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

NCT05387317 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: RCH HREC Ref 81803
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

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.

Conditions

COVID-19

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Assessed at 28 days

• 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.

  Assessed for 7 days post-vaccination

Secondary Outcomes (11)

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

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

• 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).

• 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).

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

  Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).

• Number of IFNγ producing cells/million PBMCs

  Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).

Study Arms (12)

Pfizer-BioNTech Standard dose after CoronaVac priming

EXPERIMENTAL

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

Pfizer-BioNTech Fractional dose after CoronaVac priming

EXPERIMENTAL

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

AstraZeneca Standard dose after CoronaVac priming

EXPERIMENTAL

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

AstraZeneca Fractional dose after CoronaVac priming

EXPERIMENTAL

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

Moderna Standard Dose after CoronaVac priming

EXPERIMENTAL

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

Moderna Fractional Dose after CoronaVac priming

EXPERIMENTAL

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

Pfizer-BioNTech Standard dose after AstraZeneca priming

EXPERIMENTAL

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

Pfizer-BioNTech Fractional dose after AstraZeneca priming

EXPERIMENTAL

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

AstraZeneca Standard dose after AstraZeneca priming

EXPERIMENTAL

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

AstraZeneca Fractional dose after AstraZeneca priming

EXPERIMENTAL

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

Moderna Standard Dose after AstraZeneca priming

EXPERIMENTAL

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

Moderna Fractional Dose afterAstraZeneca priming

EXPERIMENTAL

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

Interventions

Pfizer-BioNTech Standard dose BIOLOGICAL

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).

Also known as: BNT162b2, Comirnaty

Pfizer-BioNTech Standard dose after AstraZeneca priming; Pfizer-BioNTech Standard dose after CoronaVac priming

AstraZeneca Standard dose BIOLOGICAL

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

Also known as: ChAdOx1-S, Vaxzevria

AstraZeneca Standard dose after AstraZeneca priming; AstraZeneca Standard dose after CoronaVac priming

Pfizer-BioNTech Fractional dose BIOLOGICAL

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).

Also known as: BNT162b2, Comirnaty

Pfizer-BioNTech Fractional dose after AstraZeneca priming; Pfizer-BioNTech Fractional dose after CoronaVac priming

AstraZeneca Fractional dose BIOLOGICAL

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

Also known as: ChAdOx1-S, Vaxzevria

AstraZeneca Fractional dose after AstraZeneca priming; AstraZeneca Fractional dose after CoronaVac priming

Moderna Standard dose BIOLOGICAL

Standard dose (50ug in 0.25ml)

Also known as: mRNA-1273, Spikevax®

Moderna Standard Dose after AstraZeneca priming; Moderna Standard Dose after CoronaVac priming

Moderna Fractional dose BIOLOGICAL

Fractional dose (20ug in 0.1ml)

Also known as: mRNA-1273, Spikevax®

Moderna Fractional Dose after CoronaVac priming; Moderna Fractional Dose afterAstraZeneca priming

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Universitas Padjadjaran: collaborator
• Health Development Policy Agency, Ministry of Health Republic of Indonesia: collaborator
• Coalition for Epidemic Preparedness Innovations: collaborator
• The Peter Doherty Institute for Infection and Immunity: collaborator
• Indonesia University: collaborator

Study Sites (3)

Puskesmas Ciumbuleuit

Bandung, West Java, Indonesia

Location

Puskesmas Dago

Bandung, West Java, Indonesia

Location

Puskesmas Garuda

Bandung, West Java, Indonesia

Location

MeSH Terms

Conditions

COVID-19

Interventions

BNT162 Vaccine; ChAdOx1 nCoV-19; 2019-nCoV Vaccine mRNA-1273

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors; Vaccines, DNA

Study Officials

• Eddy Fadlyana, Dr

  Universitas Padjadjaran, Indonesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: May 24, 2022
• Study Start: April 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: October 1, 2025
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: IPD sharing plans in development
• Access Criteria: IPD sharing plans in development

Locations

ID (3)