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

M. Wildenberg*¹, A. Levin², A. Ceroni³, Z. Guo², F. Bloemendaal², D. Ebner³, G. van den Brink¹

¹Academic Medical Centre, Gastroenterology and Hepatology, Amsterdam, Netherlands, ²Academic Medical Centre, Tytgat Institute, Amsterdam, Netherlands, ³Oxford University, Target Discovery Institute, Oxford, United Kingdom

K. Gecse*¹, Z. Vegh¹, Z. Kurti¹, M. Rutka², K. Farkas², J. Banai³, L. Bene⁴, B. Gasztonyi⁵, P. A. Golovics¹, T. Kristof⁶, L. Lakatos⁷, P. Miheller⁸, F. Nagy⁹, K. Palatka¹⁰, M. Papp¹¹, L. Lakner¹², A. Patai¹³, A. Salamon¹⁴, T. Szamosi³, Z. Szepes⁹, B. Szalay¹⁵, G. T. Toth¹⁶, A. Vincze¹⁷, T. Molnar², P. Lakatos¹

¹Semmelweis University, First Department of Medicine, Budapest, Hungary, ²University of Szeged, First Department of Medicine, Szeged, Hungary, ³Military Hospital, State Health Centre, Department of Gastroenterology, Budapest, Hungary, ⁴Peterfy Hospital, First Department of Medicine, Budapest, Hungary, ⁵Zala County Hospital, Second Department of Medicine, Zalaegerszeg, Hungary, ⁶B-A-Z County and University Teaching Hospital, Second Department of Medicine, Miskolc, Hungary, ⁷Csolnoky F. Province Hospital, Department of Medicine, Veszprem, Hungary, ⁸Semmelweis University, Second Department of Medicine, Budapest, Hungary, ⁹University of Szeged, First Department of Internal Medicine, Szeged, Hungary, ¹⁰University of Debrecen, Institute of Medicine, Department of Gastroenterology, Debrecen, Hungary, ¹¹University of Debrecen, Institute of Internal Medicine, Department of Gastroenterology, Debrecen, Hungary, ¹²Markusovszky Hospital, Department of Medicine and Gastroenterology, Szombathely, Hungary, ¹³Markusovszky Hospital, First Department of Medicine and Gastroenterology, Szombathely, Iceland, ¹⁴Tolna County Teaching Hospital, First Department of Gastroenterology, Szekszard, Hungary, ¹⁵Semmelweis University, Department of Laboratory Medicine, Budapest, Hungary, ¹⁶Janos Hospital, Department of Gastroenterology, Budapest, Hungary, ¹⁷University of Pécs, First Department of Medicine, Pécs, Hungary

M. Bettey¹, L. Downey¹, C. Underhill¹, J. Callaghan¹, M. Rush², I. Ahmed¹, F. Cummings*¹

¹University Hospital Southampton NHS Trust, Department of Gastroenterology, Southampton, United Kingdom, ²University of Southampton, Department of Gastroenterology, Southampton, United Kingdom

L. Smits*, L. Derikx, J. Drenth, D. de Jong, A. van Esch, F. Hoentjen

Radboud University Medical Centre, Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, Nijmegen, Netherlands

K. Farkas¹, M. Rutka¹, P.A. Golovics², Z. Végh², B.D. Lovász², T. Nyári³, K.B. Gecse², M. Kolar^{4, 5}, M. Bortlik^{4, 6}, D. Duricova^{4, 7}, N. Machkova⁴, V. Hruba⁴, M. Lukas⁴, K. Mitrova^{4, 8}, K. Malickova⁹, A. Bálint¹, F. Nagy¹, R. Bor*¹, A. Milassin¹, Z. Szepes¹, K. Palatka¹⁰, P.L. Lakatos², M. Lukas^{4, 9}, T. Molnár¹

¹University of Szeged, First Department of Medicine, Szeged, Hungary, ²Semmelweis University, First Department of Medicine, Budapest, Hungary, ³University of Szeged, Department of Medical Physics and Informatics, Szeged, Hungary, ⁴IBD Clinical and Research Centre, Iscare a.s, Prague, Czech Republic, ⁵Charles University, First Medical Faculty, Prague, Czech Republic, ⁶Military Hospital, Charles University, Department of Internal Medicine, Prague, Czech Republic, ⁷ First Medical Faculty, Charles University, Institute of Pharmacology, Prague, Czech Republic, ⁸Faculty Hospital Motol, 2nd Medical Faculty, Charles University, Department of Paediatrics, Prague, Czech Republic, ⁹ First Medical Faculty and General Teaching Hospital, Charles University, Institute of Medical Biochemistry and Laboratory Diagnostics, Prague, Czech Republic, ¹⁰University of Debrecen, Second Department of Medicine, Debrecen, Hungary

