A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter, Clinical Trial to Assess the Prophylactic Efficacy, Safety, and Immunogenicity of the Investigational M72/AS01E-4 Mycobacterium Tuberculosis (Mtb) Vaccine When Administered Intramuscularly on a 0,1-month Schedule to Adolescents and Adults

Gates Medical Research Institute107 个研究点分布在 5 个国家目标入组 20,080 人2024年3月5日

适应症Tuberculosis

干预措施M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine Placebo

概览

阶段: 3 期
干预措施: M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine
疾病 / 适应症: Tuberculosis
发起方: Gates Medical Research Institute
入组人数: 20080
试验地点: 107
主要终点: IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary tuberculosis (TB)
状态: 进行中（未招募）
最后更新: 2个月前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

The study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01E-4 Mtb vaccine when administered intramuscularly (IM) on a 0,1-month schedule to adolescents and adults. This trial will be conducted in 3 cohorts: Interferon gamma release assay (IGRA)-positive Cohort, IGRA-Negative Cohort and Human Immunodeficiency virus (HIV) Cohort.

注册库

clinicaltrials.gov

开始日期

2024年3月5日

结束日期

2028年4月1日

最后更新

2个月前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

Gates Medical Research Institute

责任方

Sponsor

入排标准

入选标准

•Capable of giving informed consent or informed assent (as appropriate). For participants below the age of consent, the participant's parent, or legally authorized representative (LAR) will be required to sign a statement of informed consent, in addition to the minor's signed statement of assent.
•In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of diary cards as applicable, and return for follow-up visits).
•Agree to actively stay in contact with the trial site for the duration of the trial for the participants own safety.
•Agree to provide updated contact information as necessary, and have no current plans to relocate from the trial area for the duration of the trial.
•Healthy, or with preexisting stable disease, as established by medical history and physical examination and as determined by the investigator.
•Negative sputum Xpert Ultra or similar assay result at screening.
•Both males and females are included. Females are included with restrictions. Females must either be of non-childbearing potential, defined as pre-menarche, have a history of either current tubal ligation, hysterectomy, or ovariectomy, or post-menopause, or, if she is of childbearing potential, she has practiced abstinence from penile-vaginal intercourse or adequate contraception for 28 days prior to vaccination, has a negative pregnancy test on the day of screening and the day of first vaccination, and agrees to continue abstinence or adequate contraception until 2 months after the second dose of trial intervention.
•HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohort only).
•HIV Cohort only: Participants with documented HIV infection who fulfill all of the following criteria:
•Have reactive anti-HIV antibody at screening.

排除标准

•Current TB, or history of TB or treatment for TB disease.
•Clinical suspicion of pulmonary TB at screening, defined as a participant presenting with one or more of the following signs or symptoms: unexplained cough, unexplained fever, night sweats, unintentional weight loss, hemoptysis, pleuritic chest pain.
•Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol, or that will interfere with the assessments or the safety of the participant.
•Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., invasive, or malignant cancers), other than HIV infection in the HIV Cohort.
•Known bleeding disorder that is considered a contraindication to intramuscular injection or phlebotomy.
•Any cytotoxic drugs or administration of medications known to have a major impact on the immune system, as determined by the investigator, within 90 days prior to Day
•These include immune globulin, blood, or blood products, potent immunosuppressants and immunomodulators, and systemic corticosteroids (exceeding 20 mg/day prednisone equivalent). Inhaled, topical, and intra-articular corticosteroids are allowed.
•Planned receipt of blood, or blood products during the trial period.
•Receipt or planned receipt of any vaccine in the period starting 28 days before, and ending 28 days after, each dose of the trial vaccine.
•History of previous administration of an experimental Mtb vaccine including M72/AS01E in a previous trial.

研究组 & 干预措施

Participants receiving M72/AS01E-4

干预措施: M72/AS01E-4 Mycobacterium tuberculosis investigational vaccine

Participants receiving placebo

干预措施: Placebo

结局指标

主要结局

IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary tuberculosis (TB)

时间窗: Up to Month 49

Laboratory-confirmed pulmonary TB case is defined as a participant with suspected pulmonary TB presenting with one or more of the following signs or symptoms: unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain; who has least 2 positive Mtb test results (positive Mtb culture and/or positive test result from Xpert Ultra or similar assay, excluding "trace positive"), from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment.

次要结局

HIV Cohort: Number of participants with laboratory-confirmed pulmonary TB(Up to Month 49)
IGRA-Positive Cohort: Number of participants with laboratory-confirmed pulmonary TB (Less stringent laboratory-confirmed pulmonary TB case definition)(Up to Month 49)
All Cohorts: Number of participants with serious adverse events (SAEs)(Up to Month 13)
IGRA-Negative Cohort: Number of participants with sustained QuantiFERON®-TB Gold Plus assay conversion(Up to Month 49)
All Cohorts: Number of participants with potential immunemediated diseases (pIMDs)(Up to Month 13)
All Cohorts: Number of participants with SAEs related to trial participation(Up to Month 49)
All Cohorts: Number of participants with unsolicited AEs(Up to 28 days)
IGRA-Negative Cohort: Number of participants with laboratory-confirmed pulmonary TB(Up to Month 49)
All cohorts: Number of participants with seropositivity of M72-specific antibodies(At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49)
All Cohorts: Number of participants with solicited adverse events (AEs)(Up to 7 days)
All cohorts: Number of participants with geometric mean concentration (GMC) of M72-specific antibodies(At Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49)