A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Clinical Trial to Evaluate the Safety and Immunogenicity of the ID93 + GLA-SE Vaccine in HIV Uninfected Adult TB Patients After Treatment Completion
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 6
- 主要终点
- Number of Adverse Events
研究概览
简要总结
The purpose of this study is to evaluate the safety and immunogenicity of ID93 + GLA-SE vaccine when administered to adult pulmonary Tuberculosis (TB) patients, following successful completion of TB treatment with confirmed bacteriologic cure, in preparation for a future Phase 2b prevention of TB recurrence trial in the same population.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females 18 to 60 years of age.
- •Subjects must have been successfully treated, i.e., completed the scheduled course of TB treatment as per the prevailing South African national guidelines, for MTB culture-confirmed, drug sensitive pulmonary TB, as evidenced by a record of positive liquid MTB culture with formal drug sensitivity testing (DST) and/or by Xpert MTB/RIF test at baseline.
- •Must have two separate samples showing bacteriologic confirmation of cure - defined in the first instance as Xpert MTB/RIF test negative, or, if Xpert MTB/RIF positive, as MTB liquid culture negative - on two successive occasions at least 30 days apart. Subjects who are sputum unproductive will be deemed Xpert MTB/RIF and MTB liquid culture negative.
- •Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the day of each study injection, must not be breast-feeding, and be willing to avoid pregnancy for 3 months following first study injection. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm with spermicide gel.
- •The following screening laboratory values must be within the laboratory reference range or, if abnormal, deemed not clinically significant and less than Grade 2 severity on the FDA Toxicity Scale, as determined by the PI and LMM or Sponsor Medical Advisor: ALT, AST, total bilirubin, creatinine, total WBC count, hemoglobin, and platelet count.
- •The HIV 1/2 antibody serology tests must be negative.
- •Must give informed consent, be able and willing to make all evaluation visits, be reachable by telephone or personal contact by the study site personnel, and be willing to remain in the study area for the duration of the trial.
排除标准
- •TB treatment failure, as evidenced by clinical diagnosis or a positive MTB liquid culture at month 4 or 5 after starting treatment. A positive MTB liquid culture at, or after, end of treatment would exclude subjects from receiving further study injections.
- •Previous course of TB treatment completed within 5 calendar years prior to obtaining baseline diagnostic sputum samples.
- •Receipt of any investigational products or investigational drug in the past 6 months or investigational vaccine ever.
- •Treatment with immunosuppressive drugs (e.g., oral or injected steroids, such as prednisone; high dose inhaled steroids) in the past 6 months. Topical steroids would be allowable.
- •Received incomplete or investigational, or non-standard TB drug regimen, other than the prevailing current South African national guideline as reference standard, or poor adherence to TB treatment regimen.
- •Diagnosed with rifampicin-resistant MTB strain (by Xpert MTB/RIF and/or culture and formal DST).
- •History of autoimmune disease or other causes of immunosuppressive states.
- •History or evidence of any acute or chronic illness (including diabetes mellitus, asthma), medical or surgical condition, or chronic heavy ethanol or drug use, or use of medication that, in the opinion of the Principal Investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
- •Subjects with a history of previous anaphylaxis or severe allergic reaction to vaccines, eggs, or unknown allergens.
- •Subjects who are unlikely to cooperate with the requirements of the study protocol.
研究组 & 干预措施
2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 doses
Three intramuscular injections of ID93 + GLA-SE at Days 0, 28, and 56. Low dose of antigen and high dose of adjuvant.
干预措施: ID93 + GLA-SE (Biological)
Placebo
Two intramuscular injections of normal saline at Days 0 and 56, or Days 0, 28, and 56.
干预措施: Placebo (Other)
10 mcg ID93 + 2 mcg GLA-SE Vaccine
Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. High dose of antigen and low dose of adjuvant.
干预措施: ID93 + GLA-SE (Biological)
2 mcg ID93 + 5 mcg GLA-SE Vaccine
Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and high dose of adjuvant. Placebo injection at Day 28 to maintain blind with the 3 dose arm.
干预措施: ID93 + GLA-SE (Biological)
2 mcg ID93 + 2 mcg GLA-SE Vaccine
Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and low dose of adjuvant.
干预措施: ID93 + GLA-SE (Biological)
结局指标
主要结局
Number of Adverse Events
时间窗: 224 days
Safety outcomes will include solicited adverse events within 7 days and unsolicited adverse events within 28 days after each study injection; and serious adverse events after the first study injection until end of study follow-up.
次要结局
- Immunogenicity Responder Rate(Day 70)