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®) (POINT)

April 27, 2021 updated by: Actelion

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®)

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®).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

136

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health - Neuro-Immunology Clinical Research, Education and Support Service
  • Austria
      • Wien, Austria, 1010
        • MS Ambulanz Maida
      • Wien, Austria, 1090
        • Medizinische Universität Wien, Universitätsklinik für Neurologie
  • Belgium
      • Brussels, Belgium, 1090
        • Hospital universitair Brussels_neurology department
      • Gent, Belgium, 9000
        • Hospital - Universitair Gent __Neurology Department
      • Overpelt, Belgium, 3900
        • Hospital - Revalidatie & MS Centrum Overpelt_Neurology Department
  • Bulgaria
      • Sofia, Bulgaria, 1113
        • "Multiprofile Hospital for Active Treatment of Neurology and Psychiatry - Sveti Naum" EAD - Neurology Clinic for Movement Disorders
      • Sofia, Bulgaria, 1431
        • "University Multiprofile Hospital for Active Treatment - Alexandrovska" EAD, Neurology Clinic
      • Sofia, Bulgaria, 1431
        • University Multiprofile Hospital for Active Treatment "Sv. Ivan Rilski" EAD, Neurology Clinic
  • Canada
      • Edmonton, Canada, T6G 1Z1
        • University of Alberta
  • Czechia
      • Brno, Czechia, 656 91
        • Fakultní nemocnice u sv. Anny Brno, RS Centrum
      • Hradec Králové, Czechia, 500 05
        • Fakultní nemocnice Hradec Králové, Neurologická klinika
      • Jihlava, Czechia, 586 33
        • Nemocnice Jihlava, Neurologické oddělení
      • Pardubice, Czechia, 532 03
        • Pardubicka krajska nemocnice, MS Centrum
      • Teplice, Czechia, 415 29
        • Krajská zdravotní a.s. - Nemonice Teplice o.z., RS Centrum
  • Denmark
      • Aalborg, Denmark, 9000
        • Aalborg Universitetshospital, Skleroseklinikken Neurologisk afdelning
      • Glostrup, Denmark, 2600
        • Glostrup Hospital, Neurologisk afdelning
  • France
      • Bobigny, France, 93000
        • Hôpital Avicenne, Service de Neurologie
      • Clermont Ferrand, France, 63003
        • Hosp Gabriel Montpied, Dept Neurology
      • Corbeil-Essonnes, France, 91100
        • Centre Hospitalier Sud Francilien - Service de Neurologie
      • Dijon, France, 21079
        • CHU de Dijon - Hôpital François Miterrand, Service de Neurologie
      • Lille, France, 59037
        • CHRU de Lille - Hôpital Roger Salengro, Service de Neurologie
      • Montpellier, France, 34295
        • Hopital Gui de Chauliac - CHU Montpellier
      • Nancy, France, 54035
        • Hôpital Central - CHU Nancy, Département Neurologie
      • Nimes, France, 30029
        • Hôpital Universitaire Carémeau, Service de Neurologie
      • Poissy, France, 78303
        • CHI POISSY-Saint Germay en Laye_Service de Neurologie et Réeducation
      • Rennes, France, 35033
        • Hosp Pontchaillou, Dept Cardiology
      • Rouen, France, 76000
        • Hosp Charles Nicolle Dept Neurology
  • Germany
      • Bad Homburg, Germany, 61348
        • Zentrum für klinische Forschung Dr. med. Irma Schöll
      • Dresden, Germany, 01307
        • Neurologische Klinik und Poliklinik - Universitätsklinikum Carl Gustav Carus, Zentrum für klinische Neurowissenschaften
      • Erfurt, Germany, 99089
        • Helios Klinikum Erfurt
      • Giessen, Germany, 35385
        • Universitätsklinikum Giessen Klinik und Poliklinik für Neurologie
      • Greifswald, Germany, 17475
        • Universitätsmedizin Greifswald - Körperschaft des öffentlichen Rechts - Klinik und Poliklinik für Neurologie
      • Hannover, Germany, 30625
        • Medizinische Hochschule Hannover, Neurologie
      • Leipzig, Germany, 04107
        • AFL Arzneimittelforschung Leipzig GmbH
      • Münster, Germany, 48149
        • Universitätsklinikum Münster, Klinik für Allgemeine Neurologie
      • Siegen, Germany, 57076
        • Medizinzentrum Siegerland Weidenau
      • Ulm, Germany, 89073
        • NeuroPoint GmbH, Gesellschaft für vorbeugende Gesundheitspflege
      • Westerstede, Germany, 26655
        • Gemeinschaftspraxis Dr. med. Joachim Springub / Wolfgang Schwarz, Studienzentrum Nord-West (Study Center)
  • Greece
      • Athens, Greece, 11521
        • Naval Hospital of Athens - Neurology Dpt
      • Athens, Greece, 11525
        • 401 Military Hospital of Athens - Neurology Dept
      • Athens, Greece, 11528
        • Aeginition Hospital - Neurology Department
      • Marousi, Greece, 15125
        • Medical Center of Athens - Neurology Dpt
      • Thessaloniki, Greece, 57010
        • General Hospital of Thessaloniki
  • Hungary
      • Budapest, Hungary, 1145
        • Uzsoki utcai Kórház, Neurológiai Osztály
      • Esztergom, Hungary, 2500
        • Valeomed EGÉSZSÉGÜGYI KÖZPONT
      • Kistarcsa, Hungary, 2143
        • Pest Megyei Flór Ferenc Kórház, Neurológia és Stroke ambulancia
  • Italy
      • Cefalù, Italy, 90015
        • Fondazione Istituto San Raffaele , Unità Operativa di Neurologia
      • Firenze, Italy, 50139
        • Università degli Studi di Firenze - Azienda Ospedaliero Universitaria Careggi - CTO - SOD Neurologia 2
      • Genova, Italy, 16132
        • AOU San Martino di Genova, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI)
      • Milano, Italy, 20133
        • Istituto Neurologico Carlo Besta, UOC Neurologia 4, Neuroimmunologia e Malattie Neuromuscolari, Centro Sclerosi Multipla
      • Napoli, Italy, 80131
        • Azienda Ospedaliera Universitaria (AOU) "Federico II" - Centro Regionale Per la Sclerosi Multipla c/o Clinica Neurologica II - Dipartimento di Scienze
      • Napoli, Italy, 80138
        • AOU Università degli Studi della Campania L. Vanvitelli - I° Policlinico - DAI di Medicina Interna e Specialistica CS, Centro Sclerosi Multipla
      • Orbassano, Italy, 10043
        • Azienda Ospedaliero Universitaria San Luigi Gonzaga - Centro Sclerosi Multipla CRESM
      • Pozzilli, Italy, 86077
        • IRCCS NEUROMED - Istituto Neurologico Mediterraneo - Unità Operativa di Neurologia I
      • Roma, Italy, 00189
        • Azienda Ospedaliera S. Andrea di Roma - Unità Operativa Complessa di Neurologia
      • Siena, Italy, 53100
        • Azienda Ospedaliera Universitaria Senese - Dipartimento di Scienze Neurologiche e neurosensoriali - UOSA Neurologia Sperimentale
  • Mexico
      • Chihuahua, Mexico, 31203
        • Unidad de Investigación de Salud en Chihuahua
    • DF
      • Tlalpan, DF, Mexico, 14050
        • Unidad de Investigacion en Salud de Chihuahua SC, Médica Sur, Unidad de Neurociencias
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44500
        • Desarrollo Ético en Investigación Clínica S.C .
    • Monterrey
      • Nuevo Leon, Monterrey, Mexico, 64060
        • Axis Heilsa S. de R.L. de C.V. (Althian)
  • Poland
      • Bialystok, Poland, 15-276
        • Uniwersytecki Szpital Kliniczny w Bialymstoku, Klinika Neurologii i Oddziat Udarowy
      • Bydgoszcz, Poland, 85-795
        • B&B Robert Bonek, Pawel Bochniak S.C
      • Gdansk, Poland, 80-803
        • COPERNICUS - Podmiot Leczniczy Sp. z o.o.
      • Katowice, Poland, 40-571
        • Centrum Terapii SM
      • Katowice, Poland, 40-752
        • Neuro-Medic Janusz Zbrojkiewicz Poradnia Weilospecjalistyczna
      • Konstancin-Jeziorna, Poland, 05-510
        • Centrum Kompleksowej Rehabilitacji
      • Ksawerów, Poland, 95-054
        • Centrum Opieki Zdrowotnej Orkan - Med.
      • Warszawa, Poland, 02-957
        • Instytut Psychiatrii i Neurologii, II Klinika Neurologiczna
      • Wroclaw, Poland, 51-685
        • WroMedica, J. Bielicka A. Strzałkowska SC
  • Portugal
      • Lisboa, Portugal, 1169-050
        • Centro Hospitalar de Lisboa Central
      • Lisboa, Portugal, 1649-035
        • Hospital de Santa Maria - Neurology Department
      • Porto, Portugal, 4200-319
        • Centro Hospitalar de São João, E.P.E. - Hospital de São João - Neurology Department
  • Russian Federation
      • Chelyabinsk, Russian Federation, 454021
        • State Budgetary Healthcare Institution Regional Clinical Hospital No 3
      • Krasnodar, Russian Federation, 350051
        • Center of Professional Therapy, LLC
      • Moscow, Russian Federation, 111539
        • Moscow State Budgetary Healthcare Institution Filatov City Clinical Hospital No.15 of Moscow Health Department
      • Moscow, Russian Federation, 117186
        • Neuro-Clinic, LLC
      • Moscow, Russian Federation, 119049
        • Moscow State Budgetary Healthcare Institution Pirogov City Clinical Hospital No. 1 of Moscow Health Department
      • Moscow, Russian Federation, 127015
        • Moscow State Budgetary Healthcare Institution City Clinical Hospital No. 24 of Moscow Health Department
  • Spain
      • Barcelona, Spain, 08041
        • Hospital Santa Creu I Sant Pau - Neurology Dpt
      • El Palmar, Spain, 30120
        • Hosp Virgen de la Arrixaca, Neurology
      • Madrid, Spain, 28007
        • Hosp Gregorio Marañón, Neurology
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos, Neurology
      • Salt, Spain, 17190
        • Hospital Santa Caterina - Neurology Department
      • Santiago de Compostela, Spain, 15703
        • Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) - Neurology Department 2
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena - Neurofisiology Department
