Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis
FREEDOMS II
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
1 other identifier
interventional
1,083
7 countries
111
Brief Summary
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 multiple-sclerosis
Started Jun 2006
Typical duration for phase_3 multiple-sclerosis
111 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2006
CompletedFirst Submitted
Initial submission to the registry
July 19, 2006
CompletedFirst Posted
Study publicly available on registry
July 21, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2011
CompletedResults Posted
Study results publicly available
June 26, 2012
CompletedAugust 7, 2012
August 1, 2012
5 years
July 19, 2006
May 23, 2012
August 2, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Aggregate Annualized Relapse Rate (ARR) Estimate up to Month 24
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).
24 months
Secondary Outcomes (10)
Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study
From Baseline until end of study (up to approximately 54 months).
Percent Change From Baseline in Brain Volume
Baseline, Month 24 and end of study (up to approximately 54 months)
Number of New or Newly Enlarged T2 Lesions
From Baseline until Month 48
Number of Gadolinium-enhanced T1 Lesions
Month 24 and end of study (up to approximately 54 months)
Change From Baseline in Lesion Volume at Month 24 (Core Phase)
Baseline and Month 24
- +5 more secondary outcomes
Study Arms (3)
Fingolimod 1.25 mg
EXPERIMENTALParticipants 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.
Fingolimod 0.5 mg
EXPERIMENTALParticipants 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.
Placebo
EXPERIMENTALParticipants 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.
Interventions
Fingolimod capsules for oral administration
Eligibility Criteria
You may qualify if:
- 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
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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Novartislead
Study Sites (112)
University of Alabama Birmingham
Birmingham, Alabama, 35249, United States
North Central Neurology Associates, PC
Cullman, Alabama, 35058, United States
University of South Alabama - Dept of Neurology
Mobile, Alabama, 36693, United States
Barrow Neurology Clinic
Phoenix, Arizona, 85013, United States
Research and Education Institute of Alta Bates Summit Medical Center
Berkeley, California, 94705, United States
University of California - Irvine, Deptarment of Neurology
Irvine, California, 92697, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
The Neurology Center
Oceanside, California, 92056, United States
Neuro-Therapeutics, Inc.
Pasadena, California, 91105, United States
UC Davis Medical Center
Sacramento, California, 95817, United States
Multiple Sclerosis Center at UCSF
San Francisco, California, 94117, United States
University of Colorado
Denver, Colorado, 80262, United States
Associated Neurologists, PC
Danbury, Connecticut, 06810, United States
Associated Neurologists of Southern CT, P.C.
Fairfield, Connecticut, 06824, United States
Yale University - Yale Multiple Sclerosis Center
New Haven, Connecticut, 06510, United States
Georgetown University Hospital - Dept of Neurology
Washington D.C., District of Columbia, 20007, United States
Sunrise Clinical Research, Inc.
Hollywood, Florida, 33021, United States
University of Florida Health Sciences Center/Shands Jacksonville
Jacksonville, Florida, 32209, United States
Neurology Associates, PA
Maitland, Florida, 32751, United States
University of Miami, Department of Neurology
Miami, Florida, 33136, United States
Neurological Associates
Pompano Beach, Florida, 33060, United States
Roskamp Institute, Clinical Trials Division
Sarasota, Florida, 34243, United States
Neurology Clinical Research, Inc
Sunrise, Florida, 33351, United States
AMO Corporation
Tallahassee, Florida, 32308, United States
Axiom Clinical Research of Florida
Tampa, Florida, 33609, United States
The MS Center of Vero Beach
Vero Beach, Florida, 32960, United States
MS Center of Atlanta
Atlanta, Georgia, 30327, United States
Medical College of Georgia
Augusta, Georgia, 30912, United States
Northwestern University Medical School - Dept of Neurology
Chicago, Illinois, 60611, United States
Rush University Medical Center Department of Neurological Sciences
Chicago, Illinois, 60612, United States
University of Chicago - Dept of Neurology
Chicago, Illinois, 60637, United States
Alexian Brothers Neurosciences Research
Elk Grove Village, Illinois, 60007, United States
South Suburban Neurology
Flossmoor, Illinois, 60402, United States
Neurologic Associates, Ltd.
