Study of EXE-346 Live Biotherapeutic to Reduce High Bowel Movement Frequency in Subjects With an IPAA (PROF)

Summary

The aim of this study is to assess the safety and preliminary efficacy of treatment with EXE-346, a live biotherapeutic, which may reduce bowel movement frequency in patients with an ileal pouch-anal anastomosis (IPAA) and lead to a higher quality of life.

Timeline

Start

2023-11-06

Primary completion

2027-05-31

Completion

2027-07-31

Publications

• Background Allison J, Herrinton LJ, Liu L, Yu J, Lowder J. Natural history of severe ulcerative colitis in a community-based health plan. Clin Gastroenterol Hepatol. 2008 Sep;6(9):999-1003. doi: 10.1016/j.cgh.2008.05.022.
• Background Barnes EL, Herfarth HH, Sandler RS, Chen W, Jaeger E, Nguyen VM, Robb AR, Kappelman MD, Martin CF, Long MD. Pouch-Related Symptoms and Quality of Life in Patients with Ileal Pouch-Anal Anastomosis. Inflamm Bowel Dis. 2017 Jul;23(7):1218-1224. doi: 10.1097/MIB.0000000000001119.
• Background Biancone L, Michetti P, Travis S, Escher JC, Moser G, Forbes A, Hoffmann JC, Dignass A, Gionchetti P, Jantschek G, Kiesslich R, Kolacek S, Mitchell R, Panes J, Soderholm J, Vucelic B, Stange E; European Crohn's and Colitis Organisation (ECCO). European evidence-based Consensus on the management of ulcerative colitis: Special situations. J Crohns Colitis. 2008 Mar;2(1):63-92. doi: 10.1016/j.crohns.2007.12.001. Epub 2008 Jan 28. No abstract available.
• Background Bibiloni R, Fedorak RN, Tannock GW, Madsen KL, Gionchetti P, Campieri M, De Simone C, Sartor RB. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol. 2005 Jul;100(7):1539-46. doi: 10.1111/j.1572-0241.2005.41794.x.
• Background Bischoff SC, Escher J, Hebuterne X, Klek S, Krznaric Z, Schneider S, Shamir R, Stardelova K, Wierdsma N, Wiskin AE, Forbes A. ESPEN practical guideline: Clinical Nutrition in inflammatory bowel disease. Clin Nutr. 2020 Mar;39(3):632-653. doi: 10.1016/j.clnu.2019.11.002. Epub 2020 Jan 13.
• Background Devaraj B, Kaiser AM. Surgical management of ulcerative colitis in the era of biologicals. Inflamm Bowel Dis. 2015 Jan;21(1):208-20. doi: 10.1097/MIB.0000000000000178.
• Background Farouk R, Pemberton JH, Wolff BG, Dozois RR, Browning S, Larson D. Functional outcomes after ileal pouch-anal anastomosis for chronic ulcerative colitis. Ann Surg. 2000 Jun;231(6):919-26. doi: 10.1097/00000658-200006000-00017.
• Background Gionchetti P, Calafiore A, Riso D, Liguori G, Calabrese C, Vitali G, Laureti S, Poggioli G, Campieri M, Rizzello F. The role of antibiotics and probiotics in pouchitis. Ann Gastroenterol. 2012;25(2):100-105.
• Background Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, Vitali B, Poggioli G, Miglioli M, Campieri M. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003 May;124(5):1202-9. doi: 10.1016/s0016-5085(03)00171-9.
• Background Gionchetti P, Rizzello F, Morselli C, Poggioli G, Tambasco R, Calabrese C, Brigidi P, Vitali B, Straforini G, Campieri M. High-dose probiotics for the treatment of active pouchitis. Dis Colon Rectum. 2007 Dec;50(12):2075-82; discussion 2082-4. doi: 10.1007/s10350-007-9068-4. Epub 2007 Oct 13.
• Background Gionchetti P, Rizzello F, Venturi A, Brigidi P, Matteuzzi D, Bazzocchi G, Poggioli G, Miglioli M, Campieri M. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology. 2000 Aug;119(2):305-9. doi: 10.1053/gast.2000.9370.
• Background Gower-Rousseau C, Dauchet L, Vernier-Massouille G, Tilloy E, Brazier F, Merle V, Dupas JL, Savoye G, Balde M, Marti R, Lerebours E, Cortot A, Salomez JL, Turck D, Colombel JF. The natural history of pediatric ulcerative colitis: a population-based cohort study. Am J Gastroenterol. 2009 Aug;104(8):2080-8. doi: 10.1038/ajg.2009.177. Epub 2009 May 12.
• Background Hahnloser D, Pemberton JH, Wolff BG, Larson DR, Crownhart BS, Dozois RR. Results at up to 20 years after ileal pouch-anal anastomosis for chronic ulcerative colitis. Br J Surg. 2007 Mar;94(3):333-40. doi: 10.1002/bjs.5464.
• Background Herrinton LJ, Liu L, Lewis JD, Griffin PM, Allison J. Incidence and prevalence of inflammatory bowel disease in a Northern California managed care organization, 1996-2002. Am J Gastroenterol. 2008 Aug;103(8):1998-2006. doi: 10.1111/j.1572-0241.2008.01960.x.
• Background Hoffmann JC, Zeitz M, Bischoff SC, Brambs HJ, Bruch HP, Buhr HJ, Dignass A, Fischer I, Fleig W, Folsch UR, Herrlinger K, Hohne W, Jantschek G, Kaltz B, Keller KM, Knebel U, Kroesen AJ, Kruis W, Matthes H, Moser G, Mundt S, Pox C, Reinshagen M, Reissmann A, Riemann J, Rogler G, Schmiegel W, Scholmerich J, Schreiber S, Schwandner O, Selbmann HK, Stange EF, Utzig M, Wittekind C. [Diagnosis and therapy of ulcerative colitis: results of an evidence based consensus conference by the German society of Digestive and Metabolic Diseases and the competence network on inflammatory bowel disease]. Z Gastroenterol. 2004 Sep;42(9):979-83. doi: 10.1055/s-2004-813510. No abstract available. German.
• Background Hurst RD, Molinari M, Chung TP, Rubin M, Michelassi F. Prospective study of the incidence, timing and treatment of pouchitis in 104 consecutive patients after restorative proctocolectomy. Arch Surg. 1996 May;131(5):497-500; discussion 501-2. doi: 10.1001/archsurg.1996.01430170043007.
• Background Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, Finkelstein JA. The prevalence and geographic distribution of Crohn's disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007 Dec;5(12):1424-9. doi: 10.1016/j.cgh.2007.07.012. Epub 2007 Sep 29.
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• Background Loftus CG, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Tremaine WJ, Melton LJ 3rd, Sandborn WJ. Update on the incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000. Inflamm Bowel Dis. 2007 Mar;13(3):254-61. doi: 10.1002/ibd.20029.
• Background Madiba TE, Bartolo DC. Pouchitis following restorative proctocolectomy for ulcerative colitis: incidence and therapeutic outcome. J R Coll Surg Edinb. 2001 Dec;46(6):334-7.
• Background Michelassi F, Lee J, Rubin M, Fichera A, Kasza K, Karrison T, Hurst RD. Long-term functional results after ileal pouch anal restorative proctocolectomy for ulcerative colitis: a prospective observational study. Ann Surg. 2003 Sep;238(3):433-41; discussion 442-5. doi: 10.1097/01.sla.0000086658.60555.ea.
• Background Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, Nicholls RJ, Gionchetti P, Campieri M, Kamm MA. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut. 2004 Jan;53(1):108-14. doi: 10.1136/gut.53.1.108.
