[ PDLI/anti-IFNgamma ]
Wednesday May 8, 4:00 pm Eastern Time
Press Release
SOURCE: Protein Design Labs, Inc.
Protein Design Labs Begins Phase II Trial of SMART(R) Anti-Gamma Interferon Antibody in Crohn's Disease
FREMONT, Calif., May 8 /PRNewswire-FirstCall/ -- Protein Design Labs, Inc. (PDL) (Nasdaq: PDLI - news) today said that it has initiated a Phase II clinical trial to evaluate its humanized SMART Anti-Gamma Interferon Antibody in Crohn's disease, a form of inflammatory bowel disease.
The Phase II clinical trial is a randomized, double blind, placebo-controlled trial to be conducted at up to 25 sites in North America and Europe. The primary objective of the study is to evaluate the safety and efficacy of the antibody for induction of a clinical response, defined as a decrease of at least 100 points in the patient's Crohn's Disease Activity Index (CDAI) score at day 29 of the study. Patients eligible for the trial must have had Crohn's disease for at least six months and have received prior treatment for the disease, with a CDAI score between 250 and 450.
Up to 175 patients will be randomized into one of four treatment groups or placebo. Patients will receive an initial intravenous loading dose of 1.0 mg/kg, 4.0 mg/kg or placebo. Beginning on study day 29, patients who received active drug will be randomized to receive one subcutaneous dose of 0.1 mg/kg or 1.0 mg/kg every four weeks for a total of three additional doses. Patients who received placebo will continue to receive placebo.
"We are pleased to advance SMART Anti-Gamma Interferon Antibody to the next stage of development," said Douglas O. Ebersole, Chief Executive Officer (Acting), PDL. "Today's announcement is an indication that PDL is continuing to advance its clinical programs efficiently and on schedule."
In November 2001, PDL reported preliminary data on 29 patients from Stage A of a Phase I/II study of SMART Anti-Gamma Interferon Antibody in Crohn's disease. Although the primary purpose of the study is to gather safety information, the preliminary results indicated patient responses at all three dose levels of SMART Anti-Gamma Interferon Antibody that were administered, and a response rate that exceeded 70% in the two higher-level dose regimens.
The Phase I/II trial was designed as a two-stage study. In Stage A of the double blind, randomized, placebo-controlled multicenter trial, patients were randomized to receive a single escalating dose of SMART Anti-Gamma Interferon Antibody or a single dose of placebo. Patients who received active drug and had a predefined reduction of the CDAI after four weeks were entered into Stage B, in which they received either three additional doses of the drug or placebo at four-week intervals.
PDL currently expects to report additional data from the Phase I/II trial, including data from the multiple-dose Stage B, in an oral presentation at Digestive Disease Week in San Francisco on May 21.
SMART Anti-Gamma Interferon also is being evaluated in a Phase I/II study in psoriasis.
Crohn's disease is an inflammation primarily of the small intestine that also can affect the esophagus, stomach, colon and other organs and tissue. Symptoms include abdominal pain, diarrhea, fever and weight loss. Recurrence is common and unpredictable, and can severely affect quality of life. Current drug treatments for active disease include anti-inflammatory and immunosuppressive agents and antibiotics. The response to these medications frequently decreases over time and the disease often becomes chronic, leading in many cases to repeated surgical intervention. The prevalence of the disease in the United States is estimated at approximately 100 cases per 100,000 individuals.
The cause of Crohn's disease is unknown, but it appears at least in part to be an autoimmune disease. Gamma interferon is a cytokine that functions in the regulation of the immune system and may lead to a type of immune response typical of autoimmune diseases. Increased production of gamma interferon has been demonstrated in inflammatory cells in the intestine of patients with Crohn's disease, and antibodies against gamma interferon have been demonstrated to be effective in an animal model of Crohn's disease.
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