Efficacy and Safety Studies of Frexalimab (SAR441344) in Adults With Relapsing Forms of Multiple Sclerosis
- Conditions
- Multiple Sclerosis
- Interventions
- Drug: Placebo infusionDrug: Placebo tabletDrug: MRI contrast-enhancing agents
- Registration Number
- NCT06141473
- Lead Sponsor
- Sanofi
- Brief Summary
The purpose of each study is to independently measure the annualized relapse rate (ARR) with administration of frexalimab compared to a daily oral dose of teriflunomide in male and female participants with relapsing forms of multiple sclerosis (aged 18 to 55 years at the time of enrollment). People diagnosed with relapsing forms of multiple sclerosis are eligible for enrollment as long as they meet all the inclusion criteria and none of the exclusion criteria.
Study details include:
* This event-driven study will have variable duration of approximately 40 months for the first participant being randomized and approximately 20 months for the last participant randomized.
* The study intervention duration will vary ranging from approximately 12 to 40 months.
* The assessment of scheduled visits will include 1 common end of study \[EOS\] visit and 3 follow-up visits) with a visit frequency of every 4 weeks for the first 6 months and then every 3 months.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1400
-
The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria.
-
The participant has an EDSS score ≤5.5 at the first visit (Screening Visit)
-
The participant must have at least 1 of the following prior to screening:
- ≥1 documented relapse within the previous year OR
- ≥2 documented relapses within the previous 2 years, OR
- ≥1 documented Gd enhancing lesion on an MRI scan within the previous year.
-
Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria
- The participant has a history of infection or may be at risk for infection:
- The presence of psychiatric disturbance or substance abuse.
- History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphosholipid syndrome and any participants requiring antithrombotic treatment.
- History or current hypogammaglobulinemia defined by values below the lower limit of normal (LLN).
- A history or presence of disease that can mimic MS symptoms, such as, but not limited to neuromyelitis optica spectrum disorder, systemic lupus erythematosus, Sjogren's syndrome, acute disseminated encephalomyelitis, and myasthenia gravis.
- The participant has had a relapse in the 30 days prior to randomization.
- The participant has contraindication for MRI, ie, presence of pacemaker, metallic implants in high risk areas (ie, artificial heart valves, aneurysm/vessel clips), presence of metallic material (eg, shrapnel) in high risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol scheduled MRI scans.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Teriflunomide Placebo infusion Participants will receive teriflunomide tablet and placebo infusion. Frexalimab Placebo tablet Participants will receive Frexalimab infusion and placebo tablet. Frexalimab MRI contrast-enhancing agents Participants will receive Frexalimab infusion and placebo tablet. Frexalimab Cholestyramine Participants will receive Frexalimab infusion and placebo tablet. Frexalimab Activated charcoal Participants will receive Frexalimab infusion and placebo tablet. Frexalimab Frexalimab Participants will receive Frexalimab infusion and placebo tablet. Teriflunomide MRI contrast-enhancing agents Participants will receive teriflunomide tablet and placebo infusion. Teriflunomide Cholestyramine Participants will receive teriflunomide tablet and placebo infusion. Teriflunomide Teriflunomide Participants will receive teriflunomide tablet and placebo infusion. Teriflunomide Activated charcoal Participants will receive teriflunomide tablet and placebo infusion.
- Primary Outcome Measures
Name Time Method Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses Until Week 156 ARR during the study period assessed by protocol-defined adjudicated relapses. This endpoint will be analyzed in the ITT population of each study using a negative binomial model with the total number of adjudicated relapses per participant occurring during the observation period as the response variable and with terms for treatment group, Gd-enhancing T1 lesions at baseline (presence, absence), EDSS strata (\<4, ≥4), and geographical region (US, non-US).
