Efficacy and Safety of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase

Multiple Sclerosis Clinical Trial

— TRANSFORMS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00340834
• Other study ID #: CFTY720D2302
• Secondary ID: CFTY720D2302E1
• Status: Completed
• Phase: Phase 3
• First received: June 19, 2006
• Last updated: August 18, 2017
• Start date: May 2006
• Est. completion date: July 2011

Study information

• Verified date: August 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1292
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Fingolimod 1.25 mg
Core: Patients self-administered fingolimod 1.25 mg capsules orally once daily. In addition, they self-administered an interferon ß-1a placebo intramuscular (im) injection once weekly. Extension: Patients self-administered fingolimod 1.25 mg capsules orally once daily until switched to 0.5 mg capsules upon study protocol amendment.
• Fingolimod 0.5 mg
Core: Patients self-administered fingolimod 0.5 mg capsules orally once daily. In addition, they self-administered an interferon ß-1a placebo intramuscular (im) injection once weekly. Extension: Patients self-administered fingolimod 0.5 mg capsules orally once daily.
• Interferon ß-1a 30 µg
Core: Patients self-administered interferon ß-1a 30 µg in an intramuscular (im) injection once weekly. In addition, they self-administered a fingolimod placebo capsule orally once daily. Extension: Patients self-administered either fingolimod 1.25 mg or 0.5 mg capsules orally once daily until switched to 0.5 mg capsules upon study protocol amendment.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Fundacion Lenox Cordoba	Cordoba
Argentina	Hospital J. M. Ramos Mejia	General Urquiza 609, Buenos Aires
Argentina	Ineba	Guarda Vieja 4435, Capital Federal	Buenos Aires
Argentina	FLENI	Montaneses 2325, Buenos Aires
Argentina	Fundacion Rosarina de Neurorehabilitacion	Rosario	Santa Fe
Argentina	Instituto de Neurociencias de Rosario	Rosario	Santa Fe
Australia	Box Hill Hopsital, Level 3, 16 Arnold Street	Box Hill	Victoria
Australia	Strategic Health Evaluators	Chatswood	New South Wales
Australia	Royal Prince Alfred Hospital	Department of Medicine, Level, Missenden R, Camperdown	New South Wales
Australia	Liverpool Hospital, Neurology Department, Health Services Building, 4th Floor, Goulburn and Campbell Street	Liverpool	New South Wales
Australia	Gosford Private Hospital	North Gosford	New South Wales
Australia	Royal Melbourne Hospital	Suite 30, Grattan St., Parkbville	Victoria
Australia	St George Private Hospital	Suite 7E, Level 5, South Street, Kogarah	New South Wales
Austria	Landes-Narvenklinik Wagner-Jauregg	Abteilung fuer Neurologie, Linz
Austria	Universitätsklinik f. Neurologie Innsbruck	Anichstrasse 35, Innsbruck
Austria	Landes-Nervenklinik Christian Doppler Klinik	Ignaz Harrerstr. 79 , Salzburg
Austria	Landesklinikum St. Poelten, Probst-Ruehrer-Str. 4	St. Poelten	Sankt Poelten
Austria	Evangel.Krankenh./Wien-Waehring Außenstelle	Vienna
Austria	Univ.-Klinik fuer Neurologie AKH	Vienna
Belgium	Cliniques Universitaires Saint Luc	Avenue Hippocrate 10, Bruxelles
Belgium	UZ Brussel	Laarbeeklaan 101, Brussels
Belgium	Nationaal Multiple Sclerose Centrum v.z.w	Melsbroek
Belgium	Regionaal Ziekenhuis Sint-Trudo - Campus Sint-Jozef	Sint-Truiden
Brazil	Hospital das Clincas - UNICAMP	Campinas	SP
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Hospital das Clinicas da FMRPUSP	Ribeirao Preto	SP
Brazil	Hospital dos Servidores do Estado	Rio de Janeiro
Brazil	Hospital Universitario Gaffree e Guinle	Rio de Janeiro
Brazil	Hospital Sao Rafael	Salvador	BA
Canada	Centre Hospitalier Universitaire de Sherbrooke, 3001 12th Avenue North	Fleurimont	Quebec
