BCG vaccine to treat MAC lung disease

Safety, Immunogenicity, and Efficacy of Therapeutic Mycobacterium Bovis BCG in Patients With Mycobacterium Avium Complex Lung Disease (BOOST)

This will test whether a single BCG vaccine injection can safely boost immunity and help adults with Mycobacterium avium complex (MAC) lung disease.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Virginia (other)
• Drugs / interventions: dupilumab, teplizumab, tezepelumab, tildrakizumab, tralokinumab, ustekinumab, chemotherapy, methotrexate
• Locations: 1 site (Charlottesville, Virginia)
• Trial ID: NCT07094711 on ClinicalTrials.gov

What this trial studies

In this randomized, placebo-controlled Phase 2 trial at the University of Virginia, adults with confirmed MAC lung disease receive an intradermal BCG vaccine or a placebo and are followed for clinical, microbiologic, and immune responses. Participants have study visits at Day 0, Day 60, and at the end of the study, with blood draws at each visit, weekly symptom questionnaires for safety, and monthly sputum samples per usual care. The primary focus is on safety and immunogenicity, with secondary endpoints including microbiologic activity and reductions in respiratory illnesses needing extra antibiotics or care. Data from culture results, patient-reported symptoms, and immune assays will be compared between the BCG and placebo groups.

Who should consider this trial

Good fit: Adults (≥18 years) with documented MAC lung disease based on cultures, compatible symptoms, and characteristic chest imaging who can attend visits at the University of Virginia and provide informed consent are ideal candidates.

Not a fit: Patients who are pregnant, severely immunocompromised, unable to receive a live vaccine, or whose MAC is already well controlled are less likely to benefit from this intervention.

Why it matters

Potential benefit: If successful, BCG vaccination could improve control of MAC lung disease, reduce recurrent infections, and potentially decrease prolonged antibiotic use.

How similar studies have performed: Preclinical studies and some observational clinical data suggest BCG can affect MAC, but therapeutic use of BCG for established MAC lung disease in adults is novel and not yet proven in randomized trials.

Eligibility criteria

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Male or female aged ≥18 years
2. 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:

   1. 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.
   2. Respiratory and/or constitutional symptoms consistent with MAC lung disease
   3. Nodular or cavitary opacities on chest radiograph or bronchiectasis with multiple small nodules on high-resolution computed tomography
3. Provision of signed and dated informed consent form
4. Stated willingness to comply with all study procedures
5. 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:

   1. True abstinence (refraining from heterosexual intercourse during the entire study),
   2. Copper intrauterine device (IUD),
   3. 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

Exclusion Criteria

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:

1. Currently receiving antibiotics prescribed for their MAC lung disease
2. Having received any antibacterial antibiotics within the past 14 days prior to study vaccination, day 0
3. Known allergy, intolerance or other contraindication to isoniazid or rifampin or ethambutol
4. Expectation of starting anti-MAC lung disease antibiotics in the next 2 months per patient or their physician
5. 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.
6. Prior BCG Vaccination. If unknown Bcgatlas.org shall be consulted for local vaccination administration policies.
7. Known pregnancy at the time of screening or breastfeeding at the time of enrollment (pregnancy test negative at baseline if applicable)
8. Cystic fibrosis
9. Active tuberculosis: Active tuberculosis (respiratory AFB culture growing Mycobacterium tuberculosis complex within the past 4 months).
10. Known exposure to a case of active pulmonary tuberculosis within 10 weeks of enrollment
11. Known prior hypersensitivity reaction to BCG or any component of the BCG vaccine
12. Received live injectable vaccine within 28 days of day 0 study vaccination
13. 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.

Where this trial is running

Charlottesville, Virginia

• University of Virginia Health — Charlottesville, Virginia, United States (RECRUITING)

Study contacts

• Study coordinator: Eric R Houpt, M.D.

Conditions: Mycobacterium Avium-intracellulare Infection, Mycobacterium Infections, Nontuberculous