COVID-19 Fourth Dose Study in Australia

NCT ID: NCT05543356

Last Updated: 2024-03-15

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

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-02

Study Completion Date

2022-11-30

Brief Summary

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This clinical trial will be a blinded, randomised study to determine the safety, reactogenicity, and immunogenicity of a second booster dose of SARS-CoV-2 vaccines in adults enrolled over two consecutive stages. Stage 1 will commence at the time of study approval and transition to stage 2 once bivalent vaccines are approved and available in Australia.

Detailed Description

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Participants will be adults aged 18 years or older who have been previously primed with two doses of either Pfizer-BioNTech (BNT162b2, or Comirnaty®) or AstraZeneca (ChAdOx1-S, or Vaxzevria®) and boosted at least 3 months earlier with Pfizer BioNTech vaccine (30µg). There will be no upper age limit. Participants will be recruited from the Murdoch Children's Research Institute, the Royal Children's Hospital (RCH), the Peter Doherty Research Institute, and, if necessary, the greater Melbourne area. Ideally, 100 participants will be recruited per group unless bivalent Omicron-specific vaccines are introduced before this target is reached for monovalent ancestral vaccines. There will be 800 participants in total. Procedures will be implemented to ensure participants of all ages (aged 18 and above) are included and that there is an even age distribution in each group (\<50 and ≥50 years).

Conditions

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COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Study participants who have received two doses of either Pfizer or Astrazena vaccine as their primary vaccine and a standard dose of Pfizer for their booster will be randomised into one of four groups. The four groups consist of a standard dose of either the monovalent or bivalent Pfizer or Moderna vaccine.
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators
The participants and those evaluating reactogenicity will be blinded to the vaccine allocation for the first 7 days following vaccination. After that, both clinical investigators and participants will be aware of their investigational product. Laboratory staff will remain blinded to the investigational product.

Study Groups

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Monovalent Pfizer-BioNTech(BNT162b2): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2)

Participants who received Pfizer-BioNTech(BNT162b2) as primary series and Pfizer-BioNTech(BNT162b2) as first booster will receive a second booster dose of:

Biological/Vaccine: Tozinameran - Monovalent Tozinamrean is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Group Type ACTIVE_COMPARATOR

Tozinameran

Intervention Type BIOLOGICAL

A single standard dose (30mcg) will be administered on day 0 of the study.

Monovalent Moderna(mRNA-1273, Spikevax®): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2)

Participants who received Pfizer-BioNTech(BNT162b2) as primary series and Pfizer-BioNTech(BNT162b2) as first booster will receive a second booster dose of:

Biological/Vaccine: Elasomeran - Monovalent Elasomeran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2).

Group Type ACTIVE_COMPARATOR

Elasomeran

Intervention Type BIOLOGICAL

A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.

Monovalent Pfizer-BioNTech(BNT162b2): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2)

Participants who received AstraZeneca (ChAdOx1, or Vaxzevria®) as primary series and Pfizer-BioNTech (BNT162b2) as first booster will received a second booster dose of:

Biological/Vaccine: Tozinameran - Monovalent Tozinamrean is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Group Type ACTIVE_COMPARATOR

Tozinameran

Intervention Type BIOLOGICAL

A single standard dose (30mcg) will be administered on day 0 of the study.

Monovalent Moderna(mRNA-1273, Spikevax®):AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2)

Participants who received AstraZeneca (ChAdOx1, or Vaxzevria®) as primary series and Pfizer-BioNTech (BNT162b2) as first booster will received a second booster dose of:

Biological/Vaccine: Elasomeran - Monovalent Elasomeran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2).

Group Type ACTIVE_COMPARATOR

Elasomeran

Intervention Type BIOLOGICAL

A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.

Bivalent Pfizer-BioNTech (BNT162b2 OMI): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2)

Participants who received Pfizer-BioNTech(BNT162b2) as primary series and Pfizer-BioNTech(BNT162b2) as first booster will receive a second booster dose of:

Biological/Vaccine: Pfizer-BioNTech, BNT162b2 OMI - bivalent Pfizer-BioNTech bivalent COVID-19 vaccine contains ancestral BNT162b2 and Omicron variant BNT162b2 Omi (BA.1). The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, encodes a P2 mutant spike protein and is formulated as an RNA-lipid nanoparticle (LNP) of nucleoside-modified mRNA (modRNA).

Group Type ACTIVE_COMPARATOR

Bivalent Pfizer-BioNTech

Intervention Type BIOLOGICAL

A single standard dose (BNT162b2 15μg +BNT162b2 OMI 15μg) will be administered on day 0 of the study.

Bivalent Moderna (mRNA-1273.214): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2)

Participants who received Pfizer-BioNTech(BNT162b2) as primary series and Pfizer-BioNTech(BNT162b2) as first booster will receive a second booster dose of:

Biological/Vaccine: Moderna, mRNA-1273.214 - bivalent The Moderna bivalent vaccine (mRNA-1273.214) encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]).

Group Type ACTIVE_COMPARATOR

Bivalent Moderna

Intervention Type BIOLOGICAL

A single standard dose (BNT162b2 15μg + BNT162b2 OMI 15μg)will be administered on day 0 of the study.