Canada	Charles Lemoyne Hospital	Greenfield Park	Quebec
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	Montreal Neurological Institute, 3801 University Street	Montreal	Quebec
Canada	Nepean Medical Centre, 1 Centrepointe Drive, Suite 407	Ottawa	Ontario
Canada	The Ottawa General Hospital, 501 Smyth Rd.	Ottawa
Canada	St. Michael's Hospital, Chief, Division of Neurology, 30 Bond Street,Suite 3007 - Shuter Wing	Toronto	Ontario
Canada	Fraser Health MS Clinic, Burnaby Hospital, 3935 Kincaid Street	Vancouver	British Columbia
Canada	UBC MS Research, 2211 Westbrook Mall	Vancouver	British Columbia
Egypt	Private Clinic, 48 Sidi Gaber St.	Alexandria
Egypt	35, Dokki St., Apt. 4	Cairo
Egypt	Al Azhar University, 11 Talaat Harb St, Fourth Floor, Apt 18	Cairo
Egypt	Private Clinic, 35 Dokki St., Apt. 4	Cairo
Egypt	Private Clinic, 7 Batal Ahmed Abdelaziz St Abdeen	Cairo
France	Hopital La Timone Cpcet, Rue Jean Moulin	Marseille
France	Hopital Central, 29 Avenue du Marechal de Lattre de Tassigny	Nancy
France	Hôpital Pellegrin	Place Amélie Raba Léon, Bordeaux Cedex
France	Hopital De Purpan	Place du Dr. Baylac, Toulouse Cedex
France	Centre Hospitalier de Poissy, 10 rue du Champ Gaillard	Poissy
France	Hoppital Pasteur, Archet II, 30 avenue de la Voie	Romaine
Germany	Investigational Site	Bamberg
Germany	Investigational Site	Berlin
Germany	Investigational Site	Berlin
Germany	Investigational Site	Bremen
Germany	Investigational Site	Buchholz
Germany	Investigational Site	Dresden
Germany	Investigational Site	Dusseldorf
Germany	Investigational Site	Erbach/Odenwald
Germany	Investigational Site	Essen
Germany	Investigational Site	Freiburg
Germany	Investigational Site	Greifswald
Germany	Investigational Site	Hamburg
Germany	Investigational Site	Hannover
Germany	Investigational Site	Heidelberg
Germany	Investigational Site	Hennigsdorf
Germany	Investigational Site	Koeln
Germany	Investigational Site	Lengerich
Germany	Investigational Site	Mainz
Germany	Investigational Site	Muenchen
Germany	Investigational Site	Munchen
Germany	Investigational Site	Potsdam
Germany	Investigational Site	Teupitz
Germany	Investigational Site	Trier
Germany	Investigational Site	Tubingen
Germany	Investigational Site	Ulm
Germany	Investigational Site	Ulm
Germany	Investigational Site	Wermsdorf
Germany	Investigational Site	Wurzburg
Greece	Errikos Dinan General Hospital, 107 Mesogion Ave.	Athens
Greece	General Hospital of Athens G. Gennimatas, 154 Mesogeion Ave.	Athens
Greece	Metropolitan Hospital, Ethnarchou Makariou 6 & Eleftheriou Venizelou 1	Athens
Greece	General University Hospital of Patra-RIO	Patra - RIO
Greece	Ahepa University General Hospital of Thessaloniki, 1 Stilp. Kyriakidi Str.	Thessaloniki
Greece	Univ. Hospital of Heraklion	Voutes, Heraklion	Crete
Hungary	Debreceni Egyetem Orvos es Egszstd. Centr.	Debrecen
Hungary	Petz Aladár Megyei Oktató Kórház	Györ
Hungary	Veszprem Megyei Csolnoky Ferenc Korhaz	Korhaz u. 1, Veszprem
Hungary	Pecsi Tudomanyegyetem Neurologiai Klinika	Pecs
Hungary	Peterfy Sandor u. Hospital, Neurology	u. 8-20m, Budapest
Hungary	Uzsoki korhaz	Uzsoki u. 29., Budapest
Italy	Presidio Ospedaliero Roberto Binaghi	Cagliari
Italy	Azienda Ospedaliera Universitaria Arcispedale Sant'Anna	Ferrara
Italy	Presidio Ospedaliero di Vaio Fidenza	Fidenza
Italy	Azienda Sanitaria Osp. S. Luigi	Gonzaga	Orbassano
Italy	Az. Osp. Niguarda Ca' Granda	Milano
Italy	Osp. Magg. Pol. Mangiagalli e Regina Elena - Fond. IRCCS	Milano
Italy	Presidio Ospedaliero di Montichiari	Montichiari
Italy	IRCCS Neurologico C. Mondino	Pavia
Italy	Az. Osp. Ospedale Consorziale e Policlinico	piazza Giulio Cesare, 11 Bari
