Mycobacterium Avium-intracellulare InfectionPhase 2BOOSTNCT07094711
Safety, Immunogenicity, and Efficacy of Therapeutic Mycobacterium Bovis BCG (BOOST)
A Phase 2 study testing Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine and preservative-free saline in people with Mycobacterium Avium-intracellulare Infection and Mycobacterium Infections, Nontuberculous, run by University of Virginia at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mycobacterium Avium-intracellulare Infection, Mycobacterium Infections, Nontuberculous
- What is being tested?
- Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine and preservative-free saline
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Apr 2026to 30 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Virginia Health
Charlottesville, Virginia, 22908
Heather Haughey, PhD, 434-243-4008, MACLungDiseaseBoostStudy@uvahealth.org
About this study
Official title: Safety, Immunogenicity, and Efficacy of Therapeutic Mycobacterium Bovis BCG in Patients With Mycobacterium Avium Complex Lung Disease (BOOST)
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)
Read more
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
Read the detailed description
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:
- the microbiologic efficacy of BCG compared to placebo.
- to determine if BCG is superior to placebo in reducing all-cause respiratory illness requiring additional antibiotics, healthcare assessment, or admission.
Endpoints:
Primary endpoints:
- Safety and tolerability of intradermal BCG (TICE®) in this patient population, compared to placebo, assessed by weekly questionnaire of adverse events over 12 weeks.
- Serious adverse events related to the intradermal BCG over 12 months.
- Immunogenicity of BCG as measured by the change in BCG-induced IFN-γ production in PBMCs 60 days after vaccination, compared to placebo.
Secondary endpoints:
- Proportion of monthly sputum cultures positive for MAC after BCG vaccine or placebo over 24 months.
- Immunogenicity of BCG on MAC-specific IFN-γ responses.
- Proportion of patients with MAC culture conversion and MAC recurrence within 24 months.
- Rates of all-cause respiratory illness requiring additional antibiotics, healthcare assessment, or admission over 24 months.
- Symptom scores using the Quality of Life- Bronchiectasis Respiratory (QOL-BR) questionnaire over 24 months.
- Adverse Events of Special Interest (local/systemic M. bovis BCG infection) over 24 months.
Exploratory endpoints:
- Assess the efficacy of BCG versus placebo on chest imaging score.
- While the study is not powered to detect differences among subgroups, we will enumerate whether above endpoints are modified among these patient subgroups: cavitary versus non-cavitary disease, age, gender, the species of MAC infection, and those with higher IFN-γ responses.
- Assess PBMC cytokine responses beyond IFN-γ.
- Assess durability of immune responses at 24 months.
Study Population:
We aim to enroll a total of 48 participants with MAC, of which 24 will be randomized to receive each of BCG and placebo.
- Being tested
- Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine, preservative-free saline
- Medical subject headings
- Mycobacterium avium-intracellulare Infection, Mycobacterium Infections, Nontuberculous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccineBiological
Also called TICE® BCG
Subjects will be randomized to a single intradermal injection of BCG or placebo vaccine.
Participants randomized to the BCG arm will receive TICE® BCG. Freeze-dried vaccine is produced in vials, each containing 1 to 8 x^108 colony forming units (CFU). A vial will be reconstituted in 20 mL of preservative-free saline. Administration of 0.1 mL will contain ~2x^106 CFU, which accounts for approximately 0.25 mg of the attenuated Mycobacterium bovis. Administration of 0.1 mL of diluted vaccine will be given per dose, intradermally.
preservative-free salineDrug
Also called saline
Patients randomized to the placebo arm will receive 0.1 mL preservative-free saline alone.
| Study group | Role | What they receive |
|---|---|---|
| Active BCG | Active comparator | Biological/Vaccine: Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine Receives: Biological: Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine |
| Placebo | Placebo comparator | preservative-free saline Receives: Drug: preservative-free saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
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
Measured: 12 weeks after intervention
Serious adverse events
Serious adverse events related to the intradermal BCG over 12 months after intervention.
Measured: 12 months
Immunogenicity
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).
