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
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- COVID-19
- Sponsor
- Murdoch Childrens Research Institute
- Locations
- 3
- Primary Endpoint
- SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Outcomes
Primary Outcomes
SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination
Time Frame: 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)
Time Frame: 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 Outcomes
- 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).)
- Frequency of cytokine-expressing T cells(Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).)
- Cytokine concentrations following PBMCs stimulation(Assessed at 4 time-points (baseline, 28 days, 6 months, and 12 months).)
- Incidence of unsolicited adverse events (AE)(28 days post booster vaccination for all AE)
- 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).)
- 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).)
- Incidence of medically attended adverse events(3 months post booster vaccination for medically attended AE)
- Incidence of serious adverse events (SAE)(12 months post booster vaccination for SAE)
- Incidence of confirmed COVID-19 infection(Throughout the follow up period of 12 months.)