Clinical trial NCT02937285: National Multicenter, Controlled, Single-blind Study With Two Parallel Groups Evaluating the Safety and Efficacy of Sequential Treatment With Mitoxantrone and Interferon Versus Interferon Alone in Patients With Strong Risk of Progression in the Initial Phase of Multiple Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2016-10-18
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.
* 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.

Primary outcomes:
measure: Treatment efficacy
timeFrame: Four years after inclusion
Secondary outcomes:
measure: Time to first relapse
timeFrame: From date of randomization until the date of first documented progression, assessed up to 4 years
measure: Frequency of relapses in 2 years
timeFrame: Within two years following randomization
measure: Frequency of relapses in 4 years
timeFrame: Within four years following randomization
measure: Changes in the level of disability in 2 years
timeFrame: Two years following randomization
measure: Changes in the level of disability in 4 years
timeFrame: Four years following randomization
measure: Patients in progression
timeFrame: Four years following randomization
measure: Disease activity on MRI at 6 months
timeFrame: 6 months following randomization
measure: Patients without disease activity on MRI at 12 months
timeFrame: 12 months following randomization
measure: Patients without disease activity on MRI at 24 months
timeFrame: 24 months following randomization
measure: Patients without disease activity on MRI at 48 months
timeFrame: 48 months following randomization
measure: Number of visible lesions on MRI at 6 months
timeFrame: 6 months following randomization
measure: Number of visible lesions on MRI at 12 months
timeFrame: 12 months following randomization
measure: Number of visible lesions on MRI at 24 months
timeFrame: 24 months following randomization
measure: Number of visible lesions on MRI at 48 months
timeFrame: 48 months following randomization
measure: Lesion load on evaluated T2 weighted MRI at 12 months
timeFrame: 12 months following randomization
measure: Lesion load on evaluated T2 weighted MRI at 24 months
timeFrame: 24 months following randomization
measure: Lesion load on evaluated T2 weighted MRI at 48 months
timeFrame: 48 months following randomization
measure: Brain atrophy
timeFrame: 24 and 48 months following randomization
Other outcomes:
Locations:
city: Rennes
country: France
facility: CHU Rennes
Study officials:
affiliation: CHU Rennes
name: Gilles EDAN, MD, PhD
role: STUDY_DIRECTOR
References: