A Multicentre, Open Label, Non-Comparative Trial Investigating the Recovering of INF-Beta Efficacy in Breakthrough Relapsing-Remitting Multiple Sclerosis Patients With Neutralizing Interferon-Beta Antibodies
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Biogen
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- Reduction in the proportion of patients being neutralizing antibody (NAb) positive (titre>20)
Study Overview
Brief Summary
This study is to find out if Interferon-beta can recover its effectiveness in patients with Multiple Sclerosis who have previously developed neutralizing antibodies to Interferon-Beta.
Detailed Description
This is a multi-center, open Label, non-comparative Phase IV trial. Eligible Patients will receive treatment with Interferon-beta-1a (AVONEX) 30mcg I.M. once weekly for up to 12 months.
In the wash-out period prior to commencing treatment with AVONEX, patients will receive treatment with intermittent Methylprednisolone 500 mg PO Daily for three consecutive days at monthly intervals.
The patients will be examined clinically and laboratory tests will be performed at screening (month -1) and after 3, 9, and 15 months.
Neutralizing antibody(NAb)titres and Binding antibody(BAb)titres as well as MxA protein levels will be evaluated at screening/baseline (month -1/0) and after 3, 6, 9, 12, and 15 months.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Relapsing remitting Multiple Sclerosis according to Poser criteria (CDMS or LDMS) or Multiple Sclerosis according to McDonald criteria
- •Disability equivalent to EDSS of 6.0 or less
- •Clinical activity defined as at least one relapse rate within the last 12 months
- •NAb titre >20 (measured at least 48 hours after last interferon-beta injection
- •has been treated with subcutaneously administered interferon-beta-1b or interferon-beta-1a (Rebif) for at least 24 hours before enrollment
Exclusion Criteria
- •Any condition that might give rise to similar symptoms as MS
- •Immunomodulatory therapy other than interferon-beta-1a or interferon-beta-1b or any immunosuppressive treatment six months prior to inclusion into the trial
- •Treatment with glucocorticoids or ACTH less than one month prior to inclusion into the trial
- •History of major depression
- •Alcohol or drug dependency
- •Cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV)
- •hypertension (BP > 180/110 mmHg)
- •Renal insufficiency defined as serum creatinine > 1.5 times the upper normal reference limit
- •Any systemic disease that can influence the patient's safety and compliance, or the evaluation of the disability
- •Gastro-intestinal ulcers, gastritis, or dyspepsia
- •Women who are pregnant, breast-feeding or have the possibility for pregnancy during the trial. To avoid pregnancy, women have to be postmenopausal, surgical sterile, sexually inactive or practice reliable contraceptives
Arms & Interventions
1
Intervention: Interferon-beta-1a (Drug)
1
Intervention: methylprednisolone (Drug)
Outcomes
Primary Outcomes
Reduction in the proportion of patients being neutralizing antibody (NAb) positive (titre>20)
Time Frame: Month -1 and after 3, 6, 9, 12, and 15 months
Secondary Outcomes
- Change in MxA protein values(Month -1 and after 3, 6, 9, 12, and 15 months)
- Change in binding antibody (Bab) tires(Month -1 and after 3, 6, 9, 12, and 15 months)
- Proportion of patients with NAb positive titre <5(Month -1 and after 3, 6, 9, 12, and 15 months)
- Change in annualised relapse rate(at 3, 6, 9, 12, and 15 months)
- The number of relapse-free patients(at 3, 6, 9, 12, and 15 months)