An Extension Study of the Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing Multiple Sclerosis

This study has been completed.
Sponsor:
Collaborator:
Mitsubishi Tanabe Pharma Corporation
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00670449
First received: April 28, 2008
Last updated: June 26, 2013
Last verified: June 2013

April 28, 2008
June 26, 2013
April 2008
April 2012   (final data collection date for primary outcome measure)
Percentage of Patients Free of Gd-enhanced T1 Weighted Magnetic Resonance Imaging (MRI) Lesions [ Time Frame: Months 6, 9, 12, 18, 24, 36, and 48 ] [ Designated as safety issue: No ]
To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of Gd-enhanced T1 weighted MRI lesions were counted and recorded. Lesions expanding through several slices were counted as only 1 lesion.
To evaluate the long-term efficacy of FTY720 on MRI lesion parameters at 3 and 6 month intervals.
Complete list of historical versions of study NCT00670449 on ClinicalTrials.gov Archive Site
  • Percentage of Patients Free of New or Newly Enlarged T2 Weighted MRI Lesions [ Time Frame: Months 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36,36-48, and 48 to the end of the study (up to 4 years) ] [ Designated as safety issue: No ]
    To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of new or newly enlarged T2 weighted MRI lesions were counted and recorded. New lesions were identified by comparing each lesion with previous scans. Lesions expanding through several slices were counted as only 1 lesion.
  • Aggregate Annualized Relapse Rate (ARR) Based on Confirmed Relapses [ Time Frame: Months 0-6, 6-12, 12-24, 24-36, 36-48, and 48 to the end of the study (up to 4 years) ] [ Designated as safety issue: No ]
    The ARR was defined as the total number of relapses for all patients in the treatment arm / total number of days in the study for all patients in the treatment arm for the specific period of time × 365.25. General definition of relapse: Appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from the onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (< 37.5°C) or infection. A relapse was to be confirmed by a neurologist trained on the Expanded Disability Status Scale (EDSS). A relapse must be accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on 2 different Functional Systems (FS) of the EDSS or 2 points on 1 of the FS (excluding Bowel/Bladder or Cerebral FS).
  • Percentage of Patients Relapse-free at the End of the Study [ Time Frame: Baseline to the end of the study (up to 4 years) ] [ Designated as safety issue: No ]
    Patients who did not experience any relapses confirmed by a neurologist during the study were regarded as relapse-free patients.
  • Percentage of Patients Free From 3-month and 6-month Confirmed Disability Progression at Their Last Expanded Disability Status Scale (EDSS) Assessment [ Time Frame: Baseline to the end of the study (up to 4 years) ] [ Designated as safety issue: No ]
    Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months.
  • Change From Core Study Baseline in the Expanded Disability Status Scale (EDSS) Score [ Time Frame: Baseline to Months 12, 24, 36, 48, and end of study (up to 4 years) ] [ Designated as safety issue: No ]
    Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months.
  • To evaluate the long-term efficacy of FTY720 on proportion of patients free of relapse at 3 and 6 month intervals.
  • To evaluate the long-term safety and tolerability of two doses of FTY720 at 3 and 6 month intervals.
Not Provided
Not Provided
 
An Extension Study of the Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing Multiple Sclerosis
An Extension of the 6-month, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Comparing Efficacy and Safety of FTY720 0.5 mg and 1.25 mg Administered Orally Once Daily in Patients With Relapsing Multiple Sclerosis

This study was an extension study of NCT00537082. This study was designed to evaluate the efficacy and safety of long-term administration of 0.5 mg or 1.25 mg of fingolimod (FTY720) to relapsing multiple sclerosis.

A decision was made to switch all patients on fingolimod 1.25 mg/day to fingolimod 0.5 mg/day in an amendment to the study protocol. The study became open-label with all patients receiving fingolimod 0.5 mg/day on 22 Feb 2010.

The efficacy data for Months 0-6 in this study report is from the core study NCT00537082.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Multiple Sclerosis
Drug: Fingolimod
Fingolimod was supplied in capsules.
Other Names:
  • Gilenya
  • Imsera
  • Experimental: Fingolimod 0.5 mg
    Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.
    Intervention: Drug: Fingolimod
  • Experimental: Fingolimod 1.25 mg
    Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.
    Intervention: Drug: Fingolimod
  • Experimental: Placebo-fingolimod
    Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.
    Intervention: Drug: Fingolimod
Kira J, Itoyama Y, Kikuchi S, Hao Q, Kurosawa T, Nagato K, Tsumiyama I, von Rosenstiel P, Zhang-Auberson L, Saida T. Fingolimod (FTY720) therapy in Japanese patients with relapsing multiple sclerosis over 12 months: results of a phase 2 observational extension. BMC Neurol. 2014 Jan 29;14:21. doi: 10.1186/1471-2377-14-21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
143
April 2012
April 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients who completed 6 months of treatment with the study drug and the Month 6 visit in the core study NCT00537082.
  • Females of childbearing potential who have a negative pregnancy test in the core study NCT00537082.

Exclusion Criteria:

  • Patients who permanently discontinued study drug treatment prior to the Month 6 visit in the core study NCT00537082.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Both
18 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00670449
CFTY720D1201E1
Not Provided
Novartis
Novartis
Mitsubishi Tanabe Pharma Corporation
Principal Investigator: Novartis Pharmaceuticals, Japan 81-3-3797-8748
Novartis
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP