Evaluation of COVID-19 Vaccines Given as a Booster in Healthy Adults in Indonesia (MIACoV Indonesia)

Sponsor

Murdoch Childrens Research Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05387317

Collaborator

Universitas Padjadjaran (UNPAD) (Other), Universitas Indonesia (UI) (Other), Health Development Policy Agency, Ministry of Health Republic of Indonesia (Other), Coalition for Epidemic Preparedness Innovations (Other), The Peter Doherty Institute for Infection and Immunity (Other)

800

Enrollment

Locations

Arms

Anticipated Duration (Months)

266.7

Patients Per Site

20.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomised controlled clinical trial to determine the reactogenicity and immunogenicity of booster doses of SARS-CoV-2 vaccines (Pfizer-BioNTech, AstraZeneca or Moderna) in adults who have previously received either AstraZeneca or Coronavac as their primary doses.

Both fractional and standard doses of Pfizer-BioNTech, AstraZeneca and Moderna will be tested.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Biological: Pfizer-BioNTech Standard dose Biological: AstraZeneca Standard dose Biological: Pfizer-BioNTech Fractional dose Biological: AstraZeneca Fractional dose Biological: Moderna Standard dose Biological: Moderna Fractional dose	Phase 3

Detailed Description

There will be a total of 800 participants in the study, to be randomised and administered booster doses in this study.

The study will be conducted at 3 clinics in Bandung. Participants will have previously received primary doses of Coronavac or Astranzeneca, with the second dose administered at least 6 months previously.

Participants will be followed for 12 months following the booster vaccine adminstration, with blood samples drawn at baseline, 28 days, 6 months and 12 months following booster vaccine administration.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

800 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

A unblinded vaccinator will administer the dose and will not be involved in outcome assessment. Unblinding will occur for each participant at approximately 28 days after the study vaccine

