Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis

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

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

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: FTY720; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 281
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada
    • Novartis Investigational site
  • Ottawa, Canada
    • Novartis Investigational site
  • Toronto, Canada
    • Novartis Investigational site
  • Vancouver, Canada
    • Novartis Investigational site
• Denmark
  • Copenhagen, Denmark
    • Novartis Investigational site
• Finland
  • Helsinki, Finland
    • Novartis Investigational site
  • Turku, Finland
    • Novartis Investigational site
• France
  • Lille, France
    • Novartis Investigational site
  • Marseille, France
    • Novartis Investigational site
• Germany
  • Schwendi, Germany
    • Novartis Investigational site
  • Wurzburg, Germany
    • Novartis Investigational site
• Italy
  • Gallarate, Italy
    • Novartis Investigational site
  • Genova, Italy
    • Novartis Investigational site
  • Milano, Italy
    • Novartis Investigational site
  • Roma, Italy
    • Novartis Investigational site
• Poland
  • Warszawa, Poland
    • Novartis Investigational site
• Portugal
  • Coimbra, Portugal
    • Novartis Investigational site
  • Lisboa, Portugal
    • Novartis Investigational site
• Spain
  • Barcelona, Spain
    • Novartis Investigational site
  • Madrid, Spain
    • Novartis Investigational site
  • Malaga, Spain
    • Novartis Investigational site
  • Sevilla, Spain
    • Novartis Investigational site
  • Valencia, Spain
    • Novartis Investigational site
• Switzerland
  • Basel, Switzerland
    • Novartis Investigational site
  • Zurich, Switzerland
    • Novartis Investigational site
• United Kingdom
  • Newcastle upon Tyne, United Kingdom
    • Novartis Investigational site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: June 1, 2006
• First Submitted That Met QC Criteria: June 1, 2006
• First Posted (Estimate): June 2, 2006

Study Record Updates

• Last Update Posted (Actual): September 15, 2017
• Last Update Submitted That Met QC Criteria: August 17, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; RRMS; MS; FTY720
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Fingolimod Hydrochloride
• Other Study ID Numbers: CFTY720D2201; CFTY720D2201E1 (Other Identifier: Novartis)