National Multicenter, Controlled, Single-blind Study With Two Parallel Groups Evaluating the Safety and Efficacy of Sequential Treatment With Mitoxantrone and Interferon Beta-1a (REBIF 44mg 3 Times / Week) Versus Interferon Alone in Patients With Strong Risk of Progression in the Initial Phase of Multiple Sclerosis
Overview
- Phase
- Phase 3
- Intervention
- Interferon beta 1a
- Conditions
- Multiple Sclerosis
- Sponsor
- Rennes University Hospital
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Treatment efficacy
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The relative effectiveness of current treatments and their different mechanisms of action yield to consider more and more that the multiple sclerosis (MS) therapeutic approach must use multiple molecules, both combined and sequential.
In this sense, one can assume that the combination of two molecules with different but complementary mechanisms of action, can delay progression of the disease. Mitoxantrone has a powerful action, immediate and total, whereas interferon a selective action, immunomodulatory and delayed.
Detailed Description
This study is based on the hypothesis that there is a synergistic effect of both increasing the dose of interferon and also the use of mitoxantrone, allowing to further reduce the conversion rate MS. Because mitoxantrone decreases the rate of relapses 2 times more than interferon beta, a (at least) 2 times higher benefit on the disease activity is expected with interferon mitoxantrone combination than with interferon alone.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients should have a MS according to the McDonald criteria:
- •One relapse with time dissemination shown by an MRI performed less than 2 months before inclusion, with at least one of these criteria:
- •multifocal presentation
- •relapse determining a severe disability (EDSS greater than 3.5)
- •at least 2 lesions taking contrast on MRI
- •at least 9 T2 lesions with contrast enhancement.
- •Patients must be 18 to 50 years.
- •The duration of disease progression should be less than one year.
- •Women of childbearing age must have an effective contraception.
- •Patients have to be able to give their own informed consent before inclusion in the study.
Exclusion Criteria
- •presence of another disease that could explain the symptoms / signs of the patient.
- •Any other condition / disability that may interfere with the clinical state.
- •Prior treatment with immunosuppressive (mitoxantrone, azathioprine, cyclophosphamide) or immunomodulator.
- •Treatment with corticosteroids in the previous 2 weeks, regardless of the dose.
- •Corticosteroids for over a month.
- •Pregnancy and lactation.
- •Patient whose antecedents may contra-indicate the use of immunosuppressive therapy.
- •Hypersensitivity to mitoxantrone or one of the excipients.
- •Clinical cardiac disease with reduced ejection fraction of the left ventricle.
- •Patient suffering from myelodysplasia.
Arms & Interventions
Standard care
Interferon alone
Intervention: Interferon beta 1a
Experimental group
Mitoxantrone for 6 month followed by interferon
Intervention: Interferon beta 1a
Experimental group
Mitoxantrone for 6 month followed by interferon
Intervention: Mitoxantrone
Outcomes
Primary Outcomes
Treatment efficacy
Time Frame: Four years after inclusion
Efficacy is judged based on * the absence of relapse within the 2 first years; AND * a disease progression as determined by an increase in the Expanded Disability Status Scale (EDSS) not greater than 1 during the 4 years treatment.
Secondary Outcomes
- Time to first relapse(From date of randomization until the date of first documented progression, assessed up to 4 years)
- Frequency of relapses in 2 years(Within two years following randomization)
- Frequency of relapses in 4 years(Within four years following randomization)
- Patients in progression(Four years following randomization)
- Disease activity on MRI at 6 months(6 months following randomization)
- Changes in the level of disability in 2 years(Two years following randomization)
- Changes in the level of disability in 4 years(Four years following randomization)
- Brain atrophy(24 and 48 months following randomization)
- Patients without disease activity on MRI at 12 months(12 months following randomization)
- Patients without disease activity on MRI at 48 months(48 months following randomization)
- Number of visible lesions on MRI at 6 months(6 months following randomization)
- Number of visible lesions on MRI at 12 months(12 months following randomization)
- Patients without disease activity on MRI at 24 months(24 months following randomization)
- Number of visible lesions on MRI at 24 months(24 months following randomization)
- Number of visible lesions on MRI at 48 months(48 months following randomization)
- Lesion load on evaluated T2 weighted MRI at 12 months(12 months following randomization)
- Lesion load on evaluated T2 weighted MRI at 24 months(24 months following randomization)
- Lesion load on evaluated T2 weighted MRI at 48 months(48 months following randomization)