M. Kolar*¹, D. Duricová², M. Brotlik¹, V. Hruba¹, N. Machkova¹, K. Mitrova¹, K. Malickova³, M. Lukas¹, M. Lukas¹

¹Charles University, IBD Clinical and Research Centre, ISCARE, Prague, Czech Republic, ²Charles University, IBD Clinical and Research Centre, Iscare, Prague, Czech Republic, ³ First Medical Faculty and General Teaching Hospital, Charles University, Institute of Medical Biochemistry and Laboratory Diagnostics, Prague, Czech Republic

B. Lovasz*¹, Z. Kurti¹, M. Rutka², Z. Vegh¹, K. Gecse¹, K. Farkas², J. Banai³, L. Bene⁴, B. Gasztonyi⁵, T. Kristof⁶, L. Lakatos⁷, P. Miheller⁸, K. Palatka⁹, A. Patai¹⁰, A. Salamon¹¹, T. Szamosi³, Z. Szepes¹², E. Biro¹³, G.T. Toth¹⁴, A. Vincze¹⁵, T. Molnar², P. Lakatos¹

¹Semmelweis University, First Department of Medicine, Budapest, Hungary, ²University of Szeged, First Department of Medicine, Szeged, Hungary, ³Military Hospital, State Health Centre, Department of Gastroenterology, Budapest, Hungary, ⁴Peterfy Hospital, First Department of Medicine, Budapest, Hungary, ⁵Zala County Hospital, Second Department of Medicine, Zalaegerszeg, Hungary, ⁶B-A-Z County and University Teaching Hospital, Second Department of Medicine, Miskolc, Hungary, ⁷Csolnoky F. Province Hospital, Department of Medicine, Veszprem, Hungary, ⁸Semmelweis University, Second Department of Medicine, Budapest, Hungary, ⁹University of Debrecen, Institute of Medicine, Department of Gastroenterology, Debrecen, Hungary, ¹⁰Markusovszky Hospital, First Department of Medicine and Gastroenterology, Szombathely, Iceland, ¹¹Tolna County Teaching Hospital, First Department of Gastroenterology, Szekszard, Hungary, ¹²University of Szeged, First Department of Internal Medicine, Szeged, Hungary, ¹³Semmelweis University, Department of Laboratory Medicine, Budapest, Hungary, ¹⁴Janos Hospital, Department of Gastroenterology, Budapest, Hungary, ¹⁵University of Pécs, First Department of Medicine, Pécs, Hungary

S. Jeuring*^{1, 2}, D. Wintjens¹, T. Van den Heuvel^{1, 2}, M. Zeegers^{3, 4}, 
W. Hameeteman¹, M. Romberg-Camps⁵, L. Oostenbrug⁶, A. Masclee^{1, 2}, D. Jonkers^{1, 2}, M. Pierik^{1, 2}

¹Maastricht University Medical Centre, Internal Medicine - Division of Gastroenterology and Hepatology, Maastricht, Netherlands, ²Maastricht University Medical Centre, NUTRIM - School for Nutrition and Translational Research in Metabolism, Maastricht, Netherlands, ³Maastricht University Medical Centre, Complex Genetics - School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht, Netherlands, ⁴Maastricht University Medical Centre, CAPHRI - School for Public Health and Primary Care, Maastricht, Netherlands, ⁵Zuyderland Medical Centre, Internal Medicine and Gastroenterology-Hepatology, Sittard-Geleen, Netherlands, ⁶Zuyderland Medical Centre, Internal Medicine and Gastroenterology-Hepatology, Heerlen, Netherlands

P. Molander*^{1, 2}, M. Färkkilä^{2, 3}, H. Kemppainen⁴, T. Blomster⁵, A. Jussila⁶, H. Mustonen⁷, T. Sipponen^{2, 3}

¹Helsinki University Central Hospital, Peijas Hospital, Gastroenterology, Vantaa, Finland, ²University of Helsinki, Helsinki, Finland, ³Helsinki University Central Hospital, Abdominal Centre, Clinic of Gastroenterology, Helsinki, Finland, ⁴Turku University Central Hospital, Department of Gastroenterology, Turku, Finland, ⁵Oulu University Hospital, Department of Gastroenterology, Oulu, Finland, ⁶Tampere University Hospital, Department of Gastroenterology and Alimentary Tract Surgery, Tampere, Finland, ⁷Helsinki University Central Hospital, Department of Surgery, Helsinki, Finland

