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
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: Fingolimod
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 143
Study Start Date: April 2008
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Fingolimod
Fingolimod was supplied in capsules.
Other Names:
  • Gilenya
  • Imsera
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.
Drug: Fingolimod
Fingolimod was supplied in capsules.
Other Names:
  • Gilenya
  • Imsera
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.
Drug: Fingolimod
Fingolimod was supplied in capsules.
Other Names:
  • Gilenya
  • Imsera

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00670449

Locations
Japan
Novartis Investigative Site
Chiba, Japan, 276-8524
Novartis Investigative Site
Ehime, Japan, 791-0295
Novartis Investigative Site
Fukuoka, Japan, 807-8555
Novartis Investigative Site
Gunma, Japan, 371-8511
Novartis Investigative Site
Hyogo, Japan, 650-0017
Novartis Investigative Site
Ibaraki, Japan, 305-8576
Novartis Investigative Site
Kanagawa, Japan, 259-1193
Novartis Investigative Site
Kyoto, Japan, 604-8453
Novartis Investigative Site
Kyoto, Japan, 616-8255
Novartis Investigative Site
Morioka, Japan, 020-8505
Novartis Investigative Site
Niigata, Japan, 951-8520
Novartis Investigative Site
Osaka, Japan, 589-8511
Novartis Investigative Site
Osaka, Japan, 556-0016
Novartis Investigative Site
Osaka, Japan
Novartis Investigative Site
Sapporo, Japan, 060-8648
Novartis Investigative Site
Tochigi, Japan, 329-0498
Novartis Investigative Site
Tokyo, Japan, 145-0065
Novartis Investigative Site
Tokyo, Japan, 113-8519
Novartis Investigative Site
Tokyo, Japan, 162-8666
Novartis Investigative Site
Wakayama, Japan, 641-8510
Sponsors and Collaborators
Novartis
Mitsubishi Tanabe Pharma Corporation
Investigators
Principal Investigator: Novartis Pharmaceuticals, Japan 81-3-3797-8748
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00670449     History of Changes
Other Study ID Numbers: CFTY720D1201E1
Study First Received: April 28, 2008
Results First Received: March 8, 2013
Last Updated: June 26, 2013
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Novartis:
FTY720
multiple sclerosis
MS

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Fingolimod
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014