Bivalent Pfizer-BioNTech (BNT162b2): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2)

Participants who received AstraZeneca (ChAdOx1-S, or Vaxzevria®) as primary series and Pfizer-BioNTech (BNT162b2) as first booster will received a second booster dose of:

Biological/Vaccine: Pfizer-BioNTech, BNT162b2 OMI - bivalent Pfizer-BioNTech bivalent COVID-19 vaccine contains ancestral BNT162b2 and Omicron variant BNT162b2 Omi (BA.1). The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, encodes a P2 mutant spike protein and is formulated as an RNA-lipid nanoparticle of nucleoside-modified mRNA.

Group Type ACTIVE_COMPARATOR

Bivalent Pfizer-BioNTech

Intervention Type BIOLOGICAL

A single standard dose (BNT162b2 15μg + BNT162b2 OMI 15μg) will be administered on day 0 of the study.

Bivalent Moderna (mRNA-1273.214): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2)

Participants who received AstraZeneca (ChAdOx1-S, or Vaxzevria®) as primary series and Pfizer-BioNTech (BNT162b2) as first booster will received a second booster dose of:

Biological/Vaccine: Moderna, mRNA-1273.214 - bivalent The Moderna bivalent vaccine (mRNA-1273.214) encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]).

Group Type ACTIVE_COMPARATOR

Bivalent Moderna

Intervention Type BIOLOGICAL

A single standard dose (BNT162b2 15μg +BNT162b2 OMI 15μg) will be administered on day 0 of the study.

Interventions

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Tozinameran

A single standard dose (30mcg) will be administered on day 0 of the study.

Intervention Type BIOLOGICAL

Elasomeran

A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.

Intervention Type BIOLOGICAL

Tozinameran

A single standard dose (30mcg) will be administered on day 0 of the study.

Intervention Type BIOLOGICAL

Elasomeran

A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.

Intervention Type BIOLOGICAL

Bivalent Pfizer-BioNTech

A single standard dose (BNT162b2 15μg +BNT162b2 OMI 15μg) will be administered on day 0 of the study.

Intervention Type BIOLOGICAL

Bivalent Moderna

A single standard dose (BNT162b2 15μg + BNT162b2 OMI 15μg)will be administered on day 0 of the study.

Intervention Type BIOLOGICAL

Bivalent Pfizer-BioNTech

A single standard dose (BNT162b2 15μg + BNT162b2 OMI 15μg) will be administered on day 0 of the study.

Intervention Type BIOLOGICAL

Bivalent Moderna

A single standard dose (BNT162b2 15μg +BNT162b2 OMI 15μg) will be administered on day 0 of the study.

Intervention Type BIOLOGICAL

Other Intervention Names

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BNT162b2, Pfizer-BioNTech, Comirnaty mRNA-1273, Spikevax, Moderna BNT162b2, Pfizer-BioNTech, Comirnaty mRNA-1273, Spikevax, Moderna BNT162b2 + BNT162b2 OMI mRNA-1273.214 +B.1.1.529 OMI BNT162b2 + BNT162b2 OMI mRNA-1273.214 +B.1.1.529 OMI

Eligibility Criteria

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Inclusion Criteria

1. Have completed a primary schedule of two doses of Pfizer-BioNTech or AstraZeneca vaccines and received a booster of Pfizer-BioNTech vaccine (30µg) at least 3 months earlier.
2. No confirmed SARS-CoV-2 infection on PCR or RAT within the last 3 months.
3. Willing and able to give written informed consent.
4. Aged 18 years or above.
5. Willing to complete the follow-up requirements of the study.

Exclusion Criteria

1. Currently receiving immunosuppressive medication or anti-cancer chemotherapy.
2. Known HIV infection.
3. Congenital immune deficiency syndrome.
4. Received immunoglobulin or other blood products in the three months prior to potential study booster vaccination.
5. Study staff and their relatives.
6. Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exemption to receiving further COVID-19 vaccines.
7. Cannot read or understand English.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Coalition for Epidemic Preparedness Innovations

OTHER

Sponsor Role collaborator

The Peter Doherty Institute for Infection and Immunity

OTHER

Sponsor Role collaborator

Murdoch Childrens Research Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kim Mulholland, MD/Prof

Role: PRINCIPAL_INVESTIGATOR

Murdoch Childrens Research Institute

Locations

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Royal Children's Hospital, Murdoch Children's Research Institute

Melbourne, Victoria, Australia

Site Status

Countries

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Australia

References

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Mazarakis N, Toh ZQ, Neal E, Bright K, Luu S, Quah L, Ng YY, Nguyen C, Hart J, Do LAH, Rudel A, Dassanayake S, Higgins RA, Ong DS, Justice F, Moore KA, Watts E, Mahanty S, Subbarao K, Mulholland K, von Mollendorf C, Licciardi PV. The immunogenicity, reactogenicity, and safety of a bivalent mRNA or protein COVID-19 vaccine given as a fourth dose. J Infect. 2025 Mar;90(3):106447. doi: 10.1016/j.jinf.2025.106447. Epub 2025 Feb 18.

Reference Type DERIVED
PMID: 39978439 (View on PubMed)

Related Links

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https://www.who.int/news/item/17-05-2022-interim-statement-on-the-use-of-additional-booster-doses-of-emergency-use-listed-mrna-vaccines-against-covid-19

World Health Organization. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19 2022

https://www.fda.gov/media/73679/download

US Food and Drug Administration (FDA). Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007

https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Addendum on Estimands and Sensitivity Analysis in Clinical Trials to the Guideline on Statistical Principles for Clinical Trials 2019

Other Identifiers

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88825

Identifier Type: -

Identifier Source: org_study_id

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