Multiple SclerosisPhase 3MITOX-REBIFNCT02937285
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
A Phase 3 study testing Interferon beta 1a and Mitoxantrone in people with Multiple Sclerosis, run by Rennes University Hospital at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Interferon beta 1a and Mitoxantrone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteFrance
- Study dates
- 6 Dec 2010to 28 May 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 24Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Interferon beta 1a, Mitoxantrone
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon beta 1aDrug
Also called REBIF
Subcutaneous injection of 44µg 3 times a week
MitoxantroneDrug
Also called ELSEP
10 mg / m² monthly infusion for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Standard care | Active comparator | Interferon alone Receives: Drug: Interferon beta 1a |
| Experimental group | Experimental | Mitoxantrone for 6 month followed by interferon Receives: Drug: Interferon beta 1a; Drug: Mitoxantrone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Four years after inclusion
Secondary outcomes (18)
Time to first relapse
Measured: From date of randomization until the date of first documented progression, assessed up to 4 years
Frequency of relapses in 2 years
Measured: Within two years following randomization
Frequency of relapses in 4 years
Measured: Within four years following randomization
Changes in the level of disability in 2 years
EDSS score
Measured: Two years following randomization
Changes in the level of disability in 4 years
EDSS score
Measured: Four years following randomization
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.
Measured: Four years following randomization
Disease activity on MRI at 6 months
To compare in the two arms, the rate of patients without radiological (MRI) sign of disease activity
Measured: 6 months following randomization
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
Measured: 12 months following randomization
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
Measured: 24 months following randomization
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
Measured: 48 months following randomization
Number of visible lesions on MRI at 6 months
To compare in the two arms, the number of lesions taking contrast
Measured: 6 months following randomization
Number of visible lesions on MRI at 12 months
To compare in the two arms, the number of lesions taking contrast
Measured: 12 months following randomization
Number of visible lesions on MRI at 24 months
To compare in the two arms, the number of lesions taking contrast
Measured: 24 months following randomization
Number of visible lesions on MRI at 48 months
To compare in the two arms, the number of lesions taking contrast
Measured: 48 months following randomization
Lesion load on evaluated T2 weighted MRI at 12 months
Measured: 12 months following randomization
Lesion load on evaluated T2 weighted MRI at 24 months
Measured: 24 months following randomization
Lesion load on evaluated T2 weighted MRI at 48 months
Measured: 48 months following randomization
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.
Measured: 24 and 48 months following randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2016 (estimated)
- Study start6 Dec 2010
- Primary completion28 May 2020
- Study completion28 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gilles EDAN, MD, PhD, Study director, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02937285
- Sponsor's protocol ID
- 35RC10_8918
- Other IDs
- 2004-001601-10, 2004
- Acronym
- MITOX-REBIF
- Status last verified
- Mar 2023
- First submitted
- 9 Sep 2016
- Last updated
- 29 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02937285
- Acronym / sponsor ID
- MITOX-REBIF / 35RC10_8918
- Conditions
- Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Study start
- 6 Dec 2010 (actual)
- Primary completion
- 28 May 2020 (actual)
- Study completion
- 28 May 2020 (actual)
- First posted
- 18 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard care | Active comparator | Drug: Interferon beta 1aInterferon alone |
| Experimental group | Experimental | Drug: Interferon beta 1a, Drug: MitoxantroneMitoxantrone for 6 month followed by interferon |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interferon beta 1aAlso: REBIFSubcutaneous injection of 44µg 3 times a week | Drug | Experimental group, Standard care |
| MitoxantroneAlso: ELSEP10 mg / m² monthly infusion for 6 months | Drug | Experimental group |
Primary outcome
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.
18 secondary outcomes
Time to first relapse
Time frame: From date of randomization until the date of first documented progression, assessed up to 4 years
Frequency of relapses in 2 years
Time frame: Within two years following randomization
Frequency of relapses in 4 years
Time frame: Within four years following randomization
Changes in the level of disability in 2 years
Time frame: Two years following randomization
Changes in the level of disability in 4 years
Time frame: Four years following randomization
Patients in progression
Time frame: Four years following randomization
Disease activity on MRI at 6 months
Time frame: 6 months following randomization
Patients without disease activity on MRI at 12 months
Time frame: 12 months following randomization
Patients without disease activity on MRI at 24 months
Time frame: 24 months following randomization
Patients without disease activity on MRI at 48 months
Time frame: 48 months following randomization
Number of visible lesions on MRI at 6 months
Time frame: 6 months following randomization
Number of visible lesions on MRI at 12 months
Time frame: 12 months following randomization
Number of visible lesions on MRI at 24 months
Time frame: 24 months following randomization
Number of visible lesions on MRI at 48 months
Time frame: 48 months following randomization
Lesion load on evaluated T2 weighted MRI at 12 months
Time frame: 12 months following randomization
Lesion load on evaluated T2 weighted MRI at 24 months
Time frame: 24 months following randomization
Lesion load on evaluated T2 weighted MRI at 48 months
Time frame: 48 months following randomization
Brain atrophy
Time frame: 24 and 48 months following randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2023.
- Individual participant dataSharing planned: No
Related trials for Multiple Sclerosis
Recruiting
Dry Needling in Multiple Sclerosis
Multiple Sclerosis
RecruitingObservational study
Study of the Disease Process of Lymphangioleiomyomatosis
Lung Disease, Pneumothorax
RecruitingPhase 2
A Study to Evaluate Pharmacokinetics (PK) and Safety of Subcutaneous (SC) Ublituximab Administered at Various Injection Sites and Relative Bioavailability Via Autoinjector (AI) Versus Syringe Subcutaneously in Participants With Multiple Sclerosis (MS)
Multiple Sclerosis
Active, not recruitingPhase 2
Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Tuberous Sclerosis Complex, Epilepsy
RecruitingObservational study
Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
Progressive Multifocal Leukoencephalopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilles EDAN, MD, PhD study director
Rennes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Interferon beta 1a and Mitoxantrone in people with Multiple Sclerosis, run by Rennes University Hospital at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment efficacy (time frame: Four years after inclusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2023.