- Secondary Outcome Measures
Name Time Method Time to onset of composite confirmed disability worsening (cCDW) Until Week 156 confirmed over 6 months as assessed by the composite of:
* increase from the baseline expanded disability status scale (EDSS) score of ≥1.5 points when the baseline is 0, or ≥1.0 point when the baseline is 0.5 to 5.0, or ≥0.5 point when the baseline is ≥5.5, OR
* increase of ≥20% from the baseline time in the 9-hole peg test (9HPT), OR
* increase of ≥20% from the baseline time in the Timed 25-foot walk (T25FW) testTime to onset of cCDW, confirmed over 3 months Until Week 156 Time to onset of individual components of the composite, confirmed over 3-months or 6-months Until Week 156 Time to onset of confirmed disability improvement (CDI) Until Week 156 defined as decrease from baseline EDSS score of ≥1.0 or ≥ 0.5 points when the baseline is ≥2 to ≤5.5 or \>5.5 points, respectively, confirmed over 6 months. No improvement possible for 0 to 1.5 points
Progression independent of relapse activity defined as the time to onset of 6-month cCDW Until Week 156 defined by either no prior relapse or an onset more than 90 days after the start date of the last investigatorreported relapse
Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI Until Week 156 defined as the sum of the individual number of new and/or enlarging T2 lesions at all scheduled visits starting after baseline up to and including the EOS visit
Total number of new Gd-enhancing T1hyperintense lesions per scan as detected by MRI Until Week 156 defined as the sum of the individual number of new Gd enhancing T1-hyperintense lesions at all scheduled visits starting after baseline up to and including the EOS visit divided by the number of scans
Percent change in brain volume loss as detected by brain MRI scans at the EOS compared to Month 6 From Week 24 to Week 156 Change in cognitive function at the EOS compared to baseline as assessed by the symbol digit modalities test (SDMT) From baseline to Week 156 Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time From baseline to Week 156 Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue MS-8 over time Until Week 156 Number of participants with adverse events, SAEs, AEs leading to permanent study intervention discontinuation, AESIs and safety scales during the study period Until Week 168 Number of participants with potentially clinically significant abnormality (PCSAs) in laboratory tests, ECG and vital signs during the study period Until Week 168 12-lead ECG (electrocardiogram) will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.
Number of participants with antidrug (ADAs) over time Until Week 156 Change from baseline in plasma neurofilament light chain (NfL) levels over time Until Week 144 Frexalimab plasma concentration over time Until Week 144
Trial Locations
- Locations (328)
Investigational Site Number : 3800014
🇮🇹Chieti, Italy
Investigational Site Number : 3801027
🇮🇹Cuneo, Italy
Investigational Site Number : 3800020
🇮🇹Verona, Italy
Investigational Site Number : 1001008
🇧🇬Panagyurishte, Bulgaria
Hartford Healthcare Medical Group- Site Number : 8401069
🇺🇸Norwich, Connecticut, United States
Alabama Neurology Associates- Site Number : 8400115
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham- Site Number : 8401135
🇺🇸Birmingham, Alabama, United States
North Central Neurology Associates- Site Number : 8401100
🇺🇸Cullman, Alabama, United States
St. Joseph's Hospital and Medical Center- Site Number : 8401139
🇺🇸Phoenix, Arizona, United States
Perseverance Research Center- Site Number : 8401138
🇺🇸Scottsdale, Arizona, United States
Clinical Endpoints- Site Number : 8400050
🇺🇸Scottsdale, Arizona, United States
