Clinical trial NCT00340834: Efficacy and Safety of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase
Official title: A 12-month Double-blind, Randomized, Multicenter, Active-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Interferon ß-1a (Avonex) Administered im Once Weekly in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: FTY720
Interferon
RRMS
Multiple Sclerosis
Efficacy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-06-21
Enrollment: 1292
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 2 doses of oral fingolimod versus interferon β-1a to reduce the frequency of relapses in patients with relapsing-remitting multiple sclerosis.


Eligibility criteria: Inclusion Criteria:

* Male and female patients between ages 18-55 with a diagnosis of multiple sclerosis (MS)
* 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
* Patients who cannot tolerate treatment with an interferon

Other protocol-defined inclusion/exclusion criteria applied to the study.

Primary outcomes:
measure: Estimated Annualized Aggregate Relapse Rate (ARR) in the Core Phase of the Study
timeFrame: Baseline to Month 12
Secondary outcomes:
measure: Number of New or Newly Enlarged T2 Lesions in Comparison With Baseline in the Core Phase of the Study
timeFrame: Baseline to Month 12
measure: Percentage of Participants Free of 3-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Core Phase of the Study
timeFrame: Baseline to Month 12
measure: Estimated Annualized Aggregate Relapse Rate (ARR) in the Core and Extension Phases of the Study
timeFrame: Month 0 to end of study (up to approximately 4.5 years)
measure: Number of New or Newly Enlarged T2 Lesions in the Extension Phase of the Study
timeFrame: Month 12 to end of study (up to approximately 3.5 years)
measure: Percentage of Participants Free of 3-month and 6-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Extension Phase of the Study
timeFrame: Baseline to end of study (up to approximately 4.5 years)
Other outcomes:
Locations:
city: Cullman
country: United States
facility: North Central Neurology Associates, PC, 1809 Kress Street
state: Alabama
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Oceanside
country: United States
facility: The Neurology Center, 3907 Waring Road, Suite 3
state: California
city: Danbury
country: United States
facility: Associated Neurologists, PC, 69 Sand Pit Road, Suite 300
state: Connecticut
city: Fairfield
country: United States
facility: Associated Neurologists of Southern CT, PC, 75 Kings Highway Cutoff
state: Connecticut
city: New Haven
country: United States
facility: Yale University Multiple Sclerosis Center
state: Connecticut
city: Jacksonville
country: United States
facility: University of Florida Health Science Center
state: Florida
city: Maitland
country: United States
facility: Neurology Associates, PA, 301 N. Maitland Avenue, Suite A1
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, 2040 Whitfield Ave.
state: Florida
city: Tallahassee
country: United States
facility: AMO Corporation
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida, 2919 Swann Avenue, Suite 401
state: Florida
city: Tampa
country: United States
facility: University of South Florida, Department of Neurology
state: Florida
city: Vero Beach
country: United States
facility: The MS Center of Vero Beach
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lenexa
country: United States
facility: Mid America Neuroscience Institute, 8550 Marshall Drive, Suite 100
state: Kansas
city: Saint Louis
country: United States
facility: University Physician Group, #1 Barnes-Jewish Hospital Plaza, Suite 16304
state: Missouri
city: Charlotte
country: United States
facility: Neuroscience and Spine Center
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates, 1540 Sunday Drive
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: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Tualatin
country: United States
facility: Oregon Neurology
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Department of Neurology
state: Pennsylvania
city: Greenville
country: United States
facility: Absher Neurology, 274-A Commonwealth Drive
state: South Carolina
city: Bristol
country: United States
facility: Mountain Empire Neurological Associates, PC, 3183 West State Street, Suite 1201
state: Tennessee
city: Franklin
country: United States
facility: Advanced Neurosciences Institute
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Lubbock
country: United States
facility: Private Practice, 3815 23rd Street
state: Texas
city: San Antonio
country: United States
facility: Integra Clinical Research, 4242 Medical Drive, Suite 6100
state: Texas
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Spokane
country: United States
facility: Rockwood Clinic, P.S.
