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
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous
      system (CNS) and is one of the most common causes of neurological disability in young adults.
      It is characterised by multi-focal recurrent attacks of neurological symptoms and signs with
      variable recovery. Eventually, the majority of subjects develop a progressive clinical
      course. The exact cause of MS is unknown, although an autoimmune process has been implicated.
      Genetic susceptibility plays a role in disease initiation but unidentified environmental
      factors may also be involved. Three clinical forms of MS are recognized: primary progressive
      multiple sclerosis (PPMS), secondary progressive multiple sclerosis (SPMS) and relapsing
      remitting multiple sclerosis (RRMS). Primary progressive subjects are characterised by slow
      and steady accumulation of neurological deficits from onset without superimposed attacks.
      Subjects with RRMS have exacerbations or relapses with subsequent variable recovery
      (remission). Secondary progressive multiple sclerosis is characterised by the steady
      accumulation of significant and persistent neurological deficit with or without superimposed
      relapses.

      Rebif [recombinant interferon (IFN) beta-1a] has been tested in a series of studies in MS
      subjects at doses ranging from 22 mcg to 132 mcg weekly with a dose frequency ranging from
      weekly (qw) to tiw. Rebif has been found to be well tolerated in all clinical pharmacology
      studies, even at high doses (up to 66 mcg/m^2). In later phase trials, Rebif has been tested
      across a broad range of doses, for varying duration, and in different stages of MS disease.
      Dose testing has ranged from 22 mcg to 132 mcg weekly with frequency of administration being
      qw to tiw.

      OBJECTIVES

      Primary objective:

        -  To asses if treatment with Rebif 44 mcg tiw compared with subjects not treated during 96
           weeks can maintain or prolong clinical or magnetic resonance imaging (MRI) stability
           after previous treatment with mitoxantrone

      Secondary objectives:

        -  To compare the mean number of T2 active lesions, defined as new or enlarging T2 lesions,
           per subject per scan during 96 weeks of treatment with Rebif 44 mcg three times per week
           with subjects not treated

        -  To assess the safety and efficacy of Rebif 44 mcg

      This was an open-label, randomised, multicentric, comparative, parallel-group study with a
      neurologist blinded to treatment for performing neurologic exams and a neuro-radiologist
      blinded to treatment for assessing central MRI scans. The study was divided into a screening
      phase (up to 28 days before the start of IFN-beta-1a treatment), a treatment phase of 96
      weeks as well as a follow-up period of 4 weeks for subjects with ongoing serious adverse
      events (SAEs) at week 96. The study consisted of 2 groups to compare the therapeutic effect
      of high dose, high frequency IFN beta-1a therapy (Rebif 44 mcg) to subjects who will not be
      treated with Rebif 44 mcg. Subjects of both groups were previously treated with mitoxantrone
      in the < 3 months prior to study inclusion. Subjects assigned to no treatment were switched
      to Rebif 44 mcg x 3 after reaching the primary endpoint or defined stopping criteria. The
      treatment period of this study begun with the completion of all baseline evaluations and the
      initiation of study drug treatment on Study Day 1 (baseline visit) and continues through
      until completion of the treatment period at the Week 96 visit.
    

Intervention name(s): Interferon beta-1a (Rebif)
Intervention type(s): Drug
Intervention description(s): 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.
Other intervention name(s): Rebif
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple sclerosis; Expanded Disability Status Scale; Multiple Sclerosis, Relapsing-Remitting; Rebif; Beta-1, interferon