A Clinical Study to Evaluate the Potential Role of ACTH Gel in Patients With Scleritis

Summary

ATLAS study is a clinical trial to evaluate the potential role of subcutaneous adrenocorticotropic hormone (ACTH) gel in the management of non-infectious scleritis. Specifically, the ATLAS Study aims to evaluate the safety, tolerability and effect of 2 different dose regimens of ACTH gel administered by subcutaneous (SC) injection in patients with scleritis, over a period of 12 months. Scleritis is an inflammatory disease affecting the sclera (white outer coating of the eye), which causes blurring of vision, redness, tearing and painful ocular inflammatory episodes in one or both eyes. Scleritis may results in vision threatening ocular complications, if left untreated. Treatment of scleritis is usually chronic and requires systemic therapy with non-steroidal anti-inflammatory drugs, corticosteroids and immunosuppressive therapy. Due to its treatment resistance nature, scleritis remains a therapeutic challenge for many ophthalmologists. H.P. Acthar Gel (ACTH Gel) is a highly purified preparation of adrenocorticotropic hormone (ACTH) in a gel that is designed to provide extended release of the ACTH following injection. It is a FDA approved treatment for flares or on a regular basis (maintenance) in people with systemic lupus erythematosus (lupus), infantile spasms, adults with acute relapses or flares of multiple sclerosis (MS), patients with kidney diseases, among other indications. ACTH Gel is also approved for a wide range of allergic and inflammatory diseases of the eye. Given the established role of inflammation in the pathogenesis of scleritis and the anti-inflammatory effects of ACTH Gel treatment by blocking various inflammatory pathways, a beneficial outcome could be anticipated from ACTH Gel treatment in patients with scleritis.

