A Phase II, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Safety and Immunogenicity of AERAS-402 in BCG-vaccinated, HIV-uninfected Infants Without Evidence of Tuberculosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 487
- 试验地点
- 7
- 主要终点
- Adverse Events Collected Per Subject
研究概览
简要总结
AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.
详细描述
The only currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG), is estimated to reduce the risk of tuberculosis (TB) in children by up to 70-80%, but protection is incomplete. Efforts to increase TB protection in children include new vaccines for primary immunizations as well as combinations of vaccines given as primary and boosting vaccinations.
AERAS 402 is a live recombinant serotype 35 replication deficient adenovirus vector expressing a fusion protein of three Mycobacterium tuberculosis (Mtb) antigens (Ag85A, Ag85B and TB10.4). It presents Mtb antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. AERAS-402 appears safe and immunogenic in adults. Since BCG-vaccinated infants are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to infants of at least 16 weeks of age who have already been vaccinated with BCG. This is the first Phase II study of AERAS-402 in infants.
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
- 112 Days 至 182 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Parent/legal guardian has completed the written informed consent process
- •Is age greater than or equal to 112 days (16 weeks) and less than or equal 182 days (26 weeks) on Study Day 0
- •Has general good health, confirmed by medical history and physical examination
- •Is up to date on all Expanded Program of Immunization (EPI) immunizations for his/her age with a minimum of 14 days between the last EPI vaccination and administration of study vaccine on Study Day 0
- •Has ability to complete follow-up period of 728 days as required by the protocol
- •Parent/legal guardian is able and willing to stay in contact with the study site for the duration of the study and to provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
- •Has completed simultaneous enrollment in Aeras Vaccine Development Registry protocol
- •Had BCG vaccination ≥ 3 months prior to randomization documented by medical card
排除标准
- •Acute illness, evidence of any significant active infection or temperature >=37.5°C on the day of randomization
- •Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted)
- •Received immunoglobulin or blood products within 45 days before entry into the study
- •Ever received any investigational drug therapy or investigational vaccine
- •History or laboratory evidence of individual immunodeficiency virus (HIV-1) infection
- •History of allergic disease or reactions to any component of the study vaccine
- •Previous medical history that may compromise the safety of the participant in the study
- •Evidence of a new acute illness that may compromise the safety of the participant in the study
- •Inability to discontinue daily medications during the study
- •History or evidence of any systemic disease on physical examination or any acute or chronic illness that may interfere with the evaluation of the safety or immunogenicity of the vaccine, e.g., including masses between the leg and abdomen (e.g., inguinal hernia or lymphadenopathy)
- •History or evidence of active tuberculosis
- •A positive QuantiFERON®-TB Gold In-Tube test
- •A household contact with active TB disease
研究组 & 干预措施
Dose Finding Gr 1 placebo x 2
Subjects received two doses (x2) of placebo (sterile buffer) on study days 0 and 28.
干预措施: Placebo (Biological)
Dose Finding Gr 2 AERAS-402 (1.5 x 10^10 vp) x2
Subjects received two doses (x2) of AERAS-402 (1.5 x 10^10 vp) on study days 0 and 28.
干预措施: AERAS-402 1.5 x 10^10 vp (Biological)
Dose Finding Gr 3 AERAS-402 (3.0 x 10^10 vp) x 2
Subjects received two doses (x2) of AERAS-402 (3.0 x 10^10 vp) on study days 0 and 28.
干预措施: AERAS-402 3.0 x 10^10 vp (Biological)
Dose Finding Gr 4 AERAS-402 (1.0 x 10^11 vp) x 2
Subjects received two doses (x2) of AERAS-402 (1.0 x 10^11 vp) on study days 0 and 28.
干预措施: AERAS-402 1.0 x 10^11 vp (Biological)
Expanded Safety Phase Gr 5 AERAS-402 (1.0 X 10^11 vp) x 3
Subjects received 3 doses (x3) of AERAS-402 (1.0 X 10^11 vp) on days 0, 28 and 280.
干预措施: AERAS-402 1.5 x 10^10 vp (Biological)
Expanded Safety Phase Gr 5 Placebo x3
Subjects received 3 doses (x3) of placebo (sterile buffer) on days 0, 28 and 280.
干预措施: Placebo (Biological)
结局指标
主要结局
Adverse Events Collected Per Subject
时间窗: Up to 24 months post vaccination
Adverse Events (AEs) are recorded for 28 days post vaccination Serious Adverse Events (SAEs) are recorded for the entire study period to assess the safety profile
次要结局
- Percentage of Cells Expressing Various Cytokines Will be Measured by Intracellular Cytokine Staining (ICS) in All Subjects(28 days post last vaccination)
- Interferon-gamma (IFN-gamma) Enzyme-linked Immunospot (ELISpot) Response: Spot Forming Units/10^6 PBMC According to ELISpot Assay(28 days post last vaccination)
- Antigen-specific Antibody Response - Mean Optical Density (Mean OD)(28 day post last vaccination)
- Percentage of Subjects Converting From a Negative QuantiFERON Test (QFT) to Positive QFT After Vaccination(up to 24 months post vaccination)