Clinical trial NCT03232073: Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple Sclerosis
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2017-07-27
Enrollment: 877
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Annualized Confirmed Relapse Rate (ARR)
timeFrame: From randomization in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Time From Core Study Randomization to First Confirmed Relapse
timeFrame: From randomization in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Time to First 12-week Confirmed Disability Accumulation (CDA)
timeFrame: From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Time to First 24-week Confirmed Disability Accumulation (CDA)
timeFrame: From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Percentage of Participants With Absence of Relapses
timeFrame: From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Change From Baseline in Expanded Disability Status Scale (EDSS)
timeFrame: From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Percentage of Participants With No Evidence of Disease Activity (NEDA) Status According to NEDA With Three Components (NEDA-3) at Extension End of Study
timeFrame: From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Percentage of Participants With No Evidence of Disease Activity (NEDA) Status According to NEDA With Four Components (NEDA-4) at Extension End of Study
timeFrame: From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Percent Change From Baseline in Brain Volume (PCBV) Measured by Magnetic Resonance Imaging (MRI)
timeFrame: From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months
measure: Cumulative Number of Combined Unique Active Lesions (CUAL) Measured by MRI
timeFrame: From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Number of Gadolinium-enhancing (Gd+) T1 Lesions Measured by MRI
timeFrame: From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months
measure: Cumulative Number of New or Enlarging T2 Lesions Measured by MRI
timeFrame: From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months
measure: Change From Baseline in Volume of MRI Lesions (T2 Lesions and T1 Hypointense Lesions)
timeFrame: From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months
measure: Number of Participants With Absence of MRI Lesions (Gd+ T1 Lesions, New or Enlarging T2 Lesions)
timeFrame: From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months
measure: Percentage of Gd+ Lesions at Baseline Evolving to Persistent Black Holes (PBHs)
timeFrame: From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days
measure: Number of Participants With Treatment-emergent New Morphological Electrocardiogram (ECG) Abnormalities
timeFrame: From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days
measure: Actual Values of 12-lead ECG Measurements up to End of Study Treatment: Heart Rate
timeFrame: From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Actual Values of 12-lead ECG Measurements up to End of Study Treatment: PR, QRS, QT, QTcB, QTcF
timeFrame: From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Change in Heart Rate (HR) From Baseline up to End of Study Treatment
timeFrame: From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Change in PR, QRS, QT, QTcB, QTcF From Baseline up to End of Study Treatment
timeFrame: From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Absolute Values in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) Values
timeFrame: From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Percent Change in (FEV1) and Forced Vital Capacity (FVC) From Baseline (%)
timeFrame: From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days
measure: Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs)
timeFrame: From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days
measure: Number of Participants With AE Leading to Premature Discontinuation of Study Treatment
timeFrame: From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days
measure: Number of Participants With Treatment-emergent Decrease From Baseline >20% and >30% in FEV1 or FVC
timeFrame: From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days
measure: Number of Participants With Treatment-emergent Decrease of >20% Points in Percent Predicted FEV1 and FVC From Baseline
timeFrame: From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days
measure: Number of Participants With a Decrease of >=200 mL or >=12% in FEV1 or FVC From Baseline to EOT
timeFrame: From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Change in FEV1 and FVC (% Predicted) From Baseline to End of Treatment (EOT)
timeFrame: From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Change in FEV1 and FVC (% Predicted) From Baseline to End of Study (EOS)
timeFrame: From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months
measure: Absolute Change in Lung Diffusion Capacity as Assessed by Diffusing Capacity for the Lungs Measured Using Carbon Monoxide (DL[CO]) From Baseline
timeFrame: From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months
measure: Change in DL[CO] (% Predicted) From Baseline to EOT
timeFrame: From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months
measure: Change in DL[CO] (% Predicted) From Baseline to EOS
timeFrame: From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months
Secondary outcomes:
Other outcomes:
measure: Actual Values of 12-lead ECG Measurements on Day of First Re-initiation (Day 1) of Study Drug: Heart Rate
timeFrame: Extension analysis period: Predose, 1, 2, 3, 4 hours post dose on Day 1 of re-initiation (re-initiation could occur on any day during the treatment period when drug was interrupted for at least 3 consecutive days [up to 71.8 months])
measure: Actual Values of 12-lead ECG Measurements on Day of First Re-initiation (Day 1) of Study Drug: PR, QRS, QT, QTcB, QTcF
timeFrame: Extension analysis period: Predose, 1, 2, 3, 4 hours post dose on Day 1 of re-initiation (re-initiation could occur on any day during the treatment period when drug was interrupted for at least 3 consecutive days [up to 71.8 months])
Locations:
city: Carlsbad
country: United States
facility: The Research Center of Southern California, LLC
state: California
city: Pomona
country: United States
facility: The Neurology Group
state: California
city: Denver
country: United States
facility: Mountain View Clinical Research
state: Colorado
city: Ormond Beach
country: United States
facility: Neurology Associates of Ormond Beach
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology, PC
state: Indiana
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Columbus
country: United States
facility: Ohio Health
state: Ohio
city: Franklin
country: United States
facility: Advanced Neurosciences Institute
state: Tennessee
city: Grodno
country: Belarus
facility: Grodno University Hospital
city: Minsk
country: Belarus
facility: Minsk City Clinical Hospital 5
city: Minsk
country: Belarus
facility: Republican Scientific Clinical Centre
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Diagnostic Center
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Sarajevo
country: Bosnia and Herzegovina
facility: University Clinicl Center Sarajevo
city: Plovdiv
country: Bulgaria
facility: UMHAT Sveti Georgi
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda Hospital
city: Sofia
country: Bulgaria
facility: St Ivan Rilski University Multiprofile Hospital For Active Treatment
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Alexandrovska EAD
city: Sofia
country: Bulgaria
facility: Military Medical Academy Multiprofile Hospital for Active Treatment Sofia
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Recherche Sepmus Inc.
