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

Leiden University, Leyden, South Holland, Netherlands
Gastroenterology (Impact Factor: 16.72). 11/2007; 133(5):1414-22. DOI: 10.1053/j.gastro.2007.08.035
Source: PubMed


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.
In this open-label phase 1 study, 32 subjects received visilizumab at a dose of 10 or 15 microg/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.
Eight patients received 15 microg/kg visilizumab. Because of dose-limiting toxicities (T-cell recovery >30 days in 2 of 8 patients), the dose was reduced to 10 microg/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-microg/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.
Visilizumab had an acceptable safety profile at the 10-microg/kg dose level and may be clinically beneficial in patients with severe intravenous corticosteroid-refractory ulcerative colitis.

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    • "The early results from clinical trials using anti-CD3 antibodies, i.e. Otelixizumab (ChAgly CD3), Tepilizumab [hOKT3γ1(Ala-Ala)], and Visilizumab, in a variety of autoimmune disorders are encouraging (Keymeulen et al., 2005; Bisikirsha et al., 2005; Plevy et al., 2007). Second, agents that block T cell costimulation are currently being tested as maintenance drug in transplant patients. "

    Immunosuppression - Role in Health and Diseases, 02/2012; , ISBN: 978-953-51-0152-9
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    • "There were no serious infections. Visilizumab had an acceptable safety profile at the 10-μg/kg dose level and may be clinically beneficial in patients with severe CS-refractory UC.149 "
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