The Neurology Center of Southern California - Carlsbad- Site Number : 8400023
🇺🇸Carlsbad, California, United States
UC Irvine Healthcare - Gottschalk Medical Plaza- Site Number : 8401143
🇺🇸Irvine, California, United States
Multiple Sclerosis Center of California - Laguna Hills- Site Number : 8401122
🇺🇸Laguna Hills, California, United States
Chemidox Clinical Trials- Site Number : 8401157
🇺🇸Lancaster, California, United States
Private Practice - Dr. Regina Berkovich- Site Number : 8400005
🇺🇸West Hollywood, California, United States
University of Colorado - Anschutz Medical Campus- Site Number : 8401001
🇺🇸Aurora, Colorado, United States
Advanced Neurology of Colorado- Site Number : 8401148
🇺🇸Fort Collins, Colorado, United States
New England Institute for Clinical Research- Site Number : 8400114
🇺🇸Stamford, Connecticut, United States
MedStar Georgetown University Hospital- Site Number : 8400044
🇺🇸Washington, District of Columbia, United States
Neurology of Central Florida- Site Number : 8401147
🇺🇸Altamonte Springs, Florida, United States
Neurology Offices of South Florida - Boca Raton- Site Number : 8401169
🇺🇸Boca Raton, Florida, United States
First Choice Neurology - Espinosa Neuroscience Institute- Site Number : 8401071
🇺🇸Boca Raton, Florida, United States
Mayo Clinic Hospital Jacksonville- Site Number : 8401093
🇺🇸Jacksonville, Florida, United States
Neurology Associates - Maitland- Site Number : 8400010
🇺🇸Maitland, Florida, United States
Orlando Health Neuroscience Institute - Downtown Pavilion- Site Number : 8400060
🇺🇸Orlando, Florida, United States
Axiom Clinical Research of Florida- Site Number : 8400049
🇺🇸Tampa, Florida, United States
University of South Florida- Site Number : 8400013
🇺🇸Tampa, Florida, United States
Palm Beach Medical Group- Site Number : 8401105
🇺🇸West Palm Beach, Florida, United States
Velocity Clinical Research - Savannah Neurology- Site Number : 8400061
🇺🇸Savannah, Georgia, United States
NorthShore Medical Group - Evanston- Site Number : 8401111
🇺🇸Evanston, Illinois, United States
Consultants in Neurology- Site Number : 8401020
🇺🇸Northbrook, Illinois, United States
Springfield Clinic 1st - 800 Building- Site Number : 8400043
🇺🇸Springfield, Illinois, United States
IU Health Physicians - Fort Wayne - Hope Drive- Site Number : 8400058
🇺🇸Fort Wayne, Indiana, United States
Neuroscience Institute Center- Site Number : 8400053
🇺🇸Merrillville, Indiana, United States
University of Iowa- Site Number : 8400029
🇺🇸Iowa City, Iowa, United States
University of Kansas Medical Center- Site Number : 8400084
🇺🇸Kansas City, Kansas, United States
College Park Family Care Center - Overland Park- Site Number : 8400032
🇺🇸Overland Park, Kansas, United States
Baptist Health Lexington- Site Number : 8401149
🇺🇸Lexington, Kentucky, United States
Norton Neurology Services- Site Number : 8401103
🇺🇸Louisville, Kentucky, United States
NeuroMedical Clinic of Central Louisiana- Site Number : 8401159
🇺🇸Alexandria, Louisiana, United States
The NeuroMedical Center- Site Number : 8401182
🇺🇸Baton Rouge, Louisiana, United States
Ochsner Medical Center - Jefferson Highway- Site Number : 8400027
🇺🇸New Orleans, Louisiana, United States
International Neurorehabilitation Institute- Site Number : 8400089
🇺🇸Lutherville, Maryland, United States
Boston Clinical Trials- Site Number : 8401178
🇺🇸Boston, Massachusetts, United States
Neurology Center of New England- Site Number : 8401164
🇺🇸Foxboro, Massachusetts, United States
Henry Ford Hospital- Site Number : 8401091
🇺🇸Detroit, Michigan, United States
Michigan Institute for Neurological Disorders- Site Number : 8400004
🇺🇸Farmington Hills, Michigan, United States
Trinity Health Grand Rapids- Site Number : 8400150
🇺🇸Grand Rapids, Michigan, United States
Memorial Healthcare Institute for Neuroscience- Site Number : 8400123
🇺🇸Owosso, Michigan, United States
Rochester Medical Group- Site Number : 8401172
🇺🇸Rochester Hills, Michigan, United States
M Health Fairview University of Minnesota Medical Center - East Bank- Site Number : 8400056
🇺🇸Minneapolis, Minnesota, United States
Minnesota Center for Multiple Sclerosis- Site Number : 8400073
🇺🇸Plymouth, Minnesota, United States
Sharlin Health & Neurology- Site Number : 8400016
🇺🇸Ozark, Missouri, United States
Washington University- Site Number : 8400076
🇺🇸Saint Louis, Missouri, United States
The MS Center for Innovations in Care- Site Number : 8401141
🇺🇸Saint Louis, Missouri, United States
Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas- Site Number : 8400045
🇺🇸Las Vegas, Nevada, United States
Renown Regional Medical Center- Site Number : 8400066
🇺🇸Reno, Nevada, United States
Rutgers University- Site Number : 8401067
🇺🇸New Brunswick, New Jersey, United States
The University of New Mexico- Site Number : 8401090
🇺🇸Albuquerque, New Mexico, United States
South Shore Neurologic Associates - Patchogue- Site Number : 8400063
🇺🇸Patchogue, New York, United States
The Neurological Institute- Site Number : 8401166
🇺🇸Charlotte, North Carolina, United States
Piedmont HealthCare - Lake Norman Neurology- Site Number : 8400002
🇺🇸Charlotte, North Carolina, United States
Raleigh Neurology Associates- Site Number : 8400014
🇺🇸Raleigh, North Carolina, United States
Atrium Health Wake Forest Baptist - Digestive Health Services - Shepherd- Site Number : 8400040
🇺🇸Winston-Salem, North Carolina, United States
Sanford Neuroscience Clinic- Site Number : 8401085
🇺🇸Fargo, North Dakota, United States
Dayton Center for Neurological Disorders- Site Number : 8400079
🇺🇸Centerville, Ohio, United States
University of Cincinnati - Internal Medicine- Site Number : 8401117
🇺🇸Cincinnati, Ohio, United States
The Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute- Site Number : 8401009
🇺🇸Columbus, Ohio, United States
OhioHealth Riverside Methodist Hospital- Site Number : 8401092
🇺🇸Columbus, Ohio, United States
The Boster Center for Multiple Sclerosis- Site Number : 8400006
🇺🇸Columbus, Ohio, United States
University of Cincinnati- Site Number : 8401008
🇺🇸Dayton, Ohio, United States
Oklahoma Medical Research Foundation- Site Number : 8400039
🇺🇸Oklahoma City, Oklahoma, United States
Providence St. Vincent's Medical Center- Site Number : 8400052
🇺🇸Portland, Oregon, United States
Abington Neurological Associates- Site Number : 8401065
🇺🇸Abington, Pennsylvania, United States
Thomas Jefferson University Hospital- Site Number : 8400035
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital- Site Number : 8401173
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center Magee - Womens Hospital- Site Number : 8401133
🇺🇸Pittsburgh, Pennsylvania, United States
Premier Neurology- Site Number : 8401047
🇺🇸Greer, South Carolina, United States
Hope Neurology- Site Number : 8400019
🇺🇸Knoxville, Tennessee, United States
Neurology Consultants of Dallas - Lyndon B Johnson Freeway- Site Number : 8400152
🇺🇸Dallas, Texas, United States
North Texas Institute of Neurology & Headache - Plano- Site Number : 8401083
🇺🇸Plano, Texas, United States
Neurology Center of San Antonio- Site Number : 8400099
🇺🇸San Antonio, Texas, United States
Texas Institute for Neurological Disorders - Sherman- Site Number : 8400018
🇺🇸Sherman, Texas, United States
Inova Schar Cancer Institute - Fairfax - Innovation Park Drive- Site Number : 8401109
🇺🇸Fairfax, Virginia, United States
Multiple Sclerosis Center of Greater Washington (MSCGW)- Site Number : 8401128
🇺🇸Vienna, Virginia, United States
Swedish Medical Center - Seattle- Site Number : 8400078
🇺🇸Seattle, Washington, United States
