Natalizumab De-escalation With Interferon Beta-1b
Condition: Relapsing-remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Phase 4

Summary: 
      Multiple Sclerosis (MS) is the most common neurological disorder causing disability in young
      adults. The management of MS-patients requires treatment with disease-modifying agents,
      monoclonal antibodies such as natalizumab or immunosuppressants. Natalizumab showed good
      efficacy and is approved for treatment of relapsing MS with a number of restrictions due to
      safety issues. Cognitive data related to natalizumab treatment are still scarce.
      Interferon-beta-1b is approved for high-frequency, subcutaneous (sc) administration in the
      treatment of multiple sclerosis. It reduces the relapse rate, severity, hospitalisation and
      the disease activity as seen on MRI.

      This is a pilot study to explore the concept of de-escalating natalizumab treatment to
      interferon-beta-1b e.o.d compared to continuous treatment with natalizumab in patients with
      relapsing-remitting multiple sclerosis previously treated with natalizumab for 12 months. The
      study is designed as prospective, controlled, randomized, rater-blinded, parallel-group, two
      arm, mono-centric including patients of the Ticino Cohort. One arm will be treated with
      Interferon-beta 1b 250mcg given subcutaneously every other day, the other with Natalizumab
      300 mg given intravenously (i.v.), every four weeks. The treatment duration is 12 months, the
      follow-up period 12 months. The time to first on-study relapse will be compared between the
      to treatment arms (primary outcome). Other efficacy parameter include clinical and
      radiological parameters, patient reported outcome on quality of life and fatigue. Safety is
      assessed by reports of adverse events.
    

Detailed description: 
      At present, there is no cure for multiple sclerosis and the management of MS-patients
      requires treatment with disease-modifying agents such as interferon-beta or glatiramer
      acetate, monoclonal antibodies such as natalizumab or immunsuppressants such as mitoxantrone,
      azathioprine or methotrexate. Acute relapses are usually treated with corticosteroids.
      Natalizumab is a humanized monoclonal antibody directed against α4-integrin, a component of
      VLA-4 (very late antigen-4) present on leukocytes. Following submission of additional safety
      data, the agencies such as Swissmedic or EMEA have issued approval of natalizumab for
      treatment of relapsing MS with a number of restrictions. The preparation has been available
      in Switzerland since 2006. According to the current scientific information, natalizumab
      (Tysabri®) is indicated as a "disease-modifying monotherapy of highly active relapsing MS"
      for the following patient groups: 1) patients showing high levels of disease activity despite
      treatment with an IFN-β preparation, or 2) untreated/treatment-naive patients with rapidly
      progressing relapsing-remitting MS (at least two serious relapses per year).

      The primary objective of this pilot study is to generate first data and hypotheses on the
      concept of de-escalating natalizumab-treated relapsing-remitting multiple sclerosis patients
      to interferon-beta-1b e.o.d compared to continuous treatment on natalizumab for planning of
      further clinical studies regarding safety and efficacy.

      As secondary objectives, clinical, neuropsychological parameters, MRI and laboratory
      parameter and safety aspects will be assessed in accordance to the protocol available for the
      management of patient on natalizumab at our service.

      This is a prospective, controlled, randomized, rater-blinded, parallel-group, monocentric,
      two arm, phase IV pilot study. Patients with relapsing-remitting forms of MS, respecting all
      inclusion/exclusion criteria, will be randomized into two equal-size parallel arms for
      de-escalation to interferon beta-1b (after a month wash-out) or for continued treatment on
      natalizumab.

      it is planned to enrol 20 patients (1/2 in the natalizumab group, 1/2 in the interferon
      beta-1b group. Patients providing written informed consent will be treated for 12 months;
      pre-planned follow-up of further 12 month
    

Intervention name(s): interferon beta-1b; Natalizumab
Intervention type(s): Drug; Drug
Intervention description(s): Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 month at study entry. After a wash-out period of one month, interferon-beta-1b will be administered subcutaneously every other day as indicated by the manufacturers' instructions including the stepwise up-titration scheme as recommended for treatment start. The final dose of interferon beta-1b is 250 mcg (8 million International Units [MIU]); Eligible patients to this study have been treated with monthly infusions of natalizumab for at least 12 months at study entry. Natalizumab continues to be administered every four weeks by intravenous infusion from the beginning of the study as indicated by the manufacturers' instructions.
Other intervention name(s): Betaferon®; Tysabri
Intervention MeSH terms: Interferons; Interferon-beta; Natalizumab; Interferon beta-1b
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Natalizumab; Interferon-beta 1b; De-escalation; Ticino