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Health Associates
state: West Virginia
city: Milwaukee
country: United States
facility: Center for Neurological Disorders - Aurora St. Luke's Med Center
state: Wisconsin
city: Guarda Vieja 4435, Capital Federal
country: Argentina
facility: Ineba
state: Buenos Aires
city: Rosario
country: Argentina
facility: Fundacion Rosarina de Neurorehabilitacion
state: Santa Fe
city: Rosario
country: Argentina
facility: Instituto de Neurociencias de Rosario
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Cordoba
country: Argentina
facility: Fundacion Lenox Cordoba
city: General Urquiza 609, Buenos Aires
country: Argentina
facility: Hospital J. M. Ramos Mejia
city: Montaneses 2325, Buenos Aires
country: Argentina
facility: FLENI
city: Chatswood
country: Australia
facility: Strategic Health Evaluators
state: New South Wales
city: Department of Medicine, Level, Missenden R, Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital, Neurology Department, Health Services Building, 4th Floor, Goulburn and Campbell Street
state: New South Wales
city: North Gosford
country: Australia
facility: Gosford Private Hospital
state: New South Wales
city: Suite 7E, Level 5, South Street, Kogarah
country: Australia
facility: St George Private Hospital
state: New South Wales
city: Box Hill
country: Australia
facility: Box Hill Hopsital, Level 3, 16 Arnold Street
state: Victoria
city: Suite 30, Grattan St., Parkbville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: St. Poelten
country: Austria
facility: Landesklinikum St. Poelten, Probst-Ruehrer-Str. 4
state: Sankt Poelten
city: Abteilung fuer Neurologie, Linz
country: Austria
facility: Landes-Narvenklinik Wagner-Jauregg
city: Anichstrasse 35, Innsbruck
country: Austria
facility: Universitätsklinik f. Neurologie Innsbruck
city: Ignaz Harrerstr. 79 , Salzburg
country: Austria
facility: Landes-Nervenklinik Christian Doppler Klinik
city: Vienna
country: Austria
facility: Evangel.Krankenh./Wien-Waehring Außenstelle
city: Vienna
country: Austria
facility: Univ.-Klinik fuer Neurologie AKH
city: Avenue Hippocrate 10, Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Laarbeeklaan 101, Brussels
country: Belgium
facility: UZ Brussel
city: Melsbroek
country: Belgium
facility: Nationaal Multiple Sclerose Centrum v.z.w
city: Sint-Truiden
country: Belgium
facility: Regionaal Ziekenhuis Sint-Trudo - Campus Sint-Jozef
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
state: BA
city: Campinas
country: Brazil
facility: Hospital das Clincas - UNICAMP
state: SP
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas da FMRPUSP
state: SP
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Hospital dos Servidores do Estado
city: Rio de Janeiro
country: Brazil
facility: Hospital Universitario Gaffree e Guinle
city: Vancouver
country: Canada
facility: Fraser Health MS Clinic, Burnaby Hospital, 3935 Kincaid Street
state: British Columbia
city: Vancouver
country: Canada
facility: UBC MS Research, 2211 Westbrook Mall
state: British Columbia
city: Ottawa
country: Canada
facility: Nepean Medical Centre, 1 Centrepointe Drive, Suite 407
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital, Chief, Division of Neurology, 30 Bond Street,Suite 3007 - Shuter Wing
state: Ontario
city: Fleurimont
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke, 3001 12th Avenue North
state: Quebec
city: Greenfield Park
country: Canada
facility: Charles Lemoyne Hospital
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institute, 3801 University Street
state: Quebec
city: Ottawa
country: Canada
facility: The Ottawa General Hospital, 501 Smyth Rd.
city: Alexandria
country: Egypt
facility: Private Clinic, 48 Sidi Gaber St.
city: Cairo
country: Egypt
facility: 35, Dokki St., Apt. 4
city: Cairo
country: Egypt
facility: Al Azhar University, 11 Talaat Harb St, Fourth Floor, Apt 18
city: Cairo
country: Egypt
facility: Private Clinic, 35 Dokki St., Apt. 4
city: Cairo
country: Egypt
facility: Private Clinic, 7 Batal Ahmed Abdelaziz St Abdeen
city: Marseille
country: France
facility: Hopital La Timone Cpcet, Rue Jean Moulin
city: Nancy
country: France
facility: Hopital Central, 29 Avenue du Marechal de Lattre de Tassigny
city: Place Amélie Raba Léon, Bordeaux Cedex
country: France
facility: Hôpital Pellegrin
city: Place du Dr. Baylac, Toulouse Cedex
country: France
facility: Hopital De Purpan
city: Poissy
country: France
facility: Centre Hospitalier de Poissy, 10 rue du Champ Gaillard
city: Romaine
country: France