University of Washington Medical Center - Northwest- Site Number : 8401146
🇺🇸Seattle, Washington, United States
MultiCare Institute for Research & Innovation- Site Number : 8401140
🇺🇸Tacoma, Washington, United States
Wheaton Franciscan Healthcare - St Francis- Site Number : 8400034
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin - Milwaukee Campus- Site Number : 8400038
🇺🇸Milwaukee, Wisconsin, United States
Investigational Site Number : 0321011
🇦🇷Ciudad de Córdoba, Córdoba, Argentina
Investigational Site Number : 0320003
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 0320002
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320008
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0321010
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320009
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320001
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0400001
🇦🇹Innsbruck, Austria
Investigational Site Number : 0401002
🇦🇹Linz, Austria
Investigational Site Number : 0401003
🇦🇹Vienna, Austria
Investigational Site Number : 0560006
🇧🇪Gent, Belgium
Investigational Site Number : 0560005
🇧🇪Overpelt, Belgium
Clinica AMO- Site Number : 0761017
🇧🇷Salvador, Bahia, Brazil
L2IP - Instituto de Pesquisas Clínicas- Site Number : 0760003
🇧🇷Brasília, Distrito Federal, Brazil
Universidade Federal de Goias- Site Number : 0761024
🇧🇷Goiânia, Goiás, Brazil
Freire Pesquisa Clínica - Belo Horizonte - Rua Piauí- Site Number : 0761025
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Instituto de Neurologia de Curitiba - Ecoville- Site Number : 0761001
🇧🇷Curitiba, Paraná, Brazil
Hospital Moinhos de Vento- Site Number : 0761005
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
InsCer - Instituto do Cérebro da PUCRS- Site Number : 0761009
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Clínica Neurológica- Site Number : 0761007
🇧🇷Joinville, Santa Catarina, Brazil
Hospital E Maternidade Christovão Da Gama- Site Number : 0761022
🇧🇷Santo André, São Paulo, Brazil
CPQuali Pesquisa Clinica - São Paulo- Site Number : 0761002
🇧🇷São Paulo, Brazil
PSEG Centro de Pesquisa Clínica- Site Number : 0761021
🇧🇷São Paulo, Brazil
Jordy Sinapse- Site Number : 0761004
🇧🇷São Paulo, Brazil
Investigational Site Number : 1000009
🇧🇬Blagoevgrad, Bulgaria
Investigational Site Number : 1000007
🇧🇬Pazardzhik, Bulgaria
Investigational Site Number : 1000002
🇧🇬Pleven, Bulgaria
Investigational Site Number : 1001010
🇧🇬Pleven, Bulgaria
Investigational Site Number : 1000004
🇧🇬Sofia, Bulgaria
Investigational Site Number : 1001001
🇧🇬Sofia, Bulgaria
Investigational Site Number : 1001006
🇧🇬Sofia, Bulgaria
Investigational Site Number : 1000005
🇧🇬Sofia, Bulgaria
Investigational Site Number : 1240017
🇨🇦Edmonton, Alberta, Canada
Investigational Site Number : 1240010
🇨🇦Vancouver, British Columbia, Canada
Investigational Site Number : 1240014
🇨🇦London, Ontario, Canada
Investigational Site Number : 1240002
🇨🇦Ottawa, Ontario, Canada
Investigational Site Number : 1240001
🇨🇦Gatineau, Quebec, Canada
Investigational Site Number : 1240004
🇨🇦Granby, Quebec, Canada
Investigational Site Number : 1240008
🇨🇦Lévis, Quebec, Canada
Investigational Site Number : 1240003
🇨🇦Québec City, Quebec, Canada
Investigational Site Number : 1520002
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520004
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1521001
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1521003
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1560007
🇨🇳Beijing, China
Investigational Site Number : 1560005
🇨🇳Beijing, China
Investigational Site Number : 1560008
🇨🇳Beijing, China
Investigational Site Number : 1561024
🇨🇳Beijing, China
Investigational Site Number : 1560003
🇨🇳Changchun, China
