ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12621001524886

Ethics application status

Approved

Date submitted

4/11/2021

Date registered

9/11/2021

Date last updated

11/10/2022

Date data sharing statement initially provided

9/11/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Queensland COVID-19 Vaccination (QoVAX) Safety and Efficacy Trial Program: Mixed Dose 1 and 2 Study

Scientific title

Queensland COVID-19 Vaccination (QoVAX) Safety and Efficacy Trial Program: Mixed Dose 1 and 2 Study

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1271-3028

Trial acronym

Nil

Linked study record

Not applicable

Health condition

Health condition(s) or problem(s) studied:

COVID-19

SARS-CoV-2

Condition category

Condition code

Infection

Other infectious diseases

Inflammatory and Immune System

Normal development and function of the immune system

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Heterologous COVID-19 vaccines (BNT162b2 (BioNTech, Pfizer)/ChAdOx1 (Oxford, AstraZeneca) or ChAdOx1/BNT162b2) for doses 1 and 2

Participants complete a questionnaire and have blood and saliva samples collected at 4 - 6 months post the second vaccine dose. The questionnaire and samples are repeated at 4 weeks after the COVID-19 booster dose, and 12-months post the date of recruitment.

Intervention code [1]

Not applicable

Comparator / control treatment

Homologous COVID-19 vaccines BNT162b2/BNT162b2 (BioNTech, Pfizer) or ChAdOx1/ChAdOx1 (Oxford, AstraZeneca) for doses 1 and 2

Participants complete a questionnaire and have blood and saliva samples collected at 4 - 6 months post the second vaccine dose. The questionnaire and samples are repeated at 4 weeks after the COVID-19 booster dose, and at 12-months post the date of recruitment.

Control group

Active

Outcomes

Primary outcome [1]

Serum IgG antibodies titres to the SARS-CoV2 spike protein measured using Abbott Core Laboratories' chemiluminescent microparticle immunoassay (CMIA)

Timepoint [1]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose, and at 12 months following the date of recruitment.

Secondary outcome [1]

Serum IgG antibody titres to SARS-CoV-2 nucleocapsid protein measured by using Abbott Laboratories' chemiluminescent microparticle immunoassay (CMIA)

Timepoint [1]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose, and at 12 months following the date of recruitment.

Secondary outcome [2]

Serum IgA antibody titres to the SARS-CoV-2 spike protein measured using the Euroimmune SARS-CoV-2 domain IgA enzyme-linked immunosorbent assay (ELISA)

Timepoint [2]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose, and at 12 months following the date of recruitment. This additional collection was added after 179 participants had consented to participate in this study.

Secondary outcome [3]

Immunocompetence assessed via full blood counts with differential analysis of (CD20, CD4, CD8, CD28, CD56, CD27, with additional CD8 immunosenescence markers; CD28 and CD57, and senescent B cells; CD19 pos CD27 neg IgD negative. All components will be assessed as a composite outcome.

Timepoint [3]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose, and at 12 months following the date of recruitment.

Secondary outcome [4]

Titre of neutralizing antibody to the SARS-CoV2 spike protein for variants of concern (UK, RSA. Delta and QLD02), These will be assessed as a composite secondary outcome

Timepoint [4]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose, and at 12 months following the date of recruitment.

Secondary outcome [5]

Concentration of cytokines in peripheral blood mononuclear cells (IL-1 alpha, IFN-gamma 2, IFN gamma, TNF, MCP-1 CCL2, IL-6, IL-8 CXCL8, IL-10, IL-12p70, IL-17A, IL-18, IL-23 and IL-33) using Biolegend LegendPlex Inflammation Panel Kit. These will be assessed as a composite secondary outcome.

Timepoint [5]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose, and at 12 months following the date of recruitment.

Secondary outcome [6]

Genetic array sequences affecting immunity to heterologous and homologous doses of COVID-19 vaccines (human leukocyte antigen loci, other immune response genes). These will be assessed as a composite secondary outcome.

Timepoint [6]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose, and at 12 months following the date of recruitment.

Secondary outcome [7]

Cellular immune responses including IFN-gamma, IL-2 and TNF production. Activation-induced marker (OX40+CD137+) CD4+ T and (CD69+CD137+) CD8+ T cells, memory T cell responses defined using CD45RO, CCR7 and CD62L, and Granzyme-B and Perforin expression by activated CD8 T cells, and CD20+ and CD27+ memory B cells. These will be assessed as a composite secondary outcome

Timepoint [7]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose, and at 12 months following the date of recruitment.

Secondary outcome [8]

Participant reported local and systemic reactions following each dose of vaccine. These will be assessed as a composite secondary outcome.

Timepoint [8]

Data collected 4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose.

Secondary outcome [9]

Saliva IgA antibody titres to the SARS-CoV-2 spike protein measured using the Euroimmune SARS-CoV-2 domain IgA enzyme-linked immunosorbent assay (ELISA)

Timepoint [9]

4 - 6 months from the second dose of vaccine and repeated at 4 weeks after the COVID-19 booster dose.

Eligibility

Key inclusion criteria

People in Queensland 18 years of age and older, who have received two doses of BNT162b2 or ChAdOx1 COVID vaccines, the second of which was received between 120-180 days prior to giving consent,

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Unable or decline to give informed consent
2. Have a contraindication to venepuncture
3. Insufficient literacy to read and understand the English or translated version of the participant information and consent forms who do not have a family member or interpreter to assist
4. Do not posses a smart phone or computer to access the participant information and complete the consent form and fill the questionnaire.
5. Are unable or unwilling to reach a pathology collection centre to donate samples.

