178
Views
0
CrossRef citations to date
0
Altmetric
Review

Phase three clinical trials in idiopathic pulmonary fibrosis

ORCID Icon, & ORCID Icon
Pages 1-11 | Received 29 Oct 2020, Accepted 19 Jan 2021, Published online: 04 Feb 2021

References

  • Sgalla G, Biffi A, Richeldi L. Idiopathic pulmonary fibrosis: diagnosis, epidemiology and natural history [Internet]. Respirology. 2015 Nov26;21(3):427–437. . Available from.
  • American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):646-64. doi: 10.1164/ajrccm.161.2.ats3-00. PMID: 10673212.
  • Network IPFCR, Raghu G, Anstrom KJ, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. [Internet]. N Engl J Med. 2012;366:1968–1977. [May20]. Available from: https://pubmed.ncbi.nlm.nih.gov/22607134.
  • Richeldi L, Du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis [Internet]. N Engl J Med. 2014;370(22):2071–2082. Available from.
  • King TE, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis [Internet]. N Engl J Med. 2014;370(22):2083–2092. Available from.
  • Iyer SN, Gurujeyalakshmi G, Giri SN. Effects of pirfenidone on procollagen gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther. 1999 Apr;289(1):211–8. PMID: 10087006
  • Raghu G, Johnson WC, Lockhart D, et al. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label phase II study [Internet]. Am J Respir Crit Care Med. 1999;159(4):1061–1069. Available from.
  • Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: treatment of idiopathic pulmonary fibrosis. An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3–e19.
  • Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010. DOI:10.1183/09031936.00005209
  • Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet. 2011. DOI:10.1016/S0140-6736(11)60405-4
  • Noble PW, Albera C, Bradford WZ, et al. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials. Eur Respir J. 2016. DOI:10.1183/13993003.00026-2015
  • Wollin L, Maillet I, Quesniaux V, et al. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosiss. J Pharmacol Exp Ther. 2014. DOI:10.1124/jpet.113.208223
  • Hostettler KE, Zhong J, Papakonstantinou E, et al. Anti-fibrotic effects of nintedanib in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis. Respir Res. 2014. DOI:10.1186/s12931-014-0157-3
  • Richeldi L, Costabel U, Selman M, et al. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis [Internet]. N Engl J Med. 2011;365(12):1079–1087. Available from.
  • Richeldi L, Cottin V, du Bois RM, Selman M, Kimura T, Bailes Z, Schlenker-Herceg R, Stowasser S, Brown KK. Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS(®) trials. Respir Med. 2016 Apr;113:74-9.
  • Crestani B, Huggins JT, Kaye M, et al. Long-term safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis: results from the open-label extension study, INPULSIS-ON. Lancet Respir Med. 2019. 10.1016/S2213-2600(18)30339-4
  • Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. [Internet]. The New England Journal of Medicine. cited 2019 Sep 30. 2019;381(18):NEJMoa1908681. Available from.
  • Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis–associated interstitial lung disease. N Engl J Med. 2019. DOI:10.1056/NEJMoa1903076
  • Cantin AM, North SL, Fells GA, et al. Oxidant-mediated epithelial cell injury in idiopathic pulmonary fibrosis. J Clin Invest. 1987. DOI:10.1172/JCI113005
  • Cantin AM, Hubbard RC, Crystal RG. Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. Am Rev Respir Dis. 1989. DOI:10.1164/ajrccm/139.2.370
  • Demedts M, Behr J, Buhl R, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005. DOI:10.1056/NEJMoa042976
  • Raghu G, Anstrom KJ, King TE, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012. 10.1056/NEJMoa1113354
  • Idiopathic Pulmonary Fibrosis Clinical Research Network, Martinez FJ, de Andrade JA, Anstrom KJ, King TE Jr, Raghu G. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2093–101. Epub 2014 May 18. PMID: 24836309; PMCID: PMC4116664
  • Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management [Internet]. Am J Respir Crit Care Med. 2017 Jul 2. 2011;183(6):788–824. Available from.
