Clinical trial NCT02907177: 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®)
Official title: Multicenter, Randomized, Double-blind, Parallel-group, add-on, Superiority 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®)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2016-09-20
Enrollment: 136
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 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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Annualized Confirmed Relapse Rate (ARR)
timeFrame: Through study completion, an average of 68 weeks
Secondary outcomes:
measure: Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) as Assessed by Kaplan Meier Estimate at Week 96
timeFrame: Week 96
measure: Percentage of Participants Experiencing a Confirmed Relapse as Assessed by Kaplan Meier Estimate at Week 96
timeFrame: Week 96
measure: Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 147 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Dpt of Neurology
state: Alabama
city: Fresno
country: United States
facility: Neuro-Pain Medical Center
state: California
city: Pasadena
country: United States
facility: SC3 Research - Pasadena
state: California
city: Santa Clarita
country: United States
facility: Care Access Research - Santa Clarita
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Denver
country: United States
facility: Mountain View Clinical Research, Inc
state: Colorado
city: Danbury
country: United States
facility: Associated Neurologists
state: Connecticut
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Maitland
country: United States
facility: Neurology Associates - MS Center of Greater Orlando
state: Florida
city: Ormond Beach
country: United States
facility: Neurology Assoc of Ormond Beach - CNS Trials
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates, Inc
state: Florida
city: Vero Beach
country: United States
facility: The MS Center of Vero Beach
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center - North Office
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Med Center
state: Kansas
city: Lenexa
country: United States
facility: MidAmerica Neuroscience Research Foundation/Rowe Neurology
state: Kansas
city: Detroit
country: United States
facility: Henry Ford Health System - Neurology
state: Michigan
city: Albuquerque
country: United States
facility: Univ of New Mexico - Health Sciences Center
state: New Mexico
city: New York
country: United States
facility: NYU Langone Medical Center - MS Comprehensive Care Center
state: New York
city: Cincinnati
country: United States
facility: Riverhills Healthcare, Inc.
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Oklahoma City
country: United States
facility: Neurology and Neuromuscular Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital - Dpt Neurology MS Center
state: Pennsylvania
city: Franklin
country: United States
facility: Advanced Neuroscience Institute
state: Tennessee
city: San Antonio
country: United States
facility: Neurology Center of San Antonio
state: Texas
city: Heidelberg
country: Australia
facility: Austin Health - Neuro-Immunology Clinical Research, Education and Support Service
state: Victoria
city: Wien
country: Austria
facility: MS Ambulanz Maida
city: Wien
country: Austria
facility: Medizinische Universität Wien, Universitätsklinik für Neurologie
city: Brussels
country: Belgium
facility: Hospital universitair Brussels_neurology department
city: Gent
country: Belgium
facility: Hospital - Universitair Gent __Neurology Department
city: Overpelt
country: Belgium
facility: Hospital - Revalidatie & MS Centrum Overpelt_Neurology Department
city: Sofia
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment of Neurology and Psychiatry - Sveti Naum" EAD - Neurology Clinic for Movement Disorders
city: Sofia
country: Bulgaria
facility: "University Multiprofile Hospital for Active Treatment - Alexandrovska" EAD, Neurology Clinic
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD, Neurology Clinic
city: Edmonton
country: Canada
facility: University of Alberta
city: Brno
country: Czechia
facility: Fakultní nemocnice u sv. Anny Brno, RS Centrum
city: Hradec Králové
country: Czechia
facility: Fakultní nemocnice Hradec Králové, Neurologická klinika
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava, Neurologické oddělení
city: Pardubice
country: Czechia
facility: Pardubicka krajska nemocnice, MS Centrum
city: Teplice
country: Czechia
facility: Krajská zdravotní a.s. - Nemonice Teplice o.z., RS Centrum
city: Aalborg
country: Denmark
facility: Aalborg Universitetshospital, Skleroseklinikken Neurologisk afdelning
city: Glostrup
country: Denmark
facility: Glostrup Hospital, Neurologisk afdelning
city: Bobigny
country: France
facility: Hôpital Avicenne, Service de Neurologie
city: Clermont Ferrand
country: France
facility: Hosp Gabriel Montpied, Dept Neurology
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud Francilien - Service de Neurologie
city: Dijon
country: France
facility: CHU de Dijon - Hôpital François Miterrand, Service de Neurologie
city: Lille
country: France
facility: CHRU de Lille - Hôpital Roger Salengro, Service de Neurologie
city: Montpellier
country: France
facility: Hopital Gui de Chauliac - CHU Montpellier
city: Nancy
country: France
facility: Hôpital Central - CHU Nancy, Département Neurologie
city: Nimes
country: France
facility: Hôpital Universitaire Carémeau, Service de Neurologie
city: Poissy
country: France
facility: CHI POISSY-Saint Germay en Laye_Service de Neurologie et Réeducation
city: Rennes
country: France
facility: Hosp Pontchaillou, Dept Cardiology
city: Rouen
country: France
facility: Hosp Charles Nicolle Dept Neurology
city: Bad Homburg
country: Germany
facility: Zentrum für klinische Forschung Dr. med. Irma Schöll
city: Dresden
country: Germany
facility: Neurologische Klinik und Poliklinik - Universitätsklinikum Carl Gustav Carus, Zentrum für klinische Neurowissenschaften
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen Klinik und Poliklinik für Neurologie
