A Randomized, Placebo-controlled, Observer-blind, Phase 2 Study to Evaluate Safety and Immunogenicity of the Investigational M72/AS01E Mycobacterium Tuberculosis (Mtb) Vaccine in Virally Suppressed, Antiretroviral-treated Participants With Human Immunodeficiency Virus (HIV)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 402
- 试验地点
- 6
- 主要终点
- Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention
研究概览
简要总结
The purpose of this study is to assess the safety and immunogenicity of M72/AS01E vaccination in virally suppressed, antiretroviral-treated participants with human immunodeficiency virus infection (HIV).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant with documented human immunodeficiency virus (HIV) infection who fulfill all of the following:
- •Has reactive anti-HIV antibody at screening
- •On antiretroviral therapy (ART) for at least 3 consecutive months at screening
- •Has documented HIV RNA <200 copies/mL at screening
- •Participants with CD4+ cell counts ≥200 cells/μL at screening
- •Participants have had tuberculosis (TB) preventive therapy (TPT) in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators
- •Participants who are healthy as determined by medical evaluation including medical history, physical examination and laboratory tests
- •Capable of giving signed informed consent and informed assent (if appropriate), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) or informed assent form, and in the protocol.
- •Female participants of childbearing potential must agree not to become pregnant from the time of study enrollment for one year after study intervention. Women physically capable of pregnancy, sexually active and having no history of hysterectomy or tubal ligation or menopause must agree to use an effective method of avoiding pregnancy during this period.
- •Participants who agree to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study.
排除标准
- •Acute illness or fever ≥99.5°F (or ≥37.5˚C) on Day 1
- •History of active TB disease
- •Evidence of active TB disease with any of the following:
- •Have symptoms or signs of TB disease
- •Have a positive sputum Xpert MTB/RIF assay (only in participants with sputum sample at screening)
- •Are on treatment for active TB disease
- •Evidence and/or history of clinically significant medical conditions (other than HIV infection) as judged by the investigator, including malignancies
- •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
- •Any medications or other therapies that may impact the immune system such as immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with major organ toxicity as determined by the investigator, within 90 days prior to Day 1
- •Immunosuppressive agents including systemic steroids - prior corticosteroid therapy within 90 days prior to Day 1 (permitted: 5 mg/day prednisone equivalent, inhaled, topical, and intra-articular corticosteroids)
- •Receipt or donation of blood or blood products within 90 days prior to Day 1 or planned receipt or donation during the study period
- •Participation in an interventional clinical trial and/or receipt of any investigational drug within 180 days prior to signing informed consent or assent
- •Receipt of any vaccine in the period starting 7 days before, and ending 7 days after, each dose of the study vaccine
- •History of previous administration of experimental Mycobacterium tuberculosis vaccine
- •Safety laboratory values outside of normal range, for age and sex that are suggestive of a disease state (Grade 1 abnormalities, as per Division of AIDS [DAIDS] toxicity table version 2.1, will not lead to exclusion if the investigator considers them not clinically significant.)
- •Urinalysis abnormality greater than Grade 1 on the Toxicity Scale (with the exception of hematuria in a menstruating female), or urinalysis abnormality judged clinically significant by the investigator
- •Current hepatitis B and/or hepatitis C infection
- •Indeterminate QFT result
- •History of allergy or hypersensitivity to the study drug, excipients or related substances
- •Shared residence with an individual who is receiving TB treatment or with someone who is known to have incompletely treated TB, e.g., Xpert MTB/RIF assay-positive, polymerase chain reaction (PCR)-positive, culture-positive, smear-positive TB, or clinically diagnosed unconfirmed TB
- •Female participants with any one of the following conditions: currently pregnant or lactating/nursing; having positive serum pregnancy test during the screening window, planning a pregnancy within 1 year after first dose of study product
- •Individuals who are acting as study personnel or immediate family members (brother, sister, child, parent) or the spouse/partner of study personnel.
- •Child in Care
研究组 & 干预措施
M72/AS01E vaccine
干预措施: M72/AS01E Mycobacterium tuberculosis vaccine (Biological)
Placebo
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Participants With Solicited Adverse Events (AEs) Through 7 Days Post Dose 1 of Study Intervention
时间窗: Day 1 through Day 7 (after first vaccination)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia.
Number of Participants With Solicited AEs Through 7 Days Post Dose 2 of Study Intervention
时间窗: Day 29 through Day 35 (after second vaccination)
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Solicited AEs were defined events that participants were specifically asked about and which were noted by participants in the diary card. Solicited local AEs included pain, redness and swelling and general body symptoms such as fever, headache, fatigue, gastrointestinal symptoms, and myalgia.
Number of Participants With Unsolicited AEs Through 28 Days Post Dose 1 of Study Intervention
时间窗: Day 1 through Day 28
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after first vaccination has been presented.
Number of Participants With Unsolicited AEs Through 28 Days Post Dose 2 of Study Intervention
时间窗: Day 29 through Day 57
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An AE does not necessarily have a causal relationship with the intervention. Unsolicited AEs were all AEs for which the participant was not specifically questioned in the participant diary card. Number of Participants With Unsolicited AEs Through 28 Days after second vaccination has been presented.
Number of Participants Reporting Serious AEs (SAEs)
时间窗: Up to Day 390
An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of Participants reporting SAEs has been presented.
次要结局
- Number of Participants With Potential Immune-mediated Diseases (pIMDs)(Up to Day 390)
- Number of Participants With Clinically Significant Hematology Assessments of Grade 3 or Above After Baseline(Up to Day 390)
- Number of Participants With Clinically Significant Chemistry Assessments of Grade 3 or Above After Baseline(Up to Day 390)
- M72-specific Antibody Titers(Day 1, Day 29, Day 57, Day 210 and Day 390)
- Number of M72 Specific CD4+ and CD8+ T Cell Responders Based on Cytokine Response(Day 57 and Day 390)
- Percentage of M72-specific CD4+ T Cells and CD8+ T Cells Exhibiting Cytokine Response With Background Subtracted(At Baseline, Day 57, and Day 390)