facility: Hoppital Pasteur, Archet II, 30 avenue de la Voie
city: Bamberg
country: Germany
facility: Investigational Site
city: Berlin
country: Germany
facility: Investigational Site
city: Berlin
country: Germany
facility: Investigational Site
city: Bremen
country: Germany
facility: Investigational Site
city: Buchholz
country: Germany
facility: Investigational Site
city: Dresden
country: Germany
facility: Investigational Site
city: Dusseldorf
country: Germany
facility: Investigational Site
city: Erbach/Odenwald
country: Germany
facility: Investigational Site
city: Essen
country: Germany
facility: Investigational Site
city: Freiburg
country: Germany
facility: Investigational Site
city: Greifswald
country: Germany
facility: Investigational Site
city: Hamburg
country: Germany
facility: Investigational Site
city: Hannover
country: Germany
facility: Investigational Site
city: Heidelberg
country: Germany
facility: Investigational Site
city: Hennigsdorf
country: Germany
facility: Investigational Site
city: Koeln
country: Germany
facility: Investigational Site
city: Lengerich
country: Germany
facility: Investigational Site
city: Mainz
country: Germany
facility: Investigational Site
city: Muenchen
country: Germany
facility: Investigational Site
city: Munchen
country: Germany
facility: Investigational Site
city: Potsdam
country: Germany
facility: Investigational Site
city: Teupitz
country: Germany
facility: Investigational Site
city: Trier
country: Germany
facility: Investigational Site
city: Tubingen
country: Germany
facility: Investigational Site
city: Ulm
country: Germany
facility: Investigational Site
city: Ulm
country: Germany
facility: Investigational Site
city: Wermsdorf
country: Germany
facility: Investigational Site
city: Wurzburg
country: Germany
facility: Investigational Site
city: Voutes, Heraklion
country: Greece
facility: Univ. Hospital of Heraklion
state: Crete
city: Athens
country: Greece
facility: Errikos Dinan General Hospital, 107 Mesogion Ave.
city: Athens
country: Greece
facility: General Hospital of Athens G. Gennimatas, 154 Mesogeion Ave.
city: Athens
country: Greece
facility: Metropolitan Hospital, Ethnarchou Makariou 6 & Eleftheriou Venizelou 1
city: Patra - RIO
country: Greece
facility: General University Hospital of Patra-RIO
city: Thessaloniki
country: Greece
facility: Ahepa University General Hospital of Thessaloniki, 1 Stilp. Kyriakidi Str.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos es Egszstd. Centr.
city: Györ
country: Hungary
facility: Petz Aladár Megyei Oktató Kórház
city: Korhaz u. 1, Veszprem
country: Hungary
facility: Veszprem Megyei Csolnoky Ferenc Korhaz
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Neurologiai Klinika
city: u. 8-20m, Budapest
country: Hungary
facility: Peterfy Sandor u. Hospital, Neurology
city: Uzsoki u. 29., Budapest
country: Hungary
facility: Uzsoki korhaz
city: Gonzaga
country: Italy
facility: Azienda Sanitaria Osp. S. Luigi
state: Orbassano
city: via Pastori, 4, Gallarate
country: Italy
facility: Ospedale S. Antonio Abate
state: VA
city: Cagliari
country: Italy
facility: Presidio Ospedaliero Roberto Binaghi
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria Arcispedale Sant'Anna
city: Fidenza
country: Italy
facility: Presidio Ospedaliero di Vaio Fidenza
city: Milano
country: Italy
facility: Osp. Magg. Pol. Mangiagalli e Regina Elena - Fond. IRCCS
city: Milano
country: Italy
facility: Az. Osp. Niguarda Ca' Granda
city: Montichiari
country: Italy
facility: Presidio Ospedaliero di Montichiari
city: Pavia
country: Italy
facility: IRCCS Neurologico C. Mondino
city: piazza Giulio Cesare, 11 Bari
country: Italy
facility: Az. Osp. Ospedale Consorziale e Policlinico
city: via Antonio De Toni, 5, Genova
country: Italy
facility: Az. Osp. Ospedale S. Martino - Università degli Studi
city: Via Atinense, 18, Pozzilli
country: Italy
facility: Ist. Neurol. Mediterraneo Neuromed
city: via Conca, 71, Torrette di Ancona
country: Italy
facility: Ospedali Riuniti Umberto I - GM Lancisi - G.Salesi
city: via dei Vestini, 5 Chieti
country: Italy
facility: Osp. Clinicizzato Colle dell'Ara - Università G. D'Annunzio
city: Via di Grottarossa, 1035/1039, Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea - Università La Sapienza
city: Via Giustiniani, 2, Padova
country: Italy
facility: Azienda Ospedaliera di Padova - Università degli Studi
city: via Montpellier, 1, Roma
country: Italy
facility: Az. Osp. Universitaria Policlinico Tor Vergata
city: via Olgettina, 48/60, Milano
country: Italy
facility: Ospedale San Raffaele - IRCCS
city: via Pansini, 5, Napoli
country: Italy
facility: Policlinico - Università degli Studi Federico II
city: via Santa Sofia, 78, Catania
country: Italy
facility: Istituto di Scienze Neurologiche Università di Catania
city: via Toscana Nazionale, 17/19, Bologna
country: Italy
facility: Ospedale Bellaria Maggiore
city: Viale Giovan Battista Morgagni, 85, Firenze
country: Italy
facility: Azienda Ospedaliera Careggi - Università degli Studi
city: Kyunggi
country: Korea, Republic of
facility: National Cancer Center, 809 Madu 1-dong, Ilsan-gu
state: Goyang
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Korea
city: Seoul
country: Korea, Republic of
facility: Yonsei Univ. Med. Center,Severance Hospital, 134 Shinchon-dong, Suedaemoon-ku
city: Taegu
country: Korea, Republic of
facility: Kyung Pook National University Hospital
city: Amadora
country: Portugal
facility: Hospital Fernando Fonseca
city: Av. Dr. Bissaya Barreto, Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra
city: Capuchos
country: Portugal
facility: Hospital Sto. António dos
city: Porto
country: Portugal
facility: Hospital de São João
city: Rua Camilo Castelo Branco, Setubal
country: Portugal
facility: Hospital de S. Bernardo
city: Avda. Carlos Haya, s/n, Málaga
country: Spain
facility: Complejo Hospitalario Carlos Haya
city: Avenida Dr. Fedriani, 3, Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Barcelona
country: Spain
facility: Ciutat Sanitaria I, Universitaria De Bellvitge, c/o Feixa Llarga, Hospitalet de Llobregat
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: C/ Dr. Martin Lagos, s/n, Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: EUI-planta 2, Pg. Vall d'Hebron 119-29, Barcelona
country: Spain
facility: Unitat de Neuroimmunologia Clinica, Hospital Vall d'Hebron
city: San Martin de Porres, 4, Madrid
country: Spain
facility: Puerta de Huerro Univeristy Hospital
city: Valencia
country: Spain
facility: Hospital Universitario La Fe.
city: Neurologische Klinik, Frauenklinikstrasse 26, Zuerich
country: Switzerland
facility: Universitätsspital Zuerich
city: Petersgraben 4, Basel
country: Switzerland
facility: Universitätsspital Basel, Neurochirugishen Poliklinik
city: Investigational Site
country: United Kingdom
facility: Novartis
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: Lower Lane, Fazakerly, Liverpool
country: United Kingdom
facility: The Walton Centre for Neurology and Neurosurgery
city: Norwick
country: United Kingdom
facility: Norfolk & Norwich University Hospital
Study officials:
affiliation: Novartis Pharmacuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Cohen JA, Khatri B, Barkhof F, Comi G, Hartung HP, Montalban X, Pelletier J, Stites T, Ritter S, von Rosenstiel P, Tomic D, Kappos L; TRANSFORMS (TRial Assessing injectable interferoN vS. FTY720 Oral in RRMS) Study Group. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study. J Neurol Neurosurg Psychiatry. 2016 May;87(5):468-75. doi: 10.1136/jnnp-2015-310597. Epub 2015 Jun 25.
citation: Khatri BO, Pelletier J, Kappos L, Hartung HP, Comi G, Barkhof F, von Rosenstiel P, Meng X, Grinspan A, Hashmonay R, Cohen JA; TRANSFORMS Study Group. Effect of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod vs. interferon beta-1a intramuscular: Subgroup analyses of the Trial Assessing Injectable Interferon vs. Fingolimod Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS). Mult Scler Relat Disord. 2014 May;3(3):355-63. doi: 10.1016/j.msard.2013.11.006. Epub 2013 Dec 12.
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: Zarbin MA, Jampol LM, Jager RD, Reder AT, Francis G, Collins W, Tang D, Zhang X. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology. 2013 Jul;120(7):1432-9. doi: 10.1016/j.ophtha.2012.12.040. Epub 2013 Mar 24.
citation: Khatri B, Barkhof F, Comi G, Hartung HP, Kappos L, Montalban X, Pelletier J, Stites T, Wu S, Holdbrook F, Zhang-Auberson L, Francis G, Cohen JA; TRANSFORMS Study Group. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011 Jun;10(6):520-9. doi: 10.1016/S1474-4422(11)70099-0. Epub 2011 May 13.
citation: Twiss J, Doward LC, McKenna SP, Eckert B. Interpreting scores on multiple sclerosis-specific patient reported outcome measures (the PRIMUS and U-FIS). Health Qual Life Outcomes. 2010 Oct 11;8:117. doi: 10.1186/1477-7525-8-117.
citation: Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S, Aradhye S, Kappos L; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):402-15. doi: 10.1056/NEJMoa0907839. Epub 2010 Jan 20.