COVID-19 Fourth Dose Study in Australia

COVID-19 Clinical Trial

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05543356
• Other study ID #: 88825
• Status: Withdrawn
• Phase: Phase 3
• Start date: May 2, 2022
• Est. completion date: November 30, 2022

Study information

• Verified date: March 2024
• Source: Murdoch Childrens Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 30, 2022
• Est. primary completion date: July 25, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• Tozinameran
A single standard dose (30mcg) will be administered on day 0 of the study.
• Elasomeran
A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.
• Tozinameran
A single standard dose (30mcg) will be administered on day 0 of the study.
• Elasomeran
A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.
• Bivalent Pfizer-BioNTech
A single standard dose (BNT162b2 15µg +BNT162b2 OMI 15µg) will be administered on day 0 of the study.
• Bivalent Moderna
A single standard dose (BNT162b2 15µg + BNT162b2 OMI 15µg)will be administered on day 0 of the study.
• Bivalent Pfizer-BioNTech
A single standard dose (BNT162b2 15µg + BNT162b2 OMI 15µg) will be administered on day 0 of the study.
• Bivalent Moderna
A single standard dose (BNT162b2 15µg +BNT162b2 OMI 15µg) will be administered on day 0 of the study.

Locations

Country	Name	City	State
Australia	Royal Children's Hospital, Murdoch Children's Research Institute	Melbourne	Victoria

Sponsors (3)

Lead Sponsor	Collaborator
Murdoch Childrens Research Institute	Coalition for Epidemic Preparedness Innovations, The Peter Doherty Institute for Infection and Immunity

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	SARS-CoV-2 specific IgG antibodies at baseline (pre booster), and 6-months post booster vaccination	Serum samples collected at baseline (pre booster), and 6-months 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	Baseline (pre booster), and 6-months post booster vaccination
Secondary	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)	Serum samples collected at baseline (pre booster), 28 days- and 6-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific neutralising antibodies using the GenScript® cPass surrogate virus neutralization test (sVNT) for both wild-type and Omicron variant. Neutralising antibody response will be reported as percentage (%) inhibition of receptor binding domain-angiotensin-converting enzyme 2 (RBD-ACE2) binding relative to a positive control.	Baseline (pre booster), 28 days and 6 months post booster vaccination
Secondary	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	A subset of samples from all timepoints will be assessed using a SARS-CoV-2 microneutralisation assay to both the wild type (vaccine) strain and for two SARS-CoV-2 Variants of concern. Neutralizing antibody will be reported as endpoint titre.	Baseline (pre booster), 28 days-, and 6-months post booster vaccination
Secondary	Interferon gamma (IFN?) concentrations in International Units (IU)/mL	Interferon gamma (IFN?) concentrations as a measurement of cellular immunity will be assessed on a subset (40%) of the participants from each group. QuantiFERON Human IFN-? SARS-CoV-2 (Qiagen) will be used to stimulate IFN-? production in peripheral blood mononuclear cells (PBMCs) and then IFN-? production will be measured using ELISA. Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).	Baseline (pre booster), 28 days-, and 6-months post booster vaccination
Secondary	Number of IFN? producing cells/million PBMCs	IFN? producing cells as a measurement of cellular immunity will be assessed on a subset (40%) of the participants from each group. IFN-? Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs). Data will be reported as number of IFN? producing cells/million and presented using means and 95% confidence intervals.	Baseline (pre booster), 28 days-, and 6-months post booster vaccination
Secondary	Frequency of cytokine-expressing T cells	Frequency of cytokine-expressing T cells will be assessed on a subset (40%) of participants using Flow cytometry (intracellular staining) on PBMCs samples. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI.	Baseline (pre booster), 28 days-, and 6-months post booster vaccination
Secondary	Cytokine concentrations following PBMCs stimulation	Cytokine concentrations following PBMCs stimulation will be assessed on a subset (40%) of participants using multiplex cytokine assays.Data will be reported as cytokine concentrations in pg/ml and presented as GMC and 95% CI.	Baseline (pre booster), 28 days and 6-months post booster vaccination
Secondary	Incidence of unsolicited adverse events (AE)	All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.	28 days-post booster vaccination
Secondary	Incidence of medically attended adverse events (AE)	Participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.	3 months post booster vaccination
Secondary	Incidence of serious adverse events (SAE)	SAE will be collected throughout the follow-up period of 6 months post booster vaccination. Data will be presented as a proportion of participants who report unsolicited SAE.	6 months post booster vaccination

External Links

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