Double-blind randomized multicenter dose-comparison study of interferon-β-1a (AVONEX): rationale,design and baseline data

Abstract

We describe the rationale and design of a double-blind, randomized, multicenter, dose-comparison study of interferon-beta-1a (IFN-β-1a; Avonex®), in the treatment of relapsing multiple sclerosis (MS). The study is expected to provide quantitative insights on the dose range for optimal clinical benefits in MS. The study involves 802 patients in 10 European countries who have EDSS scores 2.0-5.5, and who have experienced at least two relapses within the 3 years prior to enrolment. Patients are randomized to receive once-weekly intramuscular injections of IFN-β-1a 30 or 60 mcg for at least 3 years. The primary endpoint of the study is the effect of IFN-β-1a therapy on the time to sustained progression of disability. For patients with a baseline EDSS ≤44.5, sustained progression of disability is defined as a 1 point increase in EDSS from baseline, maintained for 6 months. For patients with baseline EDSS ≥55, sustained progression of disability is defined as reaching an EDSS ≥56.0, maintained for 6 months. EDSS scores will be determined every 3 months. A series of prospectively defined secondary and tertiary efficacy endpoints will be examined. Safety will be monitored throughout the study. Magnetic resonance imaging (MRI) with and without gadolinium-enhancement has been performed in at least 358 patients at baseline and repeated annually after enrolment. In a subset of these patients, a frequent MRI study is also being performed.