Study design

Purpose

Screening

Duration

Longitudinal

Selection

Defined population

Timing

Both

Statistical methods / analysis

The primary outcome measure is serum IgG spike concentration at 4-6 month post vaccine Dose 2, and 4 weeks after the COVID-19 booster dose. The comparison of interest is heterologous compared to homologous vaccine groups. Data will be analysed using a General Linear Model with log-normal distribution to compare (log) fold-increase in serum IgG. Treatment group, vaccine type given at Dose 1 and 2, and age will be used as covariates to adjust for potential confounding given ATAGI has recommended the AZ vaccine for older and Pfizer for younger individuals. Values below the limit of detection (LoD) of the test will be replaced by values equal to the LoD divided by two. No replacement of missing data will be considered for the primary outcome. Univariate analysis will be used to explore the relationships between IgG and host intrinsic and extrinsic factors, pre-existing health conditions, medications and vulnerable groups. Additional exploratory descriptive analysis including IgG to SARS-CoV-2 nucleocapsid, HLA-type, gender, immunocompetence and ethnicity as covariates are planned. Secondary outcomes include for a subset of patients: neutralizing antibody titres, serum and salivary IgA levels, and cell mediated immunity to original vaccine strain. Descriptive comparative analysis between Groups 1 and 2 and other targeted subgroups for the primary outcomes will also be undertaken.
Medium-term health analysis of participants will be evaluated by integration of result test results with vaccine notification data to investigate vaccine efficacy outcomes in relation to immune response and data on other health and social determinants.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

6/12/2021

Actual

7/01/2022

Date of last participant enrolment

Anticipated

1/04/2022

Actual

3/05/2022

Date of last data collection

Anticipated

30/06/2023

Actual

Sample size

Target

2000

Accrual to date

Final

586

Recruitment in Australia

Recruitment state(s)

QLD

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Queensland Health

Address [1]

Physical address
33 Charlotte Street
Brisbane Queensland 4001

Postal address
GPO Box 48 Brisbane, Queensland 4001

Country [1]

Australia

Primary sponsor type

Government body

Name

Metro North Hospital and Health Service

Address

Physical address
33 Charlotte Street
Brisbane Queensland 4001

Postal address
GPO Box 48 Brisbane, Queensland 4001

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Brisbane and Women’s Hospital HREC (EC00172)

Ethics committee address [1]

Level 2, Building 34
Butterfield Street
HERSTON QLD 4029

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

28/09/2021

Approval date [1]

02/11/2021

Ethics approval number [1]

HREC/2021/QRBW/79314

Summary

Brief summary

The overarching primary research question for the QoVax SET Mixed Dose 1 and 2 study is;
In the Queensland community, do heterologous COVID-19 vaccine doses 1 and 2 compared with homologous doses 1 and 2, offer higher recall levels of spike IgG, spike IgA, neutralizing IgG, and cell mediated immunity at 4 months post dose 2. 
The QoVAX Mixed Dose 1 and 2 study will address these specific research questions;
1.	What are the host intrinsic (HLA type, genetic traits, immunological T and B cell receptor repertoires) and extrinsic factors (socio-economic health determinants, environmental exposures e.g. smoking) associated with variation in immune outcomes following vaccination?
2.	Do members of the community who identify as Aboriginal and/or Torres Strait and/or South Sea Islander, or as being from diverse ethnic backgrounds, show similar vaccine responses? 
3.	Do certain pre-existing health conditions (autoimmunity, cancer, immunodeficiency), and medication use effect response variation of primary immune outcome measures? 
Further research objectives are to investigate medium-term health outcomes of vaccinated research participants at 12 months following recruitment, to identify factors associated with i) safety outcomes, and ii) vaccine efficacy outcomes in the study cohort.

Trial website

Trial related presentations / publications

Nil

Public notes

The Queensland COVID-19 vaccination Safety and Efficacy Trial (QoVax SET) Pilot is a real-world community study focussed on preventative health benefits of the COVID-19 vaccine. The aim is to examine how the immune system responds to the vaccine, and what factors may effect that immune response for people in the Queensland community. In addition, a digitally integrated biobank and databank associated with this QoVax SET study will enable tracking of medium to long-term health outcomes related to the COVID-19 vaccination.

Contacts

Principal investigator

Name

Prof Janet Davies

Address

QoVAXSET Program
Level 11, Block 7
Royal Brisbane and Women's Hospital
Butterfield Street
HERSTON QLD 4006

Country

Australia

Phone

+61 7 3647 1047

Fax

[email protected]

Contact person for public queries

Name

Janet Davies

Address

QoVAXSET Program
Level 11, Block 7
Royal Brisbane and Women's Hospital
Butterfield Street
HERSTON QLD 4006

Country

Australia

Phone

+61 7 3647 1047

Fax

[email protected]

Contact person for scientific queries

Name

Janet Davies

Address

QoVAXSET Program
Level 11, Block 7
Royal Brisbane and Women's Hospital
Butterfield Street
HERSTON QLD 4006

Country

Australia

Phone

+61 7 3647 1047

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

De-identified participant data and biological samples for which the participant has consented to the future use of their data and samples.

When will data be available (start and end dates)?

Immediately following publication and no end date.

Available to whom?

Researchers undertaking projects specific to COVID-19.

Available for what types of analyses?

Analyses for specific COVID-19 related research approved by a Human Research Ethics Committee.

How or where can data be obtained?

Written requests to the Scientific Access Committee via the following email [email protected]

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
13846	Ethical approval	HREC/2021/QRBW/79314: Queensland CoViD-19 Vaccination (QoVAX SET) Safety and Efficacy Trial – Mixed Dose 1 and 2 Study				383042-(Uploaded-08-11-2021-12-28-28)-Study-related document.pdf
13955	Informed consent form	QoVAX SET Mixed Dose PICF v1.1 Participant Information and Consent Form				383042-(Uploaded-08-11-2021-12-29-37)-Study-related document.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically