Back to resultsEfficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
FTY720
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring FTY720, MS, Multiple Sclerosis, RRMS
Eligibility 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
Sites / Locations
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
- Novartis Investigational site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Fingolimod (FTY720) 1.25 mg/day
Placebo/Fingolimod (FTY720)
Fingolimod (FTY720) 5.0 mg/day
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core)
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
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
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
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
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
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
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
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00333138
Brief Title
Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis
4. Oversight
5. Study Description
Brief Summary
This study evaluated the safety, tolerability and effect on MRI lesion parameters of FTY720 in patients with relapsing multiple sclerosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
FTY720, MS, Multiple Sclerosis, RRMS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
281 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fingolimod (FTY720) 1.25 mg/day
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo/Fingolimod (FTY720)
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Fingolimod (FTY720) 5.0 mg/day
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
FTY720
Intervention Description
FTY720 capsule was taken orally once a day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 1.25 mg capsule was given once daily
Primary Outcome Measure Information:
Title
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core)
Description
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.
Time Frame
Month 6 (Core)
Title
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12
Description
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.
Time Frame
Month 12 (extension)
Title
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60
Description
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.
Time Frame
Month 60 (extension)
Title
Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study
Description
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
Time Frame
Last observation (Up to 80 months in average)
Secondary Outcome Measure Information:
Title
Percentage of Participants Free of T1-weighted Lesions
Description
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
Time Frame
Baseline, Months 6 (core), 12, 60 and Last Observation (up to 80 months in average)
Title
Percentage of Patients Free of Gd-enhanced T1-weighted and New T2- Weighted Lesions by Visit
Description
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
Time Frame
Month 6 and 12, 60, last observation (up to 80 months in average)
Title
Mean Number of New T2-weighted Lesions
Description
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
Time Frame
(Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)
Title
Volume of T2-weighted Lesions
Description
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
Time Frame
(Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)
Title
Change From Baseline in Volume of Total T2-weighted Lesions
Description
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 Frame
Baseline to month 6, 12, 60 and Last observation (up to 80 months in average)
Title
Time to Event Analysis: Kaplan Meier Estimates of Percentage of Relapse-free Patients
Description
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
Time Frame
Month 6,12,60 and Last observation (up to 80 months in average)
Title
Mean Trough Blood Concentrations of FTY720
Description
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.
Time Frame
Month 3 and 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Novartis Investigational site
City
Montreal
Country
Canada
Facility Name
Novartis Investigational site
City
Ottawa
Country
Canada
Facility Name
Novartis Investigational site
City
Toronto
Country
Canada
Facility Name
Novartis Investigational site
City
Vancouver
Country
Canada
Facility Name
Novartis Investigational site
City
Copenhagen
Country
Denmark
Facility Name
Novartis Investigational site
City
Helsinki
Country
Finland
Facility Name
Novartis Investigational site
City
Turku
Country
Finland
Facility Name
Novartis Investigational site
City
Lille
Country
France
Facility Name
Novartis Investigational site
City
Marseille
Country
France
Facility Name
Novartis Investigational site
City
Schwendi
Country
Germany
Facility Name
Novartis Investigational site
City
Wurzburg
Country
Germany
Facility Name
Novartis Investigational site
City
Gallarate
Country
Italy
Facility Name
Novartis Investigational site
City
Genova
Country
Italy
Facility Name
Novartis Investigational site
City
Milano
Country
Italy
Facility Name
Novartis Investigational site
City
Roma
Country
Italy
Facility Name
Novartis Investigational site
City
Warszawa
Country
Poland
Facility Name
Novartis Investigational site
City
Coimbra
Country
Portugal
Facility Name
Novartis Investigational site
City
Lisboa
Country
Portugal
Facility Name
Novartis Investigational site
City
Barcelona
Country
Spain
Facility Name
Novartis Investigational site
City
Madrid
Country
Spain
Facility Name
Novartis Investigational site
City
Malaga
Country
Spain
Facility Name
Novartis Investigational site
City
Sevilla
Country
Spain
Facility Name
Novartis Investigational site
City
Valencia
Country
Spain
Facility Name
Novartis Investigational site
City
Basel
Country
Switzerland
Facility Name
Novartis Investigational site
City
Zurich
Country
Switzerland
Facility Name
Novartis Investigational site
City
Newcastle upon Tyne
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23531349
Citation
Zarbin MA, Jampol LM, Jager RD, Reder AT, Francis G, Collins W, Tang D, Zhang X. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology. 2013 Jul;120(7):1432-9. doi: 10.1016/j.ophtha.2012.12.040. Epub 2013 Mar 24.
Results Reference
derived
PubMed Identifier
16971719
Citation
Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, Haas T, Korn AA, Karlsson G, Radue EW; FTY720 D2201 Study Group. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40. doi: 10.1056/NEJMoa052643.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis
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