Relapsing-Remitting Multiple Sclerosis
Conditions
Keywords
recovery of efficacy, MxA protein, neutralizing antibodies, Multiple sclerosis
Brief summary
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
Detailed description
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.
Interventions
dosage and frequency as per Biogen Idec protocol
DRUGmethylprednisolone
dosage and frequency as per Biogen Idec protocol
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| return of bioavailability of AVONEX (interferon-beta-1a) as measured by induction of MxA mRNA | screening and every 3 months from month 6 to month 27 |
Secondary
| Measure | Time frame |
|---|---|
| proportion of patients becoming neutralizing antibody positive after treatment with AVONEX | at baseline and every three months |
| proportion of patents relapse free | months 6, 12, 18 and 24 |
| Proportion of patients becoming neutralizing antibody negative | screening and every 3 months from month 3 to month 27 |
| proportion of patients with an increase in EDSS of 1 point | screening, 3, 9, 15, 21, and 27 months |
| Brain atrophy and cumulative number of enlarging T2 lesions on MRI | months 0, 12, and 27 |
| total relapses | 27 months |
Countries
Australia, New Zealand
Outcome results
None listed