A Study to Evaluate the Efficacy, Safety, and PK of AZD0292 Administered IV in Participants 12 Years of Age and Older With Bronchiectasis and Chronic Pseudomonas Aeruginosa Colonization

Summary

AZD0292 is a bispecific IgG1k mAb being evaluated for the prevention of exacerbations in bronchiectasis patients chronically colonized with PsA.

Timeline

Start

2025-11-06

Primary completion

2027-12-09

Completion

2028-06-14

Publications

• Background Araujo D, Shteinberg M, Aliberti S, Goeminne PC, Hill AT, Fardon TC, Obradovic D, Stone G, Trautmann M, Davis A, Dimakou K, Polverino E, De Soyza A, McDonnell MJ, Chalmers JD. The independent contribution of Pseudomonas aeruginosa infection to long-term clinical outcomes in bronchiectasis. Eur Respir J. 2018 Jan 31;51(2):1701953. doi: 10.1183/13993003.01953-2017. Print 2018 Feb.
• Background Artaraz A, Crichton ML, Finch S, Abo-Leyah H, Goeminne P, Aliberti S, Fardon T, Chalmers JD. Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST). Respir Res. 2020 Jan 13;21(1):18. doi: 10.1186/s12931-019-1272-y.
• Background Bellelli G, Chalmers JD, Sotgiu G, Dore S, McDonnell MJ, Goeminne PC, Dimakou K, Skrbic D, Lombi A, Pane F, Obradovic D, Fardon TC, Rutherford RM, Pesci A, Aliberti S. Characterization of bronchiectasis in the elderly. Respir Med. 2016 Oct;119:13-19. doi: 10.1016/j.rmed.2016.08.008. Epub 2016 Aug 17.
• Background CFFPR 2023 Cystic Fibrosis Foundation Patient Registry. Bethesda, MD. 2023 Annual Data Report. Available at https://www.cff.org/media/34491/download.
• Background Chalmers JD, Goeminne P, Aliberti S, McDonnell MJ, Lonni S, Davidson J, Poppelwell L, Salih W, Pesci A, Dupont LJ, Fardon TC, De Soyza A, Hill AT. The bronchiectasis severity index. An international derivation and validation study. Am J Respir Crit Care Med. 2014 Mar 1;189(5):576-85. doi: 10.1164/rccm.201309-1575OC.
• Background Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. Eur Respir J. 2015 May;45(5):1446-62. doi: 10.1183/09031936.00119114. Epub 2015 Mar 18.
• Background Chalmers JD, Chang AB, Chotirmall SH, Dhar R, McShane PJ. Bronchiectasis. Nat Rev Dis Primers. 2018 Nov 15;4(1):45. doi: 10.1038/s41572-018-0042-3.
• Background Chalmers JD, Aliberti S, Filonenko A, Shteinberg M, Goeminne PC, Hill AT, Fardon TC, Obradovic D, Gerlinger C, Sotgiu G, Operschall E, Rutherford RM, Dimakou K, Polverino E, De Soyza A, McDonnell MJ. Characterization of the "Frequent Exacerbator Phenotype" in Bronchiectasis. Am J Respir Crit Care Med. 2018 Jun 1;197(11):1410-1420. doi: 10.1164/rccm.201711-2202OC.
• Background Chalmers JD, Chotirmall SH. Bronchiectasis: new therapies and new perspectives. Lancet Respir Med. 2018 Sep;6(9):715-726. doi: 10.1016/S2213-2600(18)30053-5. Epub 2018 Feb 23.
• Background Chawla K, Vishwanath S, Manu MK, Lazer B. Influence of pseudomonas aeruginosa on exacerbation in patients with bronchiectasis. J Glob Infect Dis. 2015 Jan-Mar;7(1):18-22. doi: 10.4103/0974-777X.150885.
• Background Choate R, Aksamit TR, Mannino D, Addrizzo-Harris D, Barker A, Basavaraj A, Daley CL, Daniels MLA, Eden E, DiMango A, Fennelly K, Griffith DE, Johnson MM, Knowles MR, McShane PJ, Metersky ML, Noone PG, O'Donnell AE, Olivier KN, Salathe MA, Schmid A, Thomashow B, Tino G, Winthrop KL, Stone G. Pseudomonas aeruginosa associated with severity of non-cystic fibrosis bronchiectasis measured by the modified bronchiectasis severity score (BSI) and the FACED: The US bronchiectasis and NTM Research Registry (BRR) study. Respir Med. 2021 Feb;177:106285. doi: 10.1016/j.rmed.2020.106285. Epub 2020 Dec 24.
• Background Choi H, Xu JF, Chotirmall SH, Chalmers JD, Morgan LC, Dhar R. Bronchiectasis in Asia: a review of current status and challenges. Eur Respir Rev. 2024 Sep 25;33(173):240096. doi: 10.1183/16000617.0096-2024. Print 2024 Jul.
• Background Ciofu O, Tolker-Nielsen T. Tolerance and Resistance of Pseudomonas aeruginosa Biofilms to Antimicrobial Agents-How P. aeruginosa Can Escape Antibiotics. Front Microbiol. 2019 May 3;10:913. doi: 10.3389/fmicb.2019.00913. eCollection 2019.
