Clinical Study to Compare the Efficacy and Safety of Ponesimod to Placebo in Subjects With Active Relapsing Multiple Sclerosis Who Are Treated With Dimethyl Fumarate (Tecfidera®)
- Registration Number
- NCT02907177
- Lead Sponsor
- Actelion
- Brief Summary
This clinical study compares the efficacy, safety, and tolerability of therapy with ponesimod vs placebo in subjects with active RMS who are treated with DMF (Tecfidera®).
- Detailed Description
The study will assess the efficacy, safety, and tolerability of add-on therapy with ponesimod 20 mg vs placebo in adult participants with active relapsing multiple sclerosis (RMS) who are treated with dimethyl fumarate (DMF). Approximately 600 participants who have been receiving DMF for at least 6 months will be randomized in a 1:1 ratio to ponesimod 20 mg or placebo. The study consists of the following study periods: Pre-randomization period; Treatment period; Post-treatment observation period. The study includes one ponesimod treatment arm at the maintenance dose of 20 mg o.d. corresponding to the optimal dose when used as monotherapy based on the Phase 2 dose-finding trial and its ongoing extension. The study includes a placebo comparator arm, but all patients will remain on DMF background therapy throughout the study. Moreover, participants who experience a confirmed relapse or an event of 24-week confirmed disability accumulation (DMF) while on study drug will have the option to switch to an alternative treatment. The treatment period has a variable duration from a minimum of 60 weeks (for the last subject randomized) to a maximum of 156 weeks for the first subjects randomized in the trial and includes a gradual up-titration of ponesimod from a 2 mg starting dose to a 20 mg maintenance dose over a period of 14 days. The total duration of the study will be approximately up to 167 weeks.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 136
- Signed informed consent prior to initiation of any study-mandated procedure.
- Women of childbearing potential must have a negative pregnancy test and use reliable methods of contraception
- Presenting with a diagnosis of MS as defined by the revised (2010) McDonald Diagnostic Criteria for MS with relapsing course from onset (i.e., relapsing-remitting multiple sclerosis (RRMS), or secondary progressive multiple sclerosis (SPMS) with superimposed relapses).
- Ongoing treatment with DMF for at least 6 months prior to screening
- Active disease after at least 3 months of DMF treatment
- Ambulatory and with an EDSS score between 0 and 6.0 (inclusive).
- Lactating or pregnant women and women intending to become pregnant during the study.
- Presenting with a diagnosis of MS with progressive course from onset (i.e., primary progressive MS or progressive relapsing MS).
- Evidence of a relapse of MS with onset within 30 days prior to baseline EDSS assessment.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ponesimod Ponesimod Ponesimod Placebo Placebo Placebo
- Primary Outcome Measures
Name Time Method Annualized Confirmed Relapse Rate (ARR) Through study completion, an average of 68 weeks Relapse: occurrence of acute episode of one or more new or worsened symptoms of Multiple sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicates overall functional impairment assessing Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS in conjunction with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10(death due to MS).
- Secondary Outcome Measures
Name Time Method Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) as Assessed by Kaplan Meier Estimate at Week 96 Week 96 Percentage of participants with 12-week CDA as assessed by Kaplan Meier estimate at week 96 was defined as an increase of at least 1.5 in Expanded Disability Status Scale (EDSS) for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score greater than or equal to (\>=) 5.5, which was confirmed after 12 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS).
Percentage of Participants Experiencing a Confirmed Relapse as Assessed by Kaplan Meier Estimate at Week 96 Week 96 Percentage of participants experiencing a confirmed relapse as assessed by Kaplan Meier estimate at week 96 was reported. The time to first confirmed relapse (in days) is defined as \[Date of first confirmed relapse minus Date of randomization plus 1\] in days. Relapse: Occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple sclerosis (MS), not related with fever/infection and lasting 24 hours after 30 days stable period.
