Naslov
A Novel Pegylated Interferon Beta-1a for Multiple Sclerosis: Safety, Pharmacology, and Biology

Autori
Hu, Xiao ; Miller, Larisa ; Richman, Sandra ; Hitchman, Stacy ; Glick, Gabrielle ; Liu, Shifang ; Zhu, Ying ; Crossman, Mary ; Nestorov, Ivan ; Gronke, Robert G. ; Baker, Darren P. ; Rogge, Mark ; Subramanyam, Meena ; Davar, Gudarz

Izvornik
Journal of clinical pharmacology (0091-2700) 52 (2011), 6; 798-808

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
multiple sclerosis ; pharmacokinetics and drug

Sažetak
This study clinically evaluated a novel PEGylated form of interferon beta-1a (PEG-IFN beta-1a), a potential first-line treatment for relapsing multiple sclerosis, in healthy volunteers. Two randomized, blinded phase I studies were conducted: a single-dose study (n = 60) comparing subcutaneous or intramuscular PEG-IFN beta-1a (63, 125, or 188 μg)with intramuscular unmodified IFN beta-1a 30 μg and a multiple-dose study (n = 69) comparing subcutaneous PEG-IFN beta-1a dosed once every 2 or 4 weeks with placebo.Assessments included pharmacokinetic and pharmacodynamic (serum neopterin and 2′, 5′-OAS) measures, exploratory immune assessments, safety, and tolerability. A dose- proportional increase in PEG-IFN beta-1a exposure was observed, with a 4-fold greater exposure at 63 μg (6 million international units [MIU]) of PEG-IFN beta-1a than with 30 μg (6 MIU) intramuscular unmodified IFN beta-1a. Increases in neopterin and 2′, 5′-OAS levels and changes in T helper cell pathway gene expression and lymphocyte subsets were greater and more sustained with PEG-IFN beta-1a than with unmodified IFN beta-1a. PEG-IFN beta-1a was well tolerated, with only transient reductions in absolute neutrophils and some lymphocytes. Flu-like symptoms were a commonly reported adverse event. These data support the continued clinical development of PEG-IFN beta-1a as a potentially effective treatment for patients with relapsing multiple sclerosis.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Farmacija, Biotehnologija

POVEZANOST RADA