Safety, Immunogenicity, and Efficacy of Therapeutic Mycobacterium Bovis BCG (BOOST)

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. 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

Timeline

Start

2026-04-27

Primary completion

2028-09-30

Completion

2028-12-30

Publications

• Results 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.
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• Results Bricks LF. [Percutaneous or intradermal BCG vaccine?]. J Pediatr (Rio J). 2004 Mar-Apr;80(2):93-8. Portuguese.
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• Results Koekenbier 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 Pittet 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 Dionato 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 Tsilika 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 Giamarellos-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 Villanueva 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 Fritschi 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 Zwerling 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.
• Results Dow CT, Kidess L. BCG Vaccine-The Road Not Taken. Microorganisms. 2022 Sep 27;10(10):1919. doi: 10.3390/microorganisms10101919.
• Results Greinert 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.
• Results Gramegna 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.
• Results Winthrop K, Rivera A, Engelmann F, Rose S, Lewis A, Ku J, Bermudez L, Messaoudi I. A Rhesus Macaque Model of Pulmonary Nontuberculous Mycobacterial Disease. Am J Respir Cell Mol Biol. 2016 Feb;54(2):170-6. doi: 10.1165/rcmb.2015-0256RC.
• Results Andersen P, Doherty TM. The success and failure of BCG - implications for a novel tuberculosis vaccine. Nat Rev Microbiol. 2005 Aug;3(8):656-62. doi: 10.1038/nrmicro1211.
• Results Griffith DE, Eagle G, Thomson R, Aksamit TR, Hasegawa N, Morimoto K, Addrizzo-Harris DJ, O'Donnell AE, Marras TK, Flume PA, Loebinger MR, Morgan L, Codecasa LR, Hill AT, Ruoss SJ, Yim JJ, Ringshausen FC, Field SK, Philley JV, Wallace RJ Jr, van Ingen J, Coulter C, Nezamis J, Winthrop KL; CONVERT Study Group. Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study. Am J Respir Crit Care Med. 2018 Dec 15;198(12):1559-1569. doi: 10.1164/rccm.201807-1318OC.
• Results Field SK, Fisher D, Cowie RL. Mycobacterium avium complex pulmonary disease in patients without HIV infection. Chest. 2004 Aug;126(2):566-81. doi: 10.1378/chest.126.2.566.
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• Results Schildknecht KR, Pratt RH, Feng PI, Price SF, Self JL. Tuberculosis - United States, 2022. MMWR Morb Mortal Wkly Rep. 2023 Mar 24;72(12):297-303. doi: 10.15585/mmwr.mm7212a1.
• Results Winthrop KL, Marras TK, Adjemian J, Zhang H, Wang P, Zhang Q. Incidence and Prevalence of Nontuberculous Mycobacterial Lung Disease in a Large U.S. Managed Care Health Plan, 2008-2015. Ann Am Thorac Soc. 2020 Feb;17(2):178-185. doi: 10.1513/AnnalsATS.201804-236OC.
• Results Strollo SE, Adjemian J, Adjemian MK, Prevots DR. The Burden of Pulmonary Nontuberculous Mycobacterial Disease in the United States. Ann Am Thorac Soc. 2015 Oct;12(10):1458-64. doi: 10.1513/AnnalsATS.201503-173OC.
• Results Orujyan D, Narinyan W, Rangarajan S, Rangchaikul P, Prasad C, Saviola B, Venketaraman V. Protective Efficacy of BCG Vaccine against Mycobacterium leprae and Non-Tuberculous Mycobacterial Infections. Vaccines (Basel). 2022 Mar 3;10(3):390. doi: 10.3390/vaccines10030390.
• Results Zimmermann P, Finn A, Curtis N. Does BCG Vaccination Protect Against Nontuberculous Mycobacterial Infection? A Systematic Review and Meta-Analysis. J Infect Dis. 2018 Jul 24;218(5):679-687. doi: 10.1093/infdis/jiy207.
• Results Rais M, Abdelaal H, Reese VA, Ferede D, Larsen SE, Pecor T, Erasmus JH, Archer J, Khandhar AP, Cooper SK, Podell BK, Reed SG, Coler RN, Baldwin SL. Immunogenicity and protection against Mycobacterium avium with a heterologous RNA prime and protein boost vaccine regimen. Tuberculosis (Edinb). 2023 Jan;138:102302. doi: 10.1016/j.tube.2022.102302. Epub 2022 Dec 27.
• Results Abate G, Hamzabegovic F, Eickhoff CS, Hoft DF. BCG Vaccination Induces M. avium and M. abscessus Cross-Protective Immunity. Front Immunol. 2019 Feb 19;10:234. doi: 10.3389/fimmu.2019.00234. eCollection 2019.
• Results Larsen SE, Reese VA, Pecor T, Berube BJ, Cooper SK, Brewer G, Ordway D, Henao-Tamayo M, Podell BK, Baldwin SL, Coler RN. Subunit vaccine protects against a clinical isolate of Mycobacterium avium in wild type and immunocompromised mouse models. Sci Rep. 2021 Apr 27;11(1):9040. doi: 10.1038/s41598-021-88291-8.
• Results Harboe M, Mshana RN, Closs O, Kronvall G, Axelsen NH. Cross-reactions between mycobacteria. II. Crossed immunoelectrophoretic analysis of soluble antigens of BCG and comparison with other mycobacteria. Scand J Immunol. 1979;9(2):115-24. doi: 10.1111/j.1365-3083.1979.tb02713.x.

Drugs

Indications