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®)

NCT ID: NCT02907177

Last Updated: 2021-05-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-30
• Study Completion Date: 2020-03-26

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ponesimod

Ponesimod

Group Type: EXPERIMENTAL

Ponesimod

Intervention Type: DRUG

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).

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

One tablet of matching placebo administered orally once daily in the morning

Interventions

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).

Intervention Type: DRUG

Placebo

One tablet of matching placebo administered orally once daily in the morning

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tatiana Scherz, MD, PhD

Role: STUDY_DIRECTOR

Actelion

Locations

UAB Dpt of Neurology

Birmingham, Alabama, United States

Neuro-Pain Medical Center

Fresno, California, United States

SC3 Research - Pasadena

Pasadena, California, 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

University of Colorado Hospital

Aurora, Colorado, United States

Mountain View Clinical Research, Inc

Denver, Colorado, United States

Associated Neurologists

Danbury, Connecticut, United States

Bradenton Research Center

Bradenton, Florida, United States

Neurology Associates - MS Center of Greater Orlando

Maitland, Florida, United States

Neurology Assoc of Ormond Beach - CNS Trials

Ormond Beach, Florida, United States

Suncoast Neuroscience Associates, Inc

St. Petersburg, Florida, United States

The MS Center of Vero Beach

Vero Beach, Florida, United States

Fort Wayne Neurological Center - North Office

Fort Wayne, Indiana, United States

University of Kansas Med Center

Kansas City, Kansas, United States

MidAmerica Neuroscience Research Foundation/Rowe Neurology

Lenexa, Kansas, United States

Henry Ford Health System - Neurology

Detroit, Michigan, United States

Univ of New Mexico - Health Sciences Center

Albuquerque, New Mexico, United States

NYU Langone Medical Center - MS Comprehensive Care Center

New York, New York, United States

Riverhills Healthcare, Inc.

Cincinnati, Ohio, United States

OhioHealth Research Institute

Columbus, Ohio, United States

Neurology and Neuromuscular Center

Oklahoma City, Oklahoma, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University Hospital - Dpt Neurology MS Center

Philadelphia, Pennsylvania, United States

Advanced Neuroscience Institute

Franklin, Tennessee, United States

Neurology Center of San Antonio

San Antonio, Texas, United States

Austin Health - Neuro-Immunology Clinical Research, Education and Support Service

Heidelberg, VC, Australia

MS Ambulanz Maida

Vienna, , Austria

Medizinische Universität Wien, Universitätsklinik für Neurologie

Vienna, , Austria

Hospital universitair Brussels_neurology department

Brussels, , Belgium

Hospital - Universitair Gent __Neurology Department

Ghent, , Belgium

Hospital - Revalidatie & MS Centrum Overpelt_Neurology Department

Overpelt, , Belgium

"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, , Bulgaria

University of Alberta

Edmonton, , Canada

Fakultní nemocnice u sv. Anny Brno, RS Centrum

Brno, , Czechia

Fakultní nemocnice Hradec Králové, Neurologická klinika

Hradec Králové, , Czechia

Nemocnice Jihlava, Neurologické oddělení

Jihlava, , Czechia

Pardubicka krajska nemocnice, MS Centrum

Pardubice, , Czechia

Krajská zdravotní a.s. - Nemonice Teplice o.z., RS Centrum

Teplice, , Czechia

Aalborg Universitetshospital, Skleroseklinikken Neurologisk afdelning

Aalborg, , Denmark

Glostrup Hospital, Neurologisk afdelning

Glostrup Municipality, , Denmark

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

Nîmes, , 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, , France

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

Hanover, , 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, , Germany

Naval Hospital of Athens - Neurology Dpt

Athens, , Greece

401 Military Hospital of Athens - Neurology Dept

Athens, , Greece

Aeginition Hospital - Neurology Department

Athens, , Greece

Medical Center of Athens - Neurology Dpt

Marousi, , Greece

General Hospital of Thessaloniki

Thessaloniki, , Greece

Uzsoki utcai Kórház, Neurológiai Osztály

Budapest, , Hungary

Valeomed EGÉSZSÉGÜGYI KÖZPONT

Esztergom, , Hungary

Pest Megyei Flór Ferenc Kórház, Neurológia és Stroke ambulancia

Kistarcsa, , Hungary

Fondazione Istituto San Raffaele , Unità Operativa di Neurologia

Cefalù, , Italy

Università degli Studi di Firenze - Azienda Ospedaliero Universitaria Careggi - CTO - SOD Neurologia 2

Florence, , 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

Milan, , 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

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, , Italy

Desarrollo Ético en Investigación Clínica S.C .

Guadalajara, Jalisco, Mexico

Unidad de Investigacion en Salud de Chihuahua SC, Médica Sur, Unidad de Neurociencias

Tlalpan, Mexico City, Mexico

Axis Heilsa S. de R.L. de C.V. (Althian)

Nuevo León, Monterrey, Mexico

Unidad de Investigación de Salud en Chihuahua

Chihuahua City, , Mexico

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

Warsaw, , Poland

WroMedica, J. Bielicka A. Strzałkowska SC

Wroclaw, , Poland

Centro Hospitalar de Lisboa Central

Lisbon, , Portugal

Hospital de Santa Maria - Neurology Department

Lisbon, , Portugal

Centro Hospitalar de São João, E.P.E. - Hospital de São João - Neurology Department

Porto, , Portugal

State Budgetary Healthcare Institution Regional Clinical Hospital No 3

Chelyabinsk, , Russia

Center of Professional Therapy, LLC

Krasnodar, , Russia

Moscow State Budgetary Healthcare Institution Filatov City Clinical Hospital No.15 of Moscow Health Department

Moscow, , Russia

Neuro-Clinic, LLC

Moscow, , Russia

Moscow State Budgetary Healthcare Institution Pirogov City Clinical Hospital No. 1 of Moscow Health Department

Moscow, , Russia

Moscow State Budgetary Healthcare Institution City Clinical Hospital No. 24 of Moscow Health Department

Moscow, , Russia

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

Hospital Universitario Virgen Macarena - Neurofisiology Department

Seville, , Spain

Centro de Neurologia Avanzada, Neurology

Seville, , Spain

Univeritätsspital Basel Neurologie, Neurologische Klinik und Poliklinik

Basel, , Switzerland

Ospedale Regionale di Lugano - Civico e Italiano, Neurologia, Lugano

Lugano, , 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

Royal Hallamshire Hospital

Sheffield, , United Kingdom

University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, , United Kingdom

Countries

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

References

Kappos L, Burcklen M, D'Ambrosio D, Fox RJ, Freedman MS, Havrdova EK, Hennessy B, Hohlfeld R, Larbalestier A, Lemle A, Lindenstrom E, Lublin F, Montalban X, Sidorenko T, Sprenger T, Vaclavkova A, Wuerfel J, Pozzilli C. Ponesimod as add-on treatment in patients with active relapsing multiple sclerosis under dimethyl fumarate (POINT): A phase 3, randomized, placebo-controlled clinical trial. Mult Scler Relat Disord. 2025 Oct;102:106616. doi: 10.1016/j.msard.2025.106616. Epub 2025 Jul 13.

Reference Type: DERIVED

PMID: 40700861 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AC-058B302

Identifier Type: -

Identifier Source: org_study_id