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pfizer-BioNTech Standard dose after CoronaVac priming Pfizer-BioNTech (BNT162b2, or Comirnaty®) Dose: 30ug in 0.3ml The 50 participants in this arm received second CoronaVac priming dose at least 6 months prior to randomisation.	Biological: Pfizer-BioNTech Standard dose Standard Dose - (30ug in 0.3ml) The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, encodes a P2 mutant spike protein and is formulated as an RNA-lipid nanoparticle (LNP) of nucleoside-modified mRNA (modRNA). Other Names: BNT162b2 Comirnaty
Experimental: Pfizer-BioNTech Fractional dose after CoronaVac priming Pfizer-BioNTech (BNT162b2, or Comirnaty®) Dose: 15ug in 0.15ml The 50 participants in this arm received second CoronaVac priming dose at least 6 months prior to randomisation.	Biological: Pfizer-BioNTech Fractional dose Fractional Dose - (15ug in 0.15ml) The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, encodes a P2 mutant spike protein and is formulated as an RNA-lipid nanoparticle (LNP) of nucleoside-modified mRNA (modRNA). Other Names: BNT162b2 Comirnaty
Experimental: AstraZeneca Standard dose after CoronaVac priming AstraZeneca (ChAdOx1-S, Vaxzevria®). Dose: 0.5ml The 50 participants in this arm received second CoronaVac priming dose at least 6 months prior to randomisation.	Biological: AstraZeneca Standard dose Standard Dose (5xE10vp in 0.5ml) ChAdOx1 nCoV-19 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein Other Names: ChAdOx1-S Vaxzevria
Experimental: AstraZeneca Fractional dose after CoronaVac priming AstraZeneca (ChAdOx1-S, Vaxzevria®). Dose: 0.25ml The 50 participants in this arm received second CoronaVac priming dose at least 6 months prior to randomisation.	Biological: AstraZeneca Fractional dose Fractional Dose (2.5E10vp in 0.25ml) ChAdOx1 nCoV-19 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein Other Names: ChAdOx1-S Vaxzevria
Experimental: Moderna Standard Dose after CoronaVac priming Moderna (mRNA-1273 or Spikevax®) Dose: 50ug in 0.25ml The 100 participants in this arm received second CoronaVac priming dose at least 6 months prior to randomisation.	Biological: Moderna Standard dose Standard dose (50ug in 0.25ml) Other Names: mRNA-1273 Spikevax®
Experimental: Moderna Fractional Dose after CoronaVac priming Moderna (mRNA-1273 or Spikevax®) Dose: 20ug in 0.1ml The 100 participants in this arm received second CoronaVac priming dose at least 6 months prior to randomisation.	Biological: Moderna Fractional dose Fractional dose (20ug in 0.1ml) Other Names: mRNA-1273 Spikevax®
Experimental: Pfizer-BioNTech Standard dose after AstraZeneca priming Pfizer-BioNTech (BNT162b2, or Comirnaty®) Dose: 30ug in 0.3ml The 50 participants in this arm received second AstraZeneca priming dose at least 6 months prior to randomisation.	Biological: Pfizer-BioNTech Standard dose Standard Dose - (30ug in 0.3ml) The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, encodes a P2 mutant spike protein and is formulated as an RNA-lipid nanoparticle (LNP) of nucleoside-modified mRNA (modRNA). Other Names: BNT162b2 Comirnaty
Experimental: Pfizer-BioNTech Fractional dose after AstraZeneca priming Pfizer-BioNTech (BNT162b2, or Comirnaty®) Dose: 15ug in 0.15ml The 50 participants in this arm received second AstraZeneca priming dose at least 6 months prior to randomisation.	Biological: Pfizer-BioNTech Fractional dose Fractional Dose - (15ug in 0.15ml) The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, encodes a P2 mutant spike protein and is formulated as an RNA-lipid nanoparticle (LNP) of nucleoside-modified mRNA (modRNA). Other Names: BNT162b2 Comirnaty
Experimental: AstraZeneca Standard dose after AstraZeneca priming AstraZeneca (ChAdOx1-S, Vaxzevria®). Dose: 0.5ml The 50 participants in this arm received second AstraZeneca priming dose at least 6 months prior to randomisation.	Biological: AstraZeneca Standard dose Standard Dose (5xE10vp in 0.5ml) ChAdOx1 nCoV-19 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein Other Names: ChAdOx1-S Vaxzevria
Experimental: AstraZeneca Fractional dose after AstraZeneca priming AstraZeneca (ChAdOx1-S, Vaxzevria®). Dose: 0.25ml The 50 participants in this arm received second AstraZeneca priming dose at least 6 months prior to randomisation.	Biological: AstraZeneca Fractional dose Fractional Dose (2.5E10vp in 0.25ml) ChAdOx1 nCoV-19 is a recombinant replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 spike (S) surface glycoprotein Other Names: ChAdOx1-S Vaxzevria
Experimental: Moderna Standard Dose after AstraZeneca priming Moderna (mRNA-1273 or Spikevax®) Dose: 50ug in 0.25ml The 100 participants in this arm received second AstraZeneca priming dose at least 6 months prior to randomisation.	Biological: Moderna Standard dose Standard dose (50ug in 0.25ml) Other Names: mRNA-1273 Spikevax®
Experimental: Moderna Fractional Dose afterAstraZeneca priming Moderna (mRNA-1273 or Spikevax®) Dose: 20ug in 0.1 The 100 participants in this arm received second AstraZeneca priming dose at least 6 months prior to randomisation.	Biological: Moderna Fractional dose Fractional dose (20ug in 0.1ml) Other Names: mRNA-1273 Spikevax®

