Please select the eligibility criteria that correspond to the clinical trial below.
Title: De-escalation After Natalizumab Treatment With Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis
Brief 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.


Options:
A: Inclusion Criteria:

The target population of the survey will include:

* clinicians
* epidemiologist
* decision scientists
* health research methodologists
* experts in health technology assessment (HTA)
* and members of guideline working groups
* members from the general public

Exclusion Criteria:

• Prior participation in the survey
B: Inclusion Criteria:

Male and female subjects aged 18 to 55 years with established diagnosis of MS McDonald 2010 with relapsing course from onset (i.e., RRMS and SPMS with superimposed relapses).

Subjects must have active disease evidenced by one or more MS attacks with onset within the period of 12 to 1 months prior to randomization, or by two or more MS attacks with onset within the 24 to 1 months prior to randomization, or with one or more gadolinium-enhancing (Gd+) lesion(s) of the brain on an MRI performed within 6 months prior to randomization.

Enrolled subjects must be ambulatory (EDSS score of up to 5.5 inclusive) and may be treatment-naïve or previously treated with MS disease modifying therapy.

Exclusion Criteria:

Subjects with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic,ophthalmological conditions) or lactating or pregnant women are not eligible to enter the study.

Subjects with contraindications to MRI or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study are not eligible to enter the study.
C: 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
D: Inclusion Criteria:

1. Must be 18 to 55 years old, inclusive, at the time of informed consent.
2. Must have a confirmed diagnosis of relapsing-remitting MS according to McDonald criteria #1-4 (McDonald et al, 2001; Appendix 2).
3. Must have a baseline EDSS between 0.0 and 5.0, inclusive.
4. Must have experienced at least one relapse within the 12 months prior to randomization, with a prior cranial MRI demonstrating lesion(s) consistent with MS OR show evidence of Gd-enhancing lesions of the brain on an MRI performed within the 6 weeks.
5. Male and female subjects must be willing to take appropriate measures to prevent pregnancy.

Exclusion Criteria:

1. Primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold, 1996 \[Appendix 3\]).
2. History of malignancy.
3. History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
4. History of abnormal laboratory results indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neurologic (other than MS), and/or other major disease.
5. History of human immunodeficiency virus (HIV).
6. History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to randomization.
7. An MS relapse that has occurred within the 50 days prior to randomization AND/OR the subject has not stabilized from a previous relapse prior to randomization.
8. Body weight \>100 kg.
9. Positive for hepatitis C antibody and/or positive for hepatitis B surface antigen (HBsAg) at screening.
10. Any of the following abnormal blood tests at screening.
11. Any previous treatment with FUMADERM®, FAG-201, or BG00012.
12. A medication history that precludes entry into the study.
13. Female subjects who are currently pregnant or breast-feeding.

Answer: C