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Fontolizumab in moderate to severe Crohn's disease: A phase 2, randomized, doubleblind, placebocontrolled, multipledose study

Reinisch, Walter MD1,*; de Villiers, Williem MD, PhD2; Bene, László MD3; Simon, László MD4; Rácz, István MD5; Katz, Seymour MD6; Altorjay, István MD7; Feagan, Brian MD8; Riff, Dennis MD9; Bernstein, Charles N. MD10; Hommes, Daniel MD11; Rutgeerts, Paul MD, PhD12; Cortot, Antoine MD13; Gaspari, Michael MD14; Cheng, May BA15; Pearce, Tillman MD15; Sands, Bruce E. MD16

doi: 10.1002/ibd.21038
Original Clinical Articles

Background:: The safety and efficacy of fontolizumab, a humanized anti‐interferon gamma antibody, was investigated in patients with Crohn's disease (CD). Elevated gut mucosal levels of interferon gamma, a key cytokine involved in the inflammatory process of CD, are associated with disease symptoms.

Methods:: A total of 201 patients with Crohn's Disease Activity Index (CDAI) scores between 250 and 450 were randomized to receive an initial intravenous dose of 1.0 or 4.0 mg/kg fontolizumab or placebo, followed by up to 3 subcutaneous doses of 0.1 or 1.0 mg/kg fontolizumab or placebo every 4 weeks. Clinical response at day 29, the primary efficacy endpoint, was defined as a decrease in the CDAI of at least 100 points from baseline levels.

Results:: Of 201 patients, 135 (67%) completed the study. Day 29 response rates were similar in all treatment groups (31%–38%). At subsequent timepoints a significantly greater proportion of patients in the 1.0 mg/kg intravenous / 1.0 mg/kg subcutaneous fontolizumab group had clinical response and significantly greater improvement in the CDAI score compared with patients who received placebo. All fontolizumab groups had significant improvement in C‐reactive protein levels. The overall frequency of adverse events was similar in all groups (58%–75%); most events were related to exacerbation of CD. There was a low frequency (5.2%) of neutralizing antibodies to fontolizumab.

Conclusions:: Although a strong clinical response to fontolizumab was not observed, significant decreases in C‐reactive protein levels suggest a biological effect. Fontolizumab was well tolerated, and further studies to assess its efficacy are warranted. Inflamm Bowel Dis 2009

1Clinic of Internal Medicine III, Department of Gastroenterology and Hepatology, University of Vienna, Vienna, Austria; 10John Buhler Research Center, University of Manitoba, Winnipeg, Manitoba, Canada; 11Department of Gastroenterology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; 12Department of Gastroenterology, Universitaire Ziekenhuizen Gasthuisberg, Leuven, Belgium; 13CHU Hôpital Claude Huriez, Service des Maladies de l'Appareil Digestif et de la Nutrition, Lille Cedex, France; 14Carolina Digestive Health Associates, Charlotte, North Carolina; 15PDL BioPharma, Inc., Redwood City, California; 16MGH Crohn's and Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; 2Division of Digestive Disease and Nutrition, University of Kentucky Medical Center, Lexington, Kentucky; 3Gastroenterology, Péterfy S. Hospital, Budapest, Hungary; 4Department of Internal Medicine II, County Hospital of Szekszárd, Szekszárd, Hungary; 5Petz Aladár County Hospital, Győr, Hungary; 6Long Island Clinical Research Associates, LLP, Great Neck, New York; 7Gastroenterology, Medical University of Debrecen, Debrecen, Hungary; 8London Health Science Center, University of Western Ontario, London, Ontario, Canada; 9Advanced Clinical Research Institute,Anaheim, California

*Reprints: Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Waehringer Guertel 18–20, A‐1090 Vienna, Austria

Email: walter.reinisch@meduniwien.ac.at

Received 21 April 2009; Accepted 18 May 2009

Supported by the PDL BioPharma, Inc., Redwood City, CA.

Published online 27 July 2009 in Wiley InterScience (www.interscience.wiley.com).

© Crohn's & Colitis Foundation of America, Inc.
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