Back to resultsLong-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)
Primary Purpose
Multiple Sclerosis
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ponesimod
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent
- Subjects with MS having completed the double-blind treatment in the core study as scheduled
- Compliance with teriflunomide elimination procedure
- 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:
Any of the following cardiovascular conditions on Day 1 pre-dose:
- Resting heart rate (HR) < 50 bpm;
- Presence of second degree atrioventricular (AV) block or third degree AV block or a QTcF interval > 470 ms (females), > 450 ms (males);
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:
- Lymphocyte count: < 0.2 x 109/L;
- Neutrophil count <1.0 × 109/L;
- Platelet count < 50 × 109/L;
- Creatinine clearance < 30 mL/min
- At Visit 14 of the core study (EOT) >30% decrease from core study baseline FEV1 and/or FVC;
- Clinically significant, persistent respiratory AEs (e.g., dyspnea) not resolved prior to first dosing in the extension study.
- Macular edema at any time between Visit 1 (Screening) in the core study and Day 1 of the extension study.
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:
- Suspected opportunistic infection of the CNS or any other infection which, in the opinion of the investigator, contraindicates re-start of the study drug;
- Stevens-Johnson syndrome or toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms.
- Need for and intention to administer forbidden study treatment-concomitant therapy
- Women who are pregnant or lactating.
- Male subjects wishing to parent a child;
- Treatment with any MS Disease Modifying Therapies;
- 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;
- Subjects unlikely to comply with the extension study protocol based on investigator best judgment
Sites / Locations
- The Research Center of Southern California, LLC
- The Neurology Group
- Mountain View Clinical Research
- Neurology Associates of Ormond Beach
- University of South Florida
- Josephson Wallack Munshower Neurology, PC
- Raleigh Neurology Associates
- Ohio Health
- Advanced Neurosciences Institute
- Grodno University Hospital
- Minsk City Clinical Hospital 5
- Republican Scientific Clinical Centre
- Vitebsk Regional Diagnostic Center
- Vitebsk Regional Clinical Hospital
- University Clinicl Center Sarajevo
- UMHAT Sveti Georgi
- Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum
- Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
- Acibadem City Clinic Tokuda Hospital
- St Ivan Rilski University Multiprofile Hospital For Active Treatment
- University Multiprofile Hospital for Active Treatment Alexandrovska EAD
- Military Medical Academy, Multiprofile Hospital for Active Treatment -Sofia
- University of Alberta
- Royal Jubilee Hospital
- Ottawa Hospital
- Recherche Sepmus Inc.
- Ch Osijek
- University Hospital Center Zagreb
- Fakultní nemocnici Brno
- Fakultni nemocnice Hradec Kralove
- Nemocnice Jihlava
- Fakultni nemocnice Ostrava
- Pardubicka krajska nemocnice a.s.
- Vseobecna Fakultní Nemocnice
- FN Motol
- Krajska zdravotni, a.s. - Nemocnice Teplice, o.z.
- Suomen Terveystalo Tampere
- Mehilainen NEO
- Hopital Pellegrin CHU Bordeaux
- CHU Clermont-Ferrand - Hopital Gabriel Montpied
- Hôpital Nord Laennec - CHU NANTES
- Hopital PASTEUR
- Nouvel Hôpital Civil
- LTD 'Aversi Clinic'
- P. Sarajishvili Institute of Neurology
- Pineo Medical Ecosystem Ltd
- S.Khechinashvili University Hospital
- Curatio, Jsc
- Universitätsklinikum Carl-Gustav-Carus Dresden
- Helios Klinikum Erfurt
- Panakeia - Arzneimittelforschung GmbH
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz
- 401 Military Hospital
- Naval Hospital of Athens
- Medical Center of Athens
- Uzsoki Utcai Korhaz
- Jahn Ferenc Del-pesti Korhaz es Rendelointezet
- Valeomed EGÉSZSÉGÜGYI KÖZPONT
- Petz Aladar Megyei Oktato Korhaz
- Pest Megyei Flor Ferenc Korhaz
- Barzilai Medical Center
- Rambam Medical Center
- Hadassah Medical Center
- Ziv Medical Center
- Ospedale San Salvatore
- Azienda Ospedaliera Sant Andrea
- Pauls Stradins Clinical University Hospital
- Latvias Juras medicinas centrs Ltd
- Rīgas Austrumu klīniskā universitātes slimnīca
- Hospital of Lithuanian University of Health Sciences Kaunas Clinics
- VsI Respublikine Siauliu ligonine, V.
- Unidad de Investigacion En Salud
- CRI Centro Regiomontano de Investigacion SC
- Neurocentrum Bydgoszcz Sp Z O O
- Copernicus Podmiot Leczniczy Sp. z o.o
- NeuroCentrum. Centrum Terapii SM
- NEURO-MEDIC Janusz Zbrojkiewicz Poradnia Wielospecjalistyczna
- Centrum Kompleksowej Rehabilitacji
- Centrum Opieki Zdrowotnej Orkan-Med
- Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
- Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Po
- Clinical Research Center sp. z o.o MEDIC-R s.k.
- NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partnerska Lekarzy
- WroMedica I.Bielicka, A.Strzałkowska s.c.
- Hospital de Braga
- Hospitais da universidade de Coimbra
- Hosp. Cuf Descobertas
- H. Santo António - Centro Hospitalar do Porto
- Spitalul Universitar de Urgenta Militar Central 'Dr. Carol Davila'
- Institutul Clinic Fundeni
- Spitalul Universitar de Urgenta Bucuresti
- Spitalul Clinic Judetean de Urgenta 'Pius Brinzeu'
- Barnaul Territorial Clinical Hospital
- St. Joseph Belgorod Regional Hospital
- Bryansk Regional Hospital #1
- Sverdlovsk Region Clinical Hospital #1
- Research Medical Center Your Health
- Federal State Budgetary Institution
- State Budgetary Healthcare Institution Kursk Region Kursk Regional Clinical Hospital
- Clinical City Hospital #1
- State Health Care Institution Of Moscow
- Central Clinical Hospital N.A.Semashko
- Municipal Clinical Hospital # 3
- Siberian District Medical Center of Federal Medical-Biological Agency
- Federal Scientific Clinical Center of Physico-Chemical Medicine
- Perm State Medical Academy n.a. E. A. Vagner
- City Clinical Hospital # 2
- Pavlov First Saint Petersburg State Medical University
- State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
- Smolensk Regional Clinical Hospital
- Municipal Multi-Specialty Hospital # 2
- City Clinical Hospital #31
- Institute of Human Brain Ras
- City Hospital# 40
- Siberian State Medical University
- Tver Regional Clinical Hospital
- GUZ Novgorod Regional Clinical Hospital
- Yaroslavl Clinical Hospital #8
- Clinical Hospital Center Zvezdara
- Vojnomedicinska Akademija
- University Clinical Center Kragujevac
- University Clinical Center NIS
- Hospital del Mar
- Hospital Vall d'Hebron
- Hospital Clinic I Provincial
- Hospital Universitario de La Princesa
- Hospital Regional Universitario de Malaga
- Hospital Universitario Virgen Macarena
- Hospital Vithas Nisa Sevilla
- Sahlgrenska Universitetsjukhuset
- Centrum för Neurologi
- Karadeniz Teknik University Medical Faculty
- Public Non-profit Enterprise: Chernihiv City Hospital #4 under Chernihiv City Council
- Municipal health care institution Chernihiv Regional Hospital
- Ivano-Frankivsk Regional Clinical Hospital
- Limited Liability Company 'Neuro Global'
- Kharkiv Railway Clinical Hospital N1 Of Brance 'Health Center'
- Kharkiv Postgrad Academy, Dept of Neurology #1 At Hosp #7
- National Research Center for Radiation Medicine
- Public Non-Profit Enterprise: Lviv City Clinical Hospital #5
- Lviv Clinical Regional Hospital
- Odessa National Medical University
- ME 'Poltava Regional Clinical Hospital n.a. M.V. Sklifosovsky of the Poltava Regional Council'
- Mnce 'Ternopil Regional Clinical Psychoneurology Hospital' of Trb
- Medical Center Salutem LLC
- O.F. Herbachevskyi Regional Clinical Hospital
- Royal Preston Hospital
- Salford Royal NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ponesimod
Arm Description
20 mg administered orally once daily
Outcomes
Primary Outcome Measures
Annualized confirmed relapse rate (ARR)
defined as the number of confirmed relapses per subject-year
Time from core study randomization to first confirmed relapse
Time from enrollment in core study to first confirmed relapse
Time to first 12-week confirmed disability accumulation (CDA)
Time from core baseline to first 12-week CDA
Time to first 24-week confirmed disability accumulation (CDA)
Time from core baseline to first 24-week CDA
Patients with absence of relapses
Number of patients with absence of relapses during study period
Change from baseline in Expanded Disability Status Scale (EDSS)
Change from baseline in EDSS at all assessments
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
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
Percent change from baseline in brain volume (PCBV) measured by magnetic resonance imaging (MRI)
Change from baseline in brain volume at all assessments
