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

This study has been completed.
Sponsor:
Information provided by:
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00493116
First received: June 25, 2007
Last updated: September 12, 2013
Last verified: July 2011
  Purpose

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


Condition Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Drug: Interferon-beta-1a
Drug: methylprednisolone
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients becoming neutralizing antibody negative [ Time Frame: screening and every 3 months from month 3 to month 27 ] [ Designated as safety issue: No ]
  • proportion of patients becoming neutralizing antibody positive after treatment with AVONEX [ Time Frame: at baseline and every three months ] [ Designated as safety issue: No ]
  • proportion of patents relapse free [ Time Frame: months 6, 12, 18 and 24 ] [ Designated as safety issue: No ]
  • total relapses [ Time Frame: 27 months ] [ Designated as safety issue: No ]
  • proportion of patients with an increase in EDSS of 1 point [ Time Frame: screening, 3, 9, 15, 21, and 27 months ] [ Designated as safety issue: No ]
  • Brain atrophy and cumulative number of enlarging T2 lesions on MRI [ Time Frame: months 0, 12, and 27 ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: October 2003
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Interferon-beta-1a
dosage and frequency as per Biogen Idec protocol
Other Name: Avonex
Drug: methylprednisolone
dosage and frequency as per Biogen Idec protocol

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493116

Locations
Australia
Coordinating Research Site
NSW, Australia
New Zealand
Research Site
Hamilton, New Zealand
Sponsors and Collaborators
Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec MD, Biogen Idec
ClinicalTrials.gov Identifier: NCT00493116     History of Changes
Other Study ID Numbers: AUS-8001
Study First Received: June 25, 2007
Last Updated: September 12, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Biogen Idec:
recovery of efficacy
MxA protein
neutralizing antibodies
Multiple sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Antibodies
Interferon-beta
Interferon beta 1a
Interferons
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics

ClinicalTrials.gov processed this record on August 26, 2014