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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Treatment efficacy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •Abnormalities of Complete Blood Count.
- •History of hematologic malignancy.
- •Hepatic impairment.
- •Vaccination against yellow fever.
- •Vaccination with an attenuated vaccine assets.
- •Treatment with phenytoin or fosphenytoin.
- •Hypersensitivity to interferon beta-1a natural or recombinant or any of the excipients.
- •Current severe depression and / or suicidal thoughts.
- •Uncontrolled epilepsy.
- •History of addiction.
- •A history of hypersensitivity to gadolinium, history of severe renal impairment
- •Inability to undergo MRI (claustrophobia, tics, involuntary movements, tremor, etc.).
- •Participation in another trial in the preceding 6 months or during the study.
- •Minors, protected adults and persons deprived of their liberty.
研究组 & 干预措施
Standard care
Interferon alone
干预措施: Interferon beta 1a (Drug)
Experimental group
Mitoxantrone for 6 month followed by interferon
干预措施: Interferon beta 1a (Drug)
Experimental group
Mitoxantrone for 6 month followed by interferon
干预措施: Mitoxantrone (Drug)
结局指标
主要结局
Treatment efficacy
时间窗: 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.
次要结局
- 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)