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®)

NCT02907177 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: AC-058B302
• Study Type: interventional
• Target: 136
• Locations: 19 countries
• Sites: 118

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®).

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) 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

  Week 96

• Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability

  Up to 147 Weeks

Study Arms (2)

Ponesimod

EXPERIMENTAL

Ponesimod

Drug: Ponesimod

Placebo

PLACEBO COMPARATOR

Placebo

Other: Placebo

Interventions

Ponesimod 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).

Ponesimod

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (119)

UAB Dpt of Neurology

Birmingham, Alabama, 35233, United States

Location

Neuro-Pain Medical Center

Fresno, California, 93710, United States

Location

SC3 Research - Pasadena

Pasadena, California, 91105, United States

Location

Care Access Research - Santa Clarita

Santa Clarita, California, 91321, United States

Location

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Mountain View Clinical Research, Inc

Denver, Colorado, 80209, United States

Location

Associated Neurologists

Danbury, Connecticut, 06810, United States

Location

Bradenton Research Center

Bradenton, Florida, 34205, United States

Location

Neurology Associates - MS Center of Greater Orlando

Maitland, Florida, 32751, United States

Location

Neurology Assoc of Ormond Beach - CNS Trials

Ormond Beach, Florida, 32174, United States

Location

Suncoast Neuroscience Associates, Inc

St. Petersburg, Florida, 33713, United States

Location

The MS Center of Vero Beach

Vero Beach, Florida, 32960, United States

Location

Fort Wayne Neurological Center - North Office

Fort Wayne, Indiana, 46825, United States

Location

University of Kansas Med Center

Kansas City, Kansas, 66160, United States

Location

MidAmerica Neuroscience Research Foundation/Rowe Neurology

Lenexa, Kansas, 66214, United States

Location

Henry Ford Health System - Neurology

Detroit, Michigan, 48202, United States

Location

Univ of New Mexico - Health Sciences Center

Albuquerque, New Mexico, 87131, United States

Location

NYU Langone Medical Center - MS Comprehensive Care Center

New York, New York, 10016, United States

Location

Riverhills Healthcare, Inc.

Cincinnati, Ohio, 45212, United States

Location

OhioHealth Research Institute

Columbus, Ohio, 43214, United States

Location

Neurology and Neuromuscular Center

Oklahoma City, Oklahoma, 73102, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital - Dpt Neurology MS Center

Philadelphia, Pennsylvania, 19107, United States

Location

Advanced Neuroscience Institute

Franklin, Tennessee, 37064, United States

Location

Neurology Center of San Antonio

San Antonio, Texas, 78258, United States

Location

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

Heidelberg, VC, 3084, Australia

Location

MS Ambulanz Maida

Vienna, 1010, Austria

Location

Medizinische Universität Wien, Universitätsklinik für Neurologie

Vienna, 1090, Austria

Location

Hospital universitair Brussels_neurology department

Brussels, 1090, Belgium

Location

Hospital - Universitair Gent __Neurology Department

Ghent, 9000, Belgium

Location

Hospital - Revalidatie & MS Centrum Overpelt_Neurology Department

Overpelt, 3900, Belgium

Location

"Multiprofile Hospital for Active Treatment of Neurology and Psychiatry - Sveti Naum" EAD - Neurology Clinic for Movement Disorders

Sofia, 1113, Bulgaria

Location

"University Multiprofile Hospital for Active Treatment - Alexandrovska" EAD, Neurology Clinic

Sofia, 1431, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD, Neurology Clinic

