A Phase I, Randomised, Double-blind, Placebo-controlled, Dose-escalation Study of Adjuvanted SARS-CoV-2 (COVID-19) Beta Variant RBD Recombinant Protein (DoCo-Pro-RBD-1 + MF59®) and mRNA (MIPSCo-mRNA-RBD-1) Vaccines in Healthy Adults Aged 18 to 64 Years Previously Vaccinated With 3 Doses of Licensed SARS-CoV-2 Ancestral Strain Vaccines
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 2
- 主要终点
- Unsolicited AEs post vaccination.
研究概览
简要总结
This is a study of two experimental SARS-CoV-2 vaccines against the virus called SARS-CoV-2 virus. The first of the experimental vaccines is called DoCo-Pro-RBD-1 + M59® and contains a laboratory made protein which looks the same as a protein in the SARS-CoV-2 virus. As this protein is so similar to a protein in the SARS-CoV-2 virus, it allows the immune system to develop immunity against the real virus by producing specific antibodies against this protein. Antibodies are substances in the blood which could help protect against future infection. The second of the experimental vaccines that will be tested is called MIPSCo-mRNA-RBD-1. This type of vaccine uses messenger ribonucleic acid (mRNA) which is a set of instructions for a cell to make a viral protein called an antigen. Antigens are substances that can trigger the body's defences to produce antibodies that fight against the disease.
This study will test these two experimental COVID-19 vaccines in people who have previously received two doses of ComirnatyTM (Pfizer Australia Pty Ltd) or VaxzevriaTM (AstraZeneca Pty Ltd) and a third booster vaccination with either ComirnatyTM or SpikevaxTM (Moderna). This study is the first time this recombinant protein vaccine and this mRNA vaccine will be given to humans. The purpose of this study is to determine what amount, or dose, of the experimental vaccines is safe and produces the desired immune response and antibody level for future investigations. It will do this by testing 3 different dose levels for each of the two vaccines. Each participant will receive a single vaccine at one of the three dose levels, or a placebo injection. This study is the first time this recombinant protein vaccine and this mRNA vaccine will be given to humans.
详细描述
This is a randomised, double-blind, placebo-controlled, dose-escalation, first-in-human study to assess the safety, reactogenicity and immunogenicity of SARS-CoV-2 beta variant DoCo-Pro-RBD-1 + MF59® and MIPSCo-mRNA-RBD-1 vaccine at three dose levels, administered intramuscularly (IM) as a single booster dose in healthy adults previously vaccinated with two doses of CominartyTM (BNT162b2 [mRNA]) or VaxzevriaTM (ChAdOx1-S) COVID-19 and a third booster dose of either ComirnatyTM or SpikevaxTM vaccines. The study will comprise a Dose-Escalation Phase and an Expanded Phase.
The study vaccines, DoCo-Pro-RBD-1 + MF59®, MIPSCo-mRNA-RBD-1 or placebo (normal saline) will be administered IM in the deltoid region of the upper arm.
The study will enroll healthy adults aged 18 to 64 years of age inclusive. Participants in both the Dose-Escalation Phase and Expanded Phase of the study will be stratified by prior primary course COVID-19 vaccination with CominartyTM or VaxzevriaTM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •To be eligible for this study, participants must meet ALL of the following inclusion criteria:
- •Adults 18 to 64 years of age, inclusive at screening previously vaccinated with a 2-dose schedule of Cominarty™ or Vaxzevria™.
- •≥ 3 months (90 days) since receipt of a booster dose of either ComirnatyTM or SpikevaxTM.
- •Be in good health as determined by medical history, physical examination, vital signs, and clinical laboratory assessments with no clinically significant abnormalities as judged by the Investigator at screening and randomisation. Vital signs must be within medically acceptable ranges prior to the first vaccination.
- •Participants of childbearing potential (defined as any participant who has experienced menarche and who is NOT surgically sterile [ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or postmenopausal [defined as amenorrhea of at least 12 consecutive months]) must agree to be heterosexually inactive from at least 28 days prior to enrollment and through the end of the study OR agree to consistently use a medically acceptable method of contraception listed below from at least 28 days prior to enrollment and through the end of the study:
- •a. Condoms (male or female); Diaphragm; Cervical cap; Intrauterine device; Oral or patch contraceptives; Norplant®, Depo-Provera®, or another regulatory approved contraceptive method; Abstinence, as a form of contraception, is acceptable if in line with the participant's lifestyle.
- •NOTE: Periodic abstinence (e.g., calendar, ovulation, symptom-thermal, post- ovulation methods) and withdrawal method (coitus interruptus) are not acceptable forms of contraception.
- •Agrees to not participate in any other SARS-CoV-2 prevention or treatment trials for the duration of the study.
- •Willing and able to give informed consent prior to study enrollment and to comply with all study procedures.
排除标准
- •Potential study participants will be excluded from the study if ANY of the following criteria apply:
- •History of test-confirmed (by PCR, rapid antigen test (RAT) to SARS-CoV-2) COVID-19 infection within 3 months (90 days) prior to randomisation.
- •Participants with a BMI > 35kg/m
- •Positive result for rheumatoid factor (RF) at Screening.
- •Positive test at Screening for human immunodeficiency virus (Types 1 or 2) antibody, hepatitis B surface antigen or hepatitis C virus antibody.
- •Clinical laboratory test results not within normal range and judged to be clinically relevant abnormalities by the investigator.
- •History of prior cardiac inflammatory disease (endocarditis, myocarditis or pericarditis).
- •History of demyelinating disease or Guillain Barré syndrome.
- •Fever (non-axillary temperature >37.5°C) or any other symptoms of infection that have not completely resolved within 3 days prior to Randomisation (Day 1).
