COVID-19 Fourth Dose Study in Australia

NCT05543356 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: 88825
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COVID-19

Keywords

Booster dose Moderna and Pfizer; mRNA vaccine; monovalent, bivalent

Outcome Measures

Primary Outcomes (2)

• SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination

  Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals

  28-days post booster vaccination

• Total incidence of solicited reactions (systemic and local)

  Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration/swelling, fever, nausea/vomiting, headache, fatigue/malaise, myalgia, arthralgia will be collected from the participants 7 days post-vaccination.

  Total incidence of solicited reactions will be measured for 7 days post booster vaccination

Secondary Outcomes (10)

• SARS-CoV-2 specific IgG antibodies at baseline (pre booster), and 6-months post booster vaccination

  Baseline (pre booster), and 6-months post booster vaccination

• SARS-CoV-2 specific neutralising antibodies at baseline (pre booster), 28 days and 6-months post booster vaccination measured by surrogate virus neutralization test (sVNT)

  Baseline (pre booster), 28 days and 6 months post booster vaccination

• SARS-CoV-2 specific neutralising antibodies at baseline (pre booster), 28 days and 6- months post booster vaccination measured by SARS-CoV-2 microneutralisation assay

  Baseline (pre booster), 28 days-, and 6-months post booster vaccination

• Interferon gamma (IFNγ) concentrations in International Units (IU)/mL

  Baseline (pre booster), 28 days-, and 6-months post booster vaccination

• Number of IFNγ producing cells/million PBMCs

  Baseline (pre booster), 28 days-, and 6-months post booster vaccination

Study Arms (8)

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

ACTIVE COMPARATOR

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).

Biological: Tozinameran

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

ACTIVE COMPARATOR

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).

Biological: Elasomeran

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

ACTIVE COMPARATOR

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).

Biological: Tozinameran

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

ACTIVE COMPARATOR

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).

Biological: Elasomeran

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

ACTIVE COMPARATOR

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).

Biological: Bivalent Pfizer-BioNTech

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

ACTIVE COMPARATOR

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 \[BA.1\]).

Biological: Bivalent Moderna

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

ACTIVE COMPARATOR

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.

Biological: Bivalent Pfizer-BioNTech

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

ACTIVE COMPARATOR

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 \[BA.1\]).

Biological: Bivalent Moderna

Interventions

Tozinameran BIOLOGICAL

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

Also known as: BNT162b2, Pfizer-BioNTech, Comirnaty

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

Elasomeran BIOLOGICAL

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

Also known as: mRNA-1273, Spikevax, Moderna

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

Bivalent Pfizer-BioNTech BIOLOGICAL

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

Also known as: BNT162b2 + BNT162b2 OMI

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

Bivalent Moderna BIOLOGICAL

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

Also known as: mRNA-1273.214 +B.1.1.529 OMI

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• No confirmed SARS-CoV-2 infection on PCR or RAT within the last 3 months.
• Willing and able to give written informed consent.
• Aged 18 years or above.
• Willing to complete the follow-up requirements of the study.

You may not qualify if:

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

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Coalition for Epidemic Preparedness Innovations: collaborator
• The Peter Doherty Institute for Infection and Immunity: collaborator

Study Sites (1)

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

Melbourne, Victoria, 3052, Australia

Location

Related Publications (1)

• 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.

  PMID: 39978439 DERIVED

Related Links

• World Health Organization. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19 2022
• US Food and Drug Administration (FDA). Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007
• 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

MeSH Terms

Conditions

COVID-19

Interventions

BNT162 Vaccine; 2019-nCoV Vaccine mRNA-1273; BNT162b5

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors; Vaccines, Combined

Study Officials

• Kim Mulholland, MD/Prof

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 16, 2022
• Study Start: May 2, 2022
• Primary Completion: July 25, 2022
• Study Completion: November 30, 2022
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Individual participant data (IPD) sharing plans in development
• Access Criteria: In development

Locations

AU (1)