Measured: 24 months
Secondary outcomes (1)
Sputum cultures
Compare proportion of sputum cultures positive for MAC between the two groups
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2025
- Study start27 Apr 2026
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Mycobacterium Avium-intracellulare InfectionStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Standard two-sample comparisons will be used to compare changes in immunogenicity. The number and type of adverse events will be tabulated by treatment group. Chi-squared tests will be used to compare the groups on the proportion of patients in each group experiencing severe adverse events. Standard one-side, two-sample confidence intervals will be used to summarize the difference in proportions between the groups. Logistic regression with generalized estimating equations (GEE) will be used for the proportion of monthly sputum cultures positive for MAC after BCG vaccination or placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eric R. Houpt, MD, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07094711
- Sponsor's protocol ID
- 302296Boost
- Acronym
- BOOST
- Status last verified
- May 2026
- First submitted
- 23 Jul 2025
- Last updated
- 27 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Every attempt will be made to publish results in peer-reviewed journals. Data from this study may be requested from other researchers 2 years after the publication date of the primary endpoint by contacting Dr. Houpt. No protected health information will be shared.
Publications
Blazevic A, Edwards RL, Xia M, Eickhoff CS, Hamzabegovic F, Meza KA, Ning H, Tennant J, Mosby KJ, Ritchie JC, Girmay T, Lai L, McCullough M, Beck A, Kelley C, Edupuganti S, Kabbani S, Buchanan W, Makhene MK, Voronca D, Cherikh S, Goll JB, Rouphael NG, Mulligan MJ, Hoft DF. Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guerin Challenge Model for Assessment of Tuberculosis Immunity In Vivo. J Infect Dis. 2024 May 15;229(5):1498-1508. doi: 10.1093/infdis/jiad441.
PubMed 38019956Allen HF, Klingensmith GJ, Jensen P, Simoes E, Hayward A, Chase HP. Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study. Diabetes Care. 1999 Oct;22(10):1703-7. doi: 10.2337/diacare.22.10.1703.
PubMed 10526739Bricks LF. [Percutaneous or intradermal BCG vaccine?]. J Pediatr (Rio J). 2004 Mar-Apr;80(2):93-8. Portuguese.
PubMed 15079177Roy A, Eisenhut M, Harris RJ, Rodrigues LC, Sridhar S, Habermann S, Snell L, Mangtani P, Adetifa I, Lalvani A, Abubakar I. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ. 2014 Aug 5;349:g4643. doi: 10.1136/bmj.g4643.
PubMed 25097193Koekenbier EL, Fohse K, van de Maat JS, Oosterheert JJ, van Nieuwkoop C, Hoogerwerf JJ, Grobusch MP, van den Bosch MAAJ, van de Wijgert JHH, Netea MG, Rosendaal FR, Bonten MJM, Werkhoven CHHV; BCG-PRIME study group. Bacillus Calmette-Guerin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial. Clin Microbiol Infect. 2023 Jun;29(6):781-788. doi: 10.1016/j.cmi.2023.01.019. Epub 2023 Feb 2.
PubMed 36736662Pittet LF, Messina NL, Orsini F, Moore CL, Abruzzo V, Barry S, Bonnici R, Bonten M, Campbell J, Croda J, Dalcolmo M, Gardiner K, Gell G, Germano S, Gomes-Silva A, Goodall C, Gwee A, Jamieson T, Jardim B, Kollmann TR, Lacerda MVG, Lee KJ, Lucas M, Lynn DJ, Manning L, Marshall HS, McDonald E, Munns CF, Nicholson S, O'Connell A, de Oliveira RD, Perlen S, Perrett KP, Prat-Aymerich C, Richmond PC, Rodriguez-Bano J, Dos Santos G, da Silva PV, Teo JW, Villanueva P, Warris A, Wood NJ, Davidson A, Curtis N; BRACE Trial Consortium Group. Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers. N Engl J Med. 2023 Apr 27;388(17):1582-1596. doi: 10.1056/NEJMoa2212616.
PubMed 37099341Dionato FAV, Jalalizadeh M, Buosi K, Visacri MB, Dal Col LSB, Giacomelli CF, Leme PAF, Maia CL, Moriel P, Reis LO. BCG vaccine safety in COVID-19 convalescent adults: BATTLE a randomized controlled trial. Vaccine. 2022 Jul 30;40(32):4603-4608. doi: 10.1016/j.vaccine.2022.06.039. Epub 2022 Jun 20.
PubMed 35738969Tsilika M, Taks E, Dolianitis K, Kotsaki A, Leventogiannis K, Damoulari C, Kostoula M, Paneta M, Adamis G, Papanikolaou I, Stamatelopoulos K, Bolanou A, Katsaros K, Delavinia C, Perdios I, Pandi A, Tsiakos K, Proios N, Kalogianni E, Delis I, Skliros E, Akinosoglou K, Perdikouli A, Poulakou G, Milionis H, Athanassopoulou E, Kalpaki E, Efstratiou L, Perraki V, Papadopoulos A, Netea MG, Giamarellos-Bourboulis EJ. ACTIVATE-2: A Double-Blind Randomized Trial of BCG Vaccination Against COVID-19 in Individuals at Risk. Front Immunol. 2022 Jul 5;13:873067. doi: 10.3389/fimmu.2022.873067. eCollection 2022.
