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

Phase 4
Completed
Conditions
Relapsing-Remitting Multiple Sclerosis
Interventions
Registration Number
NCT00493116
Lead Sponsor
Biogen
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1Interferon-beta-1a-
1methylprednisolone-
Primary Outcome Measures
NameTimeMethod
return of bioavailability of AVONEX (interferon-beta-1a) as measured by induction of MxA mRNAscreening and every 3 months from month 6 to month 27
Secondary Outcome Measures
NameTimeMethod
proportion of patents relapse freemonths 6, 12, 18 and 24
total relapses27 months
proportion of patients with an increase in EDSS of 1 pointscreening, 3, 9, 15, 21, and 27 months
Brain atrophy and cumulative number of enlarging T2 lesions on MRImonths 0, 12, and 27
Proportion of patients becoming neutralizing antibody negativescreening and every 3 months from month 3 to month 27
proportion of patients becoming neutralizing antibody positive after treatment with AVONEXat baseline and every three months

Trial Locations

Locations (2)

Research Site

🇳🇿

Hamilton, New Zealand

Coordinating Research Site

🇦🇺

NSW, Australia

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