Sofia, 1431, Bulgaria

Location

University of Alberta

Edmonton, T6G 1Z1, Canada

Location

Fakultní nemocnice u sv. Anny Brno, RS Centrum

Brno, 656 91, Czechia

Location

Fakultní nemocnice Hradec Králové, Neurologická klinika

Hradec Králové, 500 05, Czechia

Location

Nemocnice Jihlava, Neurologické oddělení

Jihlava, 586 33, Czechia

Location

Pardubicka krajska nemocnice, MS Centrum

Pardubice, 532 03, Czechia

Location

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

Teplice, 415 29, Czechia

Location

Aalborg Universitetshospital, Skleroseklinikken Neurologisk afdelning

Aalborg, 9000, Denmark

Location

Glostrup Hospital, Neurologisk afdelning

Glostrup Municipality, 2600, Denmark

Location

Hôpital Avicenne, Service de Neurologie

Bobigny, 93000, France

Location

Hosp Gabriel Montpied, Dept Neurology

Clermont-Ferrand, 63003, France

Location

Centre Hospitalier Sud Francilien - Service de Neurologie

Corbeil-Essonnes, 91100, France

Location

CHU de Dijon - Hôpital François Miterrand, Service de Neurologie

Dijon, 21079, France

Location

CHRU de Lille - Hôpital Roger Salengro, Service de Neurologie

Lille, 59037, France

Location

Hopital Gui de Chauliac - CHU Montpellier

Montpellier, 34295, France

Location

Hôpital Central - CHU Nancy, Département Neurologie

Nancy, 54035, France

Location

Hôpital Universitaire Carémeau, Service de Neurologie

Nîmes, 30029, France

Location

CHI POISSY-Saint Germay en Laye_Service de Neurologie et Réeducation

Poissy, 78303, France

Location

Hosp Pontchaillou, Dept Cardiology

Rennes, 35033, France

Location

Hosp Charles Nicolle Dept Neurology

Rouen, 76000, France

Location

Zentrum für klinische Forschung Dr. med. Irma Schöll

Bad Homburg, 61348, Germany

Location

Neurologische Klinik und Poliklinik - Universitätsklinikum Carl Gustav Carus, Zentrum für klinische Neurowissenschaften

Dresden, 01307, Germany

Location

Helios Klinikum Erfurt

Erfurt, 99089, Germany

Location

Universitätsklinikum Giessen Klinik und Poliklinik für Neurologie

Giessen, 35385, Germany

Location

Universitätsmedizin Greifswald - Körperschaft des öffentlichen Rechts - Klinik und Poliklinik für Neurologie

Greifswald, 17475, Germany

Location

Medizinische Hochschule Hannover, Neurologie

Hanover, 30625, Germany

Location

AFL Arzneimittelforschung Leipzig GmbH

Leipzig, 04107, Germany

Location

Universitätsklinikum Münster, Klinik für Allgemeine Neurologie

Münster, 48149, Germany

Location

Medizinzentrum Siegerland Weidenau

Siegen, 57076, Germany

Location

NeuroPoint GmbH, Gesellschaft für vorbeugende Gesundheitspflege

Ulm, 89073, Germany

Location

Gemeinschaftspraxis Dr. med. Joachim Springub / Wolfgang Schwarz, Studienzentrum Nord-West (Study Center)

Westerstede, 26655, Germany

Location

Naval Hospital of Athens - Neurology Dpt

Athens, 11521, Greece

Location

401 Military Hospital of Athens - Neurology Dept

Athens, 11525, Greece

Location

Aeginition Hospital - Neurology Department

Athens, 11528, Greece

Location

Medical Center of Athens - Neurology Dpt

Marousi, 15125, Greece

Location

General Hospital of Thessaloniki

Thessaloniki, 57010, Greece

Location

Uzsoki utcai Kórház, Neurológiai Osztály

Budapest, 1145, Hungary

Location

Valeomed EGÉSZSÉGÜGYI KÖZPONT

Esztergom, 2500, Hungary

Location

Pest Megyei Flór Ferenc Kórház, Neurológia és Stroke ambulancia

Kistarcsa, 2143, Hungary

Location

Fondazione Istituto San Raffaele , Unità Operativa di Neurologia

Cefalù, 90015, Italy

Location

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

Florence, 50139, Italy

Location

AOU San Martino di Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI)

Genova, 16132, Italy

Location

Istituto Neurologico Carlo Besta, UOC Neurologia 4, Neuroimmunologia e Malattie Neuromuscolari, Centro Sclerosi Multipla

Milan, 20133, Italy

Location

Azienda Ospedaliera Universitaria (AOU) "Federico II" - Centro Regionale Per la Sclerosi Multipla c/o Clinica Neurologica II - Dipartimento di Scienze

Napoli, 80131, Italy

Location

AOU Università degli Studi della Campania L. Vanvitelli - I° Policlinico - DAI di Medicina Interna e Specialistica CS, Centro Sclerosi Multipla

Napoli, 80138, Italy

Location

Azienda Ospedaliero Universitaria San Luigi Gonzaga - Centro Sclerosi Multipla CRESM

Orbassano, 10043, Italy

Location

IRCCS NEUROMED - Istituto Neurologico Mediterraneo - Unità Operativa di Neurologia I

Pozzilli, 86077, Italy

Location

Azienda Ospedaliera S. Andrea di Roma - Unità Operativa Complessa di Neurologia

Roma, 00189, Italy

Location

Azienda Ospedaliera Universitaria Senese - Dipartimento di Scienze Neurologiche e neurosensoriali - UOSA Neurologia Sperimentale

Siena, 53100, Italy

Location

Desarrollo Ético en Investigación Clínica S.C .