state: Quebec
city: Osijek
country: Croatia
facility: Ch Osijek
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
city: Brno
country: Czechia
facility: Fakultní nemocnici Brno
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava
city: Ostrava-Poruba
country: Czechia
facility: Fakultni Nemocnice Ostrava
city: Pardubice
country: Czechia
facility: Pardubicka krajska nemocnice a s
city: Praha 2
country: Czechia
facility: Vseobecna Fakultní Nemocnice
city: Praha 5
country: Czechia
facility: FN Motol
city: Teplice
country: Czechia
facility: Krajska zdravotni, a.s. - Nemocnice Teplice, o.z.
city: Tampere
country: Finland
facility: Suomen Terveystalo Tampere
city: Turku
country: Finland
facility: Mehilainen NEO
city: Bordeaux cedex
country: France
facility: Hopital Pellegrin CHU Bordeaux
city: Clermont Ferrand Cedex 1
country: France
facility: CHU Clermont-Ferrand - Hopital Gabriel Montpied
city: Nantes Cedex 1
country: France
facility: Hopital Nord Laennec - CHU NANTES
city: Nice
country: France
facility: Hopital PASTEUR
city: Strasbourg CEDEX
country: France
facility: Nouvel Hopital Civil
city: T'bilisi
country: Georgia
facility: LTD 'Aversi Clinic'
city: Tbilisi
country: Georgia
facility: P. Sarajishvili Institute of Neurology
city: Tbilisi
country: Georgia
facility: Pineo Medical Ecosystem Ltd
city: Tbilisi
country: Georgia
facility: S.Khechinashvili University Hospital
city: Tbilisi
country: Georgia
facility: Curatio, Jsc
city: Dresden
country: Germany
facility: Universitätsklinikum Carl-Gustav-Carus Dresden
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Leipzig
country: Germany
facility: Panakeia - Arzneimittelforschung GmbH
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg Universitat Mainz
city: Athens
country: Greece
facility: 401 Military Hospital
city: Athens
country: Greece
facility: Naval Hospital of Athens
city: Marousi
country: Greece
facility: Medical Center of Athens
city: Budapest
country: Hungary
facility: Uzsoki Utcai Korhaz
city: Budapest
country: Hungary
facility: Jahn Ferenc Del-pesti Korhaz es Rendelointezet
city: Esztergom
country: Hungary
facility: Valeomed EGÉSZSÉGÜGYI KÖZPONT
city: Győr
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: Kistarcsa
country: Hungary
facility: Kistarcsai Flor Ferenc Korhaz
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Safed
country: Israel
facility: Ziv Medical Center
city: L' Aquila
country: Italy
facility: Ospedale San Salvatore
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant Andrea
city: Riga
country: Latvia
facility: Pauls Stradins Clinical University Hospital
city: Riga
country: Latvia
facility: Latvias Juras medicinas centrs Ltd
city: Riga
country: Latvia
facility: Rīgas Austrumu klīniskā universitātes slimnīca
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
city: Šiauliai
country: Lithuania
facility: VsI Respublikine Siauliu ligonine, V.