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
Determination of number of Gd+ T1 lesions by MRI
Number of Gd+ T1 lesions at all assessments
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
Assessment of volume of brain lesions measured by MRI
Determination of MRI lesions (T2 lesions, T1 hypointense lesions) at all assessments
Absence of MRI lesions
Absence of MRI lesions (Gd+ T1 lesions, new or enlarging T2 lesions) at all assessments
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
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
Estimation of incidence rates of treatment-emergent morphological ECG abnormalities
ECG abnormalities as defined by the ECG provider
Assessment of cardiac rhythms measured by electrocardiogram (ECG) parameters
Absolute values by visit for 12-lead ECG parameters (HR, PR, QRS, QT, QTcB, QTcF)
Change from baseline values by visit for cardiac rhythms
Change from baseline values by visit for ECG parameters (HR, PR, QRS, QT, QTcB, QTcF)
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
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
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)
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)
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03232073
Brief Title
Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple Sclerosis
Acronym
OPTIMUM-LT
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 5, 2017 (Actual)
Primary Completion Date
January 18, 2024 (Anticipated)
Study Completion Date
January 18, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
This is a single-group open-label extension study to investigate long-term safety, tolerability and control of disease of ponesimod 20 mg in subjects with RMS. Statistical analyses will be descriptive and therefore all endpoints are exploratory in nature. All exploratory endpoints are listed under primary outcomes.
Masking
None (Open Label)
Allocation
N/A
Enrollment
877 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ponesimod
Arm Type
Experimental
Arm Description
20 mg administered orally once daily
Intervention Type
Drug
Intervention Name(s)
Ponesimod
Intervention Description
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
Primary Outcome Measure Information:
Title
Annualized confirmed relapse rate (ARR)
Description
defined as the number of confirmed relapses per subject-year
Time Frame
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
Title
Time from core study randomization to first confirmed relapse
Description
Time from enrollment in core study to first confirmed relapse
Time Frame
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
Title
Time to first 12-week confirmed disability accumulation (CDA)
Description
Time from core baseline to first 12-week CDA
Time Frame
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
Title
Time to first 24-week confirmed disability accumulation (CDA)
Description
Time from core baseline to first 24-week CDA
Time Frame
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
Title
Patients with absence of relapses
Description
Number of patients with absence of relapses during study period
Time Frame
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
Title
Change from baseline in Expanded Disability Status Scale (EDSS)
Description
Change from baseline in EDSS at all assessments
Time Frame
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
Title
Assessment of no evidence of disease activity (NEDA) status at end-of-study (EOS) according to NEDA 3
Description
NEDA 3 defined by the absence of confirmed relapse, GD+ T1 lesions, new or enlarging T2 lesions and 12-week CDA
Time Frame
Up to 354 weeks
Title
Assessment of no evidence of disease activity (NEDA) status at EOS according to NEDA 4
Description
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
Time Frame
Up to 354 weeks
Title
Percent change from baseline in brain volume (PCBV) measured by magnetic resonance imaging (MRI)
Description
Change from baseline in brain volume at all assessments
Time Frame
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
Title
Cumulative number of combined unique active lesions (CUAL) measured by MRI
Description
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
Time Frame
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
Title
Determination of number of Gd+ T1 lesions by MRI
Description
