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

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— RENeu  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00493116
• Other study ID #: AUS-8001
• Status: Completed
• Phase: Phase 4
• First received: June 25, 2007
• Last updated: September 12, 2013
• Start date: October 2003
• Est. completion date: December 2009

Study information

• Verified date: July 2011
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Interferon-beta-1a
dosage and frequency as per Biogen Idec protocol
• methylprednisolone
dosage and frequency as per Biogen Idec protocol

Locations

Country	Name	City	State
Australia	Coordinating Research Site	NSW
New Zealand	Research Site	Hamilton

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Proportion of patients becoming neutralizing antibody negative		screening and every 3 months from month 3 to month 27	No
Secondary	proportion of patients becoming neutralizing antibody positive after treatment with AVONEX		at baseline and every three months	No
Secondary	proportion of patents relapse free		months 6, 12, 18 and 24	No
Secondary	total relapses		27 months	No
Secondary	proportion of patients with an increase in EDSS of 1 point		screening, 3, 9, 15, 21, and 27 months	No
Secondary	Brain atrophy and cumulative number of enlarging T2 lesions on MRI		months 0, 12, and 27	No