Investigational Site Number : 1560011
🇨🇳Changsha, China
Investigational Site Number : 1560004
🇨🇳Chengdu, China
Investigational Site Number : 1560015
🇨🇳Chongqing, China
Investigational Site Number : 1560020
🇨🇳Dongguan, China
Investigational Site Number : 1561028
🇨🇳Fuzhou, China
Investigational Site Number : 1561026
🇨🇳Guangzhou, China
Investigational Site Number : 1560002
🇨🇳Guangzhou, China
Investigational Site Number : 1561023
🇨🇳Hangzhou, China
Investigational Site Number : 1561027
🇨🇳Harbin, China
Investigational Site Number : 1560019
🇨🇳Hohhot, China
Investigational Site Number : 1560040
🇨🇳Hohhot, China
Investigational Site Number : 1560010
🇨🇳Jiazhuang, China
Investigational Site Number : 1561025
🇨🇳Jinan, China
Investigational Site Number : 1560018
🇨🇳Nanjing, China
Investigational Site Number : 1560001
🇨🇳Shanghai, China
Investigational Site Number : 1560014
🇨🇳Shenyang, China
Investigational Site Number : 1560030
🇨🇳Suzhou, China
Investigational Site Number : 1560006
🇨🇳Taiyuan, China
Investigational Site Number : 1560012
🇨🇳Tianjin, China
Investigational Site Number : 1560016
🇨🇳Wenzhou, China
Investigational Site Number : 1560009
🇨🇳Wuhan, China
Investigational Site Number : 1560013
🇨🇳Xi An, China
Investigational Site Number : 1560021
🇨🇳Yinchuan, China
Investigational Site Number : 2031011
🇨🇿Brno, Czechia
Investigational Site Number : 2030005
🇨🇿Brno, Czechia
Investigational Site Number : 2030002
🇨🇿Hradec Králové, Czechia
Investigational Site Number : 2030006
🇨🇿Jihlava, Czechia
Investigational Site Number : 2031007
🇨🇿Ostrava, Czechia
Investigational Site Number : 2030010
🇨🇿Pardubice, Czechia
Investigational Site Number : 2031003
🇨🇿Prague, Czechia
Investigational Site Number : 2031004
🇨🇿Prague, Czechia
Investigational Site Number : 2031008
🇨🇿Prague, Czechia
Investigational Site Number : 2031009
🇨🇿Teplice, Czechia
Investigational Site Number : 2030001
🇨🇿Zlín, Czechia
Investigational Site Number : 2081002
🇩🇰Esbjerg, Denmark
Investigational Site Number : 2081001
🇩🇰Glostrup, Denmark
Investigational Site Number : 2501006
🇫🇷La Tronche, France
Investigational Site Number : 2501009
🇫🇷Lille, France
Investigational Site Number : 2501002
🇫🇷Nice, France
Investigational Site Number : 2501010
🇫🇷Saint-herblain, France
Investigational Site Number : 2761009
🇩🇪Bielefeld, Germany
Investigational Site Number : 2760010
🇩🇪Bochum, Germany
Investigational Site Number : 2760002
🇩🇪Düsseldorf, Germany
Investigational Site Number : 2760003
🇩🇪Leipzig, Germany
Investigational Site Number : 2761006
🇩🇪Münster, Germany
Investigational Site Number : 2760001
🇩🇪ULM, Germany
Investigational Site Number : 3001005
🇬🇷Athens, Greece
Investigational Site Number : 3000004
🇬🇷Ioannina, Greece
Investigational Site Number : 3001001
🇬🇷Larissa, Greece
Investigational Site Number : 3000002
🇬🇷Thessaloniki, Greece
Investigational Site Number : 3001006
🇬🇷Thessaloniki, Greece
Investigational Site Number : 3481003
🇭🇺Budapest, Hungary
Investigational Site Number : 3481004
🇭🇺Budapest, Hungary
Investigational Site Number : 3480002
🇭🇺Győr, Hungary
Investigational Site Number : 3480001
🇭🇺Kaposvár, Hungary
Investigational Site Number : 3481005
🇭🇺Pécs, Hungary
Investigational Site Number : 3561008
🇮🇳Hyderabad, India
Investigational Site Number : 3760001
🇮🇱Haifa, Israel
Investigational Site Number : 3760003
🇮🇱Ramat Gan, Israel
Investigational Site Number : 3760002
🇮🇱Safed, Israel
Investigational Site Number : 3801011
🇮🇹Genoa, Genova, Italy
Investigational Site Number : 3800008
🇮🇹Pozzilli, Isernia, Italy
Investigational Site Number : 3800002
🇮🇹Milan, Milano, Italy
Investigational Site Number : 3800016
🇮🇹Milan, Milano, Italy
Investigational Site Number : 3800015
🇮🇹Rome, Roma, Italy
Investigational Site Number : 3800001
🇮🇹Rome, Roma, Italy
Investigational Site Number : 3801013