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability Up to 147 Weeks An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Trial Locations
- Locations (119)
Associated Neurologists
🇺🇸Danbury, Connecticut, United States
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
OhioHealth Research Institute
🇺🇸Columbus, Ohio, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
MS Ambulanz Maida
🇦🇹Wien, Austria
"University Multiprofile Hospital for Active Treatment - Alexandrovska" EAD, Neurology Clinic
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD, Neurology Clinic
🇧🇬Sofia, Bulgaria
Henry Ford Health System - Neurology
🇺🇸Detroit, Michigan, United States
Neurology and Neuromuscular Center
🇺🇸Oklahoma City, Oklahoma, United States
Neurology Center of San Antonio
🇺🇸San Antonio, Texas, United States
IRCCS NEUROMED - Istituto Neurologico Mediterraneo - Unità Operativa di Neurologia I
🇮🇹Pozzilli, Italy
Neurology Associates - MS Center of Greater Orlando
🇺🇸Maitland, Florida, United States
Care Access Research - Santa Clarita
🇺🇸Santa Clarita, California, United States
Aalborg Universitetshospital, Skleroseklinikken Neurologisk afdelning
🇩🇰Aalborg, Denmark
Pardubicka krajska nemocnice, MS Centrum
🇨🇿Pardubice, Czechia
Neurology Assoc of Ormond Beach - CNS Trials
🇺🇸Ormond Beach, Florida, United States
University of Alberta
🇨🇦Edmonton, Canada
Glostrup Hospital, Neurologisk afdelning
🇩🇰Glostrup, Denmark
Riverhills Healthcare, Inc.
🇺🇸Cincinnati, Ohio, United States
Hôpital Universitaire Carémeau, Service de Neurologie
🇫🇷Nimes, France
Hopital Gui de Chauliac - CHU Montpellier
🇫🇷Montpellier, France
The MS Center of Vero Beach
🇺🇸Vero Beach, Florida, United States
Nemocnice Jihlava, Neurologické oddělení
🇨🇿Jihlava, Czechia
Bradenton Research Center
🇺🇸Bradenton, Florida, United States
Fort Wayne Neurological Center - North Office
🇺🇸Fort Wayne, Indiana, United States
Univ of New Mexico - Health Sciences Center
🇺🇸Albuquerque, New Mexico, United States
Austin Health - Neuro-Immunology Clinical Research, Education and Support Service
🇦🇺Heidelberg, Victoria, Australia
SC3 Research - Pasadena
🇺🇸Pasadena, California, United States
AOU San Martino di Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI)
🇮🇹Genova, Italy
Uzsoki utcai Kórház, Neurológiai Osztály
🇭🇺Budapest, Hungary
AFL Arzneimittelforschung Leipzig GmbH
🇩🇪Leipzig, Germany
Universitätsklinikum Giessen Klinik und Poliklinik für Neurologie
🇩🇪Giessen, Germany
Fakultní nemocnice Hradec Králové, Neurologická klinika
🇨🇿Hradec Králové, Czechia
CHRU de Lille - Hôpital Roger Salengro, Service de Neurologie
🇫🇷Lille, France
Centre Hospitalier Sud Francilien - Service de Neurologie
🇫🇷Corbeil-Essonnes, France
Fakultní nemocnice u sv. Anny Brno, RS Centrum
🇨🇿Brno, Czechia
Hôpital Avicenne, Service de Neurologie
🇫🇷Bobigny, France
CHU de Dijon - Hôpital François Miterrand, Service de Neurologie
🇫🇷Dijon, France
Hosp Gabriel Montpied, Dept Neurology
🇫🇷Clermont Ferrand, France
Medical Center of Athens - Neurology Dpt
🇬🇷Marousi, Greece
CHI POISSY-Saint Germay en Laye_Service de Neurologie et Réeducation
🇫🇷Poissy, France
Hosp Pontchaillou, Dept Cardiology
🇫🇷Rennes, France
