Clinical trial NCT00355134: Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: fingolimod
FTY720
relapsing-remitting multiple sclerosis
MS
RRMS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-07-21
Enrollment: 1083
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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 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.

Primary outcomes:
measure: Aggregate Annualized Relapse Rate (ARR) Estimate up to Month 24
timeFrame: 24 months
Secondary outcomes:
measure: Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study
timeFrame: From Baseline until end of study (up to approximately 54 months).
measure: Percent Change From Baseline in Brain Volume
timeFrame: Baseline, Month 24 and end of study (up to approximately 54 months)
measure: Number of New or Newly Enlarged T2 Lesions
timeFrame: From Baseline until Month 48
measure: Number of Gadolinium-enhanced T1 Lesions
timeFrame: Month 24 and end of study (up to approximately 54 months)
measure: Change From Baseline in Lesion Volume at Month 24 (Core Phase)
timeFrame: Baseline and Month 24
measure: Percentage of Participants Free of 3-month Confirmed Disability Progression at Month 24 and End of Study
timeFrame: 24 months and end of study (up to approximately 54 months)
measure: Percentage of Participants Free of 6-month Confirmed Disability Progression at Month 24 and End of Study
timeFrame: 24 months and end of study (up to approximately 54 months)
measure: Percentage of Participants Relapse-free up to Month 24
timeFrame: 24 months
measure: Percentage of Participants Relapse-free up to End of Study
timeFrame: From Baseline until the end of study (up to approximately 54 months)
measure: Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z-score
timeFrame: Baseline, Month 24 and end of study (up to approximately 54 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Cullman
country: United States
facility: North Central Neurology Associates, PC
state: Alabama
city: Mobile
country: United States
facility: University of South Alabama - Dept of Neurology
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurology Clinic
state: Arizona
city: Berkeley
country: United States
facility: Research and Education Institute of Alta Bates Summit Medical Center
state: California
city: Irvine
country: United States
facility: University of California - Irvine, Deptarment of Neurology
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Oceanside
country: United States
facility: The Neurology Center
state: California
city: Pasadena
country: United States
facility: Neuro-Therapeutics, Inc.
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Francisco
country: United States
facility: Multiple Sclerosis Center at UCSF
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Danbury
country: United States
facility: Associated Neurologists, PC
state: Connecticut
city: Fairfield
country: United States
facility: Associated Neurologists of Southern CT, P.C.
state: Connecticut
city: New Haven
country: United States
facility: Yale University - Yale Multiple Sclerosis Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital - Dept of Neurology
state: District of Columbia
city: Hollywood
country: United States
facility: Sunrise Clinical Research, Inc.
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health Sciences Center/Shands Jacksonville
state: Florida
city: Maitland
country: United States
facility: Neurology Associates, PA
state: Florida
city: Miami
country: United States
facility: University of Miami, Department of Neurology
state: Florida
city: Pompano Beach
country: United States
facility: Neurological Associates
state: Florida
city: Sarasota
country: United States
facility: Roskamp Institute, Clinical Trials Division
state: Florida
city: Sunrise
country: United States
facility: Neurology Clinical Research, Inc
state: Florida
city: Tallahassee
country: United States
facility: AMO Corporation
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Vero Beach
country: United States
facility: The MS Center of Vero Beach
state: Florida
city: Atlanta
country: United States
facility: MS Center of Atlanta
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Medical School - Dept of Neurology
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center Department of Neurological Sciences
state: Illinois
city: Chicago
country: United States
facility: University of Chicago - Dept of Neurology
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neurosciences Research
state: Illinois
city: Flossmoor
country: United States
facility: South Suburban Neurology
state: Illinois
city: Palos Heights
country: United States
facility: Neurologic Associates, Ltd.
