William J Sandborn1, Jean-Frédéric Colombel2, Subrata Ghosh3, Bruce E Sands2, Gerald Dryden4, Xavier Hébuterne5, Rupert W Leong6, Brian Bressler7, Thomas Ullman2, Peter L Lakatos8, Walter Reinisch9, Li-An Xu10, Allison Luo11. 1. Inflammatory Bowel Disease Center, University of California San Diego, La Jolla, CA, USA wsandborn@ucsd.edu. 2. Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3. Department of Medicine, University of Calgary, Calgary, AB, Canada. 4. Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine, Louisville, KY, USA. 5. Faculté de Médecine, Université de Nice-Sophia Antipolis, Hôpital de l'Archet, Nice, France. 6. Concord Hospital, Gastroenterology and Liver Services, University of New South Wales, Sydney, Australia. 7. Division of Gastroenterology, St Paul's Hospital, Vancouver, BC, Canada. 8. 1st Department of Medicine, Semmelweis University, Budapest, Hungary. 9. Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, and McMaster University, Department of Internal Medicine, Hamilton, ON, Canada. 10. Bristol-Myers Squibb, Lawrenceville, NJ, USA. 11. Formerly of Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Abstract
BACKGROUND AND AIMS: Interferon-γ-inducible protein-10 [IP-10] mediates immune cell trafficking from the circulation to the inflamed colon and decreases gut epithelial cell survival. IP-10 expression is increased in patients with ulcerative colitis [UC]. We report efficacy and safety results from a dose-ranging induction study of eldelumab, a fully human monoclonal antibody to IP-10, in moderately to severely active UC. METHODS: A total of 252 adults with UC [Mayo score ≥ 6 and endoscopic subscore ≥ 2] were randomised 1:1:1 to placebo or eldelumab 15 or 25 mg/kg administered intravenously on Days 1 and 8 and every other week thereafter. The primary endpoint was clinical remission [Mayo score ≤ 2; no individual subscale score > 1] at Week 11. Key secondary endpoints included Mayo score clinical response and mucosal healing at Week 11. RESULTS: Neither eldelumab 15 or 25 mg/kg resulted in significant increases vs placebo in the proportion of patients achieving Week 11 clinical remission. Remission and response rates were 17.6% and 47.1% with eldelumab 25mg/kg, 13.1% and 44.0% with eldelumab 15mg/kg, and 9.6% and 31.3% with placebo. Clinical remission and response rates were higher in anti-tumour necrosis factor [TNF]-naïve patients treated with eldelumab compared with placebo. Eldelumab treatment was well tolerated and no immunogenicity was observed. CONCLUSIONS: The primary endpoint was not achieved with induction treatment with eldelumab 15 or 25 mg/kg in patients with UC. Trends towards clinical remission and response were observed in the overall population and were more pronounced in anti-TNF naïve patients. Eldelumab safety signals were consistent with those reported previously [ClinicalTrials.gov number, NCT01294410].
RCT Entities:
BACKGROUND AND AIMS: Interferon-γ-inducible protein-10 [IP-10] mediates immune cell trafficking from the circulation to the inflamed colon and decreases gut epithelial cell survival. IP-10 expression is increased in patients with ulcerative colitis [UC]. We report efficacy and safety results from a dose-ranging induction study of eldelumab, a fully human monoclonal antibody to IP-10, in moderately to severely active UC. METHODS: A total of 252 adults with UC [Mayo score ≥ 6 and endoscopic subscore ≥ 2] were randomised 1:1:1 to placebo or eldelumab 15 or 25 mg/kg administered intravenously on Days 1 and 8 and every other week thereafter. The primary endpoint was clinical remission [Mayo score ≤ 2; no individual subscale score > 1] at Week 11. Key secondary endpoints included Mayo score clinical response and mucosal healing at Week 11. RESULTS: Neither eldelumab 15 or 25 mg/kg resulted in significant increases vs placebo in the proportion of patients achieving Week 11 clinical remission. Remission and response rates were 17.6% and 47.1% with eldelumab 25mg/kg, 13.1% and 44.0% with eldelumab 15mg/kg, and 9.6% and 31.3% with placebo. Clinical remission and response rates were higher in anti-tumour necrosis factor [TNF]-naïve patients treated with eldelumab compared with placebo. Eldelumab treatment was well tolerated and no immunogenicity was observed. CONCLUSIONS: The primary endpoint was not achieved with induction treatment with eldelumab 15 or 25 mg/kg in patients with UC. Trends towards clinical remission and response were observed in the overall population and were more pronounced in anti-TNF naïve patients. Eldelumab safety signals were consistent with those reported previously [ClinicalTrials.gov number, NCT01294410].
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