Is IFN-beta Treatment in MS Useful After a Washout Period in Patients With Neutralizing Antibodies to Interferon Beta

Biogen20 enrolled

Overview

This study is to find out if Interferon-beta (IFN-beta) can recover its effectiveness after a washout period in patients with Multiple Sclerosis who have previously developed neutralizing antibodies to Interferon-Beta

This is an explorative multi-centre, open label, non-comparative trial investigating whether it is possible to recover IFN-beta efficacy in breakthrough relapsing-remitting multiple sclerosis patients with high titres of neutralizing IFN-beta antibodies. Prior to enrollment, treated MS subjects must have been on interferon-beta-1a or interferon-beta-1b for a minimum of 12 months and have reduced bioavailability as defined by the relative expression of MxA mRNA/GAPDH. Subjects will complete a washout period with concurrent methylprednisolone 500mg PO daily for 3 days every month until they become Neutralizing Antibody negative. Subjects will then be challenged with AVONEX 30mcg IM weekly. Bioavailability will be measured every three months to determine return of biological activity. Clinical and MRI parameters, safety and tolerability will be compared to baseline to determine efficacy.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Relapsing-Remitting Multiple Sclerosis

Interventions

Interferon-beta-1aDRUG

dosage and frequency as per Biogen Idec protocol

methylprednisoloneDRUG

dosage and frequency as per Biogen Idec protocol

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Must have been receiving interferon-beta-1a or interferon-beta-1b for a minimum of 12 consecutive months prior to enrollment * Relapsing-Remitting Multiple Sclerosis according to Poser or McDonald criteria * EDSS score of 6 or less * NAB titre \>or equal to 20 via CPE assay or \>or equal to 100 via MxA Protein assay measured at least 24 hours after last interferon-beta injection on two consecutive tests at least 3 months apart * Reduced bioavailability (relative expression of MxA mRNA/GAPDH Exclusion Criteria: * History of severe allergic or anaphylactic reaction to human albumin, to any interferon, Methylprednisolone or to any other component of study drugs * Clinically significant systemic illness * History of poorly controlled hypertension, diabetes, or osteoporosis * History of uncontrolled seizures within 3 months of enrollment * History of Depression or suicidal ideation within 3 months of enrollment * Serious local infection (abscess or cellulitis) or systemic infection within 8 weeks of study * abnormal screening blood tests

Locations (2)

Coordinating Research Site

NSW, Australia

Research Site

Hamilton, New Zealand

Outcomes

Primary Outcomes

return of bioavailability of AVONEX (interferon-beta-1a) as measured by induction of MxA mRNA

Time frame: screening and every 3 months from month 6 to month 27

Secondary Outcomes

Proportion of patients becoming neutralizing antibody negative

Time frame: screening and every 3 months from month 3 to month 27

proportion of patients becoming neutralizing antibody positive after treatment with AVONEX

Time frame: at baseline and every three months

proportion of patents relapse free

Time frame: months 6, 12, 18 and 24

total relapses

Time frame: 27 months

proportion of patients with an increase in EDSS of 1 point

Time frame: screening, 3, 9, 15, 21, and 27 months

Brain atrophy and cumulative number of enlarging T2 lesions on MRI

Time frame: months 0, 12, and 27

Data from ClinicalTrials.gov

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