Timeline

Start

2019-01-01

Primary completion

2024-12-08

Completion

2024-12-08

Publications

• Background Okhravi N, Odufuwa B, McCluskey P, Lightman S. Scleritis. Surv Ophthalmol. 2005 Jul-Aug;50(4):351-63. doi: 10.1016/j.survophthal.2005.04.001.
• Background Sainz de la Maza M, Jabbur NS, Foster CS. Severity of scleritis and episcleritis. Ophthalmology. 1994 Feb;101(2):389-96. doi: 10.1016/s0161-6420(94)31325-x.
• Background Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology. 2012 Jan;119(1):43-50. doi: 10.1016/j.ophtha.2011.07.013. Epub 2011 Oct 2.
• Background Akpek EK, Thorne JE, Qazi FA, Do DV, Jabs DA. Evaluation of patients with scleritis for systemic disease. Ophthalmology. 2004 Mar;111(3):501-6. doi: 10.1016/j.ophtha.2003.06.006.
• Background Keino H, Watanabe T, Taki W, Nakashima C, Okada AA. Clinical features and visual outcomes of Japanese patients with scleritis. Br J Ophthalmol. 2010 Nov;94(11):1459-63. doi: 10.1136/bjo.2009.171744. Epub 2010 Jun 24.
• Background Erkanli L, Akova YA, Guney-Tefekli E, Tugal-Tutkun I. Clinical features, prognosis, and treatment results of patients with scleritis from 2 tertiary eye care centers in Turkey. Cornea. 2010 Jan;29(1):26-33. doi: 10.1097/ICO.0b013e3181ac9fad.
• Background Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with systemic vasculitic diseases. Ophthalmology. 1995 Apr;102(4):687-92. doi: 10.1016/s0161-6420(95)30970-0.
• Background Raiji VR, Palestine AG, Parver DL. Scleritis and systemic disease association in a community-based referral practice. Am J Ophthalmol. 2009 Dec;148(6):946-50. doi: 10.1016/j.ajo.2009.07.021. Epub 2009 Oct 17.
• Background Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976 Mar;60(3):163-91. doi: 10.1136/bjo.60.3.163.
• Background Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol. 2000 Oct;130(4):469-76. doi: 10.1016/s0002-9394(00)00710-8.
• Background Kolomeyer AM, Ragam A, Shah K, Do BK, Shah VP, Chu DS. Cyclo-oxygenase inhibitors in the treatment of chronic non-infectious, non-necrotizing scleritis and episcleritis. Ocul Immunol Inflamm. 2012 Aug;20(4):293-9. doi: 10.3109/09273948.2012.689075. Epub 2012 May 29.
• Background Ragam A, Kolomeyer AM, Fang C, Xu Y, Chu DS. Treatment of chronic, noninfectious, nonnecrotizing scleritis with tumor necrosis factor alpha inhibitors. Ocul Immunol Inflamm. 2014 Dec;22(6):469-77. doi: 10.3109/09273948.2013.863944. Epub 2013 Dec 19.
• Background Jachens AW, Chu DS. Retrospective review of methotrexate therapy in the treatment of chronic, noninfectious, nonnecrotizing scleritis. Am J Ophthalmol. 2008 Mar;145(3):487-492. doi: 10.1016/j.ajo.2007.11.010.
• Background Kolomeyer AM, Ragam A, Shah K, Jachens AW, Tu Y, Chu DS. Mycophenolate mofetil in the treatment of chronic non-infectious, non-necrotizing scleritis. Ocul Immunol Inflamm. 2012 Apr;20(2):113-8. doi: 10.3109/09273948.2012.655398.
• Background Star RA, Rajora N, Huang J, Stock RC, Catania A, Lipton JM. Evidence of autocrine modulation of macrophage nitric oxide synthase by alpha-melanocyte-stimulating hormone. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8016-20. doi: 10.1073/pnas.92.17.8016.
• Background Catania A, Lonati C, Sordi A, Carlin A, Leonardi P, Gatti S. The melanocortin system in control of inflammation. ScientificWorldJournal. 2010 Sep 14;10:1840-53. doi: 10.1100/tsw.2010.173.
• Background Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics. 1996 Mar;97(3):375-9.
• Background Fiechtner JJ, Montroy T. Treatment of moderately to severely active systemic lupus erythematosus with adrenocorticotropic hormone: a single-site, open-label trial. Lupus. 2014 Aug;23(9):905-12. doi: 10.1177/0961203314532562. Epub 2014 May 2.
• Background Bomback AS, Canetta PA, Beck LH Jr, Ayalon R, Radhakrishnan J, Appel GB. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial. Am J Nephrol. 2012;36(1):58-67. doi: 10.1159/000339287. Epub 2012 Jun 19.
• Background Levine T. Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series. Drug Des Devel Ther. 2012;6:133-9. doi: 10.2147/DDDT.S33110. Epub 2012 Jun 11.
• Background Mittal T, Dedhia P, Roy-Chaudhury P, Abu Jawdeh BG, Mogilishetty G, Cuffy MC, Alloway RR, Woodle ES, Govil A. Complete Remission of Post-transplantation Recurrence of Focal Segmental Glomerulosclerosis With the Use of Adrenocorticotrophic Hormone Gel: Case Report. Transplant Proc. 2015 Sep;47(7):2219-22. doi: 10.1016/j.transproceed.2015.07.013.
• Background Hladunewich MA, Cattran D, Beck LH, Odutayo A, Sethi S, Ayalon R, Leung N, Reich H, Fervenza FC. A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar(R) Gel) in nephrotic syndrome due to idiopathic membranous nephropathy. Nephrol Dial Transplant. 2014 Aug;29(8):1570-7. doi: 10.1093/ndt/gfu069. Epub 2014 Apr 8.
• Background Simsarian JP, Saunders C, Smith DM. Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: a prospective, randomized, open-label pilot trial. Drug Des Devel Ther. 2011;5:381-9. doi: 10.2147/DDDT.S19331. Epub 2011 Jul 11.
• Background Olsen NJ, Decker DA, Higgins P, Becker PM, McAloose CA, Benko AL, Kovacs WJ. Direct effects of HP Acthar Gel on human B lymphocyte activation in vitro. Arthritis Res Ther. 2015 Oct 27;17:300. doi: 10.1186/s13075-015-0823-y.
• Background Sen HN, Sangave AA, Goldstein DA, Suhler EB, Cunningham D, Vitale S, Nussenblatt RB. A standardized grading system for scleritis. Ophthalmology. 2011 Apr;118(4):768-71. doi: 10.1016/j.ophtha.2010.08.027. Epub 2010 Nov 20.
• Background Krebs EE, Carey TS, Weinberger M. Accuracy of the pain numeric rating scale as a screening test in primary care. J Gen Intern Med. 2007 Oct;22(10):1453-8. doi: 10.1007/s11606-007-0321-2. Epub 2007 Aug 1.
• Background Williamson A, Hoggart B. Pain: a review of three commonly used pain rating scales. J Clin Nurs. 2005 Aug;14(7):798-804. doi: 10.1111/j.1365-2702.2005.01121.x.
• Background Tuft SJ, Watson PG. Progression of scleral disease. Ophthalmology. 1991 Apr;98(4):467-71. doi: 10.1016/s0161-6420(91)32269-3.
• Background McCluskey PJ, Watson PG, Lightman S, Haybittle J, Restori M, Branley M. Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients. Ophthalmology. 1999 Dec;106(12):2380-6. doi: 10.1016/S0161-6420(99)90543-2.
• Background Getting SJ. Targeting melanocortin receptors as potential novel therapeutics. Pharmacol Ther. 2006 Jul;111(1):1-15. doi: 10.1016/j.pharmthera.2005.06.022. Epub 2006 Feb 20.
• Background Montero-Melendez T. ACTH: The forgotten therapy. Semin Immunol. 2015 May;27(3):216-26. doi: 10.1016/j.smim.2015.02.003. Epub 2015 Feb 26.
• Background Brzoska T, Luger TA, Maaser C, Abels C, Bohm M. Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr Rev. 2008 Aug;29(5):581-602. doi: 10.1210/er.2007-0027. Epub 2008 Jul 8.
• Background Xing Y, Parker CR, Edwards M, Rainey WE. ACTH is a potent regulator of gene expression in human adrenal cells. J Mol Endocrinol. 2010 Jul;45(1):59-68. doi: 10.1677/JME-10-0006. Epub 2010 May 11.
• Background Manna SK, Aggarwal BB. Alpha-melanocyte-stimulating hormone inhibits the nuclear transcription factor NF-kappa B activation induced by various inflammatory agents. J Immunol. 1998 Sep 15;161(6):2873-80.
• Background Ichiyama T, Campbell IL, Furukawa S, Catania A, Lipton JM. Autocrine alpha-melanocyte-stimulating hormone inhibits NF-kappaB activation in human glioma. J Neurosci Res. 1999 Dec 1;58(5):684-9.
• Background Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. 2004 Mar;56(1):1-29. doi: 10.1124/pr.56.1.1.
• Background Lee DJ, Taylor AW. Following EAU recovery there is an associated MC5r-dependent APC induction of regulatory immunity in the spleen. Invest Ophthalmol Vis Sci. 2011 Nov 17;52(12):8862-7. doi: 10.1167/iovs.11-8153.
• Background Lee DJ, Taylor AW. Both MC5r and A2Ar are required for protective regulatory immunity in the spleen of post-experimental autoimmune uveitis in mice. J Immunol. 2013 Oct 15;191(8):4103-11. doi: 10.4049/jimmunol.1300182. Epub 2013 Sep 16.

Drugs

Indications