Hosp Charles Nicolle Dept Neurology
🇫🇷Rouen, France
Fondazione Istituto San Raffaele , Unità Operativa di Neurologia
🇮🇹Cefalù, Italy
Università degli Studi di Firenze - Azienda Ospedaliero Universitaria Careggi - CTO - SOD Neurologia 2
🇮🇹Firenze, Italy
Medizinische Hochschule Hannover, Neurologie
🇩🇪Hannover, Germany
Naval Hospital of Athens - Neurology Dpt
🇬🇷Athens, Greece
General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Istituto Neurologico Carlo Besta, UOC Neurologia 4, Neuroimmunologia e Malattie Neuromuscolari, Centro Sclerosi Multipla
🇮🇹Milano, Italy
Azienda Ospedaliera Universitaria (AOU) "Federico II" - Centro Regionale Per la Sclerosi Multipla c/o Clinica Neurologica II - Dipartimento di Scienze
🇮🇹Napoli, Italy
AOU Università degli Studi della Campania L. Vanvitelli - I° Policlinico - DAI di Medicina Interna e Specialistica CS, Centro Sclerosi Multipla
🇮🇹Napoli, Italy
Azienda Ospedaliero Universitaria San Luigi Gonzaga - Centro Sclerosi Multipla CRESM
🇮🇹Orbassano, Italy
Azienda Ospedaliera Universitaria Senese - Dipartimento di Scienze Neurologiche e neurosensoriali - UOSA Neurologia Sperimentale
🇮🇹Siena, Italy
Unidad de Investigacion en Salud de Chihuahua SC, Médica Sur, Unidad de Neurociencias
🇲🇽Tlalpan, DF, Mexico
Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Neurologii i Oddziat Udarowy
🇵🇱Bialystok, Poland
Azienda Ospedaliera S. Andrea di Roma - Unità Operativa Complessa di Neurologia
🇮🇹Roma, Italy
B&B Robert Bonek, Pawel Bochniak S.C
🇵🇱Bydgoszcz, Poland
Neuro-Medic Janusz Zbrojkiewicz Poradnia Weilospecjalistyczna
🇵🇱Katowice, Poland
Centrum Terapii SM
🇵🇱Katowice, Poland
Neuro-Clinic, LLC
🇷🇺Moscow, Russian Federation
Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Neurology Department 2
🇪🇸Santiago de Compostela, Spain
Hospital Santa Caterina - Neurology Department
🇪🇸Salt, Spain
Hosp Gregorio Marañón, Neurology
🇪🇸Madrid, Spain
Univeritätsspital Basel Neurologie, Neurologische Klinik und Poliklinik
🇨🇭Basel, Switzerland
Queen Square MS Centre / NMR research Unit UCL Institute of Neurology
🇬🇧London, United Kingdom
Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Moscow State Budgetary Healthcare Institution Pirogov City Clinical Hospital No. 1 of Moscow Health Department
🇷🇺Moscow, Russian Federation
Moscow State Budgetary Healthcare Institution City Clinical Hospital No. 24 of Moscow Health Department
🇷🇺Moscow, Russian Federation
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Gemeinschaftspraxis Dr. med. Joachim Springub / Wolfgang Schwarz, Studienzentrum Nord-West (Study Center)
🇩🇪Westerstede, Germany
Universitätsklinikum Münster, Klinik für Allgemeine Neurologie
🇩🇪Münster, Germany
Medizinzentrum Siegerland Weidenau
🇩🇪Siegen, Germany
University of Kansas Med Center
🇺🇸Kansas City, Kansas, United States
Krajská zdravotní a.s. - Nemonice Teplice o.z., RS Centrum
🇨🇿Teplice, Czechia
Mountain View Clinical Research, Inc
🇺🇸Denver, Colorado, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
Hospital Universitario Virgen Macarena - Neurofisiology Department
🇪🇸Sevilla, Spain
Advanced Neuroscience Institute
🇺🇸Franklin, Tennessee, United States
University Hospitals of North Midlands NHS Trust
