Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple Sclerosis (OPTIMUM-LT)

Multicenter, Non-comparative Extension of Study AC-058B301, to Investigate the Long-term Safety, Tolerability, and Control of Disease of Ponesimod 20 mg in Subjects With Relapsing Multiple Sclerosis

The study AC-058B301 (OPTIMUM; NCT02425644) has been designed to investigate the efficacy, safety and tolerability of ponesimod in subjects with relapsing multiple sclerosis (RMS). The AC-058B303 study is the long-term extension for the core study AC-058B301. The purpose of this long term extension of the core study AC-058B301 is to characterize the long-term safety, tolerability, and control of disease of ponesimod 20 mg in subjects with RMS.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Ponesimod

Detailed Description

The AC-058B303 study (extension study) is the long-term extension for the AC-058B301 study (core study). The core study has been designed to investigate the efficacy, safety and tolerability of ponesimod in subjects with RMS. The subjects are treated with either ponesimod or the active comparator, teriflunomide in the core study. The purpose of this long term extension of the core study is to characterize the long-term safety and control of disease of ponesimod in subjects with RMS. In particular, the study will allow to observe potential adverse events which may only occur after long term treatment with ponesimod. The study will also investigate the effect of re-initiation of ponesimod after a brief interruption in a relatively large population (all subjects treated with ponesimod in the core study and eligible for the extension study) on disease activity in terms of relapses and MS-related MRI lesions. There is currently limited guidance on when a new MS treatment should be started after discontinuation of teriflunomide and the study will contribute with data on safety and efficacy of switching from teriflunomide to ponesimod after an interruption as mandated by the protocol. The study will also allow confirmation of sustained efficacy of ponesimod in terms of relapses, MRI lesions and reduction of disability accumulation during long-term treatment. In addition, combined data from the core study together with the results of the current extension study will allow comparison of MS activity in subjects who were switched from teriflunomide to ponesimod versus those who were treated with ponesimod in both studies. A vaccination sub-study will be conducted in a sub-set of up to 50 eligible study participants from selected countries who consent to be vaccinated with the Janssen coronavirus disease-2019 (COVID-19) vaccine (Ad26.COV2.S) to investigate the immune response induced by the Janssen COVID-19 vaccine.

