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

NCT02937285 | Completed Phase 3

• 2 other identifiers: 35RC10_89182004-001601-10
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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.

  Four years after inclusion

Secondary Outcomes (18)

• 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

• 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

Study Arms (2)

Standard care

ACTIVE COMPARATOR

Interferon alone

Drug: Interferon beta 1a

Experimental group

EXPERIMENTAL

Mitoxantrone for 6 month followed by interferon

Drug: Interferon beta 1a; Drug: Mitoxantrone

Interventions

Interferon beta 1a DRUG

Subcutaneous injection of 44µg 3 times a week

Also known as: REBIF

Experimental group; Standard care

Mitoxantrone DRUG

10 mg / m² monthly infusion for 6 months

Also known as: ELSEP

Experimental group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients should have a MS according to the McDonald 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

CHU Rennes

Rennes, France

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Interferon beta-1a; Mitoxantrone

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds

Study Officials

• Gilles EDAN, MD, PhD

  CHU Rennes

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: October 18, 2016
• Study Start: December 6, 2010
• Primary Completion: May 28, 2020
• Study Completion: May 28, 2020
• Last Updated: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)