Number of Gd+ T1 lesions at all assessments
Time Frame
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
Title
Cumulative number of new or enlarging T2 lesions measured by MRI
Description
Cumulative number of new or enlarging T2 lesions (relative to baseline) at all assessments
Time Frame
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
Title
Assessment of volume of brain lesions measured by MRI
Description
Determination of MRI lesions (T2 lesions, T1 hypointense lesions) at all assessments
Time Frame
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
Title
Absence of MRI lesions
Description
Absence of MRI lesions (Gd+ T1 lesions, new or enlarging T2 lesions) at all assessments
Time Frame
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
Title
Determination of proportion of Gd+ lesions at baseline evolving to persistent black holes (PBHs)
Description
Proportion of Gd+ lesions at baseline evolving to PBHs at all assessments
Time Frame
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
Title
Estimation of incidence rates of adverse events (AEs)
Description
Incidence rates of treatment-emergent AEs, severe AEs, AEs of special interest and AEs leading to premature discontinuation of study treatment
Time Frame
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
Title
Estimation of incidence rates of treatment-emergent morphological ECG abnormalities
Description
ECG abnormalities as defined by the ECG provider
Time Frame
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
Title
Assessment of cardiac rhythms measured by electrocardiogram (ECG) parameters
Description
Absolute values by visit for 12-lead ECG parameters (HR, PR, QRS, QT, QTcB, QTcF)
Time Frame
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
Title
Change from baseline values by visit for cardiac rhythms
Description
Change from baseline values by visit for ECG parameters (HR, PR, QRS, QT, QTcB, QTcF)
Time Frame
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
Title
Change in ECG parameters from pre-dose to selected post-dose assessments
Description
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
Time Frame
Analysis period: From day 1 in extension study to end-of-treatment (EOT) in extension study, i.e. for up to 240 weeks
Title
Absolute values and percent change from baseline in forced expiratory volume and forced vital capacity
Description
Absolute values and percent change from baseline in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) at all assessments
Time Frame
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
Title
Assessment of treatment-emergent decrease from baseline in forced expiratory volume and forced vital capacity
Description
Determination of treatment-emergent decrease from baseline in FEV1 and FVC (absolute and % of predicted)
Time Frame
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
Title
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
Description
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)
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent
Subjects with MS having completed the double-blind treatment in the core study as scheduled
Compliance with teriflunomide elimination procedure
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:
Any of the following cardiovascular conditions on Day 1 pre-dose:
Resting heart rate (HR) < 50 bpm;
Presence of second degree atrioventricular (AV) block or third degree AV block or a QTcF interval > 470 ms (females), > 450 ms (males);
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:
Lymphocyte count: < 0.2 x 109/L;
Neutrophil count <1.0 × 109/L;
Platelet count < 50 × 109/L;
Creatinine clearance < 30 mL/min
At Visit 14 of the core study (EOT) >30% decrease from core study baseline FEV1 and/or FVC;
Clinically significant, persistent respiratory AEs (e.g., dyspnea) not resolved prior to first dosing in the extension study.
Macular edema at any time between Visit 1 (Screening) in the core study and Day 1 of the extension study.
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:
Suspected opportunistic infection of the CNS or any other infection which, in the opinion of the investigator, contraindicates re-start of the study drug;
Stevens-Johnson syndrome or toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms.
Need for and intention to administer forbidden study treatment-concomitant therapy
Women who are pregnant or lactating.