🇬🇧Stoke-on-Trent, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Aeginition Hospital - Neurology Department
🇬🇷Athens, Greece
Neuro-Pain Medical Center
🇺🇸Fresno, California, United States
UAB Dpt of Neurology
🇺🇸Birmingham, Alabama, United States
Suncoast Neuroscience Associates, Inc
🇺🇸Saint Petersburg, Florida, United States
NYU Langone Medical Center - MS Comprehensive Care Center
🇺🇸New York, New York, United States
Thomas Jefferson University Hospital - Dpt Neurology MS Center
🇺🇸Philadelphia, Pennsylvania, United States
Medizinische Universität Wien, Universitätsklinik für Neurologie
🇦🇹Wien, Austria
"Multiprofile Hospital for Active Treatment of Neurology and Psychiatry - Sveti Naum" EAD - Neurology Clinic for Movement Disorders
🇧🇬Sofia, Bulgaria
Hospital - Revalidatie & MS Centrum Overpelt_Neurology Department
🇧🇪Overpelt, Belgium
Hôpital Central - CHU Nancy, Département Neurologie
🇫🇷Nancy, France
Neurologische Klinik und Poliklinik - Universitätsklinikum Carl Gustav Carus, Zentrum für klinische Neurowissenschaften
🇩🇪Dresden, Germany
Universitätsmedizin Greifswald - Körperschaft des öffentlichen Rechts - Klinik und Poliklinik für Neurologie
🇩🇪Greifswald, Germany
Zentrum für klinische Forschung Dr. med. Irma Schöll
🇩🇪Bad Homburg, Germany
NeuroPoint GmbH, Gesellschaft für vorbeugende Gesundheitspflege
🇩🇪Ulm, Germany
401 Military Hospital of Athens - Neurology Dept
🇬🇷Athens, Greece
Desarrollo Ético en Investigación Clínica S.C .
🇲🇽Guadalajara, Jalisco, Mexico
COPERNICUS - Podmiot Leczniczy Sp. z o.o.
🇵🇱Gdansk, Poland
Unidad de Investigación de Salud en Chihuahua
🇲🇽Chihuahua, Mexico
State Budgetary Healthcare Institution Regional Clinical Hospital No 3
🇷🇺Chelyabinsk, Russian Federation
Center of Professional Therapy, LLC
🇷🇺Krasnodar, Russian Federation
Moscow State Budgetary Healthcare Institution Filatov City Clinical Hospital No.15 of Moscow Health Department
🇷🇺Moscow, Russian Federation
Hospital Santa Creu I Sant Pau - Neurology Dpt
🇪🇸Barcelona, Spain
Hosp Virgen de la Arrixaca, Neurology
🇪🇸El Palmar, Spain
Hospital Clinico San Carlos, Neurology
🇪🇸Madrid, Spain
Centro de Neurologia Avanzada, Neurology
🇪🇸Sevilla, Spain
Axis Heilsa S. de R.L. de C.V. (Althian)
🇲🇽Nuevo Leon, Monterrey, Mexico
Hospital - Universitair Gent __Neurology Department
🇧🇪Gent, Belgium
Hospital universitair Brussels_neurology department
🇧🇪Brussels, Belgium
Pest Megyei Flór Ferenc Kórház, Neurológia és Stroke ambulancia
🇭🇺Kistarcsa, Hungary
WroMedica, J. Bielicka A. Strzałkowska SC
🇵🇱Wroclaw, Poland
Valeomed EGÉSZSÉGÜGYI KÖZPONT
🇭🇺Esztergom, Hungary
Centro Hospitalar de Lisboa Central
🇵🇹Lisboa, Portugal
Hospital de Santa Maria - Neurology Department
🇵🇹Lisboa, Portugal
Centrum Kompleksowej Rehabilitacji
🇵🇱Konstancin-Jeziorna, Poland
Centrum Opieki Zdrowotnej Orkan - Med.
🇵🇱Ksawerów, Poland
Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna
🇵🇱Warszawa, Poland
Centro Hospitalar de São João, E.P.E. - Hospital de São João - Neurology Department
🇵🇹Porto, Portugal
Ospedale Regionale di Lugano - Civico e Italiano, Neurologia, Lugano
🇨🇭Lugano, Switzerland
MidAmerica Neuroscience Research Foundation/Rowe Neurology
🇺🇸Lenexa, Kansas, United States