Treatment safe, provides basis for phase II study
A phase I study of costimulatory blocking agent CTLA4Ig shows that the treatment appears safe for use in multiple sclerosis (MS) and that it can induce favorable immunologic changes. Results from the ITN-led study were published in the September 16, 2008 issue of the peer-reviewed journal Neurology.
A total of 20 relapsing-remitting MS subjects were enrolled in the phase 1 dose escalation study of intravenous CTLA4Ig infusions, conducted at Brigham & Women's Hospital under the direction of principal investigator Samia J. Khoury, MD. Subjects received doses ranging from 2 mg/kg up to 35 mg/kg as a single infusion, and four subjects received a total 40 mg/kg split over four infusions.
No serious adverse events occured during the study. Sixty-three adverse events (AE) were noted, of which, 59 were mild and 4 moderate. Four AE were deemed possibly related to the study drug, with 4 unrelated and 55 unlikely. The most common AE reported were lymphadenopathy (40%), urinary tract infection (15%), headache (15%), blurred vision (10%), upper respiratory tract infection (10%), worsening MS (10%) and weakness (10%).
No specific changes in clinical parameters were noted over the short, three-month observation period of the study. Favorable changes in immune responses in subjects receiving CTLA4Ig were detected, however. A decrease in myelin basic protein-specific cells and frequency of interferon-gamma producing cells (Th0) was detected following CTLA4Ig infusion. The ratio of Th2 vs Th1 cells was also observed following infusion of the study drug. These measures, although not conclusive, are all positive indicators of a shift in the immune system away from the inflammatory response against myelin that is characteristic of MS.
"We're pleased with the apparent safety and encouraging immunologic results of CTLA4Ig in MS subjects," said Dr. Khoury. "We anticipate beginning a follow-up phase II study in a larger patient population in 2009."
In addition to Dr. Khory, the first author on the manuscript was Vissia Vigliettaof Brigham and Women's Hospital.
The study was sponsored by the National Institute of Allergy and Infectious Disease and conducted by the Immune Tolerance Network.