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald - Körperschaft des öffentlichen Rechts - Klinik und Poliklinik für Neurologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Neurologie
city: Leipzig
country: Germany
facility: AFL Arzneimittelforschung Leipzig GmbH
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik für Allgemeine Neurologie
city: Siegen
country: Germany
facility: Medizinzentrum Siegerland Weidenau
city: Ulm
country: Germany
facility: NeuroPoint GmbH, Gesellschaft für vorbeugende Gesundheitspflege
city: Westerstede
country: Germany
facility: Gemeinschaftspraxis Dr. med. Joachim Springub / Wolfgang Schwarz, Studienzentrum Nord-West (Study Center)
city: Athens
country: Greece
facility: Naval Hospital of Athens - Neurology Dpt
city: Athens
country: Greece
facility: 401 Military Hospital of Athens - Neurology Dept
city: Athens
country: Greece
facility: Aeginition Hospital - Neurology Department
city: Marousi
country: Greece
facility: Medical Center of Athens - Neurology Dpt
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki
city: Budapest
country: Hungary
facility: Uzsoki utcai Kórház, Neurológiai Osztály
city: Esztergom
country: Hungary
facility: Valeomed EGÉSZSÉGÜGYI KÖZPONT
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flór Ferenc Kórház, Neurológia és Stroke ambulancia
city: Cefalù
country: Italy
facility: Fondazione Istituto San Raffaele , Unità Operativa di Neurologia
city: Firenze
country: Italy
facility: Università degli Studi di Firenze - Azienda Ospedaliero Universitaria Careggi - CTO - SOD Neurologia 2
city: Genova
country: Italy
facility: AOU San Martino di Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI)
city: Milano
country: Italy
facility: Istituto Neurologico Carlo Besta, UOC Neurologia 4, Neuroimmunologia e Malattie Neuromuscolari, Centro Sclerosi Multipla
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria (AOU) "Federico II" - Centro Regionale Per la Sclerosi Multipla c/o Clinica Neurologica II - Dipartimento di Scienze
city: Napoli
country: Italy
facility: AOU Università degli Studi della Campania L. Vanvitelli - I° Policlinico - DAI di Medicina Interna e Specialistica CS, Centro Sclerosi Multipla
city: Orbassano
country: Italy
facility: Azienda Ospedaliero Universitaria San Luigi Gonzaga - Centro Sclerosi Multipla CRESM
city: Pozzilli
country: Italy
facility: IRCCS NEUROMED - Istituto Neurologico Mediterraneo - Unità Operativa di Neurologia I
city: Roma
country: Italy
facility: Azienda Ospedaliera S. Andrea di Roma - Unità Operativa Complessa di Neurologia
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese - Dipartimento di Scienze Neurologiche e neurosensoriali - UOSA Neurologia Sperimentale
city: Tlalpan
country: Mexico
facility: Unidad de Investigacion en Salud de Chihuahua SC, Médica Sur, Unidad de Neurociencias
state: DF
city: Guadalajara
country: Mexico
facility: Desarrollo Ético en Investigación Clínica S.C .
state: Jalisco
city: Nuevo Leon
country: Mexico
facility: Axis Heilsa S. de R.L. de C.V. (Althian)
state: Monterrey
city: Chihuahua
country: Mexico
facility: Unidad de Investigación de Salud en Chihuahua
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Neurologii i Oddziat Udarowy
city: Bydgoszcz
country: Poland
facility: B&B Robert Bonek, Pawel Bochniak S.C
city: Gdansk
country: Poland
facility: COPERNICUS - Podmiot Leczniczy Sp. z o.o.
city: Katowice
country: Poland
facility: Centrum Terapii SM
city: Katowice
country: Poland
facility: Neuro-Medic Janusz Zbrojkiewicz Poradnia Weilospecjalistyczna
city: Konstancin-Jeziorna
country: Poland
facility: Centrum Kompleksowej Rehabilitacji
city: Ksawerów
country: Poland
facility: Centrum Opieki Zdrowotnej Orkan - Med.
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna
city: Wroclaw
country: Poland
facility: WroMedica, J. Bielicka A. Strzałkowska SC
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Central
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria - Neurology Department
city: Porto
country: Portugal
facility: Centro Hospitalar de São João, E.P.E. - Hospital de São João - Neurology Department
city: Chelyabinsk
country: Russian Federation
facility: State Budgetary Healthcare Institution Regional Clinical Hospital No 3
city: Krasnodar
country: Russian Federation
facility: Center of Professional Therapy, LLC
city: Moscow
country: Russian Federation
facility: Moscow State Budgetary Healthcare Institution Filatov City Clinical Hospital No.15 of Moscow Health Department
city: Moscow
country: Russian Federation
facility: Neuro-Clinic, LLC
city: Moscow
country: Russian Federation
facility: Moscow State Budgetary Healthcare Institution Pirogov City Clinical Hospital No. 1 of Moscow Health Department
city: Moscow
country: Russian Federation
facility: Moscow State Budgetary Healthcare Institution City Clinical Hospital No. 24 of Moscow Health Department
city: Barcelona
country: Spain
facility: Hospital Santa Creu I Sant Pau - Neurology Dpt
city: El Palmar
country: Spain
facility: Hosp Virgen de la Arrixaca, Neurology
city: Madrid
country: Spain
facility: Hosp Gregorio Marañón, Neurology
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos, Neurology
city: Salt
country: Spain
facility: Hospital Santa Caterina - Neurology Department
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Neurology Department 2
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena - Neurofisiology Department
city: Sevilla
country: Spain
facility: Centro de Neurologia Avanzada, Neurology
city: Basel
country: Switzerland
facility: Univeritätsspital Basel Neurologie, Neurologische Klinik und Poliklinik
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano - Civico e Italiano, Neurologia, Lugano
city: London
country: United Kingdom
facility: Queen Square MS Centre / NMR research Unit UCL Institute of Neurology
city: Oxford
country: United Kingdom
facility: Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospitals of North Midlands NHS Trust
Study officials:
affiliation: Actelion
name: Tatiana Scherz, MD, PhD
role: STUDY_DIRECTOR
References: