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

COVID-19 Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05228730
• Other study ID #: 81764
• Status: Completed
• Phase: Phase 3
• Start date: May 2, 2022
• Est. completion date: November 30, 2022

Study information

• Verified date: February 2023
• Source: Murdoch Childrens Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

As per brief summary

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• 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 two doses of Pfizer-BioNTech or AstraZeneca vaccines with the recommended schedule 6 months prior to the date of enrolment

2. Willing and able to give written informed consent

3. Aged 18 years or above

4. Willing to complete the follow-up requirements of the study

Exclusion Criteria:

1. Received 3 doses of COVID-19 vaccine

2. Received 2 doses of COVID-19 less than 6 months prior to the start of the trial

3. Received a different Covid-19 vaccine not available in Australia

4. Currently on immunosuppressive medication or anti-cancer chemotherapy

5. HIV infection

6. Congenital immune deficiency syndrome

7. Has received immunoglobulin or other blood products in the 3 months prior to vaccination

8. Study staff and their relatives

9. Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exception to receiving further COVID-19 vaccines

10. Cannot read or understand English

Related Conditions & MeSH terms

• COVID-19

Intervention

Biological:
• Tozinameran - Standard dose
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.
• Tozinameran - fractional dose
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.
• Elasomeran - standard dose
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.
• Elasomeran - fractional dose
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.

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	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, 

References & Publications (1)

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. — View Citation

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 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.	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 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.	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 16-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

•   Australian Technical Advisory Group on Immunisation (ATAGI). ATAGI recommendations on the use of a booster dose of COVID-19 vaccine 2021
•   Coalition for Epidemic Preparedness Innovations (CEPI). Priority List of Adverse Events of Special Interest
•   Indonesia reports record number of doctor deaths from COVID-19 in July
•   Quarter-dose of Moderna COVID vaccine still rouses a big immune response
•   US Food and Drug Administration (FDA). Moderna COVID-19 Vaccine
•   US Food and Drug Administration (FDA). Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007