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

NCT00662649 | Completed Phase 3 Results

• 2 other identifiers: CFTY720D2301E12007-004122-24
• Study Type: interventional
• Target: 920
• Locations: 22 countries
• Sites: 103

Brief 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).

Conditions

Multiple Sclerosis

Keywords

Multiple sclerosis.; Relapse-remitting; Fingolimod

Outcome Measures

Primary Outcomes (4)

• 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)

• 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)

• 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)

• 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)

Secondary Outcomes (5)

• 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)

  Months 0-24 (core study) and Months 24-48 (extension study)

• 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)

  Months 0-24 (core study) and Months 24-48 (extension study)

• Percent Change in Brain Volume From Month 0 to Month 24 (Core Study) and From Month 24 to Month 48 (Extension Study)

  Months 0-24 (core study) and Months 24-48 (extension study)

• Percent Change in Brain Volume From Month 0 End of Study (Core and Extension Study)

  Months 0 to end of study (maximum up to 60 months)

• 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

  Core baseline to end of study (maximum up to 60 months)

Study Arms (5)

Fingolimod 1.25 mg

EXPERIMENTAL

Patients continued the same dose to which they had been randomized in the Core study (CFTY720D2301/NCT00289978), fingolimod 1.25 mg/day, in this Extension study.

Drug: Fingolimod 1.25 mg

Fingolimod 0.5 mg

EXPERIMENTAL

Patients continued the same dose to which they had been randomized in the Core study, fingolimod 0.5 mg/day, in this Extension study.

Drug: Fingolimod 0.5 mg

Placebo-fingolimod

EXPERIMENTAL

Patients randomized to placebo in the Core study were re randomized to fingolimod (either 0.5 or 1.25 mg/day) in this Extension study.

Drug: Fingolimod 0.5 mg; Drug: Fingolimod 1.25 mg

Placebo-fingolimod 1.25 mg

EXPERIMENTAL

Patients randomized to placebo in the Core study were re randomized to fingolimod 1.25 mg/day in this Extension study.

Drug: Fingolimod 1.25 mg

Placebo-fingolimod 0.5 mg

EXPERIMENTAL

Patients randomized to placebo in the Core study were re randomized to fingolimod 0.5 mg/day in this Extension study.

Drug: Fingolimod 0.5 mg

Interventions

Fingolimod 0.5 mg DRUG

Patients self-administered fingolimod 0.5 mg capsules orally once daily.

Also known as: FTY720

Fingolimod 0.5 mg; Placebo-fingolimod; Placebo-fingolimod 0.5 mg

Fingolimod 1.25 mg DRUG

Patients self-administered fingolimod 1.25 mg capsules orally once daily.

Also known as: FTY720

Fingolimod 1.25 mg; Placebo-fingolimod; Placebo-fingolimod 1.25 mg

Eligibility Criteria

• Age: 20 Years - 58 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients should complete the 24 month core study

You may not qualify if:

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

Sponsors & Collaborators

• Novartis: lead

Study Sites (103)

Novartis Investigative Site

Chatswood, Australia

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Novartis Investigative Site

Fitzroy, 3065, Australia

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Austin Health, Department of Neurology

Heidelberg, Australia

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North Gosford, Australia

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Woodville, Australia

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Bruges, Belgium

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Brussels, Belgium

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Charleroi, Belgium

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Leuven, Belgium

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Overpelt, Belgium

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Sijsele - Damme, Belgium

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Sint-Truiden, Belgium

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Halifax, Canada

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Kingston, Canada

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London, Canada

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Montreal, Canada

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Nepean, Canada

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Regina, Canada

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Toronto, Canada

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Vancouver, Canada

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Brno, Czechia

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Olomouc, Czechia

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Ostrava-Poruba, Czechia

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Pardubice, Czechia

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Plzen - Lochotin, Czechia

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Prague, Czechia

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Rychnov nad Kněžnou, Czechia

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Teplice, Czechia

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Talinn, Estonia

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Helsinki, Finland

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Tampere, Finland

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Turku, Finland

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Clermont-Ferrand, France

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Dijon, France

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Lille, France

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Marseille, France

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Montpellier, France

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Nantes, France

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Paris, France

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Rennes, France

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Strasbourg, France

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Berlin, Germany

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Düsseldorf, Germany

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Giessen, Germany

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Hamburg, Germany

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Leipzig, Germany

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Magdeburg, Germany

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München, Germany

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Münster, Germany

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Regensburg, Germany

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Stuttgart, Germany

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Tübingen, Germany

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Athens, Greece

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Budapest, Hungary

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Miskolc, Hungary

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Székesfehérvár, Hungary

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Dublin, Ireland

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Ashkelon, Israel

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Haifa, Israel

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Ramat Gan, Israel

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Safed, Israel

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Amsterdam, Netherlands

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Nieuwegein, Netherlands

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Nijmegen, Netherlands

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Rotterdam, Netherlands

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Sittard, Netherlands

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Tilburg, Netherlands

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Bialystok, Poland

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Gdansk, Poland

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Katowice, Poland

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Lodz, Poland

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Poznan, Poland

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Warsaw, Poland

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Bucharest, Romania

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Craiova, Romania

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Lasi, Romania

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Tg. Mures, Romania

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Kazan', Russia

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Moscow, Russia

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Saint Petersburg, Russia

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Bratislava, Slovakia

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Martin, Slovakia

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Žilina, Slovakia

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Cape Town, South Africa

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Rosebank, South Africa

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Umhlanga, South Africa

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Gothenburg, Sweden

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Stockholm, Sweden

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Lausanne, Switzerland

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Zurich, Switzerland

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Ankara, Turkey (Türkiye)

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Bursa, Turkey (Türkiye)

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Cerrahpasa/Istanbul, Turkey (Türkiye)

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Gaziantep, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Izmir, Turkey (Türkiye)

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Mersin, Turkey (Türkiye)

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Yenisehir/Izmir, Turkey (Türkiye)

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Bristol, United Kingdom

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London, United Kingdom

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Newcastle upon Tyne, United Kingdom

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Nottingham, United Kingdom

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Sheffield, United Kingdom

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Related Links

• Fingolimod clinical trials information website

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Fingolimod Hydrochloride

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sphingosine; Amino Alcohols; Alcohols; Organic Chemicals; Propylene Glycols; Glycols; Amines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2008
• First Posted: April 21, 2008
• Study Start: February 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: July 12, 2012
• Results First Posted: July 12, 2012

Record last verified: 2012-06

Locations

FI (3); BE (7); HU (3); CZ (8); PL (6); SL (3); AU (5); CA (8); CH (2); ZA (3); ES (1); IL (4); RU (3); SE (2); TU (8); DE (11); GB (5); IE (1); FR (9); NL (6); RO (4); GR (1)