Male subjects wishing to parent a child;
Treatment with any MS Disease Modifying Therapies;
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;
Subjects unlikely to comply with the extension study protocol based on investigator best judgment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tatiana Sidorenko, MD, PhD
Organizational Affiliation
Actelion
Official's Role
Study Director
Facility Information:
Facility Name
The Research Center of Southern California, LLC
City
Carlsbad
State/Province
California
ZIP/Postal Code
92011
Country
United States
Facility Name
The Neurology Group
City
Pomona
State/Province
California
ZIP/Postal Code
91767
Country
United States
Facility Name
Mountain View Clinical Research
City
Denver
State/Province
Colorado
ZIP/Postal Code
80209
Country
United States
Facility Name
Neurology Associates of Ormond Beach
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Josephson Wallack Munshower Neurology, PC
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Raleigh Neurology Associates
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Ohio Health
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
Facility Name
Advanced Neurosciences Institute
City
Franklin
State/Province
Tennessee
ZIP/Postal Code
37064
Country
United States
Facility Name
Grodno University Hospital
City
Grodno
ZIP/Postal Code
230017
Country
Belarus
Facility Name
Minsk City Clinical Hospital 5
City
Minsk
ZIP/Postal Code
220026
Country
Belarus
Facility Name
Republican Scientific Clinical Centre
City
Minsk
ZIP/Postal Code
220114
Country
Belarus
Facility Name
Vitebsk Regional Diagnostic Center
City
Vitebsk
ZIP/Postal Code
210023
Country
Belarus
Facility Name
Vitebsk Regional Clinical Hospital
City
Vitebsk
ZIP/Postal Code
210037
Country
Belarus
Facility Name
University Clinicl Center Sarajevo
City
Sarajevo
ZIP/Postal Code
71000
Country
Bosnia and Herzegovina
Facility Name
UMHAT Sveti Georgi
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum
City
Sofia
ZIP/Postal Code
1113
Country
Bulgaria
Facility Name
Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
City
Sofia
ZIP/Postal Code
1309
Country
Bulgaria
Facility Name
Acibadem City Clinic Tokuda Hospital
City
Sofia
ZIP/Postal Code
1407
Country
Bulgaria
Facility Name
St Ivan Rilski University Multiprofile Hospital For Active Treatment
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
University Multiprofile Hospital for Active Treatment Alexandrovska EAD
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Military Medical Academy, Multiprofile Hospital for Active Treatment -Sofia
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z1
Country
Canada
Facility Name
Royal Jubilee Hospital
City
Victoria
State/Province
British Columbia
ZIP/Postal Code
V8R 1J8
Country
Canada
Facility Name
Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Recherche Sepmus Inc.
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2J2
Country
Canada
Facility Name
Ch Osijek
City
Osijek
ZIP/Postal Code
31000
Country
Croatia
Facility Name
University Hospital Center Zagreb
City
Zagreb
ZIP/Postal Code
10000
Country
Croatia
Facility Name
Fakultní nemocnici Brno
City
Brno
ZIP/Postal Code
65691
Country
Czechia
Facility Name
Fakultni nemocnice Hradec Kralove
City
Hradec Králové
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Nemocnice Jihlava
City
Jihlava
ZIP/Postal Code
586 33
Country
Czechia
Facility Name
Fakultni nemocnice Ostrava
City
Ostrava-Poruba
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Pardubicka krajska nemocnice a.s.
City
Pardubice
ZIP/Postal Code
532 03
Country
Czechia
Facility Name
Vseobecna Fakultní Nemocnice
City
Praha 2
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
FN Motol
City
Praha 5
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
Krajska zdravotni, a.s. - Nemocnice Teplice, o.z.
City
Teplice
ZIP/Postal Code
415 29
Country
Czechia
Facility Name
Suomen Terveystalo Tampere
City
Tampere
ZIP/Postal Code
33100
Country
Finland
Facility Name
Mehilainen NEO
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Hopital Pellegrin CHU Bordeaux
City
Bordeaux cedex
ZIP/Postal Code
