Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod

Study Overview
=================
Brief Summary
-----------------
This study evaluated disease control during different lengths of treatment transition from natalizumab to fingolimod.

Detailed Description
-----------------
Patient were screened, signed an informed consent at visit 1, at the 2nd visit, all patient received a baseline infusion of Natalizumub and subsequently randomized to one of 3 treatment arms. At the randomization visit, the Washout Phase started, and eligible patients were randomized 1:1:1 to one of three treatment groups: 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod, 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod, or 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod.

Official Title
-----------------
A 32-week, Patient- and Rater-blinded, Randomized, Multi-center, Parallel-group Study to Evaluate Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis Transferred From Previous Treatment With Natalizumab to Fingolimod (FTY720)

Conditions
-----------------
Relapsing Remitting Multiple Sclerosis (RRMS)

Intervention / Treatment
-----------------
* Drug: Fingolimod
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must: Have relapsing remitting multiple sclerosis Have been on treatment with natalizumab for at least 6 months prior to screening and discontinuation is an option. Exclusion Criteria: Patients with: History of chronic immune disease Crohn's disease Certain cancers Uncontrolled diabetes Certain eye disorders Negative for varicella-zoster virus IgG antibodies Certain hepatic conditions Low white blood cell count On certain immunosuppressive medications or heart medications Resting heart rate less than 45 bpm. Certain heart conditions or certain lung conditions Inability to undergo MRI scans Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 8-week washout + Fingolimod (FTY720)<br>8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day | Drug: Fingolimod<br>* Fingolimod 0.5 mg capsules for oral administration once daily<br>|
| Experimental: 12-week washout + Fingolimod (FTY720)<br>12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day | Drug: Fingolimod<br>* Fingolimod 0.5 mg capsules for oral administration once daily<br>Drug: Placebo<br>* Matching placebo in capsules for oral administration once daily.<br>|
| Experimental: 16-week washout + Fingolimod (FTY720)<br>16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day | Drug: Fingolimod<br>* Fingolimod 0.5 mg capsules for oral administration once daily<br>Drug: Placebo<br>* Matching placebo in capsules for oral administration once daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment | Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group. | Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment | Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment. | 8, 12 and 16 weeks (number of active T2 lesions during the washout period only) | 
| Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment | Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment. | Number of active T2 lesions during 8 wks of fingolimod treatment | 
| Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline) | Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline. | Baseline up to 24 weeks | 
| Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group | Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS. | Baseline to week 16 and week 32 | 
| Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion | Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans | 8 weeks and 24 weeks | 
| Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period | Adverse events were summarized by the number of patients having any adverse event overall. | Baseline to maximum of 16 weeks | 
| Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment | Adverse events were summarized by the number of patients having any adverse event overall. | Baseline to maximum of 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Relapsing remitting multiple sclerosis, multiple sclerosis (MS), safety, tolerability, health outcomes, fingolimod, disease control, MRI