A Partially Randomized, Partially Double-blind, Placebo-controlled Phase II Non-inferiority Study to Evaluate Immunogenicity and Safety of One and Two Doses of MVA-BN® (IMVAMUNE™) Smallpox Vaccine in 18-55 Year Old Healthy Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 745
- 试验地点
- 2
- 主要终点
- Number of Participants With ECG Changes
研究概览
简要总结
The primary objective of this study is to evaluate the immune response after a single vaccination of pre-immune subjects compared to two vaccinations in naive subjects.
In addition the study further investigates the cardiac safety profile of MVA-BN® in a healthy population compared to placebo.
详细描述
The study consists of 4 groups, which receive either MVA-BN once, MVA-BN two times, MVA-BN followed by placebo, or two administrations of placebo.
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)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects between 18 and 55 years of age.
- •Women must have a negative serum pregnancy test at screening and a negative urine or serum pregnancy test within 24 hours prior to vaccination.
- •Women of childbearing potential must have used an acceptable method of contraception for 30 days prior to the first vaccination, must agree to use an acceptable method of contraception during the study, and must not become pregnant for at least 28 days after the last vaccination. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized. (Acceptable contraception methods are restricted to abstinence, barrier contraceptives, intrauterine contraceptive devices or licensed hormonal products.)
- •Lab values without clinically significant findings
- •Electrocardiogram (ECG) without abnormal findings (e.g. any kind of atrioventricular or intraventricular conditions or blocks such as complete left or right bundle branch block, AV-node block, QTc or PR prolongation, premature atrial contractions or other atrial arrhythmia, sustained ventricular arrhythmia, 2 premature ventricular contractions (PVC) in a row, ST elevation consistent with ischemia).
- •Groups 1, 2 and 3 (All vaccinia-naïve subjects) additionally:
- •No history of known or suspected previous smallpox vaccination.
- •No detectable vaccinia scar.
- •Group 4 (All previously vaccinated subjects) additionally:
- •History of previous smallpox vaccination (documented and/or typical vaccinia scar).
- •Most recent smallpox vaccination ≥ 5 years.
排除标准
- •Uncontrolled serious infection i.e. not responding to antimicrobial therapy.
- •History of or active autoimmune disease. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.
- •Known or suspected impairment of immunologic function including, but not limited to, clinically significant liver disease; diabetes mellitus; moderate to severe kidney impairment.
- •History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure. Subjects with history of skin cancer at the vaccination site are excluded.
- •History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, or any other heart condition under the care of a doctor.
- •History of an immediate family member (father, mother, brother, or sister) who died due to ischemic heart disease before age 50 years.
- •Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool. (http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof) NOTE: This criterion applies only to volunteers 20 years of age and older.
- •History of anaphylaxis or severe allergic reaction.
- •Immune modulatory therapy.
- •History of any serious medical condition, which in the opinion of the investigator would compromise the safety of the subject.
- •History or clinical manifestation of clinically significant and severe hematological, renal, hepatic, pulmonary, central nervous, cardiovascular or gastrointestinal disorders.
研究组 & 干预措施
GP 1: two x 1x10E08 TCID, MVA-BN® s.c., vaccinia naive
vaccinia naive subjects receiving two subcutanenous vaccinations with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID)
干预措施: MVA-BN® (IMVAMUNE) (Biological)
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., vaccinia naive
vaccinica naive subjects receiving one vaccination with 0.5ml MVA-BN® IMVAMUNE(1x10E08 TCID), followed by one vaccination Placebo (0.5ml Tris Buffer)
干预措施: MVA-BN® (IMVAMUNE) (Biological)
GP 2: 1x10E08 TCID, MVA-BN®, 1x Placebo, s.c., vaccinia naive
vaccinica naive subjects receiving one vaccination with 0.5ml MVA-BN® IMVAMUNE(1x10E08 TCID), followed by one vaccination Placebo (0.5ml Tris Buffer)
干预措施: Placebo (Biological)
GP 3: two x Placebo, s.c., vaccinia naive
vaccinia naive subjects, receiving two subcutaneous vaccinations with Placebo (0.5ml Tris Buffer).
干预措施: Placebo (Biological)
GP 4: 1x10E08 TCID, MVA-BN®, s.c., vaccinia experienced
vaccinia experienced subjects, receiving one subcutaneous vaccination with 0.5ml MVA-BN® IMVAMUNE (1x10E08 TCID).
干预措施: MVA-BN® (IMVAMUNE) (Biological)
结局指标
主要结局
Number of Participants With ECG Changes
时间窗: within 2 weeks after each vaccination
Occurrence of any specific or unspecific ECG change. Assessments at Screening (SCR), Visit 2 (Week 2) and Visit 4 (Week 6).
Percentage of Participants With Seroconversion by ELISA
时间窗: 2 weeks following the last vaccination (Week 6 for Groups 1-3, Week 2 for Group 4)
Seroconversion rate based on vaccinia-specific Enzyme-linked Immunosorbent Assay (ELISA). Seroconversion is defined as the appearance of antibody titers ≥ detection limit (50) for initially seronegative subjects, or a doubling or more of the antibody titer compared to Baseline titer for initially seropositive subjects. Percentages based on number of subjects with data available.
Number of Cardiac Adverse Events (Adverse Events of Special Interest [AESI])
时间窗: within 32 weeks
Occurrence and relationship of any other cardiac symptom at any time during the study
次要结局
- Number of Participants With Related Grade>=3 Adverse Events(within 4 weeks after any vaccination)
- Number of Participants With Related Serious Adverse Events(within 32 weeks)
- Percentage of Participants With Seroconversion by PRNT(4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4))
- Number of Participants With Solicited Local Adverse Events(within 8 days after any vaccination)
- Percentage of Participants With Seroconversion by ELISA(4 weeks following the last vaccination (Week 8 for Groups 1-3, Week 4 for Group 4))
- Number of Participants With Unsolicited Non-serious Adverse Events(within 4 weeks after any vaccination)
- Number of Participants With Solicited General Adverse Events(within 8 days after any vaccination)