- •Presence of current active viral infection or bacterial infection, at Screening or Randomisation (Day 1), which is determined by the Investigator to be of clinical significance.
- •Participation in research involving receipt of an investigational product (drug/biologic/device) within 90 days prior to the first study vaccination or an intention to participate in another clinical trial at any time during the conduct of this study.
- •Received any other vaccine within 30 days prior to the first study vaccination, other than licensed influenza vaccine, which can be administered up to 14 days prior to randomization.
- •Any known allergies to products contained in the investigational products.
- •Any history of anaphylaxis to any prior vaccine, food, drug, toxin or other exposure.
- •Autoimmune or immunodeficiency disease/condition (iatrogenic or congenital) requiring ongoing immunomodulatory therapy.
- •NOTE: Stable endocrine disorders (e.g., thyroiditis, pancreatitis), including stable diabetes mellitus with no history of diabetic ketoacidosis) are NOT excluded.
- •Chronic administration (defined as > 14 continuous days) of immunosuppressant, systemic glucocorticoids, or other immune-modifying drugs within 90 days prior to first study vaccination.
- •NOTE: An immunosuppressant dose of glucocorticoid is defined as a systemic dose ≥ 10mg of prednisone per day or equivalent. The use of topical or intranasal glucocorticoids is permitted. Topical tacrolimus and ocular cyclosporin are permitted.
- •Received immunoglobulin, blood-derived products, or immunosuppressant drugs or donation of blood/blood products within 90 days prior to vaccination or planned receipt or donation during the study period.
- •Thrombocytopaenia, contraindicating intramuscular vaccination, based on the Investigator's judgment.
- •Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination based on the Investigator's judgement.
- •Active cancer (malignancy) on therapy within one year prior to first study vaccination (with the exception of adequately treated non-melanomatous skin carcinoma or lentigo malignancy and uterine cervical carcinoma in situ without evidence of disease, at the discretion of the Investigator).
- •Participants who are breastfeeding, pregnant or who plan to become pregnant prior to the end of study.
- •Suspected or known history of alcohol abuse or drug addiction within 2 years prior to the first study vaccine dose that, in the opinion of the Investigator, might interfere with protocol compliance.
- •Have a tattoo/scar/birthmark or any other skin condition affecting the deltoid area that may, in the Investigator's opinion, interfere with injection site assessments.
- •Any other condition that, in the opinion of the Investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the trial vaccine or interpretation of study results (including neurologic or psychiatric conditions likely to impair the quality of safety reporting).
- •Study team member or immediate family member of any study team member (inclusive of Sponsor, Contract Research Organization (CRO), and study site personnel involved in the conduct or planning of the study).
- •Aboriginal and Torres Strait Islander person aged 50 years or older.
研究组 & 干预措施
Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1) 5mcg + MF59
DoCo-Pro-RBD-1 antigen 5mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1
干预措施: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59) (Biological)
Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1)15mcg + MF59
DoCo-Pro-RBD-1 antigen 15mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1
干预措施: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59) (Biological)
Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1) 45mcg + MF59
DoCo-Pro-RBD-1 antigen 45mcg mixed with MF59 adjuvant in 0.5 mL suspension, administered intramuscularly in a one dose regimen, on Day 1
干预措施: Adjuvanted SARS-CoV-2 beta variant RBD recombinant protein vaccine (DoCo-Pro-RBD-1 + MF59) (Biological)
SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 10mcg
MIPSCo-mRNA-RBD-1 antigen 10mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1
干预措施: SARS-CoV-2 beta variant RBD mRNA vaccine (Biological)
SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 20mcg
MIPSCo-mRNA-RBD-1 antigen 20mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1
干预措施: SARS-CoV-2 beta variant RBD mRNA vaccine (Biological)
SARS-CoV-2 beta variant RBD mRNA vaccine (MIPSCo-mRNA-RBD-1) 50mcg
MIPSCo-mRNA-RBD-1 antigen 50mcg administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1
干预措施: SARS-CoV-2 beta variant RBD mRNA vaccine (Biological)
Normal saline (0.9%)
Normal saline (0.9%) administered intramuscularly as a 0.5 mL dose in a one dose regimen on Day 1
干预措施: Normal Saline (Other)
结局指标
主要结局
Unsolicited AEs post vaccination.
时间窗: Day 1 to Day 29 (28 days post vaccination).
Frequency
Solicited local and systemic reactogenicity AEs post vaccination.
时间窗: Within 7 days after vaccination (Day 1)
Frequency, severity, duration and peak intensity
Percentage of participants who achieve a boost response post vaccination.
时间窗: 28 days after vaccination
Defined as a 4-fold increase in SARS-CoV-2 neutralising or RBD-specific Ab titres from baseline.
Serious adverse events (SAEs), medically attended adverse events (MAAEs) and any adverse events (AEs) leading to study withdrawal at any time during the study.
时间窗: Through to study completion at Day 181.
Frequency
SAEs post vaccination.
时间窗: Day 1 to 29 (28 Days post vaccination).
Frequency
次要结局
- MAAEs from Day 1 to 6 months after vaccination.(6 months after vaccination.)
- The ratio of T cell derived type 1 versus type 2 cytokines in participants that mount a T cell response.(Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination.)
- The number of participants that develop an antibody response at least 4 times higher than baseline antibody titers.(At baseline (Day 1), Day 29 (28 days after vaccination), and 3, and 6 months after vaccination)
- Number of participants that mount a T cell response that leads to type-1 cytokines (such as Interferon-gamma) versus type-2 cytokines (such as Interleukin 4, 5 and 13).(Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination.)
- Number of participants that mount a T cell response for SARS-CoV-2 RBD-derived peptide antigens.(Baseline (Day 1), Day 8 (7 days after vaccination), Day 29 (28 days after vaccination) and 3 and 6 months after vaccination.)