Ig PRx in AECOPD: Pilot Study

Summary

This study will look at immunoglobulin (Ig) treatment in hospitalized chronic obstructive lung disease (COPD) patients with frequent exacerbations. This is a Phase II, pilot randomized double blind control study, meaning this study will help assess if this research can be expanded to evaluate Ig treatment in patients with COPD. Ig treatment is a sterile solution of human immunoglobulin proteins given intravenously (in the vein). Immunoglobulins are part of the immune system and help the body fight infections. Participants will be assigned to either receiving the Ig treatment or normal saline as a control product every 4 weeks for 12 months. Participants will continue on current standard therapy as determined by their treating physician.

Timeline

Start

2016-09

Primary completion

2019-11-20

Completion

2019-11-20

Publications

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• Background Niewoehner DE, Rice K, Cote C, Paulson D, Cooper JA Jr, Korducki L, Cassino C, Kesten S. Prevention of exacerbations of chronic obstructive pulmonary disease with tiotropium, a once-daily inhaled anticholinergic bronchodilator: a randomized trial. Ann Intern Med. 2005 Sep 6;143(5):317-26. doi: 10.7326/0003-4819-143-5-200509060-00007.
• Background Hurst JR, Vestbo J, Anzueto A, Locantore N, Mullerova H, Tal-Singer R, Miller B, Lomas DA, Agusti A, Macnee W, Calverley P, Rennard S, Wouters EF, Wedzicha JA; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010 Sep 16;363(12):1128-38. doi: 10.1056/NEJMoa0909883.
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• Background Mullerova H, Maselli DJ, Locantore N, Vestbo J, Hurst JR, Wedzicha JA, Bakke P, Agusti A, Anzueto A. Hospitalized exacerbations of COPD: risk factors and outcomes in the ECLIPSE cohort. Chest. 2015 Apr;147(4):999-1007. doi: 10.1378/chest.14-0655.
• Background Baker CL, Zou KH, Su J. Risk assessment of readmissions following an initial COPD-related hospitalization. Int J Chron Obstruct Pulmon Dis. 2013;8:551-9. doi: 10.2147/COPD.S51507. Epub 2013 Nov 12.
• Background Albert RK, Connett J, Bailey WC, Casaburi R, Cooper JA Jr, Criner GJ, Curtis JL, Dransfield MT, Han MK, Lazarus SC, Make B, Marchetti N, Martinez FJ, Madinger NE, McEvoy C, Niewoehner DE, Porsasz J, Price CS, Reilly J, Scanlon PD, Sciurba FC, Scharf SM, Washko GR, Woodruff PG, Anthonisen NR; COPD Clinical Research Network. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011 Aug 25;365(8):689-98. doi: 10.1056/NEJMoa1104623.
• Background Zheng JP, Wen FQ, Bai CX, Wan HY, Kang J, Chen P, Yao WZ, Ma LJ, Li X, Raiteri L, Sardina M, Gao Y, Wang BS, Zhong NS; PANTHEON study group. Twice daily N-acetylcysteine 600 mg for exacerbations of chronic obstructive pulmonary disease (PANTHEON): a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2014 Mar;2(3):187-94. doi: 10.1016/S2213-2600(13)70286-8. Epub 2014 Jan 30.
• Background Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009 Aug 29;374(9691):685-94. doi: 10.1016/S0140-6736(09)61255-1.
• Background Han MK, Martinez FJ. Pharmacotherapeutic approaches to preventing acute exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2011 Aug;8(4):356-62. doi: 10.1513/pats.201102-016RM.
• Background Brightling CE, Bleecker ER, Panettieri RA Jr, Bafadhel M, She D, Ward CK, Xu X, Birrell C, van der Merwe R. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014 Nov;2(11):891-901. doi: 10.1016/S2213-2600(14)70187-0. Epub 2014 Sep 7.
• Background Kawano T, Matsuse H, Obase Y, Kondo Y, Machida I, Tomari S, Mitsuta K, Fukushima C, Shimoda T, Kohno S. Hypogammaglobulinemia in steroid-dependent asthmatics correlates with the daily dose of oral prednisolone. Int Arch Allergy Immunol. 2002 Jul;128(3):240-3. doi: 10.1159/000064258.
• Background Yip NH, Lederer DJ, Kawut SM, Wilt JS, D'Ovidio F, Wang Y, Dwyer E, Sonett JR, Arcasoy SM. Immunoglobulin G levels before and after lung transplantation. Am J Respir Crit Care Med. 2006 Apr 15;173(8):917-21. doi: 10.1164/rccm.200510-1609OC. Epub 2006 Jan 6.
• Background Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med. 2001 Sep 6;345(10):747-55. doi: 10.1056/NEJMra993360. No abstract available.
• Background Ochsenbein AF, Fehr T, Lutz C, Suter M, Brombacher F, Hengartner H, Zinkernagel RM. Control of early viral and bacterial distribution and disease by natural antibodies. Science. 1999 Dec 10;286(5447):2156-9. doi: 10.1126/science.286.5447.2156.
• Background Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012 Nov 22;367(21):2015-25. doi: 10.1056/NEJMra1009433. No abstract available.
• Background Gilardin L, Bayry J, Kaveri SV. Intravenous immunoglobulin as clinical immune-modulating therapy. CMAJ. 2015 Mar 3;187(4):257-264. doi: 10.1503/cmaj.130375. Epub 2015 Feb 9. No abstract available.
• Background Sabroe I, Postma D, Heijink I, Dockrell DH. The yin and the yang of immunosuppression with inhaled corticosteroids. Thorax. 2013 Dec;68(12):1085-7. doi: 10.1136/thoraxjnl-2013-203773. Epub 2013 Aug 8. No abstract available.
• Background Fedor ME, Rubinstein A. Effects of long-term low-dose corticosteroid therapy on humoral immunity. Ann Allergy Asthma Immunol. 2006 Jul;97(1):113-6. doi: 10.1016/S1081-1206(10)61380-4.
• Background Kaveri SV, Maddur MS, Hegde P, Lacroix-Desmazes S, Bayry J. Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy. Clin Exp Immunol. 2011 Jun;164 Suppl 2(Suppl 2):2-5. doi: 10.1111/j.1365-2249.2011.04387.x.
• Background Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical studies. Clin Immunol. 2010 Oct;137(1):21-30. doi: 10.1016/j.clim.2010.06.012. Epub 2010 Aug 1.
• Cowan J, Mulpuru S, Abdallah SJ, Chopra A, Purssell A, McGuinty M, Alvarez GG, Giulivi A, Corrales-Medina V, MacFadden D, Boyle L, Hasimja D, Thavorn K, Mallick R, Aaron SD, Cameron DW. A Randomized Double-Blind Placebo-Control Feasibility Trial of Immunoglobulin Treatment for Prevention of Recurrent Acute Exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2021 Dec 3;16:3275-3284. doi: 10.2147/COPD.S338849. eCollection 2021.
• Cowan J, Mulpuru S, Aaron S, Alvarez G, Giulivi A, Corrales-Medina V, Thiruganasambandamoorthy V, Thavorn K, Mallick R, Cameron DW. Study protocol: a randomized, double-blind, parallel, two-arm, placebo control trial investigating the feasibility and safety of immunoglobulin treatment in COPD patients for prevention of frequent recurrent exacerbations. Pilot Feasibility Stud. 2018 Aug 11;4:135. doi: 10.1186/s40814-018-0327-z. eCollection 2018.

Drugs

Indications