Clinical trial NCT05543356: COVID-19 Fourth Dose Study in Australia
Official title: A Randomised Controlled Trial to Assess the Immunogenicity, Safety and Reactogenicity of a Second Standard Monovalent (Ancestral) or Bivalent Omicron-specific COVID-19 Vaccine Booster Dose (Pfizer-BioNTech or Moderna) in Healthy Adults in Australia.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: COVID-19
Keywords: Booster dose Moderna and Pfizer
mRNA vaccine
monovalent, bivalent
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
Collaborators: name: Coalition for Epidemic Preparedness Innovations
name: The Peter Doherty Institute for Infection and Immunity
First posted: 2022-09-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: PREVENTION

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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination
timeFrame: 28-days post booster vaccination
measure: Total incidence of solicited reactions (systemic and local)
timeFrame: Total incidence of solicited reactions will be measured for 7 days post booster vaccination
Secondary outcomes:
measure: SARS-CoV-2 specific IgG antibodies at baseline (pre booster), and 6-months post booster vaccination
timeFrame: Baseline (pre booster), and 6-months post booster vaccination
measure: 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)
timeFrame: Baseline (pre booster), 28 days and 6 months post booster vaccination
measure: 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
timeFrame: Baseline (pre booster), 28 days-, and 6-months post booster vaccination
measure: Interferon gamma (IFNγ) concentrations in International Units (IU)/mL
timeFrame: Baseline (pre booster), 28 days-, and 6-months post booster vaccination
measure: Number of IFNγ producing cells/million PBMCs
timeFrame: Baseline (pre booster), 28 days-, and 6-months post booster vaccination
measure: Frequency of cytokine-expressing T cells
timeFrame: Baseline (pre booster), 28 days-, and 6-months post booster vaccination
measure: Cytokine concentrations following PBMCs stimulation
timeFrame: Baseline (pre booster), 28 days and 6-months post booster vaccination
measure: Incidence of unsolicited adverse events (AE)
timeFrame: 28 days-post booster vaccination
measure: Incidence of medically attended adverse events (AE)
timeFrame: 3 months post booster vaccination
measure: Incidence of serious adverse events (SAE)
timeFrame: 6 months post booster vaccination
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Royal Children's Hospital, Murdoch Children's Research Institute
state: Victoria
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Kim Mulholland, MD/Prof
role: PRINCIPAL_INVESTIGATOR
References: