A. López García¹, M. Rovira², A. Jauregui Amezaga¹, P. Marin³, A. Salas¹, S. Pinó Donnay¹, R. Barastegui¹, F. Feu¹, J. Elizalde¹, F. Fernández-Avilés², C. Martínez⁴, G. Gutierrez², L. Rosiñol², E. Carreras², A. Urbano², M. Lozano³, J. Cid³, M. Suárez-Lledó², J. Mensa⁵, J. Rimola⁶, S. Rodriguez⁶, M. C. Masamunt¹, D. Comas¹, A. Ramirez Morros¹, M. Gallego¹, I. Ordás¹, J. Panés¹, E. Ricart*¹

¹Hospital Clinic Barcelona, Gastroenterology, Barcelona, Spain, ²Hospital Clinic Barcelona, Haematology, Barcelona, Spain, ³Hospital Clinic Barcelona, Biomedic Diagnostic Centre, Barcelona, Spain, ⁴Hospital Clinic Barcelona, Ginecology, Barcelona, Spain, ⁵Hospital Clinic Barcelona, Internal Medicine, Barcelona, Spain, ⁶Hospital Clinic Barcelona, Radiology, Barcelona, Spain

J. Lindsay*¹, M. Allez², M. Clark³, M. Labopin⁴, E. Ricart⁵, G. Rogler⁶, M. Rovira⁷, J. Satsangi⁸, D. Farge⁹, C. Hawkey³

¹Blizard Institute, Barts and the London School of Medicine, Centre for Immunobiology, London, United Kingdom, ²APHP St. Antoine Hospital, Department of Gastroenterology, Paris, France, ³Nottingham Digestive Diseases Centre, Department of Digestive Diseases, Biomedical Research Unit, Nottingham, United Kingdom, ⁴European Group for Blood and Marrow Transplantation (EBMT), Paris, France, ⁵Hospital Clinic Barcelona, Gastroenterology, Barcelona, Spain, ⁶University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland, ⁷Hospital Clinic de Barcelona, Department of Haematology, Barcelona, Spain, ⁸Western General Hospital, Gastrointestinal Unit, Edinburgh, United Kingdom, ⁹Hospital Saint-Louis, Department of Internal Medicine and Vascular Pathology, Inserm U 976, Paris, France

A. Cassinotti*¹, F. Onida², C. Annaloro², G. Saporiti², M. Fichera¹, M. Daperno³, B. Motta², P. Fociani⁴, E. Tagliaferri², G. Sampietro⁵, D. Vincenti², A. Gregorini², G. Maconi¹, M. Nebuloni⁶, A. Cortelezzi², S. Ardizzone¹

¹Gastroenterology Unit, Luigi Sacco University Hospital, Milan, Italy, ²Bone Marrow Transplantation Centre, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy, ³Gastroenterology Unit, AO Ordine Mauriziano, Turin, Italy, ⁴Luigi Sacco University Hospital, Pathology Unit, Milan, Italy, ⁵2nd Division of Surgery, Luigi Sacco University Hospital, Milan, Italy, ⁶Pathology Unit, Luigi Sacco University Hospital, Milan, Italy

L. Carter¹, R. Morgan¹, C. Lesch¹, M. Spahr¹, L. Franchi², I. Monteleone³, G. Monteleone³, G. Glick², H. J. Wilkins¹, P. Higgins*²

¹Lycera, Ann Arbor, Michigan, United States, ²University of Michigan, Ann Arbor, Michigan, United States, ³Tor Vergata, Rome, Italy

G. van Assche¹, P. Rutgeerts¹, M. Ferrante¹, M. Noman¹, H. Fidder², B. Oldenburg², J. Metselaar^{3, 4}, S. Vermeire*¹

¹University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium, ²University Medical Centre Utrecht, Department of Gastroenterology and Hepatology, Utrecht, Netherlands, ³Enceladus Pharmaceuticals, Naarden, Netherlands, ⁴University Clinic RWTH, Experimental Molecular Imaging, Aachen, Germany

Ulcerative Colitis (UC) is a chronic, relapsing inflammatory disease affecting the mucosal lining of the rectum and the colon to a variable extent. Corticosteroids have long been a cornerstone in the treatment of UC, despite considerable side effects including Cushingoid facies and weight gain, acne, hyperglycaemia, insomnia, infections, and osteoporosis after extended use. Nanocort is a novel pharmaceutical composed of prednisolone sodium phosphate enclosed in 100 nm PEGylated liposomes, which, after IV infusion, selectively target and accumulate in inflamed bowel lesions and selectively deliver high and effective concentrations of corticosteroids, thus reducing the required total steroid dose and dosing frequency.

In an exploratory, 2-centre (neoplastic lesions [NL] and BE), randomised, placebo-controlled, observer-blind phase 2a study, the safety and efficacy of Nanocort was evaluated in 18 patients aged 22–63 with moderate-to-severe active UC. Two IV doses of 150 mg Nanocort (n = 14) or saline (n = 4) were given as slow infusions 2 weeks apart. Overall safety (primary endpoint), pharmacokinetics, and efficacy were assessed at weeks 2, 4, 8, and 12 after start of treatment.

The median total Mayo score (tMS, 0–12) at baseline was 10 (range 7–12). At week 4 the Nanocort group showed clear benefit in 70% of the patients with 4 patients out of 13 in remission. Further, 7 out of 13 patients showed a reduction of the endoscopy sub score of ≥ 1 point reaching ≤ 1 point. Rapid effects on partial Mayo score (pMS, 0–9) were shown with persisting remissions in 7/13 patients treated with Nanocort. Remission was defined as a post-treatment MS of ≤ 2 points with all sub scores ≤ 1 point. Typical steroid-related adverse effects were sparse with isolated mild to moderate cases of acne, dyspepsia, nausea, and gastritis. No significant suppression of urinary cortisol was found, nor were there any indications of hyperglycaemia. Some patients experienced infusion reactions probably related to the trial medication. One patient experienced an exacerbation of psoriasis upon withdrawal.

The results of this phase 2a study demonstrate that IV Nanocort can be a safe new therapy with fast and durable therapeutic benefit for patients with active UC without the drawbacks of oral steroid standard-of-care. Larger studies are warranted.

Figure 1. Nanocort effect.

V. Sinniger^{1, 2, 3}, S. Pellissier^{3, 4}, D. Hoffmann⁵, C. Trocmé⁶, L. Vercueil^{3, 7}, 
D. Clarençon^{3, 8}, B. Bonaz*^{3, 9}

¹Hospital University Centre, Hepatogastroenterology, Grenoble Cx9, France, ²Hospital University Centre, Gastroenterology, Grenoble Cx9, France, ³Inserm U836, Grenoble, France, ⁴University of savoie Mont Blanc, Psychology department, chambéry, France, ⁵Hospital University Centre, Neurosurgery, Grenoble, France, ⁶Hospital University Centre, Biology, Grenoble, France, ⁷Hospital University Centre, Neurology, Grenoble Cx9, France, ⁸Research Institute of the French Army, Brétigny-sur-Orge, France, ⁹Hospital University Centre, Gastroenterology, Grenoble, France

W. Sandborn^{1, 2}, B. Bhandari³, R. Fogel⁴, J. Onken⁵, E. Yen⁶, E. Huntzicker⁶, Y. Xin⁶, D. French⁶, J. Silverman⁶, B. Kanwar⁶, M. Subramanian⁶, J. McHutchison⁶, S. Lee⁷, L. Shackelton⁸, L. Stitt⁸, R. Pai⁹, B. Levesque*², G. D’Haens^{10, 11}, B. Feagan^{8, 12}

¹University of California, San Diego, California, United States, ²Robarts Clinical Trials, San Diego, California, United States, ³Delta Research Partners, Monroe, Louisiana, United States, ⁴Clinical Research Institute of Michigan, LLC, Chesterfield, Michigan, United States, ⁵Duke University Medical Centre, Durham, North Carolina, United States, ⁶Gilead Sciences, Inc, Foster City, California, United States, ⁷University of Washington, Seattle, Washington, United States, ⁸Robarts Clinical Trials, London, Ontario, Canada, ⁹Mayo Clinic Arizona, Scottsdale, Arizona, United States, ¹⁰Academic Medical Centre, Amsterdam, Canada, ¹¹Robarts Clinical Trials, Amsterdam, Netherlands, ¹²University of Western Ontario, London, Ontario, Canada

R. Atreya*¹, S. Bloom², F. Scaldaferi³, V. Gerardi⁴, C. Admyre⁵, A. Karlsson⁵, T. Knittel⁵, J. Kowalski⁵, M. Lukas⁶, R. Löfberg⁷, R. Petryka⁸, R. Schnabel⁹, U. Seidler¹⁰, S. Nancey¹¹, M. Neurath¹, C. Hawkey¹²

¹University of Erlangen-Nuernberg, Department of Medicine 1, Erlangen, Germany, ²University College London Hospital, Department of Gastroenterology, London, United Kingdom, ³Catholic University of Rome, Internal Medicine Department / Gastroenterology Division, Rome, Italy, ⁴Catholic University of Rome, Rome, Italy, ⁵Index Pharmaceuticals, Stockholm, Sweden, ⁶IBD Clinical and Research Centre, Clinical Centre Isacre Lighthouse, Prague, Czech Republic, ⁷Karolinska Institute and Sophiahemmet, Stockholm, Sweden, ⁸8NZOZ Vivamed, Warsaw, Poland, ⁹Pannonia Maganorvosi Centrum, Budapest, Hungary, ¹⁰MHH, Department of Gastroenterology, Hepatology, and Endocrinology, Hannover, Germany, ¹¹Lyon-Sud Hospital, Department of Gastroenterology, Lyon, France, ¹²Nottingham University Hospitals, Department of Gastroenterology, Nottingham, United Kingdom