33076
Country
France
Facility Name
CHU Clermont-Ferrand - Hopital Gabriel Montpied
City
Clermont Ferrand Cedex 1
ZIP/Postal Code
63003
Country
France
Facility Name
Hôpital Nord Laennec - CHU NANTES
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Facility Name
Hopital PASTEUR
City
Nice
ZIP/Postal Code
6000
Country
France
Facility Name
Nouvel Hôpital Civil
City
Strasbourg CEDEX
ZIP/Postal Code
67091
Country
France
Facility Name
LTD 'Aversi Clinic'
City
T'bilisi
ZIP/Postal Code
0160
Country
Georgia
Facility Name
P. Sarajishvili Institute of Neurology
City
Tbilisi
ZIP/Postal Code
112
Country
Georgia
Facility Name
Pineo Medical Ecosystem Ltd
City
Tbilisi
ZIP/Postal Code
114
Country
Georgia
Facility Name
S.Khechinashvili University Hospital
City
Tbilisi
ZIP/Postal Code
179
Country
Georgia
Facility Name
Curatio, Jsc
City
Tbilisi
ZIP/Postal Code
186
Country
Georgia
Facility Name
Universitätsklinikum Carl-Gustav-Carus Dresden
City
Dresden
ZIP/Postal Code
1307
Country
Germany
Facility Name
Helios Klinikum Erfurt
City
Erfurt
ZIP/Postal Code
99089
Country
Germany
Facility Name
Panakeia - Arzneimittelforschung GmbH
City
Leipzig
ZIP/Postal Code
04275
Country
Germany
Facility Name
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
401 Military Hospital
City
Athens
ZIP/Postal Code
115 25
Country
Greece
Facility Name
Naval Hospital of Athens
City
Athens
ZIP/Postal Code
11521
Country
Greece
Facility Name
Medical Center of Athens
City
Marousi
ZIP/Postal Code
15125
Country
Greece
Facility Name
Uzsoki Utcai Korhaz
City
Budapest
ZIP/Postal Code
1145
Country
Hungary
Facility Name
Jahn Ferenc Del-pesti Korhaz es Rendelointezet
City
Budapest
ZIP/Postal Code
1204
Country
Hungary
Facility Name
Valeomed EGÉSZSÉGÜGYI KÖZPONT
City
Esztergom
ZIP/Postal Code
2500
Country
Hungary
Facility Name
Petz Aladar Megyei Oktato Korhaz
City
Győr
ZIP/Postal Code
9023
Country
Hungary
Facility Name
Pest Megyei Flor Ferenc Korhaz
City
Kistarcsa
ZIP/Postal Code
2143
Country
Hungary
Facility Name
Barzilai Medical Center
City
Ashkelon
ZIP/Postal Code
7830604
Country
Israel
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Ziv Medical Center
City
Safed
ZIP/Postal Code
1304300
Country
Israel
Facility Name
Ospedale San Salvatore
City
L' Aquila
ZIP/Postal Code
67100
Country
Italy
Facility Name
Azienda Ospedaliera Sant Andrea
City
Roma
ZIP/Postal Code
189
Country
Italy
Facility Name
Pauls Stradins Clinical University Hospital
City
Riga
ZIP/Postal Code
1002
Country
Latvia
Facility Name
Latvias Juras medicinas centrs Ltd
City
Riga
ZIP/Postal Code
1015
Country
Latvia
Facility Name
Rīgas Austrumu klīniskā universitātes slimnīca
City
Riga
ZIP/Postal Code
LV-1038
Country
Latvia
Facility Name
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
City
Kaunas
ZIP/Postal Code
LT50161
Country
Lithuania
Facility Name
VsI Respublikine Siauliu ligonine, V.
City
Šiauliai
ZIP/Postal Code
76231
Country
Lithuania
Facility Name
Unidad de Investigacion En Salud
City
Chihuahua
ZIP/Postal Code
31203
Country
Mexico
Facility Name
CRI Centro Regiomontano de Investigacion SC
City
Nuevo Leon
ZIP/Postal Code
64060
Country
Mexico
Facility Name
Neurocentrum Bydgoszcz Sp Z O O
City
Bydgoszcz
ZIP/Postal Code
85-796
Country
Poland
Facility Name
Copernicus Podmiot Leczniczy Sp. z o.o
City
Gdansk
ZIP/Postal Code
80-803
Country
Poland
Facility Name
NeuroCentrum. Centrum Terapii SM
City
Katowice
ZIP/Postal Code
40-571
Country
Poland
Facility Name
NEURO-MEDIC Janusz Zbrojkiewicz Poradnia Wielospecjalistyczna
City
Katowice
ZIP/Postal Code
40-686
Country
Poland
Facility Name
Centrum Kompleksowej Rehabilitacji
City
Konstancin-Jeziorna
ZIP/Postal Code
05-510
Country
Poland
Facility Name
Centrum Opieki Zdrowotnej Orkan-Med
City
Ksawerow
ZIP/Postal Code
95-054
Country
Poland
Facility Name
Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
City
Lublin
ZIP/Postal Code
20-015
Country
Poland
Facility Name
Szpital Kliniczny im. Heliodora Swiecickiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Po
City
Poznan
ZIP/Postal Code
60-355
Country
Poland
Facility Name
Clinical Research Center sp. z o.o MEDIC-R s.k.
City
Poznan
ZIP/Postal Code
61-731
Country
Poland
Facility Name
NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partnerska Lekarzy
City
Poznan
ZIP/Postal Code
61-853
Country
Poland
Facility Name
WroMedica I.Bielicka, A.Strzałkowska s.c.
City
Wrocław
ZIP/Postal Code
51-685
Country
Poland
Facility Name
Hospital de Braga
City
Braga
ZIP/Postal Code
4710-243
Country
Portugal
Facility Name
Hospitais da universidade de Coimbra
City
Coimbra
ZIP/Postal Code
3000-075
Country
Portugal
Facility Name
Hosp. Cuf Descobertas
City
Lisboa
ZIP/Postal Code
1998-018
Country
Portugal
Facility Name
H. Santo António - Centro Hospitalar do Porto
City
Porto
ZIP/Postal Code
4099-001
Country
Portugal
Facility Name
Spitalul Universitar de Urgenta Militar Central 'Dr. Carol Davila'
City
Bucuresti
ZIP/Postal Code
10825
Country
Romania
Facility Name
Institutul Clinic Fundeni
City
Bucuresti
ZIP/Postal Code
22328
Country
Romania
Facility Name
Spitalul Universitar de Urgenta Bucuresti
City
Bucuresti
ZIP/Postal Code
50098
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta 'Pius Brinzeu'
City
Timisoara
ZIP/Postal Code
300723
Country
Romania
Facility Name
Barnaul Territorial Clinical Hospital
City
Barnaul, Altai Krai
ZIP/Postal Code
656024
Country
Russian Federation
Facility Name
St. Joseph Belgorod Regional Hospital
City
Belgorod
ZIP/Postal Code
308007
Country
Russian Federation
Facility Name
Bryansk Regional Hospital #1
City
Bryansk
ZIP/Postal Code
241033
Country
Russian Federation
Facility Name
Sverdlovsk Region Clinical Hospital #1
City
Ekaterinburg
ZIP/Postal Code
620102
Country
Russian Federation
Facility Name
Research Medical Center Your Health
City
Kazan
ZIP/Postal Code
420097
Country
Russian Federation
Facility Name
Federal State Budgetary Institution
City
Krasnoyarsk
ZIP/Postal Code
660037
Country
Russian Federation
Facility Name
State Budgetary Healthcare Institution Kursk Region Kursk Regional Clinical Hospital
City
Kursk
ZIP/Postal Code
305007
Country
Russian Federation
Facility Name
Clinical City Hospital #1
City
Moscow
ZIP/Postal Code
117049
Country
Russian Federation
Facility Name
State Health Care Institution Of Moscow
City
Moscow
ZIP/Postal Code
127015
Country
Russian Federation
Facility Name
Central Clinical Hospital N.A.Semashko
City
Moscow
ZIP/Postal Code
129128
Country
Russian Federation
Facility Name
Municipal Clinical Hospital # 3
City
Nizhniy Novgorod
ZIP/Postal Code
603155
Country
Russian Federation
Facility Name
Siberian District Medical Center of Federal Medical-Biological Agency
City
Novosibirsk
ZIP/Postal Code
630007
Country
Russian Federation
Facility Name
Federal Scientific Clinical Center of Physico-Chemical Medicine
City
Odintsovo
ZIP/Postal Code
143000
Country
Russian Federation
Facility Name
Perm State Medical Academy n.a. E. A. Vagner
City
Perm
ZIP/Postal Code
614990
Country
Russian Federation
Facility Name
City Clinical Hospital # 2
City
Pyatigorsk
ZIP/Postal Code
357538
Country
Russian Federation
Facility Name
Pavlov First Saint Petersburg State Medical University
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
City
Samara
ZIP/Postal Code
443095
Country
Russian Federation
Facility Name
Smolensk Regional Clinical Hospital
City
Smolensk
ZIP/Postal Code
214018
Country
Russian Federation
Facility Name
Municipal Multi-Specialty Hospital # 2
City
St. Petersburg
ZIP/Postal Code
194354
Country
Russian Federation
Facility Name
City Clinical Hospital #31
City
St. Petersburg
ZIP/Postal Code
197110
Country
Russian Federation
Facility Name
Institute of Human Brain Ras
City
St. Petersburg
ZIP/Postal Code
197376
Country
Russian Federation
