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

Phase 3

Terminated

Conditions: Relapsing Remitting Multiple Sclerosis (RRMS)

Interventions: Drug: Fingolimod
Drug: Placebo

Registration Number: NCT01499667

Lead Sponsor: Novartis Pharmaceuticals

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 142

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
16-week washout + Fingolimod (FTY720)	Placebo	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
12-week washout + Fingolimod (FTY720)	Placebo	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day
8-week washout + Fingolimod (FTY720)	Fingolimod	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day
12-week washout + Fingolimod (FTY720)	Fingolimod	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day
16-week washout + Fingolimod (FTY720)	Fingolimod	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day

Primary Outcome Measures

Name	Time	Method
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment	Number of active T2 lesions from last natalizumab dose 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.

Secondary Outcome Measures

Name	Time	Method
Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion	8 weeks and 24 weeks	Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans
Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment	Number of active T2 lesions during 8 wks 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 (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)	Baseline up to 24 weeks	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.
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment	8, 12 and 16 weeks (number of active T2 lesions during the washout period only)	Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment.
Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group	Baseline to week 16 and week 32	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.
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period	Baseline to maximum of 16 weeks	Adverse events were summarized by the number of patients having any adverse event overall.
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment	Baseline to maximum of 16 weeks	Adverse events were summarized by the number of patients having any adverse event overall.