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

Primary Purpose

COVID-19

Status

Not yet recruiting

Phase

Phase 3

Locations

Indonesia

Study Type

Interventional

Intervention

Pfizer-BioNTech Standard dose

AstraZeneca Standard dose

Pfizer-BioNTech Fractional dose

AstraZeneca Fractional dose

Moderna Standard dose

Moderna Fractional dose

About this trial

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

Eligibility Criteria

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

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

Sites / Locations

Puskesmas Ciumbuleuit
Puskesmas Dago
Puskesmas Garuda

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Arm Label

Pfizer-BioNTech Standard dose after CoronaVac priming

Pfizer-BioNTech Fractional dose after CoronaVac priming

AstraZeneca Standard dose after CoronaVac priming

AstraZeneca Fractional dose after CoronaVac priming

Moderna Standard Dose after CoronaVac priming

Moderna Fractional Dose after CoronaVac priming

Pfizer-BioNTech Standard dose after AstraZeneca priming

Pfizer-BioNTech Fractional dose after AstraZeneca priming

AstraZeneca Standard dose after AstraZeneca priming

AstraZeneca Fractional dose after AstraZeneca priming

Moderna Standard Dose after AstraZeneca priming

Moderna Fractional Dose afterAstraZeneca priming

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 IgG CMIA. The primary endpoint is the seroresponse rate at the Day-28 visit. The Seroresponse rate at the individual level is defined as either a ≥4-fold rise in binding antibodies at the Day-28 visit compared to baseline (pre-vaccination) with a titre of <200 BAU/ml, a ≥2-fold rise among participants with a baseline (pre-vaccination) titre of >≥200 BAU/ml, or ≥4 times the lower limit of detection if baseline levels are lower than the limit of detection.

Incidence of solicited systemic and local reactions (reactogenicity)

Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report grade 3 or 4 reactions by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration, swelling, fever, nausea, vomiting, headache, fatigue/malaise, myalgia, arthralgia, diarrhea, enlarged lymph nodes 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.

Serum samples collected at baseline (pre booster), 28 days, 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 (BAU)/mL and presented as geometric mean concentration (GMC) and 95% confidence intervals (CI)

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)

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 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.

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

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

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).

Number of IFNγ producing cells/million PBMCs

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

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

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)

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

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 12 months. Data will be presented as a proportion of participants who report SAE.

Incidence of confirmed COVID-19 infection

Confirmed (Polymerase Chain Reaction [PCR] or rapid antigen test) COVID-19 infections will be documented throughout the follow-up period, by clinical severity

Full Information

NCT ID

NCT05387317

First Posted

May 19, 2022

Last Updated

October 12, 2023

Sponsor

Murdoch Childrens Research Institute

Collaborators

Universitas Padjadjaran, Health Development Policy Agency, Ministry of Health Republic of Indonesia, Coalition for Epidemic Preparedness Innovations, The Peter Doherty Institute for Infection and Immunity, Indonesia University

1. Study Identification

Unique Protocol Identification Number

NCT05387317

Brief Title

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

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 a Booster Dose After Priming With Coronavac or AstraZeneca in Healthy Adults in Indonesia

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 31, 2024 (Anticipated)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Murdoch Childrens Research Institute

Collaborators

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 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.

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.

6. Conditions and Keywords

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

COVID-19

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes 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

Allocation

Randomized

Enrollment

800 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pfizer-BioNTech Standard dose after CoronaVac priming

Arm Type

Experimental

Arm Description

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.

Arm Title

Pfizer-BioNTech Fractional dose after CoronaVac priming

Arm Type

Experimental

Arm Description

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.

Arm Title

AstraZeneca Standard dose after CoronaVac priming

Arm Type

Experimental

Arm Description

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.

Arm Title

AstraZeneca Fractional dose after CoronaVac priming

Arm Type

Experimental

Arm Description

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.

Arm Title

Moderna Standard Dose after CoronaVac priming

Arm Type

Experimental

Arm Description

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.

Arm Title

Moderna Fractional Dose after CoronaVac priming

Arm Type

Experimental

Arm Description

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.

Arm Title

Pfizer-BioNTech Standard dose after AstraZeneca priming

Arm Type

Experimental

Arm Description

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.

Arm Title

Pfizer-BioNTech Fractional dose after AstraZeneca priming

Arm Type

Experimental

Arm Description

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.

Arm Title

AstraZeneca Standard dose after AstraZeneca priming

Arm Type

Experimental

Arm Description

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.

Arm Title

AstraZeneca Fractional dose after AstraZeneca priming

Arm Type

Experimental

Arm Description

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.

Arm Title

Moderna Standard Dose after AstraZeneca priming

Arm Type

Experimental

Arm Description

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.

Arm Title

Moderna Fractional Dose afterAstraZeneca priming

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

Pfizer-BioNTech Standard dose

Other Intervention Name(s)

BNT162b2, Comirnaty

Intervention Description

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).

Intervention Type

Biological

Intervention Name(s)

AstraZeneca Standard dose

Other Intervention Name(s)

ChAdOx1-S, Vaxzevria

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Pfizer-BioNTech Fractional dose

Other Intervention Name(s)

BNT162b2, Comirnaty

Intervention Description

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).

Intervention Type

Biological

Intervention Name(s)

AstraZeneca Fractional dose

Other Intervention Name(s)

ChAdOx1-S, Vaxzevria

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Moderna Standard dose

Other Intervention Name(s)

mRNA-1273, Spikevax®

Intervention Description

Standard dose (50ug in 0.25ml)

Intervention Type

Biological

Intervention Name(s)

Moderna Fractional dose

Other Intervention Name(s)

mRNA-1273, Spikevax®

Intervention Description

Fractional dose (20ug in 0.1ml)

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Assessed at 28 days

Title

Incidence of solicited systemic and local reactions (reactogenicity)

Description

Time Frame

Assessed for 7 days post-vaccination

Secondary Outcome Measure Information:

Title

SARS-CoV-2 specific IgG antibodies at baseline (pre booster), 6- and 12-months post booster vaccination.

Description

Time Frame

Assessed at time-points: baseline, 28 days, 6 months, and 12 months).

Title

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)

Description

Time Frame