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

NCT ID: NCT05372588

Last Updated: 2024-04-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1340 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-25

Study Completion Date

2024-04-07

Brief Summary

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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.

Detailed Description

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Conditions

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COVID-19 SARS CoV 2 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group A (NVX-CoV2515 )

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

Group Type EXPERIMENTAL

NVX-CoV2515

Intervention Type DRUG

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

Group B (NVX-CoV2373 )

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

Group Type EXPERIMENTAL

NVX-Cov2373

Intervention Type DRUG

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

Group C (NVX-CoV2515 )

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

Group Type EXPERIMENTAL

NVX-CoV2515

Intervention Type DRUG

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

Group D (NVX-CoV2373)

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

Group Type EXPERIMENTAL

NVX-Cov2373

Intervention Type DRUG

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

Group E (BA.1 Bivalent Vaccine)

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

Group Type EXPERIMENTAL

NVX-CoV2373 + NVX-CoV2515

Intervention Type DRUG

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

Group F (NVX-CoV2540)

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

Group Type EXPERIMENTAL

NVX-CoV2540

Intervention Type DRUG

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

Group G (NVX-CoV2373)

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

Group Type EXPERIMENTAL

NVX-Cov2373

Intervention Type DRUG

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

Group H (NVX-CoV2373 + NVX-CoV2540)

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

Group Type EXPERIMENTAL

NVX-CoV2373 + NVX-CoV2540

Intervention Type DRUG

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

Interventions

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NVX-CoV2515

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

Intervention Type DRUG

NVX-Cov2373

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

Intervention Type DRUG

NVX-CoV2373 + NVX-CoV2515

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

Intervention Type DRUG

NVX-CoV2540

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

Intervention Type DRUG

NVX-CoV2373 + NVX-CoV2540

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

Intervention Type DRUG

Other Intervention Names

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Omicron BA.1 SARS-CoV-2 rS /Matrix-M Adjuvant SARS-CoV-2 rS/Matrix-M Adjuvant Prototype/BA.1 Bivalent Vaccine Omicron BA.5 SARS-CoV-2 rS /Matrix-M Adjuvant Prototype/BA.5 Bivalent Vaccine

Eligibility Criteria

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Inclusion Criteria

To be included in this study, each individual must satisfy all the following criteria:

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


To be included in this study, each individual must satisfy all of the following criteria:

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

Exclusion Criteria

If an individual meets any of the following criteria, he or she is ineligible for this study:

1. Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clinical trial COVID- 19 vaccines.
2. Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to study vaccination.
3. Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccination which may be received \> 14 days prior to study vaccination, or rabies vaccine which may be given if medically indicated.
4. Any known allergies to products contained in the investigational product.
5. Any history of anaphylaxis to any prior vaccine.
6. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
7. Chronic administration (defined as \> 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to study vaccination.
8. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to the first study vaccination, except for rabies immunoglobulin which may be given if medically indicated.
9. Active cancer (malignancy) on therapy within 3 years prior to study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the investigator).
10. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of the study.
11. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
12. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the study vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
13. Study team member or immediate family member of any study team member (inclusive of Sponsor, clinical research organization (CRO), and study site personnel involved in the conduct or planning of the study).

Part 2


If an individual meets any of the following criteria, he or she is ineligible for this study:

1. Received COVID-19 vaccines other than Moderna and/or Pfizer-BioNTech in the past, inclusive of clinical trial COVID-19 vaccines.
2. Participation in research involving receipt of investigational products (drug/biologic/device) within 90 days prior to first study vaccination.
3. Received any vaccine ≤ 90 days prior to study vaccination, except for influenza vaccination which may be received \> 14 days prior to first study vaccination, or rabies vaccine which may be given if medically indicated.
4. Any known allergies to products contained in the investigational product.
5. Any history of anaphylaxis to any prior vaccine.
6. Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
7. Chronic administration (defined as \> 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination.
8. Received immunoglobulin, blood-derived products, or immunosuppressant drugs within 90 days prior to first study vaccination, except for rabies immunoglobulin which may be given if medically indicated.
9. Active cancer (malignancy) on therapy within 3 years prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo maligna and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the investigator).
10. Participants who are breastfeeding, pregnant, or who plan to become pregnant prior to the end of study.
11. Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the first study vaccine dose that, in the opinion of the investigator, might interfere with protocol compliance.
12. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the study vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
13. Study team member or immediate family member of any study team member (inclusive of Sponsor, clinical research organization \[CRO\], and study site personnel involved in the conduct or planning of the study).
14. Participants with a history of myocarditis or pericarditis
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Novavax

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Development

Role: STUDY_DIRECTOR

Novavax, Inc.

Locations

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Paratus Clinical Research Canberra

Bruce, Australian Capital Territory, Australia

Site Status

Paratus Clinical Research Western Sydney

Blacktown, New South Wales, Australia

Site Status

Emeritus Research

Botany, New South Wales, Australia

Site Status

Northern Beaches Clinical Research

Brookvale, New South Wales, Australia

Site Status

Paratus Clinical Research Central Coast

Kanwal, New South Wales, Australia

Site Status

Australian Clinical Research Network (ACRN)

Maroubra, New South Wales, Australia

Site Status

AIM Centre (Hunter Diabetes Centre)

Merewether, New South Wales, Australia

Site Status

Novatrials

Newcastle, New South Wales, Australia

Site Status

Holdsworth House Medical Practice

Sydney, New South Whales, Australia

Site Status

Paratus Clinical Research Brisbane

Albion, Queensland, Australia

Site Status

Core Research Group Pty Ltd

Milton, Queensland, Australia

Site Status

Griffith University Clinical Trial Unit

Southport, Queensland, Australia

Site Status

Data Health Australia PTY Ltd t/a Austrials

Taringa, Queensland, Australia

Site Status

AusTrials Wellers Hill

Wellers Hill, Queensland, Australia

Site Status

Clinical Medical and Analytical Excellence (CMAX)

Adelaide, South Australia, Australia

Site Status

Eastern Health-Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

Emeritus Research

Camberwell, Victoria, Australia

Site Status

University Hospital Geelong-Barwon Health

Geelong, Victoria, Australia

Site Status

Monash Health -Monash Medical Centre

Melbourne, Victoria, Australia

Site Status

Countries

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Australia

References

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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.

Reference Type DERIVED
PMID: 39052718 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38460525 (View on PubMed)

Other Identifiers

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2019nCoV- 311

Identifier Type: -

Identifier Source: org_study_id

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