A Randomised Controlled Trial to Assess the Immunogenicity, Safety and Reactogenicity of Standard Dose Versus Fractional Doses of COVID-19 Vaccine (Pfizer-BioNTech) Given as a Booster Dose After Priming With Sinopharm, AstraZeneca or Sputnik in Healthy Adults in Mongolia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 601
- 试验地点
- 1
- 主要终点
- Seroresponse
研究概览
简要总结
This clinical trial is a single-blind, randomised study to determine the reactogenicity and immunogenicity of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccine (Pfizer-BioNTech) as booster dose in adults, who have previously received either Sinopharm (BBIBP-CorV®), AstraZeneca (ChAdOx1-S, or Vaxzevria®) or Sputnik V (Gam-COVID-Vac®) as their primary doses 6 to 9 months earlier. Both standard and fractional doses will be tested.
Participants are healthy adults aged 18 years or older, with no upper age limit. Procedures will be implemented to ensure participants of all ages (aged 18 and above) are included and that there is an even age distribution (<50 and ≥50 years) in each group. There will be a total of 6 groups (Sinopharm-standard dose Pfizer, Sinopharm-fractional dose Pfizer, AstraZeneca-standard dose Pfizer, AstraZeneca-fractional dose Pfizer, Sputnik - standard dose Pfizer, Sputnik - fractional dose Pfizer), with 200 participants per group for Sinopharm and 100 for AstraZeneca and Sputnik.
详细描述
As per brief summary
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
The participants and those evaluating reactogenicity will be blinded to the vaccine allocation for the first 28 days following vaccination. After that, both clinical investigators and participants will be aware of their investigational product allocation. Laboratory staff will remain blinded to the investigational product allocation during the immunology testing.
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
- •Have completed two doses of Sinopharm, AstraZeneca or Sputnik vaccines with the recommended schedule 6 months prior to the date of enrolment
- •Willing and able to give written informed consent
- •Aged 18 years or above
- •Willing to complete the follow-up requirements of the study
排除标准
- •Received 3 doses of COVID-19 vaccine
- •Received 2 doses of COVID-19 less than 6 months prior to the start of the trial
- •Currently on immunosuppressive medication or anti-cancer chemotherapy
- •HIV infection
- •Congenital immune deficiency syndrome
- •Has received immunoglobulin or other blood products in the 3 months prior to vaccination
- •Study staff and their relatives
- •Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exception to receiving further COVID-19 vaccines
研究组 & 干预措施
Standard Pfizer-BioNTech booster group
Biological/Vaccine: Tozinameran - Standard Dose
Other Names:
BNT162b2 Comirnaty Pfizer Covid-19 vaccine
Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Dose - 30 µg in 0.3 ml. Liquid for injection. Single dose.
干预措施: Tozinameran - Standard Dose (Biological)
Fractional Pfizer-BioNTech booster group
Biological/Vaccine: Tozinameran - Standard Dose
Other Names:
BNT162b2 Comirnaty Pfizer Covid-19 vaccine
Tozinameran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cellfree in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Dose - 15 µg in 0.3 ml. Liquid for injection. Single dose.
干预措施: Tozinameran - Fractional Dose (Biological)
结局指标
主要结局
Seroresponse
时间窗: 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 ELISA. 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 a ≥4-times the lower limit of detection if baseline levels are lower than the limit of detection.
Solicited Grade 3 or 4 Local or Systemic Reaction
时间窗: 7 days post booster 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
- Seroresponse by Priming Vaccine Strata(28-days post booster vaccination)
- SARS-CoV-2 Specific IgG Antibodies at Day-28(28-days post booster vaccination)
- SARS-CoV-2 Specific IgG Antibodies at Day-28 by Priming Vaccine Strata(28-days post booster vaccination)
- 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(Baseline (pre booster), 28 days-, 6- and 12-months post booster vaccination)
- Incidence of Unsolicited Adverse Events (AE)(28 days-post booster vaccination)
- Incidence of Medically Attended Adverse Events(3 months post booster vaccination)
- SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre-booster), 28 Days, 6 Months, 12 Months, 18 Months, and 24 Months Post-booster Vaccination.(Baseline (pre booster), 28 days, 6 months, 12 months, 18 months, and 24 months post-booster vaccination.)
- SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre-booster), 28 Days, 6 Months, 12 Months, 18 Months, and 24 Months Post-booster Vaccination Measured by Surrogate Virus Neutralisation Test (sVNT).(Baseline (pre-booster), 28 days, 6 months, 12 months, 18 months, and 24 months post-booster vaccination.)
- Incidence of Serious Adverse Events (SAE)(24 months post-booster)
- Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL(Baseline (pre booster), 28 days, 6-, 12 -, 18-, and 24-months post booster vaccination)
- Number of IFNγ Producing Cells/Million PBMCs(Baseline (pre-booster), 28 days, 6 and 12 months post booster vaccination)
- Frequency of Cytokine-expressing T Cells(Baseline (pre-booster), 28 days, 6 and 12 months post-booster vaccination)
- Cellular Immunity: Multiplex Cytokine Assays - Reported as Cytokine Concentrations in pg/ml and Presented as GMC and 95% CI(Baseline (pre booster), 28 days-, 6 and 12 months post booster vaccination)
- Incidence of PCR Confirmed COVID-19 Infection(Up to 24 months post booster vaccination)
- Number of IFNγ Producing Cells/Million PBMCs(At 18 and 24 months post booster vaccination)
- Frequency of Cytokine-expressing T Cells(18 and 24 months post-booster vaccination)
- Cellular Immunity: Multiplex Cytokine Assays - Reported as Cytokine Concentrations in pg/ml and Presented as GMC and 95% CI(18 and 24 months post booster vaccination)