search
Back to results

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 (MITOX-REBIF)

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Interferon beta 1a
Mitoxantrone
Sponsored by
Rennes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • CHU Rennes

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard care

Experimental group

Arm Description

Interferon alone

Mitoxantrone for 6 month followed by interferon

Outcomes

Primary Outcome Measures

Treatment efficacy
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 Outcome Measures

Time to first relapse
Frequency of relapses in 2 years
Frequency of relapses in 4 years
Changes in the level of disability in 2 years
EDSS score
Changes in the level of disability in 4 years
EDSS score
Patients in progression
Rate of patients who progressed to a clinically definite MS (according to the criteria of Mc Donald) in the subgroup of patients who had only one clinical event.
Disease activity on MRI at 6 months
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Patients without disease activity on MRI at 12 months
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Patients without disease activity on MRI at 24 months
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Patients without disease activity on MRI at 48 months
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Number of visible lesions on MRI at 6 months
To compare in the two arms, the number of lesions taking contrast
Number of visible lesions on MRI at 12 months
To compare in the two arms, the number of lesions taking contrast
Number of visible lesions on MRI at 24 months
To compare in the two arms, the number of lesions taking contrast
Number of visible lesions on MRI at 48 months
To compare in the two arms, the number of lesions taking contrast
Lesion load on evaluated T2 weighted MRI at 12 months
Lesion load on evaluated T2 weighted MRI at 24 months
Lesion load on evaluated T2 weighted MRI at 48 months
Brain atrophy
To assess the presence and progression of brain atrophy, changes in the total brain volume after 24 and 48 months will be automatically measured from MR images with dedicated software and expressed as percent change, from a standardized estimation of cerebral volume.

Full Information

First Posted
September 9, 2016
Last Updated
March 28, 2023
Sponsor
Rennes University Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT02937285
Brief Title
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
Acronym
MITOX-REBIF
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
December 6, 2010 (Actual)
Primary Completion Date
May 28, 2020 (Actual)
Study Completion Date
May 28, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rennes University Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard care
Arm Type
Active Comparator
Arm Description
Interferon alone
Arm Title
Experimental group
Arm Type
Experimental
Arm Description
Mitoxantrone for 6 month followed by interferon
Intervention Type
Drug
Intervention Name(s)
Interferon beta 1a
Other Intervention Name(s)
REBIF
Intervention Description
Subcutaneous injection of 44µg 3 times a week
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Other Intervention Name(s)
ELSEP
Intervention Description
10 mg / m² monthly infusion for 6 months
Primary Outcome Measure Information:
Title
Treatment efficacy
Description
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.
Time Frame
Four years after inclusion
Secondary Outcome Measure Information:
Title
Time to first relapse
Time Frame
From date of randomization until the date of first documented progression, assessed up to 4 years
Title
Frequency of relapses in 2 years
Time Frame
Within two years following randomization
Title
Frequency of relapses in 4 years
Time Frame
Within four years following randomization
Title
Changes in the level of disability in 2 years
Description
EDSS score
Time Frame
Two years following randomization
Title
Changes in the level of disability in 4 years
Description
EDSS score
Time Frame
Four years following randomization
Title
Patients in progression
Description
Rate of patients who progressed to a clinically definite MS (according to the criteria of Mc Donald) in the subgroup of patients who had only one clinical event.
Time Frame
Four years following randomization
Title
Disease activity on MRI at 6 months
Description
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Time Frame
6 months following randomization
Title
Patients without disease activity on MRI at 12 months
Description
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Time Frame
12 months following randomization
Title
Patients without disease activity on MRI at 24 months
Description
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Time Frame
24 months following randomization
Title
Patients without disease activity on MRI at 48 months
Description
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Time Frame
48 months following randomization
Title
Number of visible lesions on MRI at 6 months
Description
To compare in the two arms, the number of lesions taking contrast
Time Frame
6 months following randomization
Title
Number of visible lesions on MRI at 12 months
Description
To compare in the two arms, the number of lesions taking contrast
Time Frame
12 months following randomization
Title
Number of visible lesions on MRI at 24 months
Description
To compare in the two arms, the number of lesions taking contrast
Time Frame
24 months following randomization
Title
Number of visible lesions on MRI at 48 months
Description
To compare in the two arms, the number of lesions taking contrast
Time Frame
48 months following randomization
Title
Lesion load on evaluated T2 weighted MRI at 12 months
Time Frame
12 months following randomization
Title
Lesion load on evaluated T2 weighted MRI at 24 months
Time Frame
24 months following randomization
Title
Lesion load on evaluated T2 weighted MRI at 48 months
Time Frame
48 months following randomization
Title
Brain atrophy
Description
To assess the presence and progression of brain atrophy, changes in the total brain volume after 24 and 48 months will be automatically measured from MR images with dedicated software and expressed as percent change, from a standardized estimation of cerebral volume.
Time Frame
24 and 48 months following randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilles EDAN, MD, PhD
Organizational Affiliation
CHU Rennes
Official's Role
Study Director
Facility Information:
Facility Name
CHU Rennes
City
Rennes
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs