A Phase IV Study of Rebif ® 44mcg Administered Three Times Per Week by Subcutaneous Injection Compared With no Treatment in the Therapy of Relapsing Multiple Sclerosis After Mitoxantrone
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Interferon beta-1a (Rebif)
Intervention description: The dosage of IFN-beta-1a , following initial dose titration, was 44 mcg injected subcutaneously (s.c.) tiw. An auto-injector device, Rebiject, was available as an optional aid for the administration of IFN-beta-1a . IFN-beta-1a was administered, if possible, at the same time (preferably in the late afternoon or evening) on the same three days at least 48 hours apart each week.
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Multiple sclerosis; Expanded Disability Status Scale; Multiple Sclerosis, Relapsing-Remitting; Rebif; Beta-1, interferon

Summary:

      In the course of therapy escalation, the multiple sclerosis (MS) subjects with high activity
      of disease receive mainly mitoxantrone. The duration of therapy is limited because of a
      cumulative dose for life (140 mg/m^2 body surface area). In practice lower doses of
      mitoxantrone (60-120 mg/m^2 body surface area) are being used. The specific reason for this
      limited total dose are potential cardiotoxic side effects of mitoxantrone. Once this
      cumulative dose of mitoxantrone is reached and the subject becomes stable, there is the
      question for subsequent therapy. A possibility at this time, is the so-called
      "de-escalation", therefore reducing the subject back to immunomodulating basic treatment.

      The target of this open-label, randomised, multicentric, comparative, parallel-group study
      was to inquire systematically into the use and course of basic therapy with Rebif 44 mcg
      thrice weekly (tiw) for a larger number of subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject who had given written informed consent.

          -  Subjects with definite RRMS or SPMS with relapses

          -  Subjects with EDSS 1-6

          -  Subjects aged between 18-60 years

          -  Subjects who were escalated to mitoxantrone due to high relapse activity or MRI
             activity (not due to EDSS progression exclusively)

          -  Subjects who may not have a confirmed 1 point EDSS progression (0.5 points for EDSS
             >5.5) within the last 9 months

          -  Subjects free of relapses over the last 6 months

          -  Subjects with last mitoxantrone treatment between 1 and 6 months prior to screening

          -  Subjects treated with mitoxantrone for minimum 9 months and maximum 36 months, total
             cumulative dose being 40-120 mg/m^2

          -  Female subjects who must be neither pregnant nor breast-feeding and must lack
             childbearing potential, as defined by either:

               1. Being post-menopausal or surgically sterile,or

               2. Using a hormonal contraceptive, intra-uterine device, diaphragm with spermicide
                  or condom with spermicide for the duration of the study. Confirmation that the
                  subject is not pregnant must be established by a negative serum or urinary human
                  chorionic gonadotropin (hCG) test within 7 days prior to start of study
                  treatment. A pregnancy test is not required if the subject is post menopausal or
                  surgically sterile.

        Exclusion Criteria:

          -  Subject who has received any cytokine or anti-cytokine therapy within the 3 months
             prior to study Day 1

          -  Subject who has been escalated to mitoxantrone due to EDSS progression

          -  Subject with an ongoing MS relapse

          -  Subject with PPMS

          -  Subject with SPMS without superimposed relapses

          -  Subject who has received immunomodulatory treatment other than IFN-beta or glatiramer
             acetate before mitoxantrone

          -  Subject who has previously received total lymphoid irradiation

          -  Subject who has received oral or systemic corticosteroids or adrenocorticotrophic
             hormone ACTH within 30 days of study Day 1

          -  Subject who has received intravenous immunoglobulins or underwent plasmapheresis
             within the 6 months prior to study day 1

          -  Subject who has received immunomodulatory or immunosuppressive therapy (including but
             not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide,
             teriflunomide, natalizumab, laquinimod, Campath) within the 12 months prior to study
             Day 1

          -  Subject who requires chronic or monthly pulse corticosteroids during the study

          -  Subject who has received any investigational drug or experimental procedure within 12
             month of study Day 1

          -  Subject who has inadequate liver function, defined by a total bilirubin, aspartate
             aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase
             greater than 2.5 times the upper limit of the normal values.

          -  Subject who has inadequate bone marrow reserve, defined as a white blood cell count
             less than 0.5 times the lower limit of normal

          -  Subject who suffers from current autoimmune disease

          -  Subject with known allergy to IFN or the excipient(s)

          -  Subject who suffers from major medical or psychiatric illness that in the opinion of
             the investigator creates undue risk to the subject or could affect compliance with the
             study protocol

          -  Subject treated with drugs other than IFN-beta or glatiramer acetate within 2 years
             before mitoxantrone

          -  Subject with known cardiac or other systemic diseases

          -  Subjects who are pregnant.