🇮🇹Rome, Roma, Italy
Investigational Site Number : 3800021
🇮🇹Rome, Roma, Italy
AOU S. Luigi Gonzaga-Site Number : 3801024
🇮🇹Orbassano, Torino, Italy
Investigational Site Number : 3801012
🇮🇹Catania, Italy
Investigational Site Number : 3801025
🇮🇹Ferrara, Italy
AOU CAREGGI-Site Number : 3800004
🇮🇹Firenze, Italy
Policlinico "Riuniti" di Foggia-Site Number : 3800019
🇮🇹Foggia, Italy
A.O.U. Università degli studi della Campania Luigi Vanvitelli, II Clinica Neurologica-Site Number : 3801010
🇮🇹Napoli, Italy
Investigational Site Number : 3800017
🇮🇹Palermo, Italy
Investigational Site Number : 3801022
🇮🇹Palermo, Italy
Investigational Site Number : 3801029
🇮🇹Parma, Italy
Investigational Site Number : 3801005
🇮🇹Pavia, Italy
Investigational Site Number : 3801030
🇮🇹Ravenna, Italy
Investigational Site Number : 3801031
🇮🇹Udine, Italy
Investigational Site Number : 3920003
🇯🇵Koriyama, Fukushima, Japan
Investigational Site Number : 3920014
🇯🇵Asahikawa, Hokkaido, Japan
Investigational Site Number : 3920006
🇯🇵Asahikawa, Hokkaido, Japan
Investigational Site Number : 3920017
🇯🇵Sapporo, Hokkaido, Japan
Investigational Site Number : 3920008
🇯🇵Morioka, Iwate, Japan
Investigational Site Number : 3920010
🇯🇵Sagamihara, Kanagawa, Japan
Investigational Site Number : 3920015
🇯🇵Higashimatsuyama, Saitama, Japan
Investigational Site Number : 3920016
🇯🇵Kodaira, Tokyo, Japan
Investigational Site Number : 3920009
🇯🇵Tachikawa, Tokyo, Japan
Investigational Site Number : 3920002
🇯🇵Chiba, Japan
Investigational Site Number : 3920013
🇯🇵Fukuoka, Japan
Investigational Site Number : 3920001
🇯🇵Kyoto, Japan
Investigational Site Number : 3920011
🇯🇵Tokyo, Japan
Investigational Site Number : 3920004
🇯🇵Tokyo, Japan
Investigational Site Number : 3920012
🇯🇵Tokyo, Japan
Investigational Site Number : 4100001
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Investigational Site Number : 4100007
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Investigational Site Number : 4100006
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100002
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100004
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100003
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100008
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4401001
🇱🇹Vilnius, Lithuania
Investigational Site Number : 4841007
🇲🇽Guadalajara, Jalisco, Mexico
Investigational Site Number : 4841005
🇲🇽Culiacan, Sinaloa, Mexico
Investigational Site Number : 4841003
🇲🇽Tlalnepantla de Baz, Mexico
Investigational Site Number : 5280001
🇳🇱Heerlen, Netherlands
Investigational Site Number : 6160018
🇵🇱Bydgoszcz, Kujawsko-pomorskie, Poland
Investigational Site Number : 6161008
🇵🇱Lodz, Lódzkie, Poland
Investigational Site Number : 6161005
🇵🇱Krakow, Malopolskie, Poland
Investigational Site Number : 6161010
🇵🇱Katowice, Slaskie, Poland
Investigational Site Number : 6161011
🇵🇱Katowice, Slaskie, Poland
Investigational Site Number : 6160019
🇵🇱Katowice, Slaskie, Poland
Investigational Site Number : 6160004
🇵🇱Zabrze, Slaskie, Poland
Investigational Site Number : 6160020
🇵🇱Zory, Slaskie, Poland
Investigational Site Number : 6161015
🇵🇱Kielce, Swietokrzyskie, Poland
Investigational Site Number : 6160002
🇵🇱Plewiska, Wielkopolskie, Poland
Investigational Site Number : 6161014
🇵🇱Krakow, Poland
Investigational Site Number : 6161017
🇵🇱Lublin, Poland
Investigational Site Number : 6161016
🇵🇱Warszawa, Poland
Investigational Site Number : 6200001
🇵🇹Braga, Portugal
Investigational Site Number : 6201005
🇵🇹Coimbra, Portugal
Investigational Site Number : 6200009
🇵🇹Guimaraes, Portugal
Investigational Site Number : 6201011
🇵🇹Lisbon, Portugal
Investigational Site Number : 6201012
🇵🇹Lisbon, Portugal
Investigational Site Number : 6200002
🇵🇹Matosinhos, Portugal