Facility Name
City Hospital# 40
City
St.Petersburg
ZIP/Postal Code
197706
Country
Russian Federation
Facility Name
Siberian State Medical University
City
Tomsk
ZIP/Postal Code
634050
Country
Russian Federation
Facility Name
Tver Regional Clinical Hospital
City
Tver
ZIP/Postal Code
170036
Country
Russian Federation
Facility Name
GUZ Novgorod Regional Clinical Hospital
City
Velikiy Novgorod
ZIP/Postal Code
214018
Country
Russian Federation
Facility Name
Yaroslavl Clinical Hospital #8
City
Yaroslavl
ZIP/Postal Code
150003
Country
Russian Federation
Facility Name
Clinical Hospital Center Zvezdara
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Vojnomedicinska Akademija
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
University Clinical Center Kragujevac
City
Kragujevac
ZIP/Postal Code
34000
Country
Serbia
Facility Name
University Clinical Center NIS
City
Nis
ZIP/Postal Code
18000
Country
Serbia
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
8003
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Hospital Clinic I Provincial
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Hospital Universitario de La Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Regional Universitario de Malaga
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Hospital Vithas Nisa Sevilla
City
Sevilla
ZIP/Postal Code
41950
Country
Spain
Facility Name
Sahlgrenska Universitetsjukhuset
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Centrum för Neurologi
City
Stockholm
ZIP/Postal Code
113 65
Country
Sweden
Facility Name
Karadeniz Teknik University Medical Faculty
City
Trabzon
ZIP/Postal Code
61080
Country
Turkey
Facility Name
Public Non-profit Enterprise: Chernihiv City Hospital #4 under Chernihiv City Council
City
Chernihiv
ZIP/Postal Code
14001
Country
Ukraine
Facility Name
Municipal health care institution Chernihiv Regional Hospital
City
Chernihiv
ZIP/Postal Code
14029
Country
Ukraine
Facility Name
Ivano-Frankivsk Regional Clinical Hospital
City
Ivano-Frankivsk
ZIP/Postal Code
76018
Country
Ukraine
Facility Name
Limited Liability Company 'Neuro Global'
City
Ivano-Frankivsk
ZIP/Postal Code
76493
Country
Ukraine
Facility Name
Kharkiv Railway Clinical Hospital N1 Of Brance 'Health Center'
City
Kharkiv
ZIP/Postal Code
61103
Country
Ukraine
Facility Name
Kharkiv Postgrad Academy, Dept of Neurology #1 At Hosp #7
City
Kharkiv
ZIP/Postal Code
61176
Country
Ukraine
Facility Name
National Research Center for Radiation Medicine
City
Kyiv
ZIP/Postal Code
3115
Country
Ukraine
Facility Name
Public Non-Profit Enterprise: Lviv City Clinical Hospital #5
City
Lviv
ZIP/Postal Code
79000
Country
Ukraine
Facility Name
Lviv Clinical Regional Hospital
City
Lviv
ZIP/Postal Code
79010
Country
Ukraine
Facility Name
Odessa National Medical University
City
Odesa
ZIP/Postal Code
65009
Country
Ukraine
Facility Name
ME 'Poltava Regional Clinical Hospital n.a. M.V. Sklifosovsky of the Poltava Regional Council'
City
Poltava
ZIP/Postal Code
36024
Country
Ukraine
Facility Name
Mnce 'Ternopil Regional Clinical Psychoneurology Hospital' of Trb
City
Ternopil
ZIP/Postal Code
46027
Country
Ukraine
Facility Name
Medical Center Salutem LLC
City
Vinnytsia
ZIP/Postal Code
21000
Country
Ukraine
Facility Name
O.F. Herbachevskyi Regional Clinical Hospital
City
Zhytomyr
ZIP/Postal Code
10008
Country
Ukraine
Facility Name
Royal Preston Hospital
City
Preston
ZIP/Postal Code
PR2 9HT
Country
United Kingdom
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
ZIP/Postal Code
M6 8HD
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple Sclerosis
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