Clinical–Alimentary TractA Phase I Study of Visilizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Severe Steroid-Refractory Ulcerative Colitis
Section snippets
Patients
Male and nonpregnant female patients, 18–70 years of age, who were diagnosed with UC verified by colonoscopy or barium enema within 36 months before study entry and who had active disease were eligible for the study. Active disease was documented by a Modified Truelove and Witts Severity Index (MTWSI) score of 11–21 and ongoing treatment with IV corticosteroids for at least 5 days before study entry.4, 13 Each patient provided written informed consent to participate in the trial before
Patient Screening and Demographics
Of 58 patients who were screened for enrollment, 32 were enrolled and received study drug. Hospitalized patients received IV corticosteroids for a median of 7 days (range, 5–17) before receiving visilizumab. Twenty-five potential patients who were hospitalized with severe UC and treated with IV corticosteroids had measurable EBV DNA levels in whole blood (median, 747 copies/mL; range, 97–10,500 copies/mL) at screening. Six patients with measurable whole blood EBV DNA levels were enrolled in the
Discussion
In a phase 1 dose-finding study, visilizumab had an acceptable safety profile and demonstrated clinical activity in hospitalized patients with IV corticosteroid–refractory UC. There were no serious infectious complications during the study. In this preliminary open-label analysis, visilizumab appeared to produce durable clinical responses that exceeded its pharmacokinetic and pharmacodynamic properties (ie, elimination half-life of 17 hours and transient peripheral blood T-cell lymphopenia
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2020, Pharmacological ResearchCitation Excerpt :By binding to the TCR/CD3 complex, visilizumab induces apoptosis in activated T cells, ultimately leading to their selective clonal deletion. Visilizumab 10 μg/kg administrated intravenously for two consecutive days was shown to be effective in patients with steroid-refractory UC in an open-label phase 1 trial [20]. The dose of 5 μg/kg visilizumab induced clinical response at day 30 in UC patients at the same percentage of higher doses in a phase 2a trial [21].
Immunotoxicology of Biopharmaceutics
2018, Comprehensive Toxicology: Third Edition
Supported by the sponsor, PDL BioPharma, Fremont, CA.
The authors declare the following conflicts of interest: consultant, PDL BioPharma (S.P., G.V., M.R., D.H., W.S., S.H., S.T., L.M., U.M.); research support for clinical trial, PDL BioPharma (S.P., B.S., G.V., M.R., D.H., W.S., S.H., S.T., L.M., U.M.); speaker at continuing medical education symposia sponsored by PDL BioPharma (S.P., W.S., S.H., D.H.).
ClinicalTrials.gov identifier: NCT00032305.