Guadalajara, Jalisco, 44500, Mexico

Location

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

Tlalpan, Mexico City, 14050, Mexico

Location

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

Nuevo León, Monterrey, 64060, Mexico

Location

Unidad de Investigación de Salud en Chihuahua

Chihuahua City, 31203, Mexico

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Neurologii i Oddziat Udarowy

Bialystok, 15-276, Poland

Location

B&B Robert Bonek, Pawel Bochniak S.C

Bydgoszcz, 85-795, Poland

Location

COPERNICUS - Podmiot Leczniczy Sp. z o.o.

Gdansk, 80-803, Poland

Location

Centrum Terapii SM

Katowice, 40-571, Poland

Location

Neuro-Medic Janusz Zbrojkiewicz Poradnia Weilospecjalistyczna

Katowice, 40-752, Poland

Location

Centrum Kompleksowej Rehabilitacji

Konstancin-Jeziorna, 05-510, Poland

Location

Centrum Opieki Zdrowotnej Orkan - Med.

Ksawerów, 95-054, Poland

Location

Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna

Warsaw, 02-957, Poland

Location

WroMedica, J. Bielicka A. Strzałkowska SC

Wroclaw, 51-685, Poland

Location

Centro Hospitalar de Lisboa Central

Lisbon, 1169-050, Portugal

Location

Hospital de Santa Maria - Neurology Department

Lisbon, 1649-035, Portugal

Location

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

Porto, 4200-319, Portugal

Location

State Budgetary Healthcare Institution Regional Clinical Hospital No 3

Chelyabinsk, 454021, Russia

Location

Center of Professional Therapy, LLC

Krasnodar, 350051, Russia

Location

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

Moscow, 111539, Russia

Location

Neuro-Clinic, LLC

Moscow, 117186, Russia

Location

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

Moscow, 119049, Russia

Location

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

Moscow, 127015, Russia

Location

Hospital Santa Creu I Sant Pau - Neurology Dpt

Barcelona, 08041, Spain

Location

Hosp Virgen de la Arrixaca, Neurology

El Palmar, 30120, Spain

Location

Hosp Gregorio Marañón, Neurology

Madrid, 28007, Spain

Location

Hospital Clinico San Carlos, Neurology

Madrid, 28040, Spain

Location

Hospital Santa Caterina - Neurology Department

Salt, 17190, Spain

Location

Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Neurology Department 2

Santiago de Compostela, 15703, Spain

Location

Hospital Universitario Virgen Macarena - Neurofisiology Department

Seville, 41009, Spain

Location

Centro de Neurologia Avanzada, Neurology

Seville, 41013, Spain

Location

Univeritätsspital Basel Neurologie, Neurologische Klinik und Poliklinik

Basel, 4031, Switzerland

Location

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

Lugano, 6903, Switzerland

Location

Queen Square MS Centre / NMR research Unit UCL Institute of Neurology

London, WC1N 3BG, United Kingdom

Location

Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

University Hospitals of North Midlands NHS Trust

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40700861 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ponesimod

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Due to slow recruitment rate the study was considered futile by the Independent Data Monitoring Committee and the sponsor agreed to prematurely terminate the study. Due to this premature termination of study, the insufficient sample size did not allow to detect the differences for the main efficacy endpoints. The safety profile of ponesimod as add-on to DMF therapy could not be fully characterized due to limited data.

Results Point of Contact

• Title: Clinical Leader
• Organization: Actelion Pharmaceuticals Ltd (a Janssen Pharmaceutical Company of Johnson & Johnson)

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Tatiana Scherz, MD, PhD

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2016
• First Posted: September 20, 2016
• Study Start: March 30, 2017
• Primary Completion: March 26, 2020
• Study Completion: March 26, 2020
• Last Updated: May 18, 2021
• Results First Posted: May 18, 2021

Record last verified: 2021-04

Locations

DE (11); PT (3); PL (9); CZ (5); AU (2); DK (2); RU (6); GR (5); CH (2); BE (3); ME (4); CA (1); BU (3); FR (11); ES (8); GB (4); HU (3); US (26); IT (10)