A Randomised, Placebo Controlled, Double-blind, Dose Escalation, Single Centre Trial to Evaluate the Safety and Immunogenicity of PnuBioVax Administered on Three Occasions 28 Days Apart at Three Dose Levels in Healthy Adult Subjects.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Incidence of all treatment emergent adverse events
研究概览
简要总结
Streptococcus pneumoniae is a type of bacteria that can cause infections of the ears, sinuses or lungs. It can also cause more serious infections of the blood or brain. The elderly and young children are more vulnerable to these types of infections.
The vaccines available at present are effective only on a certain number of strains of the bacteria. The PnuBioVax vaccine is being developed to work on a broader range of strains. This study will be looking at the safety and tolerability of the study drug for three different dosages: 50 μg, 200 μg, and 500 μg compared to placebo.
The population eligible to take part in the study are healthy male and female subjects between 18 and 40 years of age.
Volunteers for the study will be recruited through advertisements. Each volunteer will have received an information sheet concerning the study and will have agreed to participate in writing. Volunteers will be given at least 48 hours between reading the information leaflet and agreeing to participate. Only subjects who agree to undertake precautions to avoid pregnancy of either themselves of their partner during the study period will be eligible. Volunteers will give signed consent for their physician to be notified about their participation in the trial.
详细描述
This is a phase I study to assess the safety and immunogenicity of PnuBioVax administered on three occasions 28 days apart at dose levels of 50 µg, 200 µg, and 500 µg in healthy adult subjects.
The study will involve 8 visits in total; screening period to determine eligibility, 3 treatment periods comprising of an overnight stay at the clinic (days 1, 29 and 57) and 4 outpatient follow up visits (7 days after each dosing period and one on day 85). Volunteers will also be requested to complete a diary card from day 1 to day 85.
36 Volunteers will take part in this study and will be randomly assigned to each sequential dose group as follows:
- Cohort 1: up to 3 doses of 50 µg of PnuBioVax or placebo
- Cohort 2: up to 3 doses of 200 µg of PnuBioVax or placebo
- Cohort 3: up to 3 doses of 500 µg of PnuBioVax or placebo Within each cohort, nine subjects will receive PnuBioVax and three subjects will receive placebo. Each subject will receive administrations of PnuBioVax or placebo on Days 1, 29 and 57.
The lowest dose of PnuBioVax will be evaluated first (i.e. Cohort 1). Dose escalation will only proceed in the subsequent cohorts if blinded safety data (adverse events, injection site reactions, concomitant medication, vital signs and routine laboratory assessments) from day 8 from the 12 subjects in the preceding cohort have been reviewed by the Sponsor and Principal Investigator and are found to be satisfactory. The Sponsor and Principal Investigator will also review the safety data after each subsequent dose to ensure repeat dosing does not give rise to safety issues.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •healthy male and female subjects between 18 and 40 years of age (inclusive).
- •female subjects of child bearing potential with negative pregnancy test at screening and willing to use 2 effective methods of contraception (i.e. established method of contraception plus condom, or where abstaining from heterosexual intercourse is in line with the preferred and usual lifestyle of the subject) from Day 1 until 3 months after the last dose of PnuBioVax/Placebo.
- •male subjects willing to use 2 effective methods of contraception unless anatomically sterile, or where abstaining from heterosexual intercourse is in line with the preferred and usual lifestyle of the subject, from Day 1 until 3 months after the last dose of PnuBioVax/Placebo.
- •subjects with a Body Mass Index (BMI) of <30 kg/m
- •subjects with a negative urinary drugs of abuse screen determined within 28 days of the first dose.
- •subjects with negative HIV and Hepatitis B and C results.
- •subjects must be willing and able to comply with the requirements of the protocol and must be available to complete the trial, including all follow up visits.
- •subject must provide written informed consent to participate in the trial.
排除标准
- •any relevant abnormality in medical history examination, vital signs laboratory tests or ECG.
- •any reason that would make the assessment of any injection site reaction difficult (e.g. tattoos at injections site, black skin).
- •history of migraine or asthma (no inhaler use for 5 years).
- •proven diagnosis of pneumonia within last 5 years.
- •current smokers.
- •history of anaphylaxis or hypersensitivity to previous vaccinations.
- •known impairment of the immune system or chronic diseases, e.g. autoimmune diseases, diabetes, cancer.
- •anticipation that the subject may require any other vaccination during the trial period.
- •subjects who are antinuclear antibody (ANA) positive (above a titre of 1:80).
- •subjects with haemoglobin level < 8.4 mmol/ L (males) and <7.8 mmol/L (females).
- •palpable cervical or axillary lymph nodes.
- •receipt of regular prescribed medication within 28 days of the first trial day and / or receipt of vitamins, minerals, herbal remedies and nutritional supplements within 7 days of the first trial day.
结局指标
主要结局
Incidence of all treatment emergent adverse events
时间窗: Baseline to Day 85
Number of subjects with adverse events reported from first dosing to last follow up visit.
次要结局
- The proportion of subjects who develop an immune response to PnuBioVax(Baseline to Day 85)