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Phase II Clinical Trial Initiated for Alicaforsen In Patients With Ulcerative Colitis

CARLSBAD, Calif., April 8 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today it has initiated a Phase II clinical trial of alicaforsen (ISIS 2302), an antisense inhibitor of intercellular adhesion molecule-1 (ICAM-1), in people with active ulcerative colitis (UC). The study will compare the safety and efficacy of different dosing-regimens of the enema formulation of alicaforsen to placebo. An intravenous formulation of alicaforsen is being evaluated in a Phase III clinical program in people with Crohn's disease.

"Alicaforsen is one of the most advanced drugs in the company's antisense pipeline," said Mark Wedel, Isis' Vice President of Clinical Research and Chief Medical Officer. "Based on the data from initial studies of this drug for the treatment of Crohn's disease and ulcerative colitis, we are enthusiastic about the potential of alicaforsen in inflammatory bowel disease."

In the randomized, double-masked, placebo-controlled Phase II study approximately 100 patients will be enrolled at sites in the U.S. and Europe. The primary endpoint of the study is improvement in the Disease Activity Index (DAI) upon completion of the six-week dosing period. Patients with an improvement in DAI will be followed for up to a year. DAI is a common clinical index scoring system for the severity of symptoms related to UC. This trial is being conducted in parallel with a Phase II 170-patient study comparing alicaforsen enema to mesalamine enema.

In October 2001, Isis reported results from a six-month, 40-patient Phase II study of alicaforsen enema in UC. In the study, patients demonstrated median improvement in DAI and Clinical Activity Index (CAI) scores (73% and 58%, respectively) after one month of nightly 240 mg alicaforsen enemas. CAI is a commonly used clinical scoring system for the severity of symptoms and quality of life related to UC. The improvements in DAI and CAI were well maintained at month three and month six of the study. No patients in the 240 mg dose group required additional medications during the six-month trial. No serious adverse events were observed in this trial.

Alicaforsen is an antisense inhibitor of ICAM-1, a molecule that plays a key role in a wide range of inflammatory and autoimmune conditions such as UC. ICAM-1 is part of a family of molecules, the cellular adhesion molecules, that can be found on the surface of virtually every cell in the body, including cells that line the colon. It is involved in the production of immune factors that cause the inflammatory response in UC.

According to the Crohn's and Colitis Foundation of America, UC is an inflammatory disease of the colon, the large intestine, which is characterized by inflammation and ulceration of the innermost lining of the colon. Symptoms characteristically include diarrhea, rectal bleeding and abdominal pain. UC disease differs from another inflammatory bowel disease (IBD), Crohn's disease, as it only affects the colon. Up to one million people have IBD, evenly split between Crohn's disease and UC. According to the European Federation of Crohn's and Ulcerative Colitis Associations, a similar number of people are affected in Europe.

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