  • Behr J, Bendstrup E, Crestani B, et al. Safety and tolerability of acetylcysteine and pirfenidone combination therapy in idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2016. DOI:10.1016/S2213-2600(16)30044-3
  • Oldham JM, Ma SF, Martinez FJ, Anstrom KJ, Raghu G, Schwartz DA, Valenzi E, Witt L, Lee C, Vij R, Huang Y, Strek ME, Noth I; IPFnet Investigators. TOLLIP, MUC5B, and the Response to N-Acetylcysteine among Individuals with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2015 Dec 15;192(12):1475–82.
  • Homma S, Azuma A, Taniguchi H, et al. Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis[Internet]. Respirology. 2012;17(3):467–477. Available from.
  • Gurujeyalakshmi G, Giri SN. Molecular mechanisms of antifibrotic effect of interferon gamma in bleomycin-mouse model of lung fibrosis: downregulation of TGF-beta and procollagen I and III gene expression. Exp Lung Res. 1995 Sep-Oct;21(5):791–808.
  • Prior C, Haslam PL. In vivo levels and in vitro production of interferon-gamma in fibrosing interstitial lung diseases. Clin Exp Immunol. 1992 May;88(2):280–7.
  • Ziesche R, Hofbauer E, Wittmann K, et al. A preliminary study of long-term treatment with interferon gamma-1b and low-dose prednisolone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 1999. DOI:10.1056/NEJM199910213411703
  • Raghu G, Brown KK, Bradford WZ, et al. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2004. DOI:10.1056/NEJMoa030511
  • King TE, Albera C, Bradford WZ, et al. Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial [Internet]. Lancet. 2009;374(9685):222–228. Available from.
  • Diaz KT, Skaria S, Harris K, Solomita M, Lau S, Bauer K, Smaldone GC, Condos R. Delivery and safety of inhaled interferon-γ in idiopathic pulmonary fibrosis. J Aerosol Med Pulm Drug Deliv. 2012 Apr;25(2):79–87.
  • Chambers RC. Procoagulant signalling mechanisms in lung inflammation and fibrosis: novel opportunities for pharmacological intervention? BrJ Pharmacol. 2008;153(S1):S367-S378.
  • Kubo H, Nakayama K, Yanai M, et al. Anticoagulant therapy for idiopathic pulmonary fibrosis [Internet]. Chest. 2005;128(3):1475–1482. Available from.
  • Noth I, Anstrom KJ, Calvert SB, et al. A placebo-controlled randomized trial of warfarin in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012. DOI:10.1164/rccm.201202-0314OC
  • King TE, Behr J, Brown KK, et al. BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008. DOI:10.1164/rccm.200705-732OC
  • Raghu G, King TE, Behr J, et al. Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1). Eur Respir J. 2010. DOI:10.1183/09031936.00188108
  • King TE, Brown KK, Raghu G, et al. BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011. DOI:10.1164/rccm.201011-1874OC
  • Raghu G, Behr J, Brown KK, et al. Treatment of idiopathic pulmonary fibrosis with Ambrisentan: a parallel, randomized trial. Ann Int Med. 2013. DOI:10.7326/0003-4819-158-9-201305070-00003
  • Ghofrani HA, Wiedemann R, Rose F, et al. Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet. 2002. DOI:10.1016/S0140-6736(02)11024-5
  • Zisman DA, Zisman DA, Schwarz M, et al. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis.. The New England Journal of Medicine. 2010. DOI:10.1056/NEJMoa1002110
  • Kolb M, Raghu G, Wells AU, et al. Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2018. DOI:10.1056/NEJMoa1811737
  • Behr J, Kolb M, Song JW, et al. Nintedanib and sildenafil in patients with idiopathic pulmonary fibrosis and right heart dysfunction: a prespecified subgroup analysis of a double-blind randomized clinical trial (instage). Am J Respir Crit Care Med. 2019. DOI:10.1164/rccm.201903-0488OC
  • Behr J, Nathan SD, Wuyts WA, et al. Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med. 2020. DOI:10.1016/S2213-2600(20)30356-8
  • Yung YC, Stoddard NC, Chun J. LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res. 2014
  • Oikonomou N, Mouratis MA, Tzouvelekis A, et al. Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol. 2012. DOI:10.1165/rcmb.2012-0004OC
  • Maher TM, van der Aar EM, Van de Steen O, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial. Lancet Respir Med. 2018. DOI:10.1016/S2213-2600(18)30181-4
  • Lipson KE, Wong C, Teng Y, et al. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair. 2012. DOI:10.1186/1755-1536-5-S1-S24
  • Wang Q, Usinger W, Nichols B, et al. Cooperative interaction of CTGF and TGF-β in animal models of fibrotic disease. [Internet]. Fibrogenesis Tissue Repair. 2011;4(1):4. Available from.