Italy	Az. Osp. Ospedale S. Martino - Università degli Studi	via Antonio De Toni, 5, Genova
Italy	Ist. Neurol. Mediterraneo Neuromed	Via Atinense, 18, Pozzilli
Italy	Ospedali Riuniti Umberto I - GM Lancisi - G.Salesi	via Conca, 71, Torrette di Ancona
Italy	Osp. Clinicizzato Colle dell'Ara - Università G. D'Annunzio	via dei Vestini, 5 Chieti
Italy	Azienda Ospedaliera Sant'Andrea - Università La Sapienza	Via di Grottarossa, 1035/1039, Roma
Italy	Azienda Ospedaliera di Padova - Università degli Studi	Via Giustiniani, 2, Padova
Italy	Az. Osp. Universitaria Policlinico Tor Vergata	via Montpellier, 1, Roma
Italy	Ospedale San Raffaele - IRCCS	via Olgettina, 48/60, Milano
Italy	Policlinico - Università degli Studi Federico II	via Pansini, 5, Napoli
Italy	Ospedale S. Antonio Abate	via Pastori, 4, Gallarate	VA
Italy	Istituto di Scienze Neurologiche Università di Catania	via Santa Sofia, 78, Catania
Italy	Ospedale Bellaria Maggiore	via Toscana Nazionale, 17/19, Bologna
Italy	Azienda Ospedaliera Careggi - Università degli Studi	Viale Giovan Battista Morgagni, 85, Firenze
Korea, Republic of	National Cancer Center, 809 Madu 1-dong, Ilsan-gu	Kyunggi	Goyang
Korea, Republic of	Samsung Medical Center	Seoul	Korea
Korea, Republic of	Yonsei Univ. Med. Center,Severance Hospital, 134 Shinchon-dong, Suedaemoon-ku	Seoul
Korea, Republic of	Kyung Pook National University Hospital	Taegu
Portugal	Hospital Fernando Fonseca	Amadora
Portugal	Hospitais da Universidade de Coimbra	Av. Dr. Bissaya Barreto, Coimbra
Portugal	Hospital Sto. António dos	Capuchos
Portugal	Hospital de São João	Porto
Portugal	Hospital de S. Bernardo	Rua Camilo Castelo Branco, Setubal
Spain	Complejo Hospitalario Carlos Haya	Avda. Carlos Haya, s/n, Málaga
Spain	Hospital Universitario Virgen Macarena	Avenida Dr. Fedriani, 3, Sevilla
Spain	Ciutat Sanitaria I, Universitaria De Bellvitge, c/o Feixa Llarga, Hospitalet de Llobregat	Barcelona
Spain	Hospital de Basurto	Bilbao
Spain	Hospital Clinico San Carlos	C/ Dr. Martin Lagos, s/n, Madrid
Spain	Unitat de Neuroimmunologia Clinica, Hospital Vall d'Hebron	EUI-planta 2, Pg. Vall d'Hebron 119-29, Barcelona
Spain	Puerta de Huerro Univeristy Hospital	San Martin de Porres, 4, Madrid
Spain	Hospital Universitario La Fe.	Valencia
Switzerland	Universitätsspital Zuerich	Neurologische Klinik, Frauenklinikstrasse 26, Zuerich
Switzerland	Universitätsspital Basel, Neurochirugishen Poliklinik	Petersgraben 4, Basel
United Kingdom	Novartis	Investigational Site
United Kingdom	Charing Cross Hospital	London
United Kingdom	The Walton Centre for Neurology and Neurosurgery	Lower Lane, Fazakerly, Liverpool
United Kingdom	Norfolk & Norwich University Hospital	Norwick
United States	Neurology & Neuroscience Associates, Inc	Akron	Ohio
United States	Northern Ohio Neuroscience, LLC	Bellevue	Ohio
United States	Mountain Empire Neurological Associates, PC, 3183 West State Street, Suite 1201	Bristol	Tennessee
United States	Neuroscience and Spine Center	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	North Central Neurology Associates, PC, 1809 Kress Street	Cullman	Alabama
United States	Associated Neurologists, PC, 69 Sand Pit Road, Suite 300	Danbury	Connecticut
United States	Associated Neurologists of Southern CT, PC, 75 Kings Highway Cutoff	Fairfield	Connecticut
United States	Advanced Neurosciences Institute	Franklin	Tennessee
United States	Absher Neurology, 274-A Commonwealth Drive	Greenville	South Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	University of Florida Health Science Center	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Mid America Neuroscience Institute, 8550 Marshall Drive, Suite 100	Lenexa	Kansas
United States	Private Practice, 3815 23rd Street	Lubbock	Texas