PubMed 35865520Giamarellos-Bourboulis EJ, Tsilika M, Moorlag S, Antonakos N, Kotsaki A, Dominguez-Andres J, Kyriazopoulou E, Gkavogianni T, Adami ME, Damoraki G, Koufargyris P, Karageorgos A, Bolanou A, Koenen H, van Crevel R, Droggiti DI, Renieris G, Papadopoulos A, Netea MG. Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly. Cell. 2020 Oct 15;183(2):315-323.e9. doi: 10.1016/j.cell.2020.08.051. Epub 2020 Sep 1.
PubMed 32941801Villanueva P, Crawford NW, Garcia Croda M, Collopy S, Araujo Jardim B, de Almeida Pinto Jardim T, Marshall H, Prat-Aymerich C, Sawka A, Sharma K, Troeman D, Wadia U, Warris A, Wood N, Messina NL, Curtis N, Pittet LF. Safety of BCG vaccination and revaccination in healthcare workers. Hum Vaccin Immunother. 2023 Aug 1;19(2):2239088. doi: 10.1080/21645515.2023.2239088.
PubMed 37551885Fritschi N, Curtis N, Ritz N. Bacille Calmette Guerin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects. Paediatr Respir Rev. 2020 Nov;36:57-64. doi: 10.1016/j.prrv.2020.08.004. Epub 2020 Aug 20.
PubMed 32958428Zwerling A, Behr MA, Verma A, Brewer TF, Menzies D, Pai M. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Med. 2011 Mar;8(3):e1001012. doi: 10.1371/journal.pmed.1001012. Epub 2011 Mar 22.
PubMed 21445325Dow CT, Kidess L. BCG Vaccine-The Road Not Taken. Microorganisms. 2022 Sep 27;10(10):1919. doi: 10.3390/microorganisms10101919.
PubMed 36296196Greinert U, Schlaak M, Rusch-Gerdes S, Flad HD, Ernst M. Low in vitro production of interferon-gamma and tumor necrosis factor-alpha in HIV-seronegative patients with pulmonary disease caused by nontuberculous mycobacteria. J Clin Immunol. 2000 Nov;20(6):445-52. doi: 10.1023/a:1026407815946.
PubMed 11202234Gramegna A, Lombardi A, Lore NI, Amati F, Barone I, Azzara C, Cirillo D, Aliberti S, Gori A, Blasi F. Innate and Adaptive Lymphocytes in Non-Tuberculous Mycobacteria Lung Disease: A Review. Front Immunol. 2022 Jun 28;13:927049. doi: 10.3389/fimmu.2022.927049. eCollection 2022.
PubMed 35837393
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Immunogenicity, and Efficacy of Therapeutic Mycobacterium Bovis BCG in Patients With Mycobacterium Avium Complex Lung Disease (BOOST)
- ClinicalTrials.gov ID
- NCT07094711
- Acronym / sponsor ID
- BOOST / 302296Boost
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 27 Apr 2026 (actual)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 30 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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:
- the microbiologic efficacy of BCG compared to placebo.
- to determine if BCG is superior to placebo in reducing all-cause respiratory illness requiring additional antibiotics, healthcare assessment, or admission.
Endpoints:
Primary endpoints:
- Safety and tolerability of intradermal BCG (TICE®) in this patient population, compared to placebo, assessed by weekly questionnaire of adverse events over 12 weeks.
- Serious adverse events related to the intradermal BCG over 12 months.
- Immunogenicity of BCG as measured by the change in BCG-induced IFN-γ production in PBMCs 60 days after vaccination, compared to placebo.
Secondary endpoints:
- Proportion of monthly sputum cultures positive for MAC after BCG vaccine or placebo over 24 months.
- Immunogenicity of BCG on MAC-specific IFN-γ responses.
- Proportion of patients with MAC culture conversion and MAC recurrence within 24 months.
- Rates of all-cause respiratory illness requiring additional antibiotics, healthcare assessment, or admission over 24 months.
- Symptom scores using the Quality of Life- Bronchiectasis Respiratory (QOL-BR) questionnaire over 24 months.
- Adverse Events of Special Interest (local/systemic M. bovis BCG infection) over 24 months.
Exploratory endpoints:
- Assess the efficacy of BCG versus placebo on chest imaging score.