• Background DiGiandomenico A, Warrener P, Hamilton M, Guillard S, Ravn P, Minter R, Camara MM, Venkatraman V, Macgill RS, Lin J, Wang Q, Keller AE, Bonnell JC, Tomich M, Jermutus L, McCarthy MP, Melnick DA, Suzich JA, Stover CK. Identification of broadly protective human antibodies to Pseudomonas aeruginosa exopolysaccharide Psl by phenotypic screening. J Exp Med. 2012 Jul 2;209(7):1273-87. doi: 10.1084/jem.20120033. Epub 2012 Jun 25.
• Background Emerson J, Rosenfeld M, McNamara S, Ramsey B, Gibson RL. Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol. 2002 Aug;34(2):91-100. doi: 10.1002/ppul.10127.
• Background FLETCHER CM, ELMES PC, FAIRBAIRN AS, WOOD CH. The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. Br Med J. 1959 Aug 29;2(5147):257-66. doi: 10.1136/bmj.2.5147.257. No abstract available.
• Background Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, Kaminsky DA, McCarthy K, McCormack MC, Oropez CE, Rosenfeld M, Stanojevic S, Swanney MP, Thompson BR. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019 Oct 15;200(8):e70-e88. doi: 10.1164/rccm.201908-1590ST.
• Background Guo J, Garratt A, Hill A. Worldwide rates of diagnosis and effective treatment for cystic fibrosis. J Cyst Fibros. 2022 May;21(3):456-462. doi: 10.1016/j.jcf.2022.01.009. Epub 2022 Feb 4.
• Background Harrington NE, Kottara A, Cagney K, Shepherd MJ, Grimsey EM, Fu T, Hull RC, Chong CE, Baker KS, Childs DZ, Fothergill JL, Chalmers JD, Brockhurst MA, Paterson S. Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis. J Infect. 2024 Nov;89(5):106275. doi: 10.1016/j.jinf.2024.106275. Epub 2024 Sep 16.
• Background Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, Chalmers JD, De Soyza A, Dimakou K, Elborn JS, Feldman C, Flume P, Goeminne PC, Loebinger MR, Menendez R, Morgan L, Murris M, Polverino E, Quittner A, Ringshausen FC, Tino G, Torres A, Vendrell M, Welte T, Wilson R, Wong C, O'Donnell A, Aksamit T; EMBARC/BRR definitions working group. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur Respir J. 2017 Jun 8;49(6):1700051. doi: 10.1183/13993003.00051-2017. Print 2017 Jun.
• Background Horcajada JP, Montero M, Oliver A, Sorli L, Luque S, Gomez-Zorrilla S, Benito N, Grau S. Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections. Clin Microbiol Rev. 2019 Aug 28;32(4):e00031-19. doi: 10.1128/CMR.00031-19. Print 2019 Sep 18.
• Background Jones PW, Quirk FH, Baveystock CM. The St George's Respiratory Questionnaire. Respir Med. 1991 Sep;85 Suppl B:25-31; discussion 33-7. doi: 10.1016/s0954-6111(06)80166-6.
• Background Jones 2022 Jones P. St George's Respiratory Questionnaire Manual. Version 2.4. St George's University of London. March 2022. Available at https://www.sgul.ac.uk/research/researchoperations/ research-administration/st-georges-respiratory-questionnaire/docs/SGRQ-Manual- March-2022.pdf.
• Background Laska IF, Crichton ML, Shoemark A, Chalmers JD. The efficacy and safety of inhaled antibiotics for the treatment of bronchiectasis in adults: a systematic review and meta-analysis. Lancet Respir Med. 2019 Oct;7(10):855-869. doi: 10.1016/S2213-2600(19)30185-7. Epub 2019 Aug 9.
• Background Long MB, Gilmour A, Kehl M, Tabor DE, Keller AE, Warrener P, Gopalakrishnan V, Rosengren S, Crichton ML, McIntosh E, Giam YH, Keir HR, Brailsford W, Hughes R, Belvisi MG, Sellman BR, DiGiandomenico A, Chalmers JD. A Bispecific Monoclonal Antibody Targeting Psl and PcrV Enhances Neutrophil-Mediated Killing of Pseudomonas aeruginosa in Patients with Bronchiectasis. Am J Respir Crit Care Med. 2024 Jul 1;210(1):35-46. doi: 10.1164/rccm.202308-1403OC.
• Background Long et al 2025 Long MB, Hull RC, Gilmour A, Viligorska K, Richardson H, New BJM, et al. A bispecific monoclonal antibody targeting Psl and PcrV for chronic pseudomonas aeruginosa infection in patients With bronchiectasis: results From a randomized, double-blind placebo-controlled trial (GREAT-2) [abstract]. Am J Respir Crit Care Med 2025;211:A3117.