United States	Neurology Associates, PA, 301 N. Maitland Avenue, Suite A1	Maitland	Florida
United States	University of Miami, Department of Neurology	Miami	Florida
United States	Center for Neurological Disorders - Aurora St. Luke's Med Center	Milwaukee	Wisconsin
United States	West Virginia University Health Associates	Morgantown	West Virginia
United States	Yale University Multiple Sclerosis Center	New Haven	Connecticut
United States	The Neurology Center, 3907 Waring Road, Suite 3	Oceanside	California
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	University of Pittsburgh, Department of Neurology	Pittsburgh	Pennsylvania
United States	Neurological Associates	Pompano Beach	Florida
United States	Raleigh Neurology Associates, 1540 Sunday Drive	Raleigh	North Carolina
United States	University Physician Group, #1 Barnes-Jewish Hospital Plaza, Suite 16304	Saint Louis	Missouri
United States	Integra Clinical Research, 4242 Medical Drive, Suite 6100	San Antonio	Texas
United States	Roskamp Institute, 2040 Whitfield Ave.	Sarasota	Florida
United States	Swedish Neuroscience Institute	Seattle	Washington
United States	Rockwood Clinic, P.S.	Spokane	Washington
United States	AMO Corporation	Tallahassee	Florida
United States	Axiom Clinical Research of Florida, 2919 Swann Avenue, Suite 401	Tampa	Florida
United States	University of South Florida, Department of Neurology	Tampa	Florida
United States	Oregon Neurology	Tualatin	Oregon
United States	The MS Center of Vero Beach	Vero Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Egypt,  France,  Germany,  Greece,  Hungary,  Italy,  Korea, Republic of,  Portugal,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimated Annualized Aggregate Relapse Rate (ARR) in the Core Phase of the Study	The 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 calculated using negative binomial regression adjusted by treatment, country, number of relapses in the previous 2 years, and the baseline Expanded Disability Status Scale score.	Baseline to Month 12
Secondary	Number of New or Newly Enlarged T2 Lesions in Comparison With Baseline in the Core Phase of the Study	The number of new or newly enlarged T2 lesions in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.	Baseline to Month 12
Secondary	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	The EDSS is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. Percent of patients free of disability progression was calculated using the Kaplan-Meier method.	Baseline to Month 12
Secondary	Estimated Annualized Aggregate Relapse Rate (ARR) in the Core and Extension Phases of the Study	The 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 calculated using negative binomial regression adjusted by treatment, country, number of relapses in the previous 2 years, and the baseline Expanded Disability Status Scale score.	Month 0 to end of study (up to approximately 4.5 years)
Secondary	Number of New or Newly Enlarged T2 Lesions in the Extension Phase of the Study	The number of new or newly enlarged T2 lesions in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.	Month 12 to end of study (up to approximately 3.5 years)
Secondary	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	The EDSS is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. Percent of patients free of disability progression was calculated using the Kaplan-Meier method.	Baseline to end of study (up to approximately 4.5 years)

External Links

•   Cohen JA, Barkhof F, Comi G, et al., Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis. Published January 20 2010 (10.1056/NEJMoa0907839)
•   Fingolimod clinical trials information website
•   Novartis Clinical Trial Results Database