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Evaluation of Full Versus Fractional Doses of COVID-19 Vaccines Given as a Booster in Adults in Australia - Mongolia, Indonesia, Australia Coronavirus (MIACoV). (MIACoV)

Primary Purpose

COVID-19

Status

Completed

Phase

Phase 3

Locations

Australia

Study Type

Interventional

Intervention

Tozinameran - Standard dose

Tozinameran - fractional dose

Elasomeran - standard dose

Elasomeran - fractional dose

About this trial

This is an interventional prevention trial for COVID-19 focused on measuring Booster dose, Moderna, Pfizer, fractional and standard doses, COVID-19 vaccination, mRNA vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Have completed two doses of Pfizer-BioNTech or AstraZeneca vaccines with the recommended schedule 6 months prior to the date of enrolment
Willing and able to give written informed consent
Aged 18 years or above
Willing to complete the follow-up requirements of the study

Exclusion Criteria:

Received 3 doses of COVID-19 vaccine
Received 2 doses of COVID-19 less than 6 months prior to the start of the trial
Received a different Covid-19 vaccine not available in Australia
Currently on immunosuppressive medication or anti-cancer chemotherapy
HIV infection
Congenital immune deficiency syndrome
Has received immunoglobulin or other blood products in the 3 months prior to vaccination
Study staff and their relatives
Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exception to receiving further COVID-19 vaccines
Cannot read or understand English

Sites / Locations

Royal Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Active Comparator

Experimental

Arm Label

AstraZeneca (ChAdOx1-S, or Vaxzevria®)-Standard Pfizer-BioNTech booster group

AstraZeneca (ChAdOx1-S, or Vaxzevria®)-Fractional Pfizer-BioNTech booster group

AstraZeneca (ChAdOx1-S, or Vaxzevria®) Standard Elasomeran booster group

AstraZeneca (ChAdOx1-S, or Vaxzevria®)-Fractional Elasomeran booster group

Pfizer-BioNTech (BNT162b2, or Comirnaty®)-Standard Pfizer-BioNTech booster group

Pfizer-BioNTech (BNT162b2, or Comirnaty®)-Fractional Pfizer-BioNTech booster group

Pfizer-BioNTech (BNT162b2, or Comirnaty®)-Standard Elasomeran booster group

Pfizer-BioNTech (BNT162b2, or Comirnaty®)-Fractional Elasomeran booster group

Arm Description

Received two doses of AstraZeneca as primary COVID-19 vaccine

Received two doses of Pfizer-BioNTech as primary COVID-19 vaccine

Outcomes

Primary Outcome Measures

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

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.

Secondary Outcome Measures

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

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 Delta 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.

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 four 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.

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

Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset (40%) of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in peripheral blood mononuclear cells (PBMCs) and then IFN-γ production will be measured using ELISA. Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).

Number of IFNγ producing cells/million PBMCs

IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset (40%) of the participants from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs). Data will be reported as number of IFNγ producing cells/million and presented using means and 95% confidence intervals.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT05228730

First Posted

February 5, 2022

Last Updated

February 6, 2023

Sponsor

Murdoch Childrens Research Institute

Collaborators

Coalition for Epidemic Preparedness Innovations, The Peter Doherty Institute for Infection and Immunity

1. Study Identification

Unique Protocol Identification Number

NCT05228730

Brief Title

Evaluation of Full Versus Fractional Doses of COVID-19 Vaccines Given as a Booster in Adults in Australia - Mongolia, Indonesia, Australia Coronavirus (MIACoV).

Acronym

MIACoV

Official Title

A Randomised Controlled Trial to Assess the Immunogenicity, Safety, and Reactogenicity of Standard-dose Versus Fractional Doses of COVID-19 Vaccines (Pfizer-BioNTech or Moderna) Given as an Additional Dose After Priming With Pfizer-BioNTech or AstraZeneca in Healthy Adults in Australia-MIACoV

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

May 2, 2022 (Actual)

Primary Completion Date

July 25, 2022 (Actual)

Study Completion Date

November 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Murdoch Childrens Research Institute

Collaborators

Coalition for Epidemic Preparedness Innovations, The Peter Doherty Institute for Infection and Immunity

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a single-blind, randomised controlled clinical trial to determine the reactogenicity and immunogenicity of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccines (Pfizer-BioNTech or Moderna) as booster dose in adults, who have previously received either Pfizer-BioNTech or AstraZeneca as their primary doses. Both fractional and standard doses of Pfizer-BioNTech or Moderna will be tested. The trial intervention will be given in line with Australian Technical Advisory Group on Immunisation (ATAGI) recommendations for booster vaccine doses which allows booster doses from 5 months onwards . There will be a total of 8 groups, with 100 individuals of even spread of participants above and below 50 years in each group. The trial will be single site, based at Royal Children's Hospital, Melbourne, Australia

Detailed Description

As per brief summary

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19

Keywords

Booster dose, Moderna, Pfizer, fractional and standard doses, COVID-19 vaccination, mRNA vaccine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Study participants who have received two doses of either Pfizer or Astrazena vaccine as their primary vaccine will be randomised into one of four groups. The four groups consists of a standard or fractional dose of either Pfizer or Moderna vaccine.

Masking

ParticipantOutcomes Assessor

Masking Description

The participants and those evaluating reactogenicity will be blinded to the vaccine allocation for the first 28 days following vaccination. After that, both clinical investigators and participants will be aware of their investigational product allocation. Laboratory staff will remain blinded to the investigational product allocation during the immunology testing.

Allocation

Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AstraZeneca (ChAdOx1-S, or Vaxzevria®)-Standard Pfizer-BioNTech booster group

Arm Type

Active Comparator

Arm Description

Received two doses of AstraZeneca as primary COVID-19 vaccine

Arm Title

AstraZeneca (ChAdOx1-S, or Vaxzevria®)-Fractional Pfizer-BioNTech booster group

Arm Type

Experimental

Arm Description

Received two doses of AstraZeneca as primary COVID-19 vaccine

Arm Title

AstraZeneca (ChAdOx1-S, or Vaxzevria®) Standard Elasomeran booster group

Arm Type

Active Comparator

Arm Description

Received two doses of AstraZeneca as primary COVID-19 vaccine

Arm Title

AstraZeneca (ChAdOx1-S, or Vaxzevria®)-Fractional Elasomeran booster group

Arm Type

Experimental

Arm Description

Received two doses of AstraZeneca as primary COVID-19 vaccine

Arm Title

Pfizer-BioNTech (BNT162b2, or Comirnaty®)-Standard Pfizer-BioNTech booster group

Arm Type

Active Comparator

Arm Description

Received two doses of Pfizer-BioNTech as primary COVID-19 vaccine

Arm Title

Pfizer-BioNTech (BNT162b2, or Comirnaty®)-Fractional Pfizer-BioNTech booster group

Arm Type

Experimental

Arm Description

Received two doses of Pfizer-BioNTech as primary COVID-19 vaccine

Arm Title

Pfizer-BioNTech (BNT162b2, or Comirnaty®)-Standard Elasomeran booster group

Arm Type

Active Comparator

Arm Description

Received two doses of Pfizer-BioNTech as primary COVID-19 vaccine

Arm Title

Pfizer-BioNTech (BNT162b2, or Comirnaty®)-Fractional Elasomeran booster group

Arm Type

Experimental

Arm Description

Received two doses of Pfizer-BioNTech as primary COVID-19 vaccine

Intervention Type

Biological

Intervention Name(s)

Tozinameran - Standard dose

Other Intervention Name(s)

BNT162b2, Pfizer-BioNTech, Comirnaty

Intervention Description

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). A standard dose will be administered on day 0 of the study.

Intervention Type

Biological

Intervention Name(s)

Tozinameran - fractional dose

Other Intervention Name(s)

BNT162b2, Comirnaty, Pfizer-BioNTech

Intervention Description

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). A fractional dose (15mcg) of the intervention will be administered on day 0 of the study.

Intervention Type

Biological

Intervention Name(s)

Elasomeran - standard dose

Other Intervention Name(s)

mRNA-1273, Spikevax, Moderna

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Elasomeran - fractional dose

Other Intervention Name(s)

mRNA-1273, Spikevax, Moderna

Intervention Description

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). A fractional dose (20mcg) of the intervention will be administered on day 0 of the study.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

28-days post booster vaccination.

Title

Total incidence of solicited reactions (systemic and local)

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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)

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

Number of IFNγ producing cells/million PBMCs

Description

Time Frame

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

Title

Frequency of cytokine-expressing T cells

Description

Time Frame

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

Title

Cytokine concentrations following PBMCs stimulation

Description

Time Frame

Baseline (pre booster), 28 days-, and 16-months post booster vaccination

Title

Incidence of unsolicited adverse events (AE)

Description

All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.

Time Frame

28 days-post booster vaccination

Title

Incidence of medically attended adverse events (AE)

Description

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.

Time Frame

3 months post booster vaccination

Title

Incidence of serious adverse events (SAE)

Description

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.

Time Frame

6 months post booster vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have completed two doses of Pfizer-BioNTech or AstraZeneca vaccines with the recommended schedule 6 months prior to the date of enrolment Willing and able to give written informed consent Aged 18 years or above Willing to complete the follow-up requirements of the study Exclusion Criteria: Received 3 doses of COVID-19 vaccine Received 2 doses of COVID-19 less than 6 months prior to the start of the trial Received a different Covid-19 vaccine not available in Australia Currently on immunosuppressive medication or anti-cancer chemotherapy HIV infection Congenital immune deficiency syndrome Has received immunoglobulin or other blood products in the 3 months prior to vaccination Study staff and their relatives Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exception to receiving further COVID-19 vaccines Cannot read or understand English

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kim Mulholland, MD

Organizational Affiliation

Murdoch Childrens Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Royal Children's Hospital

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3010

Country

Australia

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

We will share de-identified data to ethically approved studies in cases where participants have indicated on the consent form that they consent to the use of their data and where consistent with terms of collaboration agreements.

IPD Sharing Time Frame

Individual participant data (IPD) sharing plans in development

IPD Sharing Access Criteria

IPD sharing plans in development

Citations:

PubMed Identifier

34863358

Citation

Munro APS, Janani L, Cornelius V, Aley PK, Babbage G, Baxter D, Bula M, Cathie K, Chatterjee K, Dodd K, Enever Y, Gokani K, Goodman AL, Green CA, Harndahl L, Haughney J, Hicks A, van der Klaauw AA, Kwok J, Lambe T, Libri V, Llewelyn MJ, McGregor AC, Minassian AM, Moore P, Mughal M, Mujadidi YF, Murira J, Osanlou O, Osanlou R, Owens DR, Pacurar M, Palfreeman A, Pan D, Rampling T, Regan K, Saich S, Salkeld J, Saralaya D, Sharma S, Sheridan R, Sturdy A, Thomson EC, Todd S, Twelves C, Read RC, Charlton S, Hallis B, Ramsay M, Andrews N, Nguyen-Van-Tam JS, Snape MD, Liu X, Faust SN; COV-BOOST study group. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet. 2021 Dec 18;398(10318):2258-2276. doi: 10.1016/S0140-6736(21)02717-3. Epub 2021 Dec 2. Erratum In: Lancet. 2021 Dec 18;398(10318):2246.

Results Reference

background

Links:

URL

https://www.reuters.com/business/healthcare-pharmaceuticals/indonesia-reports-record-number-doctor-deaths-covid-19-july-2021-07-18/.

Description

Indonesia reports record number of doctor deaths from COVID-19 in July

URL

https://www.nature.com/articles/d41586-021-01893-0

Description

Quarter-dose of Moderna COVID vaccine still rouses a big immune response

URL

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

Description

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

URL

https://www.health.gov.au/resources/publications/atagi-recommendations-on-the-use-of-a-booster-dose-of-covid-19-vaccine

Description

Australian Technical Advisory Group on Immunisation (ATAGI). ATAGI recommendations on the use of a booster dose of COVID-19 vaccine 2021

Learn more about this trial

Evaluation of Full Versus Fractional Doses of COVID-19 Vaccines Given as a Booster in Adults in Australia - Mongolia, Indonesia, Australia Coronavirus (MIACoV).

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