Efficacy and Safety of FTY720 in Patients With Relapsing Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT00333138
• Recruitment Status: Completed
• First Posted: June 2, 2006
• Results First Posted: October 30, 2012
• Last Update Posted: September 15, 2017
• Sponsor: Novartis
• Information provided by (Responsible Party): Novartis

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: FTY720; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 281 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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
• Study Start Date: May 2003
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: April 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 6 (Core) [ Time Frame: 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.
2. Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 12 [ Time Frame: Month 12 (extension) ]
   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.
3. Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at Month 60 [ Time Frame: Month 60 (extension) ]
   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.
4. Mean Number of Gadolinium (Gd)-Enhanced T1-weighted Lesions at End of Study [ Time Frame: Last observation (Up to 80 months in average) ]
   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 :

1. 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) ]
   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
2. 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) ]
   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
3. Mean Number of New T2-weighted Lesions [ Time Frame: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average) ]
   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
4. Volume of T2-weighted Lesions [ Time Frame: (Core) Month 6 and (Extension) 12, 60, last observation (up to 80 months in average) ]
   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
5. 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) ]
   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.
6. 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) ]
   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
7. Mean Trough Blood Concentrations of FTY720 [ Time Frame: Month 3 and 6 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• 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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00333138
• Obsolete Identifiers: NCT00235430
• Other Study ID Numbers: CFTY720D2201; CFTY720D2201E1 ( Other Identifier: Novartis )
• First Posted: June 2, 2006
• Results First Posted: October 30, 2012
• Last Update Posted: September 15, 2017
• Last Verified: August 2017

Keywords provided by Novartis:

FTY720; MS; Multiple Sclerosis; RRMS

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Fingolimod Hydrochloride; Sphingosine 1 Phosphate Receptor Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs