A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-404 Administered as Different Amounts of Antigen and Adjuvant Combinations in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Evaluate the safety of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant
研究概览
简要总结
Phase I, randomized, double blinded, Placebo-controlled, immunogenicity and dose-range finding study of AERAS-404 in Bacille Calmette-Guerin (BCG) healthy adult male and sterile females.
详细描述
This ia a Phase I, randomized, placebo-controlled, double-blind study in three groups of healthy adult males or sterile females who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection.
Sixty-four subjects assigned to one of eight treatment groups to receive one of four different antigen/adjuvant combinations of study vaccine, or placebo control. Within each study group, subjects will be randomized to receive either a single-dose antigen/adjuvant regimen of study vaccine (vaccination with study vaccine on Study Day 0 followed by vaccination with placebo control on Study Day 56) or a two-dose antigen/adjuvant regimen of study vaccine (vaccination with study vaccine on Study Days 0 and 56).
All subjects will be followed for safety and immunogenicity evaluations for 182 days.
The sample sizes specified for each study group were selected because they are judged to be adequate for preliminary safety and immunogenicity evaluations for a Phase I study rather than for statistical reasons. If no SAE are observed among 56 subjects receiving active study vaccine, an approximation to the upper 95% confidence bound on the rate of SAE occurrence would be 5.4%.
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female
- •Age 18 through 50 years on Study Day 0
- •Completed wriiten Informed Consent
- •BCG vaccination at least 5 years ago,
- •General good health, confirmed by medical history
- •(BMI) between 19 and 33 (kg/m2)
- •Has ability to complete follow-up period of 182 days as required
- •Females must be physically incapable of conception
- •Avoiding elective surgery for the duration of the study
- •Stay in contact with the investigative site for the duration of the study
- •Complete simultaneous enrollment in Aeras Vaccine Development Registry protocol
排除标准
- •Acute illness on the day of randomization
- •Oral temperature >=37.5 degree Celcius on the day of randomization
- •Evidence of significant active infection
- •Used immunosuppressive medication within 42 days before entry into the study
- •Received immunoglobulin or blood products within 42 days before entry into the study
- •Received any investigational drug therapy or investigational vaccine within 182 days
- •Received inactivated influenza vaccine or inactivated tick-borne encephalitis vaccine within 14 days before entry into the study.
- •Current chronic drug therapy including hormone replacement such as thyroxin, insulin, etc.
- •History or laboratory evidence of any past, present or future possible immunodeficiency state which will include any laboratory indication of virus type 1 (HIV-1) infection
- •History of allergic disease or reactions, including eczema.
- •Previous medical history that may compromise safety of subject
- •Evidence of new acute illness that may compromise safety of subject
- •Evidence of chronic hepatitis
- •Inability to discontinue daily medication except contraception
- •History of alcohol or drug abuse within 2yrs
- •Tobacco or cannabis smoking three
- •Positive urine test for illicit drugs
- •History or evidence of any systemic disease on physical examination
- •History of active TB
- •Shared residence within 1 year with an individual on anti-TB treatment
- •All females: nursing
- •Abnormal hemoglobin,hematocrit etc drawn within 36 hours prior to randomization
- •Laboratory test evidence of Mtb infection
- •History of positive tuberculin skin test within past 10 years
- •Received a tuberculin skin test within 3 years
- •History of autoimmune disease
结局指标
主要结局
Evaluate the safety of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant
时间窗: All subjects will be followed for safety and immunogenicity evaluations for 182 days. A total of eleven clinic visits are planned (excluding screening) for all subjects
Serious adverse events (SAE) will be collected on subjects throughout their participation in the study. Solicited and unsolicited AEs will be collected through 28 days after each vaccination.The safety profile of the different antigen/adjuvant treatment regimens will be described. Listings will be provided for all subjects with serious adverse events (SAE). All adverse events and clinically relevant laboratory results will be summarized across time points to examine the relationship between treatment regimens (i.e., number of doses and level of antigen/adjuvant) and key safety endpoints including number (percentage) of solicited and spontaneous adverse events and number (percentage) of subjects with newly abnormal post-vaccination laboratory values based on predefined toxicity criteria. Adverse events will also be summarized by severity and relationship to study vaccine by treatment regimen.
次要结局
- Evaluate the immunogenicity of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant.(all subjects will have immunology samples taken at 9 time points over 182 days)