Trial Of IW001 in Patients With Idiopathic Pulmonary Fibrosis

Summary

This is an open label, Phase One, multicenter study, designed to evaluate the safety, tolerability, to explore the biologic effects, and to explore the clinical effects of the following doses of IW001: 0.1mg/day, 0.5 mg/day, and 1.0 mg/day, when administered once a day orally for 24 weeks in patients with IPF.

Timeline

Start

2010-09

Primary completion

2012-10

Completion

2012-10

Publications

• Background 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. No abstract available.
• Background Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2006 Oct 1;174(7):810-6. doi: 10.1164/rccm.200602-163OC. Epub 2006 Jun 29.
• Background Martinez FJ, Safrin S, Weycker D, Starko KM, Bradford WZ, King TE Jr, Flaherty KR, Schwartz DA, Noble PW, Raghu G, Brown KK; IPF Study Group. The clinical course of patients with idiopathic pulmonary fibrosis. Ann Intern Med. 2005 Jun 21;142(12 Pt 1):963-7. doi: 10.7326/0003-4819-142-12_part_1-200506210-00005.
• Background Walter N, Collard HR, King TE Jr. Current perspectives on the treatment of idiopathic pulmonary fibrosis. Proc Am Thorac Soc. 2006 Jun;3(4):330-8. doi: 10.1513/pats.200602-016TK.
• Background Trulock EP, Edwards LB, Taylor DO, Boucek MM, Keck BM, Hertz MI. Registry of the International Society for Heart and Lung Transplantation: twenty-second official adult lung and heart-lung transplant report--2005. J Heart Lung Transplant. 2005 Aug;24(8):956-67. doi: 10.1016/j.healun.2005.05.019. No abstract available.
• Background Kim DS, Collard HR, King TE Jr. Classification and natural history of the idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun;3(4):285-92. doi: 10.1513/pats.200601-005TK.
• Background Maher TM, Wells AU, Laurent GJ. Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms? Eur Respir J. 2007 Nov;30(5):835-9. doi: 10.1183/09031936.00069307.
• Background Hunninghake GW, Schwarz MI. Does current knowledge explain the pathogenesis of idiopathic pulmonary fibrosis? A perspective. Proc Am Thorac Soc. 2007 Aug 15;4(5):449-52. doi: 10.1513/pats.200702-036MS.
• Background Bobadilla JL, Love RB, Jankowska-Gan E, Xu Q, Haynes LD, Braun RK, Hayney MS, Munoz del Rio A, Meyer K, Greenspan DS, Torrealba J, Heidler KM, Cummings OW, Iwata T, Brand D, Presson R, Burlingham WJ, Wilkes DS. Th-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation. Am J Respir Crit Care Med. 2008 Mar 15;177(6):660-8. doi: 10.1164/rccm.200612-1901OC. Epub 2008 Jan 3.
• Background Burlingham WJ, Love RB, Jankowska-Gan E, Haynes LD, Xu Q, Bobadilla JL, Meyer KC, Hayney MS, Braun RK, Greenspan DS, Gopalakrishnan B, Cai J, Brand DD, Yoshida S, Cummings OW, Wilkes DS. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest. 2007 Nov;117(11):3498-506. doi: 10.1172/JCI28031.
• Background Faria AM, Weiner HL. Oral tolerance. Immunol Rev. 2005 Aug;206:232-59. doi: 10.1111/j.0105-2896.2005.00280.x.
• Background Whitacre CC, Song F, Wardrop RM 3rd, Campbell K, McClain M, Benson J, Guan Z, Gienapp I. Regulation of autoreactive T cell function by oral tolerance to self-antigens. Ann N Y Acad Sci. 2004 Dec;1029:172-9. doi: 10.1196/annals.1309.033.
• Background Nussenblatt R. Orally and nasally induced tolerance studies in ocular inflammatory disease: guidance for future interventions. Ann N Y Acad Sci. 2004 Dec;1029:278-85. doi: 10.1196/annals.1309.058.
• Background Artik S, Haarhuis K, Wu X, Begerow J, Gleichmann E. Tolerance to nickel: oral nickel administration induces a high frequency of anergic T cells with persistent suppressor activity. J Immunol. 2001 Dec 15;167(12):6794-803. doi: 10.4049/jimmunol.167.12.6794.
• Background Barnett ML, Kremer JM, St Clair EW, Clegg DO, Furst D, Weisman M, Fletcher MJ, Chasan-Taber S, Finger E, Morales A, Le CH, Trentham DE. Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 1998 Feb;41(2):290-7. doi: 10.1002/1529-0131(199802)41:23.0.CO;2-R.
• Background McKown KM, Carbone LD, Bustillo J, Seyer JM, Kang AH, Postlethwaite AE. Induction of immune tolerance to human type I collagen in patients with systemic sclerosis by oral administration of bovine type I collagen. Arthritis Rheum. 2000 May;43(5):1054-61. doi: 10.1002/1529-0131(200005)43:53.0.CO;2-W.
• Background Carbone LD, McKown K, Pugazhenthi M, Barrow KD, Warrington K, Somes G, Postlethwaite AE. Dosage effects of orally administered bovine type I collagen on immune function in patients with systemic sclerosis. Arthritis Rheum. 2004 Aug;50(8):2713-5. doi: 10.1002/art.20361. No abstract available.
• Background Postlethwaite AE, Wong WK, Clements P, Chatterjee S, Fessler BJ, Kang AH, Korn J, Mayes M, Merkel PA, Molitor JA, Moreland L, Rothfield N, Simms RW, Smith EA, Spiera R, Steen V, Warrington K, White B, Wigley F, Furst DE. A multicenter, randomized, double-blind, placebo-controlled trial of oral type I collagen treatment in patients with diffuse cutaneous systemic sclerosis: I. oral type I collagen does not improve skin in all patients, but may improve skin in late-phase disease. Arthritis Rheum. 2008 Jun;58(6):1810-22. doi: 10.1002/art.23501.
• Background Baccarani U, Adani GL, Montanaro D, Risaliti A, Lorenzin D, Avellini C, Tulissi P, Groppuzzo M, Curro G, Luvisetto F, Beltrami A, Bresadola V, Viale PL, Bresadola F. De novo malignancies after kidney and liver transplantations: experience on 582 consecutive cases. Transplant Proc. 2006 May;38(4):1135-7. doi: 10.1016/j.transproceed.2006.02.016.
• Background Yasufuku K, Heidler KM, O'Donnell PW, Smith GN Jr, Cummings OW, Foresman BH, Fujisawa T, Wilkes DS. Oral tolerance induction by type V collagen downregulates lung allograft rejection. Am J Respir Cell Mol Biol. 2001 Jul;25(1):26-34. doi: 10.1165/ajrcmb.25.1.4431.
• Background Mizobuchi T, Yasufuku K, Zheng Y, Haque MA, Heidler KM, Woods K, Smith GN Jr, Cummings OW, Fujisawa T, Blum JS, Wilkes DS. Differential expression of Smad7 transcripts identifies the CD4+CD45RChigh regulatory T cells that mediate type V collagen-induced tolerance to lung allografts. J Immunol. 2003 Aug 1;171(3):1140-7. doi: 10.4049/jimmunol.171.3.1140.

Drugs

Indications