• Study Type: Interventional
• Enrollment (Actual): 877
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belarus
  • Grodno, Belarus, 230017
    • Grodno University Hospital
  • Minsk, Belarus, 220026
    • Minsk City Clinical Hospital 5
  • Minsk, Belarus, 220114
    • Republican Scientific Clinical Centre
  • Vitebsk, Belarus, 210037
    • Vitebsk Regional Clinical Hospital
  • Vitebsk, Belarus, 210023
    • Vitebsk Regional Diagnostic Center
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71000
    • University Clinicl Center Sarajevo
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sveti Georgi
  • Sofia, Bulgaria, 1309
    • Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Tokuda Hospital
  • Sofia, Bulgaria, 1431
    • St Ivan Rilski University Multiprofile Hospital For Active Treatment
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment Alexandrovska EAD
  • Sofia, Bulgaria, 1606
    • Military Medical Academy, Multiprofile Hospital for Active Treatment -Sofia
  • Sofia, Bulgaria, 1113
    • Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z1
      • University of Alberta
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 1J8
      • Royal Jubilee Hospital
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Recherche Sepmus Inc.
• Croatia
  • Osijek, Croatia, 31000
    • Ch Osijek
  • Zagreb, Croatia, 10000
    • University hospital center Zagreb
• Czechia
  • Brno, Czechia, 65691
    • Fakultní nemocnici Brno
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Jihlava, Czechia, 586 33
    • Nemocnice Jihlava
  • Ostrava-Poruba, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Pardubice, Czechia, 532 03
    • Pardubicka krajska nemocnice a.s.
  • Praha 2, Czechia, 128 08
    • Vseobecna Fakultní Nemocnice
  • Praha 5, Czechia, 150 06
    • FN Motol
  • Teplice, Czechia, 415 29
    • Krajska zdravotni, a.s. - Nemocnice Teplice, o.z.
• Finland
  • Tampere, Finland, 33100
    • Suomen Terveystalo Tampere
  • Turku, Finland, 20520
    • Mehiläinen Neo
• France
  • Bordeaux cedex, France, 33076
    • Hopital Pellegrin CHU Bordeaux
  • Clermont Ferrand Cedex 1, France, 63003
    • CHU Clermont-Ferrand - Hopital Gabriel Montpied
  • Nantes Cedex 1, France, 44093
    • Hôpital Nord Laennec - CHU NANTES
  • Nice, France, 6000
    • Hopital PASTEUR
  • Strasbourg CEDEX, France, 67091
    • Nouvel Hopital Civil
• Georgia
  • T'bilisi, Georgia, 0160
    • LTD 'Aversi Clinic'
  • Tbilisi, Georgia, 112
    • P. Sarajishvili Institute of Neurology
  • Tbilisi, Georgia, 114
    • Pineo Medical Ecosystem LTD
  • Tbilisi, Georgia, 179
    • S.Khechinashvili University Hospital
  • Tbilisi, Georgia, 186
    • Curatio, Jsc
• Germany
  • Dresden, Germany, 1307
    • Universitätsklinikum Carl-Gustav-Carus Dresden
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt
  • Leipzig, Germany, 04275
    • Panakeia - Arzneimittelforschung GmbH
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
• Greece
  • Athens, Greece, 115 25
    • 401 Military Hospital
  • Athens, Greece, 11521
    • Naval Hospital of Athens
  • Marousi, Greece, 15125
    • Medical Center of Athens
• Hungary
  • Budapest, Hungary, 1204
    • Jahn Ferenc Del-pesti Korhaz es Rendelointezet
  • Budapest, Hungary, 1145
    • Uzsoki Utcai Kórház
  • Esztergom, Hungary, 2500
    • Valeomed EGÉSZSÉGÜGYI KÖZPONT
  • Győr, Hungary, 9023
    • Petz Aladar Megyei Oktato Korhaz
  • Kistarcsa, Hungary, 2143
    • Pest Megyei Flor Ferenc Korhaz
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center
  • Safed, Israel, 1304300
    • Ziv Medical Center
• Italy
  • L' Aquila, Italy, 67100
    • Ospedale San Salvatore
  • Roma, Italy, 189
    • Azienda Ospedaliera Sant Andrea
• Latvia
  • Riga, Latvia, 1002
    • Pauls Stradins Clinical University Hospital