• Background Nigro M, Laska IF, Traversi L, Simonetta E, Polverino E. Epidemiology of bronchiectasis. Eur Respir Rev. 2024 Oct 9;33(174):240091. doi: 10.1183/16000617.0091-2024. Print 2024 Oct.
• Background O'Donnell AE. Bronchiectasis - A Clinical Review. N Engl J Med. 2022 Aug 11;387(6):533-545. doi: 10.1056/NEJMra2202819. No abstract available.
• Background Oswalt ML, Kemp SF. Anaphylaxis: office management and prevention. Immunol Allergy Clin North Am. 2007 May;27(2):177-91, vi. doi: 10.1016/j.iac.2007.03.004.
• Background Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J, Stocks J; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40(6):1324-43. doi: 10.1183/09031936.00080312. Epub 2012 Jun 27.
• Background Quittner AL, Marciel KK, Salathe MA, O'Donnell AE, Gotfried MH, Ilowite JS, Metersky ML, Flume PA, Lewis SA, McKevitt M, Montgomery AB, O'Riordan TG, Barker AF. A preliminary quality of life questionnaire-bronchiectasis: a patient-reported outcome measure for bronchiectasis. Chest. 2014 Aug;146(2):437-448. doi: 10.1378/chest.13-1891.
• Background Quittner AL, O'Donnell AE, Salathe MA, Lewis SA, Li X, Montgomery AB, O'Riordan TG, Barker AF. Quality of Life Questionnaire-Bronchiectasis: final psychometric analyses and determination of minimal important difference scores. Thorax. 2015 Jan;70(1):12-20. doi: 10.1136/thoraxjnl-2014-205918. Epub 2014 Oct 16.
• Background Sampson HA, Munoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, Brown SG, Camargo CA Jr, Cydulka R, Galli SJ, Gidudu J, Gruchalla RS, Harlor AD Jr, Hepner DL, Lewis LM, Lieberman PL, Metcalfe DD, O'Connor R, Muraro A, Rudman A, Schmitt C, Scherrer D, Simons FE, Thomas S, Wood JP, Decker WW. Second symposium on the definition and management of anaphylaxis: summary report--Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7. doi: 10.1016/j.jaci.2005.12.1303.
• Background Sibila O, Laserna E, Shoemark A, Keir HR, Finch S, Rodrigo-Troyano A, Perea L, Lonergan M, Goeminne PC, Chalmers JD. Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis. Am J Respir Crit Care Med. 2019 Jul 1;200(1):33-41. doi: 10.1164/rccm.201809-1651OC.
• Background Song J, Sin S, Kang HR, Oh YM, Jeong I; KMBARC. Clinical Impacts of Pseudomonas aeruginosa Isolation in Patients with Bronchiectasis: Findings from KMBARC Registry. J Clin Med. 2024 Aug 24;13(17):5011. doi: 10.3390/jcm13175011.
• Background Tabor DE, Oganesyan V, Keller AE, Yu L, McLaughlin RE, Song E, Warrener P, Rosenthal K, Esser M, Qi Y, Ruzin A, Stover CK, DiGiandomenico A. Pseudomonas aeruginosa PcrV and Psl, the Molecular Targets of Bispecific Antibody MEDI3902, Are Conserved Among Diverse Global Clinical Isolates. J Infect Dis. 2018 Nov 5;218(12):1983-1994. doi: 10.1093/infdis/jiy438.
• Background Tomaszewski EL, Atkinson MJ, Janson C, Karlsson N, Make B, Price D, Reddel HK, Vogelmeier CF, Mullerova H, Jones PW; NOVELTY Scientific Community; NOVELTY study investigators. Chronic Airways Assessment Test: psychometric properties in patients with asthma and/or COPD. Respir Res. 2023 Apr 8;24(1):106. doi: 10.1186/s12931-023-02394-6.
• Background WHO 2017 WHO. WHO/EMP/IAU/2017.12 Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Report. World Health Organization, WHO, Antimicrobial Resistance Division Global Coordination and Partnership, Medicines Selection, IP and Affordability. Available from: http://www.who.int/publications/i/item/WHO-EMP-IAU-2017.02.
• Background Wilson R, Aksamit T, Aliberti S, De Soyza A, Elborn JS, Goeminne P, Hill AT, Menendez R, Polverino E. Challenges in managing Pseudomonas aeruginosa in non-cystic fibrosis bronchiectasis. Respir Med. 2016 Aug;117:179-89. doi: 10.1016/j.rmed.2016.06.007. Epub 2016 Jun 7.
• Background Zolin et al 2024 Zolin A, Adamoli A, Bakkeheim E, van Rens J, et al. ECFSPR Annual Report 2022. Published 2024. Available at https://www.ecfs.eu/sites/default/files/Annual%20Report_2022_ECFSPR_20240603.pdf.

Drugs

Indications