A Phase I Study Evaluating the Safety and Immunogenicity of a New TB Vaccine, MVA85A, in Healthy Volunteers Who Are Infected With HIV
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Safety of MVA85A
研究概览
简要总结
This is an open Phase I study of a candidate TB vaccine, MVA85A, in healthy subjects who are infected with HIV. It is designed to study the safety and immunogenicity of the vaccine.
详细描述
This study is designed to evaluate the safety of MVA85A in healthy volunteers in Senegal who are infected with HIV. In phase I studies, a single vaccination with MVA85A, when administered at a dose of 5 x 107pfu intradermally, has been shown to be safe in both mycobacterially naïve individuals, those previously vaccinated with BCG and latently infected individuals. We will use 1 x 10^8 pfu MVA85A intradermally in this study. A trial in BCG vaccinated subjects showed that the higher dose (1 x 10^8 pfu MVA85A) induced a significantly higher immune response but did not have a higher AE profile. In addition, because of a variable immune response, the trial in HIV positive subjects in the UK is split into two groups, the first getting 5 x 10^7 pfu and the second getting 1 x 10^8 pfu MVA85A. It has, therefore, been decided to use the higher dose in order to maximise the immune response whilst maintaining a good safety profile.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Healthy adults aged 18 to 50 years
- •Resident in or near Dakar for the duration of the study
- •Willingness to allow the investigators to discuss the volunteer's medical history with the volunteer's HIV lead physician
- •Willing to use effective contraception throughout duration of study (if female)
- •HIV antibody positive; diagnosed at least 6 months previously
- •CD4 count >300
- •Arm 1: HIV viral load not >100,000 copies per millilitre
- •Arm 2: Undetectable HIV viral load
- •Written informed consent
排除标准
- •Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or on urinalysis
- •Group 1 only: Any ARV therapy within the past 6 months
- •Previous history of TB disease and/or treatment
- •Any AIDS defining illness
- •Group 1: CD4 count nadir <300
- •Group 2: CD4 count nadir <100
- •CXR showing TB or evidence of other active infection
- •Prior receipt of a recombinant MVA or Fowlpox vaccine
- •Use of any investigational or non-registered drug, live vaccine or medical device other than the study vaccine within 30 days preceding dosing of study vaccine, or planned use during the study period
- •Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune modifying drugs within six months of vaccination. (For corticosteroids, this will mean prednisolone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
- •History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g. egg products
- •Presence of any underlying disease that compromises the diagnosis and evaluation of response to the vaccine (including evidence of cardiovascular disease, history of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ), history of insulin requiring diabetes mellitus, any ongoing chronic illness requiring ongoing specialist supervision (e.g., gastrointestinal), and chronic or active neurological disease)
- •History of > 2 hospitalisations for invasive bacterial infections (pneumonia, meningitis)
- •Suspected or known current drug and/or alcohol abuse
- •Seropositive for hepatitis B surface antigen (HBsAg) and/ or hepatitis C (antibodies to HCV)
- •Evidence of serious psychiatric condition
- •Any other on-going chronic illness requiring hospital specialist supervision
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, other than HIV infection, such as asplenia
- •Evidence of hepatomegaly
- •Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
- •Pregnant/lactating female and any female who is willing or intends to become pregnant during the study
- •Any history of anaphylaxis in reaction to vaccination
- •PI assessment of lack of willingness to participate and comply with all requirements of the protocol, or identification of any factor felt to significantly increase the participant's risk of suffering an adverse outcome
结局指标
主要结局
Safety of MVA85A
时间窗: Six months
次要结局
- Immunogenicity of MVA85A(Six months)