Long-term Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

An Extension of the 24-month, Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing Efficacy and Safety of Fingolimod (FTY720) 1.25 mg and 0.5 mg Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00662649
• Other study ID #: CFTY720D2301E1
• Secondary ID: 2007-004122-24
• Status: Completed
• Phase: Phase 3
• First received: April 17, 2008
• Last updated: June 9, 2012
• Start date: February 2008
• Est. completion date: June 2011

Study information

• Verified date: June 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial Summary

This extension study of was designed to evaluate the long-term safety, tolerability, and efficacy of fingolimod (FTY720) in patients with multiple sclerosis. The Extension study was an extension to the 24-month Core study (CFTY720D2301/NCT00289978).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 920
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 58 Years

Eligibility

Inclusion Criteria:

• Patients should complete the 24 month core study

Exclusion Criteria:

• Patients with other chronic disease of the immune system, malignancies, acute pulmonary disease, cardiac failure, etc.

• Pregnant or nursing women

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, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Fingolimod 0.5 mg
Patients self-administered fingolimod 0.5 mg capsules orally once daily.
• Fingolimod 1.25 mg
Patients self-administered fingolimod 1.25 mg capsules orally once daily.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Chatswood
Australia	Novartis Investigative Site	Fitzroy
Australia	Austin Health, Department of Neurology	Heidelberg
Australia	Novartis Investigative Site	North Gosford
Australia	Novartis Investigative Site	Woodville
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Overpelt
Belgium	Novartis Investigative Site	Sijsele - Damme
Belgium	Novartis Investigative Site	Sint-Truiden
Canada	Novartis Investigative Site	Halifax
Canada	Novartis Investigative Site	Kingston
Canada	Novartis Investigative Site	London
Canada	Novartis Investigative Site	Montreal
Canada	Novartis Investigative Site	Nepean
Canada	Novartis Investigative Site	Regina
Canada	Novartis Investigative Site	Toronto
Canada	Novartis Investigative Site	Vancouver
Czech Republic	Novartis Investigative Site	Brno
Czech Republic	Novartis Investigative Site	Olomouc
Czech Republic	Novartis Investigative Site	Ostrava-Poruba
Czech Republic	Novartis Investigative Site	Pardubice
Czech Republic	Novartis Investigative Site	Plzen - Lochotin
Czech Republic	Novartis Investigative Site	Prague 5
Czech Republic	Novartis Investigative Site	Praha 2
Czech Republic	Novartis Investigative Site	Rychnov nad Kneznou
Czech Republic	Novartis Investigative Site	Teplice
Estonia	Novartis Investigative Site	Talinn
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Tampere
Finland	Novartis Investigative Site	Turku
France	Novartis Investigative Site	Clermont Ferrand Cedex
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Marseille cedex 05
France	Novartis Investigative Site	Montpellier cedex 5
France	Novartis Investigative Site	Nantes
France	Novartis Investigative Site	Paris Cedex 13
France	Novartis Investigative Site	Rennes
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Gießen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Stuttgart
Germany	Novartis Investigative Site	Tübingen
Greece	Novartis Investigative Site	Athens
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Szekesfehervar
Ireland	Novartis Investigative Site	Dublin 4
Israel	Novaratis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Safed
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Nieuwegein
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Sittard
Netherlands	Novartis Investigative Site	Tilburg
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Warsaw
Poland	Novartis Investigative Site	Warszawa
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Craiova
Romania	Novartis Investigative Site	Lasi
Romania	Novartis Investigative Site	Tg. Mures
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	St. Petersburg
Slovakia	Novartis Investigational Site	Bratislava
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigational Site	Zilina
South Africa	Novartis Investigational Site	Cape Town
South Africa	Novartis Investigational Site	Rosebank
South Africa	Novartis Investigational Site	Umhlanga
Sweden	Novartis Investigational Site	Göteborg
Sweden	Novartis Investigational Site	Stockholm
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Zuerich
Turkey	Novartis Investigational Site	Ankara
Turkey	Novartis Investigational Site	Bursa
Turkey	Novartis Investigational Site	Cerrahpasa/Istanbul
Turkey	Novartis Investigational Site	Gaziantep
Turkey	Novartis Investigational Site	Istanbul
Turkey	Novartis Investigational Site	Izmir
Turkey	Novartis Investigational Site	Mersin
Turkey	Novartis Investigational Site	Yenisehir/Izmir
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Czech Republic,  Estonia,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Netherlands,  Poland,  Romania,  Russian Federation,  Slovakia,  South Africa,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Aggregate Relapse Rate (ARR) During Months 0 to End of Study(Core [CFTY720D2301/NCT00289978] and Extension Study)	ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25.	Months 0 to end of study (maximum up to 60 months)	No
Primary	Time to First Confirmed Relapse up to End of Study: Kaplan-Meier Estimate of Percentage of Patients Relapse-free	A relapse was confirmed when it was accompanied by an increase of at least half a step (0.5) on the Expanded Disability Status Scale (EDSS) or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Kaplan-Meier estimates of the percentage of relapse-free patients at end of study and and 95% confidence intervals (CIs) were presented for the treatment groups.	Core baseline to end of study (maximum up to 60 months)	No
Primary	Annualized Aggregate Relapse Rate (ARR) During Months 0-24 (Core Study) and Months 24-48 (Extension Study)	ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25.	Months 0-24 (core study) and Months 24-48 (extension study)	No
Primary	Change (Expressed as Ratio) in the Annualized Aggregate Relapse Rate (ARR) From Months 0-24 (Core Study) to Months 24-48 (Extension Study)	ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25.	Months 0-24 (core study) and Months 24-48 (extension study)	No
Secondary	Change in Mean Number of New or Newly Enlarged T2 Magnetic Resonance Imaging (MRI) Lesions During Months 0-24 (Core Study) and Months 24-48 (Extension Study)	The number of new or newly enlarged T2 lesions was assessed with T2-weighted MRI scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2 weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.	Months 0-24 (core study) and Months 24-48 (extension study)	No
Secondary	Percentage of Patients Free of New or Newly Enlarged T2 Magnetic Resonance Imaging (MRI) Lesions During Months 0-24 (Core Study) and Months 24-48 (Extension Study)	The number of new or newly enlarged T2 lesions was assessed with T2-weighted MRI scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2 weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.	Months 0-24 (core study) and Months 24-48 (extension study)	No
Secondary	Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study)	Calculations of brain volume change were performed using the structural image evaluation of normalized atrophy (SIENA), software included in the Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library. SIENA is a fully automated method for estimating temporal brain volume change.	Months 0-24 (core study) and Months 24-48 (extension study)	No
Secondary	Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study)	Calculations of brain volume change were performed using the structural image evaluation of normalized atrophy (SIENA), software included in the Functional Magnetic Resonance Imaging of the Brain (FMRIB) software library. SIENA is a fully automated method for estimating temporal brain volume change.	Months 0 to end of study (maximum up to 60 months)	No
Secondary	Time to First 3-month Confirmed Disability Progression up to End of Study Based on Expanded Disability Status Scale (EDSS): Kaplan-Meier Estimate of Percentage of Patients Free of Disability Progression	Kurtzke's Expanded Disability Status Scale (EDSS) is a scale for assessing neurologic impairment in multiple sclerosis (MS) includes a series of scores in each of eight functional systems such as Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, Cerebral, and Other. The EDSS steps range from 0 (normal) to 10 (death due to MS). The Kaplan-Meier estimates of the percentage of participants free of disability progression at end of study and their 95% CIs were provided for each treatment group.	Core baseline to end of study (maximum up to 60 months)	No

External Links

•   Fingolimod clinical trials information website