Clinical trial NCT00493116: Is IFN-beta Treatment in MS Useful After a Washout Period in Patients With Neutralizing Antibodies to Interferon Beta
Official title: A Multi-Centre, Open Label Study to Investigate the Recovery of IFN-beta Efficacy in Relapsing-Remitting Multiple Sclerosis Patients With Neutralising IFN-beta Antibodies and Reduced Bioavailability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: recovery of efficacy
MxA protein
neutralizing antibodies
Multiple sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2007-06-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: return of bioavailability of AVONEX (interferon-beta-1a) as measured by induction of MxA mRNA
timeFrame: screening and every 3 months from month 6 to month 27
Secondary outcomes:
measure: Proportion of patients becoming neutralizing antibody negative
timeFrame: screening and every 3 months from month 3 to month 27
measure: proportion of patients becoming neutralizing antibody positive after treatment with AVONEX
timeFrame: at baseline and every three months
measure: proportion of patents relapse free
timeFrame: months 6, 12, 18 and 24
measure: total relapses
timeFrame: 27 months
measure: proportion of patients with an increase in EDSS of 1 point
timeFrame: screening, 3, 9, 15, 21, and 27 months
measure: Brain atrophy and cumulative number of enlarging T2 lesions on MRI
timeFrame: months 0, 12, and 27
Other outcomes:
Locations:
city: NSW
country: Australia
facility: Coordinating Research Site
city: Hamilton
country: New Zealand
facility: Research Site
Study officials:
References: