Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00333138
First received: June 1, 2006
Last updated: December 24, 2013
Last verified: December 2013
  Purpose

This study evaluated the safety, tolerability and effect on MRI lesion parameters of FTY720 in patients with relapsing multiple sclerosis.


Condition Intervention Phase
Multiple Sclerosis
Drug: FTY720
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Evaluating the Safety, Tolerability and Effect on MRI Lesion Parameters of FTY720 vs Placebo in Patients With Relapsing Multiple Sclerosis Including 18 Month Extension Phase

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core) [ Time Frame: Month 6 (Core) ] [ Designated as safety issue: No ]
    Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.

  • Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12 [ Time Frame: Month 12 (extension) ] [ Designated as safety issue: No ]
    Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.

  • Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60 [ Time Frame: Month 60 (extension) ] [ Designated as safety issue: No ]
    Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis.

  • Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study [ Time Frame: Last observation (Up to 80 months in average) ] [ Designated as safety issue: No ]
    Total number of post-baseline Gd-enhanced lesions is calculated as a sum of all Gd-enhanced lesions seen on post-baseline scans per visit. Real (not per slice) lesions are counted in this analysis. The last observation was the last observation available for each patient which ranged from 1 to 2801 days


Secondary Outcome Measures:
  • Percentage of Participants Free of T1-weighted Lesions [ Time Frame: Baseline, Months 6 (core), 12, 60 and Last Observation (up to 80 months in average) ] [ Designated as safety issue: No ]
    A patient was defined as free of lesions if s/he had zero lesions. The last observation was the last observation available for each patient which ranged from 1 to 2801 days

  • Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit [ Time Frame: Month 6 and 12, 60, last observation (up to 80 months in average) ] [ Designated as safety issue: No ]
    A patient was defined as free of lesions if s/he had zero lesions. The sum of all new T2-weighted lesions at Month 1 to last observation was zero (the sum is missing if one of the assessments was missing). New T2 lesions at a specific visit were assessed relative to the previous visit scan. Exception: new T2 lesions at Month 24 were assessed relative to Month 12. The last observation was the last observation available for each patient which ranged from 1 to 2801 days

  • Mean Number of New T2-weighted Lesions [ Time Frame: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average) ] [ Designated as safety issue: No ]
    New T2 lesions at a specific visit were assessed relative to the previous visit scan. The total number of lesions (Month 1 to end of study) is calculated as the sum of the number of lesions at Months 1 to 6, Month 12, Month 60 and last observation. The last observation was the last observation available for each patient which ranged from 1 to 2801 days

  • Volume of T2-weighted Lesions [ Time Frame: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average) ] [ Designated as safety issue: No ]
    Volume of total T2-weighted lesions by visit were summarized. The last observation was the last observation available for each patient which ranged from 1 to 2801 days

  • Change From Baseline in Volume of Total T2-weighted Lesions [ Time Frame: Baseline to month 6, 12, 60 and Last observation (up to 80 months in average) ] [ Designated as safety issue: No ]
    Change in volume of total T2-weighted lesions by visit were summarized. Negative values indicate improvement (reduction in lesion volume) and positive values worsening (increase in lesion volume). The last observation was the last observation available for each patient which ranged from 1 to 2801 days.

  • Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients [ Time Frame: Month 6,12,60 and Last observation (up to 80 months in average) ] [ Designated as safety issue: No ]
    The Expanded Disability Status Scale (EDSS) is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. Percent of patients free of disability progression was calculated using the Kaplan-Meier method. The last observation was the last observation available for each patient which ranged from 1 to 2801 days

  • Mean Trough Blood Concentrations of FTY720 [ Time Frame: Month 3 and 6 ] [ Designated as safety issue: No ]
    For each patient, the arithmetic mean of the two FTY720 trough blood levels from month 3 and 6 was calculated. This was taken as the patient's steady-state trough levels. Venous blood samples (3 mL) were collected before the dose in ethylenediaminetetraacetic acid (EDTA)-containing tubes at protocol-scheduled visits at months 3 and 6 in all patients.


Enrollment: 281
Study Start Date: May 2003
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fingolimod (FTY720) 1.25 mg/day
Core study: patients received fingolimod 1.25 mg, once daily for 6 months. Extension: In dose -blind period and open label, fingolimod 1.25 mg once daily for 9-18 months (6 months to 24 months). Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
Drug: FTY720
FTY720 capsule was taken orally once a day
Placebo Comparator: Placebo/Fingolimod (FTY720)
Core study: patients received placebo, once daily for 6 months. Extension: In dose-blind period patients were re-randomized into either fingolimod 1.25 mg or 5.0 mg once per day for 6-15 months. In open-label period patients received fingolimod 1.25 mg once per day for 15 to 24 months. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
Drug: Placebo
Placebo 1.25 mg capsule was given once daily
Experimental: Fingolimod (FTY720) 5.0 mg/day
Core study: patients received fingolimod 5.0 mg, once daily for 6 months. Extension: In dose-blind period fingolimod 5.0 mg once daily for 6-15 months. For open-label phase 15 to 24 months 1.25mg once daily. Later, all patients converted to fingolimod 0.5 mg, once daily for rest of the study participation.
Drug: FTY720
FTY720 capsule was taken orally once a day

  Eligibility

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

Core Study

Inclusion Criteria:

  • Diagnosis of relapsing multiple Sclerosis (MS)
  • Patients with at least two documented relapses in the previous 2 years or one documented relapse in the last year
  • Patients with an Expanded Disability Status Scale (EDSS) score of 0-6

Extension Study

  • A positive Gd-enhanced MRI scan at screening (in case the first MRI scan obtained at screening was negative, a second scan could have been obtained 1 month later)
  • Neurologically stable with no evidence of relapse within 30 days prior to randomization,or during the Screening and Baseline periods.
  • Female patients either post-menopausal, surgically incapable of bearing children, or practicing an acceptable method of birth control. Females of childbearing potential with a negative pregnancy test at baseline prior to entry into the treatment period.

Exclusion Criteria:

Core Study

  • Patients with other chronic disease of the immune system, malignancies, pulmonary or heart disease, etc
  • Pregnant or nursing women

Extension Study

  • Patients who had permanently discontinued study drug prior to the Month 6 visit of the core study
  • Patients with diabetes mellitus (to reduce the risk of ME), and therefore ongoing patients with diabetes mellitus or who developed diabetes mellitus were discontinued from the study)

Other protocol-defined inclusion/exclusion criteria may apply

  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: NCT00333138

Locations
Canada
Novartis Investigational site
Montreal, Canada
Novartis Investigational site
Ottawa, Canada
Novartis Investigational site
Toronto, Canada
Novartis Investigational site
Vancouver, Canada
Denmark
Novartis Investigational site
Copenhagen, Denmark
Finland
Novartis Investigational site
Helsinki, Finland
Novartis Investigational site
Turku, Finland
France
Novartis Investigational site
Lille, France
Novartis Investigational site
Marseille, France
Germany
Novartis Investigational site
Schwendi, Germany
Novartis Investigational site
Wurzburg, Germany
Italy
Novartis Investigational site
Gallarate, Italy
Novartis Investigational site
Genova, Italy
Novartis Investigational site
Milano, Italy
Novartis Investigational site
Roma, Italy
Poland
Novartis Investigational site
Warszawa, Poland
Portugal
Novartis Investigational site
Coimbra, Portugal
Novartis Investigational site
Lisboa, Portugal
Spain
Novartis Investigational site
Barcelona, Spain
Novartis Investigational site
Madrid, Spain
Novartis Investigational site
Malaga, Spain
Novartis Investigational site
Sevilla, Spain
Novartis Investigational site
Valencia, Spain
Switzerland
Novartis Investigational site
Basel, Switzerland
Novartis Investigational site
Zurich, Switzerland
United Kingdom
Novartis Investigational site
Newcastle upon Tyne, United Kingdom
Sponsors and Collaborators
Novartis
Investigators
Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals
  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: NCT00333138     History of Changes
Obsolete Identifiers: NCT00235430
Other Study ID Numbers: CFTY720D2201, CFTY720D2201E1
Study First Received: June 1, 2006
Results First Received: April 5, 2012
Last Updated: December 24, 2013
Health Authority: Canada: Health Canada
Denmark: Ethics Committee
Italy: Ethics Committee
Poland: Ministry of Health
Portugal: National Pharmacy and Medicines Institute
Spain: Ministry of Health
Switzerland: Swissmedic
Finland: Ethics Committee
France: Institutional Ethical Committee
Germany: Ethics Commission
United Kingdom: Research Ethics Committee

Keywords provided by Novartis:
FTY720
MS
Multiple Sclerosis
RRMS

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

ClinicalTrials.gov processed this record on October 19, 2014