- While the study is not powered to detect differences among subgroups, we will enumerate whether above endpoints are modified among these patient subgroups: cavitary versus non-cavitary disease, age, gender, the species of MAC infection, and those with higher IFN-γ responses.
- Assess PBMC cytokine responses beyond IFN-γ.
- Assess durability of immune responses at 24 months.
Study Population:
We aim to enroll a total of 48 participants with MAC, of which 24 will be randomized to receive each of BCG and placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Standard two-sample comparisons will be used to compare changes in immunogenicity. The number and type of adverse events will be tabulated by treatment group. Chi-squared tests will be used to compare the groups on the proportion of patients in each group experiencing severe adverse events. Standard one-side, two-sample confidence intervals will be used to summarize the difference in proportions between the groups. Logistic regression with generalized estimating equations (GEE) will be used for the proportion of monthly sputum cultures positive for MAC after BCG vaccination or placebo.
| Arm | Type | Receives |
|---|---|---|
| Active BCG | Active comparator | Biological: Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccineBiological/Vaccine: Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine |
| Placebo | Placebo comparator | Drug: preservative-free salinepreservative-free saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccineAlso: TICE® BCGSubjects will be randomized to a single intradermal injection of BCG or placebo vaccine. Participants randomized to the BCG arm will receive TICE® BCG. Freeze-dried vaccine is produced in vials, each containing 1 to 8 x^108 colony forming units (CFU). A vial will be reconstituted in 20 mL of preservative-free saline. Administration of 0.1 mL will contain ~2x^106 CFU, which accounts for approximately 0.25 mg of the attenuated Mycobacterium bovis. Administration of 0.1 mL of diluted vaccine will be given per dose, intradermally. | Biological | Active BCG |
| preservative-free salineAlso: salinePatients randomized to the placebo arm will receive 0.1 mL preservative-free saline alone. | Drug | Placebo |
Primary outcome
Adverse events
Time frame: 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
Time frame: 12 months
Serious adverse events related to the intradermal BCG over 12 months after intervention.
Immunogenicity
Time frame: 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).
1 secondary outcome
Sputum cultures
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
- Results publication: PubMed 38019956Blazevic A, Edwards RL, Xia M, Eickhoff CS, Hamzabegovic F, Meza KA, Ning H, Tennant J, Mosby KJ, Ritchie JC, Girmay T, Lai L, McCullough M, Beck A, Kelley C, Edupuganti S, Kabbani S, Buchanan W, Makhene MK, Voronca D, Cherikh S, Goll JB, Rouphael NG, Mulligan MJ, Hoft DF. Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guerin Challenge Model for Assessment of Tuberculosis Immunity In Vivo. J Infect Dis. 2024 May 15;229(5):1498-1508. doi: 10.1093/infdis/jiad441.
- Results publication: PubMed 10526739Allen HF, Klingensmith GJ, Jensen P, Simoes E, Hayward A, Chase HP. Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study. Diabetes Care. 1999 Oct;22(10):1703-7. doi: 10.2337/diacare.22.10.1703.
- Results publication: PubMed 15079177Bricks LF. [Percutaneous or intradermal BCG vaccine?]. J Pediatr (Rio J). 2004 Mar-Apr;80(2):93-8. Portuguese.
- Results publication: PubMed 25097193Roy A, Eisenhut M, Harris RJ, Rodrigues LC, Sridhar S, Habermann S, Snell L, Mangtani P, Adetifa I, Lalvani A, Abubakar I. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ. 2014 Aug 5;349:g4643. doi: 10.1136/bmj.g4643.
- Results publication: PubMed 36736662Koekenbier EL, Fohse K, van de Maat JS, Oosterheert JJ, van Nieuwkoop C, Hoogerwerf JJ, Grobusch MP, van den Bosch MAAJ, van de Wijgert JHH, Netea MG, Rosendaal FR, Bonten MJM, Werkhoven CHHV; BCG-PRIME study group. Bacillus Calmette-Guerin vaccine for prevention of COVID-19 and other respiratory tract infections in older adults with comorbidities: a randomized controlled trial. Clin Microbiol Infect. 2023 Jun;29(6):781-788. doi: 10.1016/j.cmi.2023.01.019. Epub 2023 Feb 2.
