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

We describe the rationale and design of a double-blind, randomized multicen ter, dose-comparison study of interferon-beta-Ia (IFN-beta -Ia: AVONEX(R) i n the treatment of relapsing multiple sclerosis (MS). The study is expected to provide quantitative insights on the dose range for optimal clinical be nefits 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 wi thin the 3 years prior to enrolment Patients ore randomized to receive once -weekly intramuscular injections of IFN-beta -Ia 30 or 60 mcg for at least 3 years. The primary endpoint of the study is the effect of IFN-beta -Ia th erapy on the time to sustained progression of disability. For patients with a baseline EDSS less than or equal to 4.5, sustained progression of disabi lity is defined as a I point increase in EDSS from baseline, maintained for 6 months. For patients with baseline EDSS less than or equal to 5, sustain ed progression of disability is defined as reaching on EDSS greater than or equal to 6.0 maintained for 6 months. EDSS scores will be determined every 3 months. A series of prospectively defined secondary and tertiary efficac y endpoints will be examined Safety will be monitored throughout the study. Magnetic resonance imaging (MRI) with and without gadolinium-enhancement h as been Performed in at least 358 patients at baseline and repeated annuall y after enrolment In a subset of these patients, a frequent MRI study is al so being performed.