San Juan MS Center- Site Number : 8401106
🇵🇷Guaynabo, Puerto Rico
Investigational Site Number : 6421004
🇷🇴Bucharest, Romania
Investigational Site Number : 6421001
🇷🇴Constanta, Romania
Investigational Site Number : 6420002
🇷🇴Câmpulung, Romania
Investigational Site Number : 7030007
🇸🇰Martin, Slovakia
Investigational Site Number : 7030004
🇸🇰Nitra, Slovakia
Investigational Site Number : 7030003
🇸🇰Trnava, Slovakia
Investigational Site Number : 7101002
🇿🇦Cape Town, South Africa
Investigational Site Number : 7101001
🇿🇦Pretoria, South Africa
Investigational Site Number : 7240018
🇪🇸Murcia, Almería, Spain
Investigational Site Number : 7921009
🇹🇷Istanbul, Turkey
Investigational Site Number : 7241016
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240010
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7241012
🇪🇸Donostia-san Sebastian, Gipuzkoa, Spain
Investigational Site Number : 7240013
🇪🇸Las Palmas de Gran Canaria, Las Palmas, Spain
Investigational Site Number : 7240001
🇪🇸Pozuelo de Alarcón, Madrid, Spain
Investigational Site Number : 7241009
🇪🇸Barakaldo, Pais Vasco, Spain
Investigational Site Number : 7241014
🇪🇸Pontevedra, Pontevedra [Pontevedra], Spain
Investigational Site Number : 7240007
🇪🇸Seville, Sevilla, Spain
Investigational Site Number : 7240004
🇪🇸Córdoba, Spain
Investigational Site Number : 7240006
🇪🇸Madrid, Spain
Investigational Site Number : 7241023
🇪🇸Madrid, Spain
Investigational Site Number : 7240002
🇪🇸Madrid, Spain
Investigational Site Number : 7240003
🇪🇸Madrid, Spain
Investigational Site Number : 7241022
🇪🇸Madrid, Spain
Investigational Site Number : 7240005
🇪🇸Málaga, Spain
Investigational Site Number : 7241008
🇪🇸Valencia, Spain
Investigational Site Number : 7240011
🇪🇸Valladolid, Spain
Investigational Site Number : 7561001
🇨🇭Bern, Switzerland
Investigational Site Number : 1581001
🇨🇳Kaohsiung City, Taiwan
Investigational Site Number : 7921006
🇹🇷Akdeniz, Turkey
Investigational Site Number : 7921018
🇹🇷Ankara, Turkey
Investigational Site Number : 7920011
🇹🇷Ankara, Turkey
Investigational Site Number : 7921020
🇹🇷Bursa, Turkey
Investigational Site Number : 7921013
🇹🇷Bursa, Turkey
Investigational Site Number : 7921005
🇹🇷Eskişehir, Turkey
Investigational Site Number : 7920012
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920002
🇹🇷Istanbul, Turkey
Investigational Site Number : 7921016
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920007
🇹🇷Istanbul, Turkey
Investigational Site Number : 7921019
🇹🇷Izmir, Turkey
Investigational Site Number : 7920008
🇹🇷Izmir, Turkey
Investigational Site Number : 7920001
🇹🇷Izmit, Turkey
Investigational Site Number : 7921014
🇹🇷Kayseri, Turkey
Investigational Site Number : 7920015
🇹🇷Konya, Turkey
Investigational Site Number : 7921004
🇹🇷Samsun, Turkey
Investigational Site Number : 7920003
🇹🇷Sultangazi, Turkey
Investigational Site Number : 7920017
🇹🇷VAN, Turkey
Investigational Site Number : 8040007
🇺🇦Chernivtsi, Ukraine
Investigational Site Number : 8040001
🇺🇦Chernivtsi, Ukraine
Investigational Site Number : 8040009
🇺🇦Ivano-frankivsk, Ukraine
Investigational Site Number : 8041003
🇺🇦Krykhivtsi, Ukraine
Investigational Site Number : 8041006
🇺🇦Kyiv, Ukraine
Investigational Site Number : 8040008
🇺🇦Lutsk, Ukraine
Investigational Site Number : 8040004
🇺🇦Lviv, Ukraine
Investigational Site Number : 8041002
🇺🇦Lviv, Ukraine
Investigational Site Number : 8041005
🇺🇦Vinnytsia, Ukraine
Investigational Site Number : 8260001
🇬🇧Exeter, Devon, United Kingdom
Investigational Site Number : 8260013
🇬🇧London, England, United Kingdom
Investigational Site Number : 8261003
🇬🇧Canterbury, Kent, United Kingdom
Investigational Site Number : 8261008
🇬🇧Salford, Manchester, United Kingdom
Investigational Site Number : 8260010
🇬🇧Inverness, United Kingdom