A Randomised Controlled Trial to Assess the Immunogenicity, Safety and Reactogenicity of a Bivalent mRNA Moderna COVID-19 Vaccine or a Protein-based Novavax COVID-19 Vaccine Given as a Fourth Dose in Healthy Adults in Australia
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 496
- 试验地点
- 1
- 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 double-blinded, randomised study to determine the safety, reactogenicity, and immunogenicity of a bivalent mRNA Moderna COVID-19 vaccine or a protein-based Novavax COVID-19 vaccine given as a fourth dose in healthy adults in Australia.
详细描述
This is a blinded, two-arm randomised study to determine the safety, reactogenicity and immunogenicity of a fourth dose of SARS-CoV-2 vaccines in Australia in adults 18 years or older who have received their third dose of COVID-19 vaccine at least six months previously. Participants will be randomised to receive either bivalent Moderna (mRNA-1273.214) or Novavax. A separate non-randomised control arm (no vaccine given), frequency matched by age to the vaccine groups will also be enrolled for comparison. A total of 200 participants per group will be recruited.
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
- Double (Participant, Investigator)
盲法说明
The participants and those evaluating reactogenicity will be blinded to the vaccine allocation for the first 7 days following vaccination. After that, both clinical investigators and participants will be aware of their investigational product. Laboratory staff will remain blinded to the investigational product.
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 received three doses of COVID-19 vaccines at least 6 months earlier.
- •No confirmed SARS-CoV-2 infection on PCR or RAT within the last 3 months.
- •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
- •Currently receiving immunosuppressive medication or anti-cancer chemotherapy.
- •Known HIV infection.
- •Congenital immune deficiency syndrome.
- •Received immunoglobulin or other blood products in the three months prior to potential study booster vaccination.
- •Study staff and their relatives.
- •Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exemption to receiving further COVID-19 vaccines.
- •Cannot read or understand English.
研究组 & 干预措施
Bivalent Moderna (mRNA-1273.214)
Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214)
The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 [BA.1]).
干预措施: Bivalent Moderna (Biological)
Novavax
Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine.
Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms).
干预措施: Novavax (Biological)
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: 28-days post booster vaccination
Serum samples collected at 28-days post booster vaccination from the two intervention groups will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals
Total Incidence of Solicited Reactions (Systemic and Local)
时间窗: Total incidence of solicited reactions will be measured for 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 by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration/swelling, fever, nausea/vomiting, headache, fatigue/malaise, myalgia, arthralgia will be collected from the participants 7 days post-vaccination. Reactogenicity was graded on a 0-4 scale: Grade 0 = no symptom; Grade 1 = mild and does not interfere with activity; Grade 2 = moderate or requiring repeated non-narcotic analgesia; Grade 3 = severe, limiting or preventing daily activity; Grade 4 = potentially life-threatening, requiring ER visit or hospitalisation.
次要结局
- SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination(Baseline (pre booster), 6-months,12-months and 18-months post booster vaccination)
- SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT)(Baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination)
- SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days and 6, 12 and 18 Months Post Booster Vaccination Measured by SARS-CoV-2 Microneutralisation Assay(Baseline (pre booster), 6,12 and 18-months post booster vaccination)
- Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL(Baseline (pre booster), Day 28, 6-months and 12-months post booster vaccination)
- Number of IFNγ Producing Cells/Million PBMCs(Baseline (pre booster), 6, 12 and 18-months post booster vaccination)
- Frequency of Cytokine-expressing T Cells(Baseline (pre booster), 6, 12 and 18 -months post booster vaccination)
- Cytokine Concentrations Following PBMCs Stimulation(Baseline (pre booster), 6, 12 and 18-months post booster vaccination)
- Incidence of Unsolicited Adverse Events (AE)(28 days-post booster vaccination)
- Incidence of Medically Attended Adverse Events (AE)(3 months post booster vaccination)
- Incidence of Serious Adverse Events (SAE)(24 months post booster vaccination)