trial. Lancet Infect Dis. 2024 Jun;24(6):581-593. doi: 10.1016/S1473-3099(24)00077-X. Epub 2024 Mar 6.

  PMID: 38460525 DERIVED

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

NVX-CoV2373 adjuvated lipid nanoparticle

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Clinical Development

  Novavax, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: May 9, 2022
• First Posted: May 12, 2022
• Study Start: May 25, 2022
• Primary Completion: July 17, 2022
• Study Completion: April 7, 2024
• Last Updated: April 23, 2024

Record last verified: 2024-04

Locations

AU (19)