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
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 3
- 主要终点
- SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
结局指标
主要结局
SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination
时间窗: 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)
时间窗: 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.
次要结局
- 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.)