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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00355134
First received: July 19, 2006
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

This study assessed the safety, tolerability and efficacy of two doses of oral fingolimod compared to placebo on efficacy parameters in patients with relapsing-remitting multiple sclerosis (RRMS).


Condition Intervention Phase
Multiple Sclerosis
Drug: Fingolimod
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 24-month Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Aggregate Annualized Relapse Rate (ARR) Estimate up to Month 24 [ Time Frame: 24 months ] [ Designated as safety issue: No ]

    ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25.

    A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist).

    ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).



Secondary Outcome Measures:
  • Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study [ Time Frame: From Baseline until end of study (up to approximately 54 months). ] [ Designated as safety issue: No ]

    ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25.

    A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist).

    ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).


  • Percent Change From Baseline in Brain Volume [ Time Frame: Baseline, Month 24 and end of study (up to approximately 54 months) ] [ Designated as safety issue: No ]
    Brain volume was measured using magnetic resonance imaging (MRI). Change from Baseline in brain volume is expressed as a percentage of the Baseline brain volume.

  • Number of New or Newly Enlarged T2 Lesions [ Time Frame: From Baseline until Month 48 ] [ Designated as safety issue: No ]
    Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new or newly enlarged T2 lesions, by year.

  • Number of Gadolinium-enhanced T1 Lesions [ Time Frame: Month 24 and end of study (up to approximately 54 months) ] [ Designated as safety issue: No ]
    Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of gadolinium-enhanced T1 lesions.

  • Change From Baseline in Lesion Volume at Month 24 (Core Phase) [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    Change from Baseline in lesion volume was measured by MRI for T2 lesions and for T1 hypointense lesions.

  • Percentage of Participants Free of 3-month Confirmed Disability Progression at Month 24 and End of Study [ Time Frame: 24 months and end of study (up to approximately 54 months) ] [ Designated as safety issue: No ]
    Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression was defined as a 3-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method.

  • Percentage of Participants Free of 6-month Confirmed Disability Progression at Month 24 and End of Study [ Time Frame: 24 months and end of study (up to approximately 54 months) ] [ Designated as safety issue: No ]
    Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined as a 6-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method.

  • Percentage of Participants Relapse-free up to Month 24 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Estimates of the percentage of participants relapse-free at 24 months were generated from Kaplan-Meier curves of the time to first relapse. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician.

  • Percentage of Participants Relapse-free up to End of Study [ Time Frame: From Baseline until the end of study (up to approximately 54 months) ] [ Designated as safety issue: No ]
    Estimates of the percentage of participants relapse-free at end of study were generated from Kaplan-Meier curves of the time to first relapse. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician.

  • Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z-score [ Time Frame: Baseline, Month 24 and end of study (up to approximately 54 months) ] [ Designated as safety issue: No ]
    The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The overall MSFC z-score as an average of the three standardized scores derived using baseline data pooled over each treatment arm as reference population. Higher scores reflect better neurological function and a positive change from Baseline indicates improvement.


Enrollment: 1083
Study Start Date: June 2006
Study Completion Date: August 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fingolimod 1.25 mg

Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally once a day.

Note: Upon implementation of a protocol amendment all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.

Drug: Fingolimod
Fingolimod capsules for oral administration
Other Names:
  • FTY720
  • Gilenya®
Experimental: Fingolimod 0.5 mg
Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.
Drug: Fingolimod
Fingolimod capsules for oral administration
Other Names:
  • FTY720
  • Gilenya®
Experimental: Placebo

Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day.

Note: Upon implementation of a protocol amendment all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.

Drug: Placebo
Matching placebo capsules for oral administration.

Detailed Description:

This randomized, multicenter, parallel-group study consisted of 2 phases: a 24-month double-blind, randomized, multicenter, placebo-controlled, parallel-group study and an Extension phase which consisted of a dose-blinded period and an open-label period.

In the Core phase, patients were randomized to receive a fixed dose of fingolimod (0.5 mg/day), fingolimod (1.25 mg/day) or placebo for up to 24 months.

For the Extension phase, patients who were treated with fingolimod during the Core phase continued treatment at the assigned dose level, while those previously treated with placebo during the Core phase were re-randomized in a 1:1 ratio to receive one of the two doses of fingolimod (1.25 mg or 0.5 mg). All patients in the extension received blinded investigational drug: fingolimod 1.25 mg and 0.5 mg in capsules for oral administration once daily until the decision to discontinue the fingolimod 1.25 mg dose became effective and subsequently all patients were switched to open-label fingolimod 0.5 mg.

With the implementation of Amendment 11, the 1.25 mg dose was discontinued and all patients were switched to fingolimod 0.5 mg dose. With the implementation of Amendment 12, all patients treated with Placebo in the fingolimod Core phase were switched to treatment with 0.5 mg fingolimod per day. The Extension phase continued until all patients either discontinued or transferred to Study CFTY720D2399 (NCT01201356; initiated in September 2010).