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Des Moines
country: United States
facility: Ruan Neurology Clinical Research Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lenexa
country: United States
facility: Mid America Neuroscience Institute
state: Kansas
city: Louisville
country: United States
facility: Kentucky Research Associates
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins MS Center
state: Maryland
city: Brighton
country: United States
facility: Caritas St. Elizabeth's Medical Center
state: Massachusetts
city: Newton
country: United States
facility: Newton Wesley Hospital
state: Massachusetts
city: Springfield
country: United States
facility: Springfield Neurology
state: Massachusetts
city: Worchester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Mulitiple Sclerosis Clinic
state: Michigan
city: Detroit
country: United States
facility: Wayne State University MS Clinic
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital, Department of Neurology
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University MS Clinic
state: Michigan
city: Grand Rapids
country: United States
facility: Michigan Medical, P.C.
state: Michigan
city: St. Clair Shores
country: United States
facility: Michigan Neurology Associates, PC
state: Michigan
city: Kansas City
country: United States
facility: St. Luke's Hospital - Mid-America Brain and Stroke Institute
state: Missouri
city: St. Louis
country: United States
facility: The MS Center for Innovation in Care
state: Missouri
city: Reno
country: United States
facility: Institute for Neurosciences
state: Nevada
city: Lebanon
country: United States
facility: Multiple Sclerosis Center
state: New Hampshire
city: Teaneck
country: United States
facility: Gimbel Multiple Sclerosis Center at Holy Name Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Health Science Center
state: New Mexico
city: Latham
country: United States
facility: Empire Neurology, PC
state: New York
city: New York
country: United States
facility: NYU Hospital for Joint Diseases
state: New York
city: New York
country: United States
facility: Cornell University - NY Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Plainview
country: United States
facility: Island Neurological Associates, PC
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Staten Island
country: United States
facility: Alpha Neurology
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: UNC - Chapel Hill Neuroscience Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Akron
country: United States
facility: Neurology & Neuroscience Associates, Inc.
state: Ohio
city: Bellevue
country: United States
facility: Northern Ohio Neuroscience, LLC.
state: Ohio
city: Canton
country: United States
facility: NeuroCare Center, Inc
state: Ohio
city: Cincinnati
country: United States
facility: River Hills Health Care
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Health Science Campus
state: Ohio
city: Uniontown
country: United States
facility: Oak Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: MS Center of Oklahoma, Mercy Neuroscience Institute
state: Oklahoma
city: Tulsa
country: United States
facility: Neurologial Associates of Tulsa
state: Oklahoma
city: Tualatin
country: United States
facility: Oregon Neurology
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania, Department of Neurology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital, Department of Neurology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Neurological Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh - Dept of Neurology
state: Pennsylvania
city: Greenville
country: United States
facility: Absher Neurology
state: South Carolina
city: Bristol
country: United States
facility: Mountain Empire Neurological Associates, PC
state: Tennessee
city: Nashville
country: United States
facility: Advanced Neurosciences Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Stallworth Rehabilitation Hospital
state: Tennessee
city: Houston
country: United States
facility: University of Texas - Houston Medical School
state: Texas
city: Lubbock
country: United States
facility: Investigational Site - Private Practice
state: Texas
city: San Antonio
country: United States
facility: Integra Clinical Research, LLC
state: Texas
city: Burlington
country: United States
facility: Neurology Health Care Service - Fletcher Allen Hospital
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia - Fontaine Adult Neurology
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Multiple Sclerosis Center
state: Washington
city: Seattle
country: United States
facility: Seattle Neuroscience Institute at Swedish Medical Center
state: Washington
city: Morgantown
country: United States
facility: University Health Associates - West Virgina University
state: West Virginia
city: Madison
country: United States
facility: Dean Foundation
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Medical School
state: Wisconsin
city: Milwaukee
country: United States
facility: St. Luke's Medical Center
state: Wisconsin
city: North Gosford
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Greenfield Park
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Bialystok
country: Poland
facility: Novartis Investigative Site
city: Warsaw
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Targu Mures
country: Romania
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Yenisehir/Izmir
country: Turkey
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_CHAIR
References:
citation: 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.
citation: Fox 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.
citation: Derfuss 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.
citation: Chinea 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.
citation: Calabresi 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.
citation: Winges 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.