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

NCT ID: NCT02937285

Last Updated: 2023-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-06
• Study Completion Date: 2020-05-28

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard care

Interferon alone

Group Type: ACTIVE_COMPARATOR

Interferon beta 1a

Intervention Type: DRUG

Subcutaneous injection of 44µg 3 times a week

Experimental group

Mitoxantrone for 6 month followed by interferon

Group Type: EXPERIMENTAL

Interferon beta 1a

Intervention Type: DRUG

Subcutaneous injection of 44µg 3 times a week

Mitoxantrone

Intervention Type: DRUG

10 mg / m² monthly infusion for 6 months

Interventions

Interferon beta 1a

Subcutaneous injection of 44µg 3 times a week

Intervention Type: DRUG

Mitoxantrone

10 mg / m² monthly infusion for 6 months

Intervention Type: DRUG

Other Intervention Names

REBIF; ELSEP

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilles EDAN, MD, PhD

Role: STUDY_DIRECTOR

CHU Rennes

Locations

CHU Rennes

Rennes, , France

Countries

France

Other Identifiers

2004-001601-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

35RC10_8918

Identifier Type: -

Identifier Source: org_study_id