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients between ages 18-55 with a diagnosis of multiple sclerosis
  • Patients with a relapsing-remitting disease course
  • Patients with expanded disability status scale (EDSS) score of 0-5.5

Exclusion Criteria:

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

For inclusion in the extension phase patients should complete the 24 month core study with or without 24 months on study drug. If a patient discontinued study drug during the core study due to an adverse event, serious adverse event, laboratory abnormality etc. they would be excluded from the Extension Phase.

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00355134

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Birmingham
Birmingham, Alabama, United States, 35249
North Central Neurology Associates, PC
Cullman, Alabama, United States, 35058
University of South Alabama - Dept of Neurology
Mobile, Alabama, United States, 36693
United States, Arizona
Barrow Neurology Clinic
Phoenix, Arizona, United States, 85013
United States, California
Research and Education Institute of Alta Bates Summit Medical Center
Berkeley, California, United States, 94705
University of California - Irvine, Deptarment of Neurology
Irvine, California, United States, 92697
Cedars Sinai Medical Center
Los Angeles, California, United States, 90048
The Neurology Center
Oceanside, California, United States, 92056
Neuro-Therapeutics, Inc.
Pasadena, California, United States, 91105
UC Davis Medical Center
Sacramento, California, United States, 95817
Multiple Sclerosis Center at UCSF
San Francisco, California, United States, 94117
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80262
United States, Connecticut
Associated Neurologists, PC
Danbury, Connecticut, United States, 06810
Associated Neurologists of Southern CT, P.C.
Fairfield, Connecticut, United States, 06824
Yale University - Yale Multiple Sclerosis Center
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Georgetown University Hospital - Dept of Neurology
Washington, District of Columbia, United States, 20007
United States, Florida
Sunrise Clinical Research, Inc.
Hollywood, Florida, United States, 33021
University of Florida Health Sciences Center/Shands Jacksonville
Jacksonville, Florida, United States, 32209
Neurology Associates, PA
Maitland, Florida, United States, 32751
University of Miami, Department of Neurology
Miami, Florida, United States, 33136
Neurological Associates
Pompano Beach, Florida, United States, 33060
Roskamp Institute, Clinical Trials Division
Sarasota, Florida, United States, 34243
Neurology Clinical Research, Inc
Sunrise, Florida, United States, 33351
AMO Corporation
Tallahassee, Florida, United States, 32308
Axiom Clinical Research of Florida
Tampa, Florida, United States, 33609
The MS Center of Vero Beach
Vero Beach, Florida, United States, 32960
United States, Georgia
MS Center of Atlanta
Atlanta, Georgia, United States, 30327
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
University of Chicago - Dept of Neurology
Chicago, Illinois, United States, 60637
Northwestern University Medical School - Dept of Neurology
Chicago, Illinois, United States, 60611
Rush University Medical Center Department of Neurological Sciences
Chicago, Illinois, United States, 60612
Alexian Brothers Neurosciences Research
Elk Grove Village, Illinois, United States, 60007
South Suburban Neurology
Flossmoor, Illinois, United States, 60402
Neurologic Associates, Ltd.
Palos Heights, Illinois, United States, 60453
United States, Indiana
Fort Wayne Neurological Center
Fort Wayne, Indiana, United States, 46805
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Iowa
Ruan Neurology Clinical Research Center
Des Moines, Iowa, United States, 50314
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Mid America Neuroscience Institute
Lenexa, Kansas, United States, 66214
United States, Kentucky
Kentucky Research Associates
Louisville, Kentucky, United States, 40202
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
Johns Hopkins MS Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Caritas St. Elizabeth's Medical Center
Brighton, Massachusetts, United States, 02135
Newton Wesley Hospital
Newton, Massachusetts, United States, 02462
Springfield Neurology
Springfield, Massachusetts, United States, 01104
UMass Memorial Medical Center
Worchester, Massachusetts, United States, 01605
United States, Michigan
University of Michigan Mulitiple Sclerosis Clinic
Ann Arbor, Michigan, United States, 48109
Henry Ford Hospital, Department of Neurology
Detroit, Michigan, United States, 48202
Wayne State University MS Clinic
Detroit, Michigan, United States, 48201
Michigan State University MS Clinic
East Lansing, Michigan, United States, 48824
Michigan Medical, P.C.
Grand Rapids, Michigan, United States, 49525
Michigan Neurology Associates, PC
St. Clair Shores, Michigan, United States, 48080
United States, Missouri
St. Luke's Hospital - Mid-America Brain and Stroke Institute
Kansas City, Missouri, United States, 64111
The MS Center for Innovation in Care
