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®)

Multiple Sclerosis Clinical Trial

— POINT  

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®)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02907177
• Other study ID #: AC-058B302
• Status: Terminated
• Phase: Phase 3
• Start date: March 30, 2017
• Est. completion date: March 26, 2020

Study information

• Verified date: April 2021
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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®).

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 information / eligibility

• Status: Terminated
• Enrollment: 136
• Est. completion date: March 26, 2020
• Est. primary completion date: March 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Ponesimod
One tablet of ponesimod 20 mg administered orally once daily in the morning from Day 15 to EOT. To reduce the first-dose effect of ponesimod, an uptitration scheme will be implemented from Day 1 to Day 14 (with dose strength increasing from 2 mg to 20 mg).

Other:
• Placebo
One tablet of matching placebo administered orally once daily in the morning

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Mexico,  Poland,  Portugal,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Confirmed Relapse Rate (ARR)	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).	Through study completion, an average of 68 weeks
Secondary	Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) as Assessed by Kaplan Meier Estimate at 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).	Week 96
Secondary	Percentage of Participants Experiencing a Confirmed Relapse as Assessed by Kaplan Meier Estimate at 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.	Week 96
Secondary	Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability	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.	Up to 147 Weeks