city: Chihuahua
country: Mexico
facility: Unidad de Investigacion En Salud
city: Nuevo Leon
country: Mexico
facility: CRI Centro Regiomontano de Investigacion SC
city: Bydgoszcz
country: Poland
facility: Neurocentrum Bydgoszcz Sp Z O O
city: Gdansk
country: Poland
facility: Copernicus Podmiot Leczniczy Sp. z o.o
city: Katowice
country: Poland
facility: Neuro Centrum Centrum Terapii SM
city: Katowice
country: Poland
facility: NEURO MEDIC Janusz Zbrojkiewicz Poradnia Wielospecjalistyczna
city: Konstancin Jeziorna
country: Poland
facility: Centrum Kompleksowej Rehabilitacji
city: Ksawerow
country: Poland
facility: Centrum Opieki Zdrowotnej Orkan Med
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
city: Poznan
country: Poland
facility: Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Po
city: Poznan
country: Poland
facility: Clinical Research Center sp z o o MEDIC R s k
city: Poznan
country: Poland
facility: NZOZ NEURO KARD Ilkowski i Partnerzy Sp Partnerska Lekarzy
city: Wroclaw
country: Poland
facility: WroMedica I Bielicka A Strzalkowska s c
city: Braga
country: Portugal
facility: Hospital de Braga
city: Coimbra
country: Portugal
facility: Hospitais da universidade de Coimbra
city: Lisboa
country: Portugal
facility: Hosp. Cuf Descobertas
city: Porto
country: Portugal
facility: H. Santo António - Centro Hospitalar do Porto
city: Bucuresti
country: Romania
facility: Spitalul Universitar de Urgenta Militar Central 'Dr. Carol Davila'
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni
city: Bucuresti
country: Romania
facility: Spitalul Universitar de Urgenta Bucuresti
city: Timisoara
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Pius Brinzeu
city: Barnaul
country: Russian Federation
facility: Barnaul Territorial Clinical Hospital
city: Belgorod
country: Russian Federation
facility: St. Joseph Belgorod Regional Hospital
city: Bryansk
country: Russian Federation
facility: Bryansk Regional Hospital #1
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Region Clinical Hospital #1
city: Kazan
country: Russian Federation
facility: Research Medical Center Your Health
city: Krasnoyarsk
country: Russian Federation
facility: Federal State Budgetary Institution
city: Kursk
country: Russian Federation
facility: State Budgetary Healthcare Institution Kursk Region Kursk Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Clinical City Hospital #1
city: Moscow
country: Russian Federation
facility: State Health Care Institution Of Moscow
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital N.A.Semashko
city: Nizhniy Novgorod
country: Russian Federation
facility: Municipal Clinical Hospital # 3
city: Novosibirsk
country: Russian Federation
facility: Siberian District Medical Center of Federal Medical-Biological Agency
city: Odintsovo
country: Russian Federation
facility: Federal Scientific Clinical Center of Physico-Chemical Medicine
city: Perm
country: Russian Federation
facility: Perm State Medical Academy n.a. E. A. Vagner
city: Pyatigorsk
country: Russian Federation
facility: City Clinical Hospital # 2
city: Saint Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: Samara
country: Russian Federation
facility: State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
city: Smolensk
country: Russian Federation
facility: Smolensk Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Municipal Multi-Specialty Hospital # 2
city: St. Petersburg
country: Russian Federation
facility: City Clinical Hospital #31
city: St. Petersburg
country: Russian Federation
facility: Institute of Human Brain Ras
city: St.Petersburg
country: Russian Federation
facility: City Hospital# 40
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Tver
country: Russian Federation
facility: Tver Regional Clinical Hospital
city: Velikiy Novgorod
country: Russian Federation
facility: GUZ Novgorod Regional Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: Yaroslavl Clinical Hospital #8
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zvezdara
city: Belgrade
country: Serbia
facility: Vojnomedicinska Akademija
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Nis
country: Serbia
facility: University Clinical Center NIS
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Vithas Nisa Sevilla
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetsjukhuset
city: Stockholm
country: Sweden
facility: Centrum för Neurologi
city: Trabzon
country: Turkey
facility: Karadeniz Teknik University Medical Faculty
city: Chernihiv
country: Ukraine
facility: Public Non-profit Enterprise: Chernihiv City Hospital #4 under Chernihiv City Council
city: Chernihiv
country: Ukraine
facility: Municipal health care institution Chernihiv Regional Hospital
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Ivano-Frankivsk
country: Ukraine
facility: Limited Liability Company 'Neuro Global'
city: Kharkiv
country: Ukraine
facility: Kharkiv Railway Clinical Hospital N1 Of Brance 'Health Center'
city: Kharkiv
country: Ukraine
facility: Kharkiv Postgrad Academy, Dept of Neurology #1 At Hosp #7
city: Kyiv
country: Ukraine
facility: National Research Center for Radiation Medicine
city: Lviv
country: Ukraine
facility: Public Non-Profit Enterprise: Lviv City Clinical Hospital #5
city: Lviv
country: Ukraine
facility: Lviv Clinical Regional Hospital
city: Odesa
country: Ukraine
facility: Odessa National Medical University
city: Poltava
country: Ukraine
facility: ME 'Poltava Regional Clinical Hospital n.a. M.V. Sklifosovsky of the Poltava Regional Council'
city: Ternopil
country: Ukraine
facility: Mnce 'Ternopil Regional Clinical Psychoneurology Hospital' of Trb
city: Vinnytsia
country: Ukraine
facility: Medical Center Salutem LLC
city: Zhytomyr
country: Ukraine
facility: O.F. Herbachevskyi Regional Clinical Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
affiliation: Actelion
name: Tatiana Sidorenko, MD, PhD
role: STUDY_DIRECTOR
References: