Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00333138
• Other study ID #: CFTY720D2201
• Secondary ID: CFTY720D2201E1
• Status: Completed
• Phase: Phase 2
• First received: June 1, 2006
• Last updated: December 24, 2013
• Start date: May 2003
• Est. completion date: April 2011

Study information

• Verified date: December 2013
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaDenmark: Ethics CommitteeItaly: Ethics CommitteePoland: Ministry of HealthPortugal: National Pharmacy and Medicines InstituteSpain: Ministry of HealthSwitzerland: SwissmedicFinland: Ethics CommitteeFrance: Institutional Ethical CommitteeGermany: Ethics CommissionUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

Other known NCT identifiers

• NCT00235430

Recruitment information / eligibility

• Status: Completed
• Enrollment: 281
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• FTY720
FTY720 capsule was taken orally once a day
• Placebo
Placebo 1.25 mg capsule was given once daily

Locations

Country	Name	City	State
Canada	Novartis Investigational site	Montreal
Canada	Novartis Investigational site	Ottawa
Canada	Novartis Investigational site	Toronto
Canada	Novartis Investigational site	Vancouver
Denmark	Novartis Investigational site	Copenhagen
Finland	Novartis Investigational site	Helsinki
Finland	Novartis Investigational site	Turku
France	Novartis Investigational site	Lille
France	Novartis Investigational site	Marseille
Germany	Novartis Investigational site	Schwendi
Germany	Novartis Investigational site	Wurzburg
Italy	Novartis Investigational site	Gallarate
Italy	Novartis Investigational site	Genova
Italy	Novartis Investigational site	Milano
Italy	Novartis Investigational site	Roma
Poland	Novartis Investigational site	Warszawa
Portugal	Novartis Investigational site	Coimbra
Portugal	Novartis Investigational site	Lisboa
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
Switzerland	Novartis Investigational site	Basel
Switzerland	Novartis Investigational site	Zurich
United Kingdom	Novartis Investigational site	Newcastle upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

Canada,  Denmark,  Finland,  France,  Germany,  Italy,  Poland,  Portugal,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Month 6 (Core)	No
Primary	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.	Month 12 (extension)	No
Primary	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.	Month 60 (extension)	No
Primary	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	Last observation (Up to 80 months in average)	No
Secondary	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	Baseline, Months 6 (core), 12, 60 and Last Observation (up to 80 months in average)	No
Secondary	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	Month 6 and 12, 60, last observation (up to 80 months in average)	No
Secondary	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	(Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)	No
Secondary	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	(Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average)	No
Secondary	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.	Baseline to month 6, 12, 60 and Last observation (up to 80 months in average)	No
Secondary	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	Month 6,12,60 and Last observation (up to 80 months in average)	No
Secondary	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.	Month 3 and 6	No