Palos Heights, Illinois, 60453, United States
Fort Wayne Neurological Center
Fort Wayne, Indiana, 46805, United States
Indiana University Medical Center
Indianapolis, Indiana, 46202, United States
Ruan Neurology Clinical Research Center
Des Moines, Iowa, 50314, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Mid America Neuroscience Institute
Lenexa, Kansas, 66214, United States
Kentucky Research Associates
Louisville, Kentucky, 40202, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Johns Hopkins MS Center
Baltimore, Maryland, 21287, United States
Caritas St. Elizabeth's Medical Center
Brighton, Massachusetts, 02135, United States
Newton Wesley Hospital
Newton, Massachusetts, 02462, United States
Springfield Neurology
Springfield, Massachusetts, 01104, United States
UMass Memorial Medical Center
Worchester, Massachusetts, 01605, United States
University of Michigan Mulitiple Sclerosis Clinic
Ann Arbor, Michigan, 48109, United States
Wayne State University MS Clinic
Detroit, Michigan, 48201, United States
Henry Ford Hospital, Department of Neurology
Detroit, Michigan, 48202, United States
Michigan State University MS Clinic
East Lansing, Michigan, 48824, United States
Michigan Medical, P.C.
Grand Rapids, Michigan, 49525, United States
Michigan Neurology Associates, PC
Saint Clair Shores, Michigan, 48080, United States
St. Luke's Hospital - Mid-America Brain and Stroke Institute
Kansas City, Missouri, 64111, United States
The MS Center for Innovation in Care
St Louis, Missouri, 63110, United States
Institute for Neurosciences
Reno, Nevada, 85902, United States
Multiple Sclerosis Center
Lebanon, New Hampshire, 03756, United States
Gimbel Multiple Sclerosis Center at Holy Name Hospital
Teaneck, New Jersey, 07666, United States
University of New Mexico Health Science Center
Albuquerque, New Mexico, 87131, United States
Empire Neurology, PC
Latham, New York, 12110, United States
NYU Hospital for Joint Diseases
New York, New York, 10003, United States
Cornell University - NY Presbyterian Hospital
New York, New York, 10021, United States
Mount Sinai School of Medicine
New York, New York, 10029, United States
Island Neurological Associates, PC
Plainview, New York, 11803, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
Alpha Neurology
Staten Island, New York, 10306, United States
SUNY Stony Brook
Stony Brook, New York, 11794, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
UNC - Chapel Hill Neuroscience Hospital
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27705, United States
Raleigh Neurology Associates
Raleigh, North Carolina, 27607, United States
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
Neurology & Neuroscience Associates, Inc.
Akron, Ohio, 44302, United States
Northern Ohio Neuroscience, LLC.
Bellevue, Ohio, 44811, United States
NeuroCare Center, Inc
Canton, Ohio, 44718, United States
River Hills Health Care
Cincinnati, Ohio, 45219, United States
Ohio State University
Columbus, Ohio, 48221, United States
University of Toledo Health Science Campus
Toledo, Ohio, 43614, United States
Oak Clinic
Uniontown, Ohio, 44685, United States
MS Center of Oklahoma, Mercy Neuroscience Institute
Oklahoma City, Oklahoma, 73120, United States
Neurologial Associates of Tulsa
Tulsa, Oklahoma, 74137, United States
Oregon Neurology
Tualatin, Oregon, 97062, United States
University of Pennsylvania, Department of Neurology
Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University Hospital, Department of Neurology
Philadelphia, Pennsylvania, 19107, United States
Allegheny Neurological Associates
Pittsburgh, Pennsylvania, 15212, United States
University of Pittsburgh - Dept of Neurology
Pittsburgh, Pennsylvania, 15213, United States
Absher Neurology
Greenville, South Carolina, 29615, United States
Mountain Empire Neurological Associates, PC
Bristol, Tennessee, 37620, United States
Advanced Neurosciences Institute
Nashville, Tennessee, 37205, United States
Vanderbilt Stallworth Rehabilitation Hospital
