A Phase 1b, Dose-escalating Safety and Immunogenicity Trial of the Novel Monovalent Ebola Zaire Candidate Vaccine, cAd3-EBO Z and the Heterologous Prime-boost Candidate Vaccine Regimen of cAD3-EBO Z Followed by MVA-BN® Filo in Malian Adults Aged 18-50 Years.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 91
- 试验地点
- 1
- 主要终点
- Occurrence of unsolicited adverse events
研究概览
简要总结
Ebola virus causes an infection known as Ebola virus disease (EVD). This is generally a severe disease which can also lead to death. The 2014 outbreak of EVD in West Africa is the largest ever. Researchers want to develop a vaccine to prevent Ebola infection. It is impossible for someone to get an Ebola infection from this vaccine.
详细描述
This is a Phase 1b (1b implies that the trial is occurring in a geographic region where cases of the disease against which the vaccine is directed, i.e. Ebola disease, may occur before, during or after the clinical trial), open label, dose-escalation study to examine the safety, tolerability and immunogenicity of an investigational Ebola virus vaccine, cAD3-EB) Z, in Malian healthy adults. The vaccine is a recombinant chimpanzee adenovirus Type-3 vectored Ebola Zaire vaccine (cAd3-EBO Z) and consists of a recombinant replication-deficient adenovirus chimpanzee serotype 3 (cAd3) vector expressing wild-type (WT) Ebola glycoprotein (GP) from the Zaire strain.
A revision of the protocol on 14Dec2014 added a booster dose with MVA-BN® Filo or placebo in 56 subjects in groups 1 (except for first 5 vaccines), 2, 3A and 4. The multivalent vectored vaccine MVA-BN® Filo contains an insert for the Zaire Ebola virus glycoprotein, as well as the Sudan strain Ebola virus glycoprotein, the Musoke strain Marburg virus glycoprotein, and a nucleoprotein from the Tai-Forest Ebola virus.
Forty volunteers will be enrolled into two dosage groups. Another group of 40 volunteers (Groups 3A-C) with group 3A receiving 1.0x10(10)vp. All study participants will receive one dose of the study vaccine by intramuscular injection. Group 4 was added to include another 11 volunteers to receive 1.-X10(11)vp. A total of 91 volunteers have been included.
Group 1 will include 20 participants who will receive the lower dose of the vaccine at 2.5 x 10(10) vp
Group 2 will include 20 participants who will receive the higher does of vaccine at 5 x 10(10) vp.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults aged 18 to 50 years
- •Able and willing (in the Investigator's opinion) to comply with all study requirements
- •Willing to allow the investigators to discuss the volunteer's medical history with his/her health care provider
- •For females only, willingness to practice continuous effective contraception (see section 6.4.3) during the study and a negative urine pregnancy test on the day(s) of screening and vaccination
- •Agreement to refrain from blood donation during the course of the study
- •Provide written informed consent
排除标准
- •Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
- •Prior receipt of an investigational Ebola or Marburg vaccine, a chimpanzee adenovirus vectored vaccine, MVA vectored vaccine or any other investigational vaccine likely to impact on interpretation of the trial data
- •Receipt of any live, attenuated vaccine within 28 days prior to enrolment
- •Receipt of any subunit or killed vaccine within 14 days prior to enrolment
- •Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
- •Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including urticaria, respiratory difficulty or abdominal pain
- •Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
- •Any history of anaphylaxis in reaction to vaccination
- •Pregnancy, lactation or willingness/intention to become pregnant during the study
- •History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
- •History of serious psychiatric condition
- •Poorly controlled asthma or thyroid disease
- •Seizure in the past 3 years or treatment for seizure disorder in the past 3 years
- •Bleeding disorder (eg. Factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture
- •Any known history of cardiac disease
- •Any other serious chronic illness requiring hospital specialist supervision
- •Current anti-tuberculosis prophylaxis or therapy
- •Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
- •Suspected or known injecting drug abuse in the 5 years preceding enrolment
- •Seropositive for hepatitis B surface antigen (HBsAg)
- •Travel to an Ebola or Marburg endemic region during the study period or within the previous six months or history of recovery from Ebola or Marburg virus disease.
- •Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
- •Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
结局指标
主要结局
Occurrence of unsolicited adverse events
时间窗: 28 days following the vaccination
Occurrence of solicited local and systemic reactogenicity signs and symptoms
时间窗: Daily for 7 days following each vaccination.
Change from baseline for safety laboratory measures
时间窗: 6 months for each volunteer
Occurrence of serious adverse events and incident chronic medical conditions
时间窗: 6 months for each volunteer
次要结局
- T cell immune responses as measured by intracellular cytokine staining assay(Day 1, 7 and 14 after vaccination)
- Antibody responses as measured by ELISA and neutralization assays(Day 1, 7, 14, 28, 90 and 180 after vaccination)
研究者
Milagritos Tapia
Assistant Professor, Pediatrics & Infectious Tropical Diseases
University of Maryland, Baltimore