Safety, Immunogenicity, and Efficacy of Therapeutic Mycobacterium Bovis BCG in Patients With Mycobacterium Avium Complex Lung Disease (BOOST)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Serious adverse events
研究概览
简要总结
The purpose of this study is to find out if the Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine can be used safely to treat Mycobacterium avium complex (MAC) lung disease.
Researchers will compare responses from patients with MAC lung disease after receiving an injection of BCG or placebo (a look-alike substance that contains no drug)
Participants in the study:
- Receive a BCG or placebo injection at UVA study center on Day 0
- Come to UVA study center on Day 60
- Come to UVA study center at the end of the study
- Answer surveys and questionnaires about how you are doing
- Have blood drawn 3 times, on injection day, day 60, and at end of study
- Give the study team personal and demographic information
- Discuss any new symptoms with the study team
- Provide monthly sputum samples per usual care
详细描述
Mycobacterium avium complex (MAC) lung disease (LD) is an increasingly prevalent condition in the United States. Treatment involves administration of multiple antibiotics for at least 12 months and many patients still fail, or infection recurs. New therapeutic strategies are needed. We hypothesize that Mycobacterium bovis Bacillus Calmette Guerin (BCG) will have microbiologic activity against MAC during lung disease, because of
- Its mycobacterium antigens shared with MAC (1).
- In vitro evidence that BCG stimulates MAC-specific immune responses in mice and humans (2, 3).
- In vivo evidence that BCG reduces MAC in mice with established infection (4). Clinical evidence for BCG protection against MAC infection in HIV patients and in children (5, 6).
Objectives:
The primary objective is to determine the safety and immunogenicity of BCG against MAC lung disease after intradermal vaccination with BCG or placebo.
The secondary objectives include:
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Male or female aged ≥18 years
- •Mycobacterium avium complex lung disease as evidenced by diagnosis or treatment for MAC lung disease by pulmonologist or infectious disease physician in the medical record. The following data will be extracted from the medical record:
- •History of at least 2 MAC positive respiratory cultures, one of which is within 1 year of enrollment. In the event a MAC positive culture is from bronchial lavage or biopsy, one culture rather than 2 will meet criteria.
- •Respiratory and/or constitutional symptoms consistent with MAC lung disease
- •Nodular or cavitary opacities on chest radiograph or bronchiectasis with multiple small nodules on high-resolution computed tomography
- •Provision of signed and dated informed consent form
- •Stated willingness to comply with all study procedures
- •Women of childbearing potential (WOCBP) (i.e., fertile following menarche and until becoming postmenopausal unless permanently sterile) agree to practice a highly effective method of birth control from Day 0 to at least 90 days after study intervention. Some examples of acceptable birth controls are:
- •True abstinence (refraining from heterosexual intercourse during the entire study),
- •Copper intrauterine device (IUD),
- •Hormonal methods (levonorgestrel-releasing intrauterine system, progestogen implant, combined oral contraceptive pill [combined with barrier method]), exclusive homosexual relationship) sole male partner who has undergone surgical sterilization
排除标准
- •Selection of study participants will be equitable, but an individual who meets any of the following criteria will be excluded from participation in this study:
- •Currently receiving antibiotics prescribed for their MAC lung disease
- •Having received any antibacterial antibiotics within the past 14 days prior to study vaccination, day 0
- •Known allergy, intolerance or other contraindication to isoniazid or rifampin or ethambutol
- •Expectation of starting anti-MAC lung disease antibiotics in the next 2 months per patient or their physician
- •Persons with congenital or acquired immune deficiencies (e.g., HIV infection; leukemia, lymphoma, or cancer therapy within the past 2 years; immunosuppressive therapy such as anti B cell depleting therapies, corticosteroids (>20 mg/day for > 14 days), dupilumab, elivaldogene, etrasimod, cytotoxic chemotherapy, miscellaneous oncologic agents, therapeutic immunosuppressant agents, methotrexate, teplizumab, tezepelumab, tildrakizumab, tralokinumab, ustekinumab). Persons with lung and other solid organ transplants/hematologic stem cell transplants who may be contraindicated to receive a live vaccine. Point of care HIV testing must be negative at baseline.
- •Prior BCG Vaccination. If unknown Bcgatlas.org shall be consulted for local vaccination administration policies.
- •Known pregnancy at the time of screening or breastfeeding at the time of enrollment (pregnancy test negative at baseline if applicable)
- •Cystic fibrosis
- •Active tuberculosis: Active tuberculosis (respiratory AFB culture growing Mycobacterium tuberculosis complex within the past 4 months).
- •Known exposure to a case of active pulmonary tuberculosis within 10 weeks of enrollment
- •Known prior hypersensitivity reaction to BCG or any component of the BCG vaccine
- •Received live injectable vaccine within 28 days of day 0 study vaccination
- •Any condition in the opinion of the investigator that may confound the study endpoints Note that colonization or co-infection with other nontuberculous mycobacteria is not exclusionary, as MAC will be the endpoint.
研究组 & 干预措施
Placebo
preservative-free saline
干预措施: preservative-free saline (Drug)
Active BCG
Biological/Vaccine: Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine
干预措施: Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine (Biological)
结局指标
主要结局
Serious adverse events
时间窗: 12 months
Serious adverse events related to the intradermal BCG over 12 months after intervention.
Immunogenicity
时间窗: 24 months
Compare changes in immunogenicity, as measured by IFN-gamma production between the BCG and placebo groups. We will assess for increases in T cell immune responses against BCG and MAC, as measured by cytokine production, in those who received the BCG vaccine and those that received placebo. We will use ex vivo T cell stimulation assays to quantify the antigen specific T cell responses and assess cytokine production via flow cytometry and/or multiplexed enzyme-linked immunosorbent assay (Luminex).
Adverse events
时间窗: 12 weeks after intervention
Safety and tolerability of intradermal BCG (TICE®) in this patient population, compared to placebo, assessed by weekly questionnaire of adverse events. Licensed study team member will follow-up on any events reported to be more than mild. Follow-up will be completed as a telemedicine or in person visit
Adverse events
时间窗: 12 weeks after intervention
Safety and tolerability of intradermal BCG (TICE®) in this patient population, compared to placebo, assessed by weekly questionnaire of adverse events. Licensed study team member will follow-up on any events reported to be more than mild. Follow-up will be completed as a telemedicine or in person visit
Serious adverse events
时间窗: 12 months
Serious adverse events related to the intradermal BCG over 12 months after intervention.
Immunogenicity
时间窗: 24 months
Compare changes in immunogenicity, as measured by IFN-gamma production between the BCG and placebo groups. We will assess for increases in T cell immune responses against BCG and MAC, as measured by cytokine production, in those who received the BCG vaccine and those that received placebo. We will use ex vivo T cell stimulation assays to quantify the antigen specific T cell responses and assess cytokine production via flow cytometry and/or multiplexed enzyme-linked immunosorbent assay (Luminex).
次要结局
- Sputum cultures(24 months)
研究者
Eric R. Houpt, MD
Professor and Chief, Division of Infectious Diseases and International Health, Medicine: Infectious Diseases and International Health
University of Virginia