Nashville, Tennessee, 37212, United States
University of Texas - Houston Medical School
Houston, Texas, 77030, United States
Investigational Site - Private Practice
Lubbock, Texas, 79410, United States
Integra Clinical Research, LLC
San Antonio, Texas, 78231, United States
Neurology Health Care Service - Fletcher Allen Hospital
Burlington, Vermont, 05401, United States
University of Virginia - Fontaine Adult Neurology
Charlottesville, Virginia, 22903, United States
Virginia Mason Multiple Sclerosis Center
Seattle, Washington, 98111, United States
Seattle Neuroscience Institute at Swedish Medical Center
Seattle, Washington, 98122, United States
University Health Associates - West Virgina University
Morgantown, West Virginia, 26506, United States
Dean Foundation
Madison, Wisconsin, 53715, United States
University of Wisconsin Medical School
Madison, Wisconsin, 53792, United States
St. Luke's Medical Center
Milwaukee, Wisconsin, 53215, United States
Novartis Investigative Site
North Gosford, New South Wales, Australia
Novartis Investigative Site
Vienna, Austria
Novartis Investigative Site
Ottawa, Ontario, Canada
Novartis Investigative Site
Greenfield Park, Quebec, Canada
Novartis Investigative Site
Bialystok, Poland
Novartis Investigative Site
Warsaw, Poland
Novartis Investigative Site
Bucharest, Romania
Novartis Investigative Site
Târgu Mureş, Romania
Novartis Investigative Site
Istanbul, Turkey (Türkiye)
Novartis Investigative Site
Izmir, Turkey (Türkiye)
Novartis Investigative Site
Yenisehir/Izmir, Turkey (Türkiye)
Novartis Investigative Site
Bristol, United Kingdom
Related Publications (6)
Wang L, Tan H, Yu J, ZhangBao J, Huang W, Chang X, Zhou L, Lu C, Xiao Y, Lu J, Zhao C, Wang M, Wu X, Wu M, Dong Q, Ngew KY, Quan C. Baseline retinal nerve fiber layer thickness as a predictor of multiple sclerosis progression: New insights from the FREEDOMS II study. Eur J Neurol. 2023 Feb;30(2):443-452. doi: 10.1111/ene.15612. Epub 2022 Nov 15.
PMID: 36286605DERIVEDFox RJ, Chan A, Zhang A, Xiao J, Levison D, Lewin JB, Edwards MR, Marantz JL. Comparative effectiveness using a matching-adjusted indirect comparison between delayed-release dimethyl fumarate and fingolimod for the treatment of multiple sclerosis. Curr Med Res Opin. 2017 Feb;33(2):175-183. doi: 10.1080/03007995.2016.1248380. Epub 2016 Nov 10.
PMID: 27733070DERIVEDDerfuss T, Bergvall NK, Sfikas N, Tomic DL. Efficacy of fingolimod in patients with highly active relapsing-remitting multiple sclerosis. Curr Med Res Opin. 2015;31(9):1687-91. doi: 10.1185/03007995.2015.1067191. Epub 2015 Aug 20.
PMID: 26121423DERIVEDChinea Martinez AR, Correale J, Coyle PK, Meng X, Tenenbaum N. Efficacy and safety of fingolimod in Hispanic patients with multiple sclerosis: pooled clinical trial analyses. Adv Ther. 2014 Oct;31(10):1072-81. doi: 10.1007/s12325-014-0154-4. Epub 2014 Sep 23.
PMID: 25245812DERIVEDCalabresi PA, Radue EW, Goodin D, Jeffery D, Rammohan KW, Reder AT, Vollmer T, Agius MA, Kappos L, Stites T, Li B, Cappiello L, von Rosenstiel P, Lublin FD. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2014 Jun;13(6):545-56. doi: 10.1016/S1474-4422(14)70049-3. Epub 2014 Mar 28.
PMID: 24685276DERIVEDWinges KM, Werner JS, Harvey DJ, Cello KE, Durbin MK, Balcer LJ, Calabresi PA, Keltner JL. Baseline retinal nerve fiber layer thickness and macular volume quantified by OCT in the North American phase 3 fingolimod trial for relapsing-remitting multiple sclerosis. J Neuroophthalmol. 2013 Dec;33(4):322-9. doi: 10.1097/WNO.0b013e31829c51f7.
PMID: 24051419DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY CHAIR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
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, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 19, 2006
First Posted
July 21, 2006
Study Start
June 1, 2006
Primary Completion
June 1, 2011
Study Completion
August 1, 2011
Last Updated
August 7, 2012
Results First Posted
June 26, 2012
Record last verified: 2012-08