  • Riga, Latvia, 1015
    • Latvias Juras medicinas centrs Ltd
  • Riga, Latvia, LV-1038
    • Rīgas Austrumu klīniskā universitātes slimnīca
• Lithuania
  • Kaunas, Lithuania, LT50161
    • Hospital of Lithuanian University of Health Sciences Kaunas Clinics
  • Šiauliai, Lithuania, 76231
    • VsI Respublikine Siauliu ligonine, V.
• Mexico
  • Chihuahua, Mexico, 31203
    • Unidad de Investigación en Salud
  • Nuevo Leon, Mexico, 64060
    • CRI Centro Regiomontano de Investigacion SC
• Poland
  • Bydgoszcz, Poland, 85-796
    • Neurocentrum Bydgoszcz Sp Z O O
  • Gdansk, Poland, 80-803
    • Copernicus Podmiot Leczniczy Sp. z o.o
  • Katowice, Poland, 40-571
    • NeuroCentrum. Centrum Terapii SM
  • Katowice, Poland, 40-686
    • NEURO-MEDIC Janusz Zbrojkiewicz Poradnia Wielospecjalistyczna
  • Konstancin-Jeziorna, Poland, 05-510
    • Centrum Kompleksowej Rehabilitacji
  • Ksawerow, Poland, 95-054
    • Centrum Opieki Zdrowotnej Orkan-Med
  • Lublin, Poland, 20-410
    • Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
  • Poznan, Poland, 60-355
    • Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Po
  • Poznan, Poland, 61-853
    • NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partnerska Lekarzy
  • Poznan, Poland, 61-731
    • Clinical Research Center sp. z o.o MEDIC-R s.k.
  • Wrocław, Poland, 51-685
    • WroMedica I.Bielicka, A.Strzałkowska s.c.
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga
  • Coimbra, Portugal, 3000-075
    • Hospitais da universidade de Coimbra
  • Lisboa, Portugal, 1998-018
    • Hosp. Cuf Descobertas
  • Porto, Portugal, 4099-001
    • H. Santo António - Centro Hospitalar do Porto
• Romania
  • Bucuresti, Romania, 10825
    • Spitalul Universitar de Urgenta Militar Central 'Dr. Carol Davila'
  • Bucuresti, Romania, 22328
    • Institutul Clinic Fundeni
  • Bucuresti, Romania, 50098
    • Spitalul Universitar de Urgenta Bucuresti
  • Timisoara, Romania, 300723
    • Spitalul Clinic Judetean de Urgenta 'Pius Brinzeu'
• Russian Federation
  • Barnaul, Altai Krai, Russian Federation, 656024
    • Barnaul Territorial Clinical Hospital
  • Belgorod, Russian Federation, 308007
    • St. Joseph Belgorod Regional Hospital
  • Bryansk, Russian Federation, 241033
    • Bryansk Regional Hospital #1
  • Ekaterinburg, Russian Federation, 620102
    • Sverdlovsk Region Clinical Hospital #1
  • Kazan, Russian Federation, 420097
    • Research Medical Center Your Health
  • Krasnoyarsk, Russian Federation, 660037
    • Federal State Budgetary Institution
  • Kursk, Russian Federation, 305007
    • State Budgetary Healthcare Institution Kursk Region Kursk Regional Clinical Hospital
  • Moscow, Russian Federation, 117049
    • Clinical City Hospital #1
  • Moscow, Russian Federation, 127015
    • State Health Care Institution Of Moscow
  • Moscow, Russian Federation, 129128
    • Central Clinical Hospital N.A.Semashko
  • Nizhniy Novgorod, Russian Federation, 603155
    • Municipal Clinical Hospital # 3
  • Novosibirsk, Russian Federation, 630007
    • Siberian District Medical Center of Federal Medical-Biological Agency
  • Odintsovo, Russian Federation, 143000
    • Federal Scientific Clinical Center of Physico-Chemical Medicine
  • Perm, Russian Federation, 614990
    • Perm State Medical Academy n.a. E. A. Vagner
  • Pyatigorsk, Russian Federation, 357538
    • City Clinical Hospital # 2
  • Saint Petersburg, Russian Federation, 197022
    • Pavlov First Saint Petersburg State Medical University
  • Samara, Russian Federation, 443095
    • State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
  • Smolensk, Russian Federation, 214018
    • Smolensk Regional Clinical Hospital
  • St. Petersburg, Russian Federation, 194354
    • Municipal Multi-Specialty Hospital # 2
  • St. Petersburg, Russian Federation, 197110
    • City Clinical Hospital #31
  • St. Petersburg, Russian Federation, 197376
    • Institute of Human Brain Ras
  • St.Petersburg, Russian Federation, 197706
    • City Hospital# 40
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University
  • Tver, Russian Federation, 170036
    • Tver Regional Clinical Hospital
  • Velikiy Novgorod, Russian Federation, 214018
    • GUZ Novgorod Regional Clinical Hospital
  • Yaroslavl, Russian Federation, 150003
    • Yaroslavl Clinical Hospital #8
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Zvezdara
  • Belgrade, Serbia, 11000
    • Vojnomedicinska akademija
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac
  • Nis, Serbia, 18000
    • University Clinical Center Nis
• Spain
  • Barcelona, Spain, 8003
    • Hospital del Mar
  • Barcelona, Spain, 8035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 8036
    • Hospital Clinic I Provincial
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Sevilla, Spain, 41950
    • Hospital Vithas NISA Sevilla
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska Universitetsjukhuset
  • Stockholm, Sweden, 113 65
    • Centrum för Neurologi
• Turkey
  • Trabzon, Turkey, 61080
    • Karadeniz Teknik University Medical Faculty
• Ukraine
  • Chernihiv, Ukraine, 14001
    • Public Non-profit Enterprise: Chernihiv City Hospital #4 under Chernihiv City Council
  • Chernihiv, Ukraine, 14029
    • Municipal health care institution Chernihiv Regional Hospital
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Regional Clinical Hospital
  • Ivano-Frankivsk, Ukraine, 76493
    • Limited Liability Company 'Neuro Global'
  • Kharkiv, Ukraine, 61103
    • Kharkiv Railway Clinical Hospital N1 Of Brance 'Health Center'
  • Kharkiv, Ukraine, 61176
    • Kharkiv Postgrad Academy, Dept of Neurology #1 At Hosp #7
  • Kyiv, Ukraine, 3115
    • National Research Center for Radiation Medicine
  • Lviv, Ukraine, 79000
    • Public Non-Profit Enterprise: Lviv City Clinical Hospital #5
  • Lviv, Ukraine, 79010
    • Lviv Clinical Regional Hospital
  • Odesa, Ukraine, 65009
    • Odessa National Medical University
  • Poltava, Ukraine, 36024
    • ME 'Poltava Regional Clinical Hospital n.a. M.V. Sklifosovsky of the Poltava Regional Council'
  • Ternopil, Ukraine, 46027
    • Mnce 'Ternopil Regional Clinical Psychoneurology Hospital' of Trb
  • Vinnytsia, Ukraine, 21000
    • Medical Center Salutem LLC
  • Zhytomyr, Ukraine, 10008
    • O.F. Herbachevskyi Regional Clinical Hospital
• United Kingdom
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
• United States
  • California
    • Carlsbad, California, United States, 92011
      • The Research Center of Southern California, LLC
    • Pomona, California, United States, 91767
      • The Neurology Group
  • Colorado
    • Denver, Colorado, United States, 80209
      • Mountain View Clinical Research
  • Florida
    • Ormond Beach, Florida, United States, 32174
      • Neurology Associates of Ormond Beach
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology, PC
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Ohio Health
  • Tennessee
    • Franklin, Tennessee, United States, 37064
      • Advanced Neurosciences Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent
2. Subjects with MS having completed the double-blind treatment in the core study as scheduled
3. Compliance with teriflunomide elimination procedure
4. Women of childbearing potential (WOCBP) must have a negative pre-treatment urine pregnancy test, must agree to undertake 4-weekly urine pregnancy tests, and must have been using reliable methods of contraception. Fertile male subjects participating in the study must agree to use a condom.