G. Fiorino*¹, P. Ellul², M. Muscat², P. Karatzas³, M. Silva⁴, A. Peixoto⁴, C. Felice⁵, F. Bossa⁶, P.L. Lakatos⁷, S. Sebastian⁸, B. Ungar⁹, F. Furfaro¹, K. Karmiris¹⁰, K.H. Katsanos¹¹, P. Navarro Cortes¹², M.M. Boscà Watts¹², D.K. Christodoulou¹¹, G. Maconi¹³, U. Kopylov⁹, A. Armuzzi⁵, F. Magro⁴, G. Mantzaris³, S. Ben-Horin⁹, S. Danese^{1, 14}

¹Humanitas Research Hospital, IBD Centre, Gastroenterology, Rozzano, Milan, Italy, ²Mater Dei Hospital, Department of Gastroenterology, Msida, Malta, ³Evangelismos Hospital, Department of Gastroenterology, Athens, Greece, ⁴Centro Hospitalar São João, Oporto, Portugal, Gastrenterology, Oporto, Portugal, ⁵Complesso Integrato Columbus, Gemelli Hospital Catholic University Foundation, IBD Unit, Rome, Italy, ⁶Casa Sollievo della Sofferenza Hospital, Division of Gastroenterology, San Giovanni Rotondo, Italy, ⁷Semmelweis University, 1st Department of Medicine, Budapest, Hungary, ⁸Hull & East Yorkshire NHS Trust, Hull & York Medical School, Hull, United Kingdom, ⁹Sheba Medical Centre, Gastroenterology, Tel Hashomer, Tel-Aviv, Israel, ¹⁰Venizelion General Hospital, Department of Gastroenterology, Heraklion, Greece, ¹¹University Hospital of Ioannina - Greece, Department of Gastroenterology, Ioannina, Greece, ¹²University Clinic Hospital of Valencia, Department of Gastroenterology, Valencia, Spain, ¹³Luigi Sacco University Hospital, Department of Gastroenterology, Milan, Italy, ¹⁴Humanitas University, Department of Biomedical Sciences, Rozzano, Italy

T. Raine¹, A. Bassi², E. Fogden³, B. Hayee⁴, J. K. Limdi⁵, H. Ludlow⁶, S. McLaughlin⁷, G. C. Parkes⁸, P. Patel⁹, M. Smith¹⁰, C. Selinger*¹¹

¹Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Department of Gastroenterology Research, Cambridge, United Kingdom, ²Whiston Hospital, Department of Gastroenterology, Prescot, United Kingdom, ³Sandwell District General Hospital, Department of Gastroenterology, West Bromwich, United Kingdom, ⁴King’s College Hospital, Department of Gastroenterology, London, United Kingdom, ⁵Pennine Acute Hospitals NHS Trust, Department of Gastroenterology, Manchester, United Kingdom, ⁶University Hospital Llandough, Department of Gastroenterology, Penarth, Cardiff, United Kingdom, ⁷Royal Bournemouth Hospital, Department of Gastroenterology, Bournemouth, United Kingdom, ⁸Barts and The London, Queen Mary’s School of Medicine and Dentistry, Department of Gastroenterology, London, United Kingdom, ⁹Epsom General Hospital, Department of Gastroenterology, Epsom, United Kingdom, ¹⁰Brighton and Sussex University Hospitals Trust, Digestive Diseases, Hove, East Sussex, United Kingdom, ¹¹St James University Hospital, Gastroenterology, Leeds, United Kingdom

T. Van Stappen*¹, L. Bollen¹, N. Vande Casteele¹, K. Papamichail^{1, 2}, 
N. Geukens¹, C. Barthel³, Y. Kölmel³, N. Zali³, S. Rameil³, G. Van Assche², M. Ferrante², S. Vermeire², A. Gils¹

¹KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium, ²UZ Leuven, Department of Clinical and Experimental Medicine, Leuven, Belgium, ³R-Biopharm AG, Darmstadt, Germany