  • Wang X, Wu G, Gou L, et al. A novel single-chain-Fv antibody against connective tissue growth factor attenuates bleomycin-induced pulmonary fibrosis in mice [Internet]. Respirology. 2011;16(3):500–507. Available from.
  • Pan L-H, Yamauchi K, Uzuki M, et al. Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF. Eur Respir J. 2001;17(6):1220.
  • Allen JT, Knight RA, Bloor CA, et al. Enhanced insulin-like growth factor binding protein-related protein 2 (connective tissue growth factor) expression in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. [Internet]. Am J Respir Cell Mol Biol. 1999;7(6):693–700. Available from.
  • Raghu G, Scholand MB, De Andrade J, et al. FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in idiopathic pulmonary fibrosis. Eur Respir J. 2016. DOI:10.1183/13993003.01030-2015
  • Richeldi L, Fernández Pérez ER, Costabel U, et al. Pamrevlumab, an anti-connective tissue growth factor therapy, for idiopathic pulmonary fibrosis (PRAISE): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2020. DOI:10.1016/S2213-2600(19)30262-0
  • Pilling D, Gomer RH The development of serum amyloid p as a possible therapeutic. Front. Immunol. 2018.
  • Murray LA, Rosada R, Moreira AP, et al. Serum amyloid P therapeutically attenuates murine bleomycin-induced pulmonary fibrosis via its effects on macrophages. PLoS One. 2010. DOI:10.1371/journal.pone.0009683
  • Murray LA, Chen Q, Kramer MS, et al. TGF-beta driven lung fibrosis is macrophage dependent and blocked by Serum amyloid P. Int J Biochem Cell Biol. 2011. DOI:10.1016/j.biocel.2010.10.013
  • Dillingh MR, van den Blink B, Moerland M, et al. Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis. Pulm. [Internet]. Pharmacol Ther. 2013;26:672–676. Available from http://linkinghub.elsevier.com/retrieve/pii/S1094553913000540.
  • Raghu G, Van Den Blink B, Hamblin MJ, et al. Effect of recombinant human pentraxin 2 vs placebo on change in forced vital capacity in patients with idiopathic pulmonary fibrosis a randomized clinical trial. JAMA - J Am Med Assoc. 2018. DOI:10.1001/jama.2018.6129
  • Raghu G, van den Blink B, Hamblin MJ, et al. Long-term treatment with recombinant human pentraxin2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study. Lancet Respir Med. 2019. 10.1016/S2213-2600(19)30172-9
  • Raghu G, Collard HR, Egan JJ, et al. An Official ATS/ERS/JRS/ALAT Statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management [Internet]. Am. J. Respir. Crit. Care Med. 2011;183(6):788–824. 2017 Jul 2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21471066.
  • Parker JM, Glaspole IN, Lancaster LH, et al. A phase 2 randomized controlled study of tralokinumab in subjects with idiopathic pulmonary fibrosis.. Am J Respir Crit Care Med. 2018. 10.1164/rccm.201704-0784OC
  • Swigris JJ, Ogura T, Scholand MB, et al. The RIFF study (cohort A): a phase II, randomized, double-blind, placebo-controlled trial of lebrikizumab as monotherapy in patients with idiopathic pulmonary fibrosis. D12. Immunother. LUNG dis. [Internet]. Am Thorac Soc. 2018;A6167–A6167. Available from. 10.1164/ajrccm-conference.2018.197.1_MeetingAbstracts.A6167.
  • Maher TM, Costabel U, Glassberg MK, Kondoh Y, Ogura T, Scholand MB, Kardatzke D, Howard M, Olsson J, Neighbors M, Belloni P, Swigris JJ. Phase 2 trial to assess lebrikizumab in patients with idiopathic pulmonary fibrosis. Eur Respir J. 2020 Oct 2:1902442.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.