Prospective randomized open-label multicenter phase I/II dose escalation trial of visilizumab (HuM291) in severe steroid-refractory ulcerative colitis.
BACKGROUND
Visilizumab is a humanized IgG(2) monoclonal anti-CD3 antibody. We evaluated its safety and dose response in severe intravenous steroid-refractory ulcerative colitis (UC).


METHODS
In all, 104 patients were treated. In Stage I, 73 patients were randomly assigned to receive intravenous visilizumab 5, 7.5, 10, or 12.5 microg/kg/day for 2 consecutive days. In Stage II, 33 patients received visilizumab at the optimal clinical dose (OCD) of 5 microg/kg/day for 2 days. Symptomatic response and remission were defined by the modified Truelove-Witts severity index. Clinical response and remission were defined by the Mayo score.


RESULTS
The rates of symptomatic response at day 15 in the 5, 7.5, 10, or 12.5 microg/kg dose groups were 71%, 70%, 50%, and 61%, respectively, in Stage I and in 54% in Stage II. The symptomatic remission rates were 35%, 5%, 22%, and 11% in Stage I and 18% in Stage II. The rates of clinical response at day 30 in the 5, 7.5, 10, or 12.5 microg/kg dose groups were 71%, 65%, 50%, and 67%, respectively, in Stage I and 55% in Stage II. The clinical remission rates were 6%, 5%, 0%, and 11% in Stage I and 6% in Stage II. All patients experienced adverse events. Serious adverse events included abdominal abscess, cytomegalovirus infection, atrial fibrillation, herpes zoster, and esophageal candidiasis.


CONCLUSIONS
Treatment with visilizumab induced symptomatic response and clinical response. Results with 5 microg/kg/day were similar to those observed with higher doses.
Baumgart
Daniel C
DC
Department of Medicine, Divisions of Gastroenterology and Hepatology, Charité Medical School of the Humboldt-University of Berlin, Germany. daniel.baumgart@charite.de
Targan
Stephan R
SR
Dignass
Axel U
AU
Mayer
Lloyd
L
van Assche
Gert
G
Hommes
Daan W
DW
Hanauer
Stephen B
SB
Mahadevan
Uma
U
Reinisch
Walter
W
Plevy
Scott E
SE
Salzberg
Bruce A
BA
Buchman
Alan L
AL
Mechkov
Grigor M
GM
Krastev
Zahariy A
ZA
Lowder
James N
JN
Frankel
Matthew B
MB
Sandborn
William J
WJ
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D017252:CD3 Complex / Q000276:immunology*; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017252:CD3 Complex; C456519:visilizumab