Exclusion Criteria:

1. Any of the following cardiovascular conditions on Day 1 pre-dose:

   1. Resting heart rate (HR) < 50 bpm;
   2. Presence of second degree atrioventricular (AV) block or third degree AV block or a QTcF interval > 470 ms (females), > 450 ms (males);

2. Any of the following alerts from central laboratory at Visit 14 of the core study (EOT) which was confirmed as an alert at repeated testing or not repeated prior to FU1 of the core study:

   1. Lymphocyte count: < 0.2 x 109/L;
   2. Neutrophil count <1.0 × 109/L;
   3. Platelet count < 50 × 109/L;
   4. Creatinine clearance < 30 mL/min
3. At Visit 14 of the core study (EOT) >30% decrease from core study baseline FEV1 and/or FVC;
4. Clinically significant, persistent respiratory AEs (e.g., dyspnea) not resolved prior to first dosing in the extension study.
5. Macular edema at any time between Visit 1 (Screening) in the core study and Day 1 of the extension study.

6. Presence of the following at core study Visit 14 (EOT, Week 108), FU1, or abbreviated visit FU2, or on Day 1 of the extension study pre-dose:

   1. Suspected opportunistic infection of the CNS or any other infection which, in the opinion of the investigator, contraindicates re-start of the study drug;
   2. Stevens-Johnson syndrome or toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms.
7. Need for and intention to administer forbidden study treatment-concomitant therapy
8. Women who are pregnant or lactating.
9. Male subjects wishing to parent a child;
10. Treatment with any MS Disease Modifying Therapies;
11. Any other clinically relevant medical or surgical condition, which, in the opinion of the investigator, would put the subject at risk by participating in the study;
12. Subjects unlikely to comply with the extension study protocol based on investigator best judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ponesimod; 20 mg administered orally once daily	Drug: Ponesimod; Ponesimod; Film-coated tablet; Oral use. From Day 1 to Day 14, ponesimod is gradually up-titrated until a maintenance dose of 20 mg is reached from Day 15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized confirmed relapse rate (ARR)	defined as the number of confirmed relapses per subject-year	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Time from core study randomization to first confirmed relapse	Time from enrollment in core study to first confirmed relapse	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Time to first 12-week confirmed disability accumulation (CDA)	Time from core baseline to first 12-week CDA	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Time to first 24-week confirmed disability accumulation (CDA)	Time from core baseline to first 24-week CDA	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Patients with absence of relapses	Number of patients with absence of relapses during study period	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Change from baseline in Expanded Disability Status Scale (EDSS)	Change from baseline in EDSS at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Assessment of no evidence of disease activity (NEDA) status at end-of-study (EOS) according to NEDA 3	NEDA 3 defined by the absence of confirmed relapse, GD+ T1 lesions, new or enlarging T2 lesions and 12-week CDA	Up to 354 weeks
Assessment of no evidence of disease activity (NEDA) status at EOS according to NEDA 4	NEDA 4 defined by the absence of confirmed relapse, GD+ T1 lesions, new or enlarging T2 lesions and 12-week CDA, and annual brain volume change ≥ -0.4% from baseline to all assessments	Up to 354 weeks
Percent change from baseline in brain volume (PCBV) measured by magnetic resonance imaging (MRI)	Change from baseline in brain volume at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Cumulative number of combined unique active lesions (CUAL) measured by MRI	Cumulative number of combined unique active lesions (CUAL) defined as new Gd+ T1 lesions plus new or enlarging T2 lesions (without double-counting the lesions) at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Determination of number of Gd+ T1 lesions by MRI	Number of Gd+ T1 lesions at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Cumulative number of new or enlarging T2 lesions measured by MRI	Cumulative number of new or enlarging T2 lesions (relative to baseline) at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Assessment of volume of brain lesions measured by MRI	Determination of MRI lesions (T2 lesions, T1 hypointense lesions) at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Absence of MRI lesions	Absence of MRI lesions (Gd+ T1 lesions, new or enlarging T2 lesions) at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Determination of proportion of Gd+ lesions at baseline evolving to persistent black holes (PBHs)	Proportion of Gd+ lesions at baseline evolving to PBHs at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Estimation of incidence rates of adverse events (AEs)	Incidence rates of treatment-emergent AEs, severe AEs, AEs of special interest and AEs leading to premature discontinuation of study treatment	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Estimation of incidence rates of treatment-emergent morphological ECG abnormalities	ECG abnormalities as defined by the ECG provider	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Assessment of cardiac rhythms measured by electrocardiogram (ECG) parameters	Absolute values by visit for 12-lead ECG parameters (HR, PR, QRS, QT, QTcB, QTcF)	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Change from baseline values by visit for cardiac rhythms	Change from baseline values by visit for ECG parameters (HR, PR, QRS, QT, QTcB, QTcF)	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Change in ECG parameters from pre-dose to selected post-dose assessments	Change in ECG parameters (HR, PR, QRS, QT, QTcB, QTcF) from pre-dose to selected post-dose assessments (1h, 2h, 3h, 4h) on day 1 of extension study and on day of re-initiation of study treatment	Analysis period: From day 1 in extension study to end-of-treatment (EOT) in extension study, i.e. for up to 240 weeks
Absolute values and percent change from baseline in forced expiratory volume and forced vital capacity	Absolute values and percent change from baseline in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) at all assessments	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Assessment of treatment-emergent decrease from baseline in forced expiratory volume and forced vital capacity	Determination of treatment-emergent decrease from baseline in FEV1 and FVC (absolute and % of predicted)	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks
Absolute change from baseline to end-of-study (EOS) versus change from baseline to end-of-treatment (EOT) in forced expiratory volume and forced vital capacity	Absolute change from baseline to end-of-study (EOS) versus change from baseline to end-of-treatment (EOT) in FEV1 and FVC (absolute and % of predicted)	Analysis period: From day 1 in core study (Enrollment) to end-of-treatment (EOT) in the extension study, i.e. for up to 354 weeks

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Study Director: Tatiana Sidorenko, MD, PhD, Actelion

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2017
• Primary Completion (Actual): January 16, 2024
• Study Completion (Actual): January 16, 2024

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: July 26, 2017
• First Posted (Actual): July 27, 2017

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Ponesimod
• Other Study ID Numbers: AC-058B303; 2016-004719-10 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No