• Background Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, Mitton S, Orchard T, Rutter M, Younge L, Lees C, Ho GT, Satsangi J, Bloom S; IBD Section of the British Society of Gastroenterology. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011 May;60(5):571-607. doi: 10.1136/gut.2010.224154.
• Background Ng SC, Plamondon S, Kamm MA, Hart AL, Al-Hassi HO, Guenther T, Stagg AJ, Knight SC. Immunosuppressive effects via human intestinal dendritic cells of probiotic bacteria and steroids in the treatment of acute ulcerative colitis. Inflamm Bowel Dis. 2010 Aug;16(8):1286-98. doi: 10.1002/ibd.21222.
• Background Nguyen N, Zhang B, Holubar SD, Pardi DS, Singh S. Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis. Cochrane Database Syst Rev. 2019 Nov 30;11(11):CD001176. doi: 10.1002/14651858.CD001176.pub5.
• Background Pardi DS, D'Haens G, Shen B, Campbell S, Gionchetti P. Clinical guidelines for the management of pouchitis. Inflamm Bowel Dis. 2009 Sep;15(9):1424-31. doi: 10.1002/ibd.21039.
• Background Pathirana WGW, Chubb SP, Gillett MJ, Vasikaran SD. Faecal Calprotectin. Clin Biochem Rev. 2018 Aug;39(3):77-90.
• Background Pronio A, Montesani C, Butteroni C, Vecchione S, Mumolo G, Vestri A, Vitolo D, Boirivant M. Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm Bowel Dis. 2008 May;14(5):662-8. doi: 10.1002/ibd.20369.
• Background Sagar PM, Taylor BA, Godwin P, Holdsworth PJ, Johnston D, Lewis W, Miller A, Quirke P, Williamson M. Acute pouchitis and deficiencies of fuel. Dis Colon Rectum. 1995 May;38(5):488-93. doi: 10.1007/BF02148848.
• Background Sedano R, Ma C, Pai RK, D' Haens G, Guizzetti L, Shackelton LM, Remillard J, Gionchetti P, Gordon IO, Holubar S, Kayal M, Lauwers GY, Pai RK, Pardi DS, Samaan MA, Schaeffer DF, Shen B, Silverberg MS, Feagan BG, Sandborn WJ, Jairath V. An expert consensus to standardise clinical, endoscopic and histologic items and inclusion and outcome criteria for evaluation of pouchitis disease activity in clinical trials. Aliment Pharmacol Ther. 2021 May;53(10):1108-1117. doi: 10.1111/apt.16328. Epub 2021 Mar 18.
• Background Shen B. Acute and chronic pouchitis--pathogenesis, diagnosis and treatment. Nat Rev Gastroenterol Hepatol. 2012 Apr 17;9(6):323-33. doi: 10.1038/nrgastro.2012.58.
• Background Shen B, Achkar JP, Connor JT, Ormsby AH, Remzi FH, Bevins CL, Brzezinski A, Bambrick ML, Fazio VW, Lashner BA. Modified pouchitis disease activity index: a simplified approach to the diagnosis of pouchitis. Dis Colon Rectum. 2003 Jun;46(6):748-53. doi: 10.1007/s10350-004-6652-8.
• Background Shen B, Achkar JP, Lashner BA, Ormsby AH, Remzi FH, Brzezinski A, Bevins CL, Bambrick ML, Seidner DL, Fazio VW. A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis. Inflamm Bowel Dis. 2001 Nov;7(4):301-5. doi: 10.1097/00054725-200111000-00004.
• Background Singh S, Feuerstein JD, Binion DG, Tremaine WJ. AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis. Gastroenterology. 2019 Feb;156(3):769-808.e29. doi: 10.1053/j.gastro.2018.12.008. Epub 2018 Dec 18.
• Background Sood A, Midha V, Makharia GK, Ahuja V, Singal D, Goswami P, Tandon RK. The probiotic preparation, VSL#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2009 Nov;7(11):1202-9, 1209.e1. doi: 10.1016/j.cgh.2009.07.016. Epub 2009 Jul 22.
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Drugs

Indications