St. Louis, Missouri, United States, 63110
United States, Nevada
Institute for Neurosciences
Reno, Nevada, United States, 85902
United States, New Hampshire
Multiple Sclerosis Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Gimbel Multiple Sclerosis Center at Holy Name Hospital
Teaneck, New Jersey, United States, 07666
United States, New Mexico
University of New Mexico Health Science Center
Albuquerque, New Mexico, United States, 87131
United States, New York
Empire Neurology, PC
Latham, New York, United States, 12110
Mount Sinai School of Medicine
New York, New York, United States, 10029
Cornell University - NY Presbyterian Hospital
New York, New York, United States, 10021
NYU Hospital for Joint Diseases
New York, New York, United States, 10003
Island Neurological Associates, PC
Plainview, New York, United States, 11803
University of Rochester Medical Center
Rochester, New York, United States, 14642
Alpha Neurology
Staten Island, New York, United States, 10306
SUNY Stony Brook
Stony Brook, New York, United States, 11794
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
UNC - Chapel Hill Neuroscience Hospital
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27705
Raleigh Neurology Associates
Raleigh, North Carolina, United States, 27607
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Neurology & Neuroscience Associates, Inc.
Akron, Ohio, United States, 44302
Northern Ohio Neuroscience, LLC.
Bellevue, Ohio, United States, 44811
NeuroCare Center, Inc
Canton, Ohio, United States, 44718
River Hills Health Care
Cincinnati, Ohio, United States, 45219
Ohio State University
Columbus, Ohio, United States, 48221
University of Toledo Health Science Campus
Toledo, Ohio, United States, 43614
Oak Clinic
Uniontown, Ohio, United States, 44685
United States, Oklahoma
MS Center of Oklahoma, Mercy Neuroscience Institute
Oklahoma City, Oklahoma, United States, 73120
Neurologial Associates of Tulsa
Tulsa, Oklahoma, United States, 74137
United States, Oregon
Oregon Neurology
Tualatin, Oregon, United States, 97062
United States, Pennsylvania
Thomas Jefferson University Hospital, Department of Neurology
Philadelphia, Pennsylvania, United States, 19107
University of Pennsylvania, Department of Neurology
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh - Dept of Neurology
Pittsburgh, Pennsylvania, United States, 15213
Allegheny Neurological Associates
Pittsburgh, Pennsylvania, United States, 15212
United States, South Carolina
Absher Neurology
Greenville, South Carolina, United States, 29615
United States, Tennessee
Mountain Empire Neurological Associates, PC
Bristol, Tennessee, United States, 37620
Advanced Neurosciences Institute
Nashville, Tennessee, United States, 37205
Vanderbilt Stallworth Rehabilitation Hospital
Nashville, Tennessee, United States, 37212
United States, Texas
University of Texas - Houston Medical School
Houston, Texas, United States, 77030
Investigational Site - Private Practice
Lubbock, Texas, United States, 79410
Integra Clinical Research, LLC
San Antonio, Texas, United States, 78231
United States, Vermont
Neurology Health Care Service - Fletcher Allen Hospital
Burlington, Vermont, United States, 05401
United States, Virginia
University of Virginia - Fontaine Adult Neurology
Charlottesville, Virginia, United States, 22903
United States, Washington
Seattle Neuroscience Institute at Swedish Medical Center
Seattle, Washington, United States, 98122
Virginia Mason Multiple Sclerosis Center
Seattle, Washington, United States, 98111
United States, West Virginia
University Health Associates - West Virgina University
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
University of Wisconsin Medical School
Madison, Wisconsin, United States, 53792
Dean Foundation
Madison, Wisconsin, United States, 53715
St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Australia, New South Wales
Novartis Investigative Site
North Gosford, New South Wales, Australia
Austria
Novartis Investigative Site
Vienna, Austria
Canada, Ontario
Novartis Investigative Site
Ottawa, Ontario, Canada
Canada, Quebec
Novartis Investigative Site
Greenfield Park, Quebec, Canada
Poland
Novartis Investigative Site
Bialystok, Poland
Novartis Investigative Site
Warsaw, Poland
Novartis Investigative Site
Warszawa, Poland
Romania
Novartis Investigative Site
Bucharest, Romania
Novartis Investigative Site
Targu Mures, Romania
Turkey
Novartis Investigative Site
Istanbul, Turkey
Novartis Investigative Site
Izmir, Turkey
Novartis Investigative Site
Yenisehir/Izmir, Turkey
United Kingdom
Novartis Investigative Site
Bristol, United Kingdom
Sponsors and Collaborators
Novartis
Investigators
Study Chair: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00355134     History of Changes
Obsolete Identifiers: NCT00774670
Other Study ID Numbers: CFTY720D2309
Study First Received: July 19, 2006
Results First Received: May 23, 2012
Last Updated: August 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
fingolimod
FTY720
relapsing-remitting multiple sclerosis
MS
RRMS

Additional relevant MeSH terms:
Fingolimod
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2014