COVID-19
Conditions
Keywords
Booster, fractional and standard doses, Pfizer, Astrazeneca, Moderna, COVID-19 vaccination, mRNA vaccine
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.
Interventions
BIOLOGICALPfizer-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).
BIOLOGICALAstraZeneca 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
BIOLOGICALPfizer-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).
BIOLOGICALAstraZeneca 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
BIOLOGICALModerna Standard dose
Standard dose (50ug in 0.25ml)
BIOLOGICALModerna Fractional dose
Fractional dose (20ug in 0.1ml)
Sponsors
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
Murdoch Childrens Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. 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. 2. Signed written informed consent form and willing to comply with the instructions of the investigator and the schedule of the trial.
Exclusion criteria
1. Those who have already received a third dose of SARS-CoV-2 vaccine 2. Concomitantly enrolled or scheduled to be enrolled in another trial. 3. 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. 4. Blood pressure ˃ 180/110 mmHg. 5. History of confirmed COVID-19 within one month prior to study enrolment. 6. History of allergy to vaccines or vaccine ingredients, and severe adverse reactions to vaccines, such as urticaria, dyspnoea, and angioneurotic oedema. 7. Those with uncontrolled autoimmune disease such as systemic lupus erythematosis. 8. History of uncontrolled coagulopathy or blood disorders, immune deficiency. 9. History of having received blood derived product/transfusion within 3 months prior to enrolment. 10. Those who received immunosuppressant therapy such as high-dose corticosteroid or cancer chemotherapy 11. Those with uncontrolled chronic disease, such as severe heart disease, asthma exacerbation 12. Those who have history of uncontrolled epilepsy (within the last 2 years) or other progressive neurological disorders, such as Guillain-Barre Syndrome 13. 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. 14. Pregnant woman 15. 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). 16. Those who are study staff working on the study or the immediate family of study investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. 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) | 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 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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). | 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) |
| 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, by clinical severity |
| 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) |
| 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 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. |
Countries
Indonesia
Outcome results
None listed