A Phase I Study of Visilizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Severe Steroid-Refractory Ulcerative Colitis

Scott Plevy*, Bruce Salzberg, Gert Van Assche, Miguel Regueiro, Daniel Hommes, William Sandborn, Stephen Hanauer, Stephan Targan, Lloyd Mayer, Uma Mahadevan, Matthew Frankel, James Lowder

*Corresponding author for this work

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Background & Aims: To evaluate the safety and biological activity of visilizumab (a humanized anti-CD3 monoclonal antibody) and to determine a maximum tolerated dose in patients with severe ulcerative colitis that had not responded to 5 days of treatment with intravenous corticosteroids. Methods: In this open-label phase 1 study, 32 subjects received visilizumab at a dose of 10 or 15 μg/kg, administered intravenously on 2 consecutive days. Clinical response was defined as a Modified Truelove and Witts Severity Index <10 with a minimum decrease of 3 points; remission was <4 points. Endoscopic remission was a Mayo endoscopic subscore of 0 or 1. Results: Eight patients received 15 μg/kg visilizumab. Because of dose-limiting toxicities (T-cell recovery >30 days in 2 of 8 patients), the dose was reduced to 10 μg/kg in 24 patients. On day 30, 84% of patients demonstrated a clinical response, 41% achieved clinical remission, and 44% achieved endoscopic remission. Forty-five percent of patients did not require salvage therapies or colectomy during the first year postdose. Mild to moderate symptoms of cytokine release occurred in 100% and 83% of patients in the 15- and 10-μg/kg dose groups, respectively. All patients exhibited a rapid decrease in circulating CD4+ T-cell counts, which returned to baseline values by day 30 in 26 of 30 evaluable patients (86%). There were no serious infections. Conclusions: Visilizumab had an acceptable safety profile at the 10-μg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid-refractory ulcerative colitis.

Original languageEnglish (US)
Pages (from-to)1414-1422
Number of pages9
JournalGastroenterology
Volume133
Issue number5
DOIs
StatePublished - Nov 1 2007

ASJC Scopus subject areas

  • Gastroenterology

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    Plevy, S., Salzberg, B., Van Assche, G., Regueiro, M., Hommes, D., Sandborn, W., Hanauer, S., Targan, S., Mayer, L., Mahadevan, U., Frankel, M., & Lowder, J. (2007). A Phase I Study of Visilizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Severe Steroid-Refractory Ulcerative Colitis. Gastroenterology, 133(5), 1414-1422. https://doi.org/10.1053/j.gastro.2007.08.035