The results from a double-blind, multicenter phase II trial of the investigational drug MLN02 in patients with ulcerative colitis showed that MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in these patients.
A total of 181 patients with moderately active ulcerative colitis were randomized to receive either a 0.5 mg/kg dose of MLN02, a 2.0 mg/kg dose of MLN02 or placebo at days one and 29.
The primary outcome was clinical remission at week six, as defined as a score of zero or one on the Ulcerative Colitis Clinical Score ( UCCS ) and a score of zero or one on the Modified Baron Score ( MBS ) with no evidence of rectal bleeding at the study's conclusion.
Clinical remission was achieved in 33 percent of the patients receiving 0.5 mg/kg of MLN02 and 32 percent of the patients receiving 2.0 mg/kg of MLN02 versus 14 percent in those who had received placebo.
Endoscopic remission was achieved in 28 percent of patients receiving 0.5 mg/kg of MLN02 and 12 percent of patients receiving 2.0 mg/kg of MLN02, compared to eight percent of those who received placebo.
Statistically significant clinical response was achieved in 66 percent of patients ( 0.5 mg/kg ) and 53 percent ( 2.0 mg/kg ) in the treatment groups, compared to 33 percent of those who received placebo. Clinical response is defined as an improvement of three or more points on the UCCS from baseline.
The drug was generally well tolerated.
Serious adverse events were comparable in the three treatment groups and were mainly related to exacerbations of underlying ulcerative colitis, which occurred in 15 percent of patients in the two treatment groups, compared to 10 percent in the placebo group. An infusion reaction occurred in one MLN02 treated patient who developed hives and mild angioedema.
MLN02 is a novel monoclonal antibody that binds to alpha 4 beta 7, a T-cell integrin ( a cell surface protein ).
In laboratory studies, the mechanism of action has shown to prevent the migration of T-cells specifically to the GI tract.
Increased T-cell trafficking is believed to play a role in the pathogenesis of inflammatory bowel disease ( IBD ), including conditions such as ulcerative colitis and Crohn's disease.
Source: The New Englang Journal of Medicine, 2005