Optimizing IFN Beta - 1B Dose

University of Turin, Italy217 enrolled

Overview

BetaferonR is effective in reducing relapse rate and MRI T2-weighted lesion frequency in MS patients at the dose of 8 MIU on alternate days (THE IFNB MS Study Group, 1993). Relapse rate is reduced by 30-35% (The IFNB MS Study Group, 1993), MRI activity is decreased up to 100% in most cases (Stone et al 1995). In some patients, however, MRI activity still occurs or reappears during treatment (Stone et al 1995). MRI activity has been demonstrated to correlate with relapse occurrence (McFarland et al, 1992; Miller et al, 1996), and in some patients relapses still occur during IFN beta treatment. In other patients relapses may occur in association with the appearance, after 9-18 months of treatment, of anti-IFN beta NAB (The IFNB M S Study Group, 1995). This protocol hypothesizes that the dose of 12 MIU BetaferonR on alternate days has more pronounced MRI and clinical effects in MS patients than that of 8 MIU. MS patients who do not respond to 8 MIU may take advantage of a higher dose. We, therefore decided to assess MRI effects after increasing the Betaferon dose (12 MIU) in RRMS patients showing a residual MRI activity (at least one new Gd enhancing lesion) during six months of standard Betaferon dose treatment (8 MIU).

Comparing the frequency of new Gd enhancing lesions in a group of patients presenting a residual MRI activity during the last four months of the six month standard dose (8MIU) Betaferon treatment randomized to continue the standard dose or to increase the dose to 12 MIU Betaferon

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

217

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Written informed consent obtained. 2. Age between 18 and 50 years inclusive. 3. Male and female patients. 4. Clinically definite or laboratory supported definite RR MS (Poser et al, 1983) for not less than 2 year. 5. Two clinically documented relapses during the preceding 24 months. 6. No relapse or relapse related neurological deterioration for at least 30 days prior to entry in the study. 7. Patients EDSS score from 1 to 3.5 (probably to be extended to 5.5). 8. MRI activity. At least one enhancing lesion during the baseline MRI run-in study . 9. Women capable of having children must agree to use adequate con-traceptive methods (condoms with spermicides, IUCD, oral contraceptives or other adequate barrier contraception). 10. Caregivers agreement to assist the patient to comply with study requirements, if neces-sary (e.g. study drug administration, visits to center). Exclusion Criteria: 1. Any form of Multiple Sclerosis other than relapsing-remitting. 2. Any other disease which could better explain the patient's signs and symptoms. 3. Any other disabling condition, which could interfere with the clinical evaluation. 4. Pregnancy or lactation. 5. Medical psychiatric, or other conditions that compromise patient's ability to give informed consent, to comply with the trial protocol, or to complete the study. 6. Alcohol or drug abuse in the 90 days preceding screening visit. 7. Uncontrolled clinically significant heart diseases, i.e., cardiac arrhythmias, uncon-trolled angina pectoris, uncompensated congestive heart failure 8. Clinically significant liver, renal and bone marrow dysfunction as defined by the ran-ges of laboratory evaluations. The following ranges (see table 1) for key laboratory evaluations will be considered as adequate for inclusion:

Outcomes

Primary Outcomes

the effects of BetaferonR on MRI enhancing lesion frequency are detectable very early.Differently from clinical effects on relapse rate, BetaferonR administration results in an almost immediate reduction of enhancing lesion frequency at MRI.

Time frame: two year

Secondary Outcomes

Monitoring MRI effects (evaluating the number of total active lesions, areas of gadolinium-enhancing, T1 hypointense, and T2 hyperintense lesions)Monitoring clinical effects (relapse frequency and severity, changes in EDSS)

Time frame: two years