Natalizumab De-escalation With Interferon Beta-1b
Condition: Relapsing-remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: interferon beta-1b; Natalizumab
Intervention description: 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.
Intervention MeSH terms: Interferons; Interferon-beta; Natalizumab; Interferon beta-1b
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Natalizumab; Interferon-beta 1b; De-escalation; Ticino

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female or male patients with relapsing-remitting forms of multiple sclerosis
             (according to McDonald's criteria)

          -  Age between 18 and 60 years

          -  Natalizumab-treatment for at least 12 month following the current Swiss guidelines for
             treatment initiation

          -  Eligible patients are clinically stable (free from relapses and 6-month confirmed
             disability progression for at least 6 months) while on natalizumab-treatment

          -  Women of potential childbearing with active contraceptive methods

          -  Patients who are willing to undergo study procedures

          -  Patients who are willing and able to sign informed consent

        Exclusion Criteria:

          -  Patients who have previously entered this study

          -  Natalizumab-treatment for less than 12 month following the current Swiss guidelines
             for treatment initiation

          -  Sign of clinical disease activity within the 6 month

          -  One or more relapses and/or 6-month confirmed disability progression during the 6
             months prior to the study

          -  Any disease other than multiple sclerosis that would better explain the patient's
             signs and symptoms

          -  Secondary progressive MS

          -  Primary progressive MS

          -  Pregnancy - Urine pregnancy test at baseline visit - or breast feeding

          -  Uncontrolled, clinically significant heart diseases, such as arrhythmias, angina, or
             uncompensated congestive heart failure

          -  History of severe depression or attempted suicide or current suicidal ideation

          -  Medical or psychiatric conditions that compromise the ability to give informed
             consent, to comply with the protocol, or to complete the study

          -  Uncontrolled seizure disorder

          -  Myopathy or clinically significant liver disease

          -  Inability, in the opinion of the principal investigator or staff, to comply with
             protocol requirements for the duration of the study

          -  Known hypersensitivity to interferon-beta or other human proteins including albumin

          -  Any contraindication for MRI or contrast administration

          -  A history of drug abuse in the 6 months prior to screening

          -  Treatment with any of the following in the 30 days before day 1: systemic
             corticosteroids, ACTH, or other investigational drugs.

          -  Participation in any other study involving investigational or marketed products,
             concomitantly or within 30 days prior to entry in the study

          -  Current participation on other clinical trials

          -  Treatment with drugs which might interfere with the evaluation of study drugs during
             the study protocol

          -  Likelihood of requiring treatment during the study period with drugs not permitted by
             the study protocol