      • Sevilla, Spain, 41013
        • Centro de Neurologia Avanzada, Neurology
  • Switzerland
      • Basel, Switzerland, 4031
        • Univeritätsspital Basel Neurologie, Neurologische Klinik und Poliklinik
      • Lugano, Switzerland, 6903
        • Ospedale Regionale di Lugano - Civico e Italiano, Neurologia, Lugano
  • United Kingdom
      • London, United Kingdom, WC1N 3BG
        • Queen Square MS Centre / NMR research Unit UCL Institute of Neurology
      • Oxford, United Kingdom, OX3 9DU
        • Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital
      • Sheffield, United Kingdom, S10 2JF
        • Royal Hallamshire Hospital
      • Stoke-on-Trent, United Kingdom, St4 6QG
        • University Hospitals of North Midlands NHS Trust
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • UAB Dpt of Neurology
    • California
      • Fresno, California, United States, 93710
        • Neuro-Pain Medical Center
      • Pasadena, California, United States, 91105
        • SC3 Research - Pasadena
      • Santa Clarita, California, United States, 91321
        • Care Access Research - Santa Clarita
      • Torrance, California, United States, 90502
        • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Hospital
      • Denver, Colorado, United States, 80209
        • Mountain View Clinical Research, Inc
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Associated Neurologists
    • Florida
      • Bradenton, Florida, United States, 34205
        • Bradenton Research Center
      • Maitland, Florida, United States, 32751
        • Neurology Associates - MS Center of Greater Orlando
      • Ormond Beach, Florida, United States, 32174
        • Neurology Assoc of Ormond Beach - CNS Trials
      • Saint Petersburg, Florida, United States, 33713
        • Suncoast Neuroscience Associates, Inc
      • Vero Beach, Florida, United States, 32960
        • The MS Center of Vero Beach
    • Indiana
      • Fort Wayne, Indiana, United States, 46825
        • Fort Wayne Neurological Center - North Office
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Med Center
      • Lenexa, Kansas, United States, 66214
        • MidAmerica Neuroscience Research Foundation/Rowe Neurology
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System - Neurology
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Univ of New Mexico - Health Sciences Center
    • New York
      • New York, New York, United States, 10016
        • NYU Langone Medical Center - MS Comprehensive Care Center
    • Ohio
      • Cincinnati, Ohio, United States, 45212
        • Riverhills Healthcare, Inc.
      • Columbus, Ohio, United States, 43214
        • OhioHealth Research Institute
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73102
        • Neurology and Neuromuscular Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital - Dpt Neurology MS Center
    • Tennessee
      • Franklin, Tennessee, United States, 37064
        • Advanced Neuroscience Institute
    • Texas
      • San Antonio, Texas, United States, 78258
        • Neurology Center of San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 53 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
One tablet of matching placebo administered orally once daily in the morning
Experimental: Ponesimod
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized Confirmed Relapse Rate (ARR)
Time Frame: 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).
Through study completion, an average of 68 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With 12-Week Confirmed Disability Accumulation (CDA) as Assessed by Kaplan Meier Estimate at Week 96
Time Frame: 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
Percentage of Participants Experiencing a Confirmed Relapse as Assessed by Kaplan Meier Estimate at Week 96
Time Frame: 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
Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame: 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.
Up to 147 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Actelion

Investigators

  • Study Director: Tatiana Scherz, MD, PhD, Actelion

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 30, 2017

Primary Completion (Actual)

March 26, 2020

Study Completion (Actual)

March 26, 2020

Study Registration Dates

First Submitted

August 25, 2016

First Submitted That Met QC Criteria

September 15, 2016

First Posted (Estimate)

September 20, 2016

Study Record Updates

Last Update Posted (Actual)

May 18, 2021

Last Update Submitted That Met QC Criteria

April 27, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-058B302

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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