Outcome Measures

Primary Outcome Measures

SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination [Assessed at 28 days]
Serum samples collected at 28-days post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG CMIA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals
Incidence of solicited systemic and local reactions (reactogenicity) [Assessed for 7 days post-vaccination]
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), 6- and 12-months post booster vaccination. [Assessed at time-points: baseline, 6 months, and 12 months).]
Serum samples collected at baseline (pre booster), and 6- and 12-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific IgG antibodies using IgG CMIA. 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-, 6- and 12-months post booster vaccination measured by surrogate virus neutralization test (sVNT) [Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).]
Serum samples collected at baseline (pre booster), 28 days-, 6- and 12-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-, 6- and 12-months post booster vaccination measured by SARS-CoV-2 microneutralisation assay [Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).]
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 [Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).]
Applicable to the subset participants with additional blood collection. Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset 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 (enzyme-linked immunosorbent assay). Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).IFN-γ Elispot, intracellular cytokine assays (flow cytometry) and multiplex cytokine assays will be performed on isolated peripheral blood mononuclear cells (PBMCs)
Number of IFNγ producing cells/million PBMCs [Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).]
Applicable to the subset participants with additional blood collection. IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset 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 [Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).]
Applicable to the subset participants with additional blood collection. Frequency of cytokine-expressing T cells will be assessed on a subset 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 [Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).]
Applicable to the subset participants with additional blood collection. 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.IFN-γ Elispot, intracellular cytokine assays (flow cytometry) and multiplex cytokine assays will be performed on isolated peripheral blood mononuclear cells (PBMCs)
Incidence of unsolicited adverse events (AE) [28 days post booster vaccination for all 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 [3 months post booster vaccination for medically attended 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) [12 months post booster vaccination for SAE]
SAE will be collected throughout the follow up period of 12 months. Data will be presented as a proportion of participants who report SAE.
Incidence of confirmed COVID-19 infection [Throughout the follow up period of 12 months.]
Confirmed (Polymerase Chain Reaction [PCR] or rapid antigen test) COVID-19 infections will be documented throughout the follow-up period

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Clinically healthy adults aged 18 years and above who had completed the primary series of COVID-19 vaccine with CoronaVac or AstraZeneca more than 6 months prior to enrolment to the study.
Signed written informed consent form and willing to comply with the instructions of the investigator and the schedule of the trial.

Exclusion Criteria:

Those who have already received a third dose of SARS-CoV-2 vaccine
Concomitantly enrolled or scheduled to be enrolled in another trial.
Those with fever (temperature ˃ 37.5℃, measured with infrared thermometer/thermal gun), upper respiratory tract infection symptoms such as sneezing, nasal congestion, runny nose, cough, sore throat, loss of taste, chills and shortness of breath within 72 hours before enrolment.
Blood pressure ˃ 180/110 mmHg.
History of confirmed COVID-19 within one month prior to study enrolment.
History of allergy to vaccines or vaccine ingredients, and severe adverse reactions to vaccines, such as urticaria, dyspnoea, and angioneurotic oedema.
Those with uncontrolled autoimmune disease such as systemic lupus erythematosis.
History of uncontrolled coagulopathy or blood disorders, immune deficiency.
History of having received blood derived product/transfusion within 3 months prior to enrolment.
Those who received immunosuppressant therapy such as high-dose corticosteroid or cancer chemotherapy
Those with uncontrolled chronic disease, such as severe heart disease, asthma exacerbation
Those who have history of uncontrolled epilepsy (within the last 2 years) or other progressive neurological disorders, such as Guillain-Barre Syndrome
Those who have receive any vaccination within 2 weeks before study vaccine administration for this protocol, or intended to receive any vaccination within 2 weeks after study vaccine administration.
Pregnant woman
Those aged ≥60 years old with difficulty in climbing 10 steps of stairs, frequently experiencing fatigue, difficulty in walking 100-200 m, or having at least 5 comorbidities (hypertension, diabetes, cancer, chronic lung disease, heart attack, congestive heart failure, chest pain, asthma, joint pain, stroke, and kidney disease).
Those who are study staff working on the study or the immediate family of study investigators