- Results publication: PubMed 37099341Pittet LF, Messina NL, Orsini F, Moore CL, Abruzzo V, Barry S, Bonnici R, Bonten M, Campbell J, Croda J, Dalcolmo M, Gardiner K, Gell G, Germano S, Gomes-Silva A, Goodall C, Gwee A, Jamieson T, Jardim B, Kollmann TR, Lacerda MVG, Lee KJ, Lucas M, Lynn DJ, Manning L, Marshall HS, McDonald E, Munns CF, Nicholson S, O'Connell A, de Oliveira RD, Perlen S, Perrett KP, Prat-Aymerich C, Richmond PC, Rodriguez-Bano J, Dos Santos G, da Silva PV, Teo JW, Villanueva P, Warris A, Wood NJ, Davidson A, Curtis N; BRACE Trial Consortium Group. Randomized Trial of BCG Vaccine to Protect against Covid-19 in Health Care Workers. N Engl J Med. 2023 Apr 27;388(17):1582-1596. doi: 10.1056/NEJMoa2212616.
- Results publication: PubMed 35738969Dionato FAV, Jalalizadeh M, Buosi K, Visacri MB, Dal Col LSB, Giacomelli CF, Leme PAF, Maia CL, Moriel P, Reis LO. BCG vaccine safety in COVID-19 convalescent adults: BATTLE a randomized controlled trial. Vaccine. 2022 Jul 30;40(32):4603-4608. doi: 10.1016/j.vaccine.2022.06.039. Epub 2022 Jun 20.
- Results publication: PubMed 35865520Tsilika M, Taks E, Dolianitis K, Kotsaki A, Leventogiannis K, Damoulari C, Kostoula M, Paneta M, Adamis G, Papanikolaou I, Stamatelopoulos K, Bolanou A, Katsaros K, Delavinia C, Perdios I, Pandi A, Tsiakos K, Proios N, Kalogianni E, Delis I, Skliros E, Akinosoglou K, Perdikouli A, Poulakou G, Milionis H, Athanassopoulou E, Kalpaki E, Efstratiou L, Perraki V, Papadopoulos A, Netea MG, Giamarellos-Bourboulis EJ. ACTIVATE-2: A Double-Blind Randomized Trial of BCG Vaccination Against COVID-19 in Individuals at Risk. Front Immunol. 2022 Jul 5;13:873067. doi: 10.3389/fimmu.2022.873067. eCollection 2022.
- Results publication: PubMed 32941801Giamarellos-Bourboulis EJ, Tsilika M, Moorlag S, Antonakos N, Kotsaki A, Dominguez-Andres J, Kyriazopoulou E, Gkavogianni T, Adami ME, Damoraki G, Koufargyris P, Karageorgos A, Bolanou A, Koenen H, van Crevel R, Droggiti DI, Renieris G, Papadopoulos A, Netea MG. Activate: Randomized Clinical Trial of BCG Vaccination against Infection in the Elderly. Cell. 2020 Oct 15;183(2):315-323.e9. doi: 10.1016/j.cell.2020.08.051. Epub 2020 Sep 1.
- Results publication: PubMed 37551885Villanueva P, Crawford NW, Garcia Croda M, Collopy S, Araujo Jardim B, de Almeida Pinto Jardim T, Marshall H, Prat-Aymerich C, Sawka A, Sharma K, Troeman D, Wadia U, Warris A, Wood N, Messina NL, Curtis N, Pittet LF. Safety of BCG vaccination and revaccination in healthcare workers. Hum Vaccin Immunother. 2023 Aug 1;19(2):2239088. doi: 10.1080/21645515.2023.2239088.
- Results publication: PubMed 32958428Fritschi N, Curtis N, Ritz N. Bacille Calmette Guerin (BCG) and new TB vaccines: Specific, cross-mycobacterial and off-target effects. Paediatr Respir Rev. 2020 Nov;36:57-64. doi: 10.1016/j.prrv.2020.08.004. Epub 2020 Aug 20.
- Results publication: PubMed 21445325Zwerling A, Behr MA, Verma A, Brewer TF, Menzies D, Pai M. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS Med. 2011 Mar;8(3):e1001012. doi: 10.1371/journal.pmed.1001012. Epub 2011 Mar 22.
- Individual participant dataSharing planned: No. Every attempt will be made to publish results in peer-reviewed journals. Data from this study may be requested from other researchers 2 years after the publication date of the primary endpoint by contacting Dr. Houpt. No protected health information will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycobacterium bovis Bacillus Calmette Guerin (BCG) vaccine and preservative-free saline in people with Mycobacterium Avium-intracellulare Infection and Mycobacterium Infections, Nontuberculous, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Eric R Houpt, M.D. (+1 434 243 9326, erh6k@virginia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: 12 weeks after intervention). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07094711, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.