Clinical trial NCT04411641: Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (HERCULES)
Official title: A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-relapsing Secondary Progressive Multiple Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-06-02
Enrollment: 1131
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS

Secondary Objective:

To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites in NRSPMS and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168

Detailed description: This was an event-driven (6-month CDP) trial with a variable treatment duration (end-of-study \[EOS\] duration: up to approximately 47months).

Participants with 6-month confirmed disability progression (CDP) had an option to receive tolebrutinib in the open-label (OL).

Eligibility criteria: Inclusion criteria :

* 18 to 60 years of age inclusive
* Diagnosis of nonrelapsing secondary progressive multiple sclerosis according to the 2017 McDonald criteria
* Expanded disability status scale (EDSS) between 3.0 to 6.5 points inclusive, at screening
* The participant must have documented evidence of disability progression observed during the 12 months before screening
* Absence of clinical relapses for at least 24 months
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
* Is not a WOCBP OR
* Is a WOCBP and agrees to use an acceptable contraceptive method

Exclusion criteria:

* The participant has conditions that would adversely affect study participation such as short life expectancy.
* Evidence of infection with human immuodeficiency virus (HIV), transplantation, progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infections that would adversely affect study participation.
* Persistent chronic or active or recurring system infection, that may adversely affect participation or IMP administration in this study, as judged by the Investigator.
* History of malignancy within 5 years prior to screening.
* History of alcohol or drug abuse within 1 year prior to screening.
* Hospitalized for psychiatric disease within 2 years prior to screening.
* Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at screening
* Bleeding disorder, known platelet dysfunctionat any time prior to the screening visit
* A platelet count \<150 000/μL at the screening visit
* A history of significant bleeding event within 6 months prior to screening, according to the Investigator's judgment such as, but not limited to cerebral or gastrointestinal bleeding.
* Lymphocyte count below the lower limit of normal at screening.
* Recent live (attenuated) vaccine within 2 months before the first treatment visit.
* Recent major surgery (within 4 weeks of screening) or planned major surgery during the study.
* The participant has received medications/treatments for MS within a specified time frame.
* Receiving potent and moderate inducers or inhibitors of cytochrome P450 3A (CYP3A) or potent inhibitors of CYP2C8 hepatic enzymes.
* Receiving anticoagulant or antiplatelet therapy (such as aspirin\>81mg/day, clopidogrel, warfarin).
* Contraindications to magnetic resonance imaging (MRI).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Primary outcomes:
measure: Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS)
timeFrame: Baseline (Day 1) up to approximately 47 months
Secondary outcomes:
measure: Time to Onset of 3-month Confirmed Disability Progression as Assessed by Expanded Disability Status Scale
timeFrame: Baseline (Day 1) up to approximately 47 months
measure: Mean Number of New and/or Enlarging T2-hyperintense Lesions Per Year
timeFrame: Baseline (Day 1) up to approximately 47 months
measure: Time to Onset of Sustained 20% Increase in the 9-hole Peg Test (HPT) for at Least 3 Months
timeFrame: Baseline (Day 1) up to approximately 47 months
measure: Time to Onset of Sustained 20% Increase in the Timed 25-foot Walk (T25-FW) for at Least 3 Months
timeFrame: Baseline (Day 1) up to approximately 47 months
measure: Time to Onset of 6-month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale
timeFrame: Baseline (Day 1) up to approximately 47 months
measure: Percent Change in Brain Volume at EOS Compared to Month 6
timeFrame: Month 6 to EOS (up to approximately 47 months)
measure: Change From Baseline in Cognitive Function as Assessed by Symbol Digit Modalities Test (SDMT) at EOS
timeFrame: Baseline (Day 1) to EOS (up to approximately 47 months)
measure: Change From Baseline in Cognitive Function as Assessed by California Verbal Learning Test Second Edition (CVLT-II) at EOS
timeFrame: Baseline (Day 1) to EOS (up to approximately 47 months)
measure: Change From Baseline in Multiple Sclerosis Quality of Life-54 (MSQoL-54) Questionnaire Score at EOS
timeFrame: Baseline (Day 1) to EOS (up to approximately 47 months)
measure: Number of Participants With Treatment-emergent Adverse Events (AEs), Treatment-emergent Serious AEs, Treatment-emergent AEs Leading to Permanent Study Intervention Discontinuation, and Treatment-emergent Adverse Events of Special Interest (AESIs)
timeFrame: From first dose of study intervention (Day 1) up to end of follow-up, up to approximately 47 months
measure: Maximum Observed Plasma Concentration (Cmax) of Tolebrutinib and M2 Metabolite
timeFrame: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12
measure: Time to Maximum Observed Plasma Concentration (Tmax) of Tolebrutinib and M2 Metabolite
timeFrame: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12
measure: Area Under the Plasma Concentration-time Curve Over the Last 24-hours Dosing Interval (AUC0-24) of Tolebrutinib and M2 Metabolite
timeFrame: 30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12
measure: Change From Baseline in Plasma Neurofilament Light Chain (NfL) and Serum Chitinase-3 Like Protein-1 (Chi3L1) Levels at EOS
timeFrame: Baseline (Day 1) to EOS (up to approximately 47 months)
measure: Change From Baseline in Cluster of Differentiation (CD)19+ B Cells at EOS
timeFrame: Baseline (Day 1) to EOS (up to approximately 47 months)
measure: Change From Baseline in Serum Immunoglobulin (Ig) Levels at EOS
timeFrame: Baseline (Day 1) to EOS (up to approximately 47 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama MS Center-Site Number:8400013
state: Alabama
city: Phoenix
country: United States
facility: Center for Neurology and Spine-Site Number:8400089
state: Arizona
city: Arcadia
country: United States
facility: Arcadia Neurology Center-Site Number:8400070
state: California
city: La Jolla
country: United States
facility: UC San Diego ACTRI-Site Number:8400101
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research-Site Number:8400045
state: California
city: Los Angeles
country: United States
facility: Multiple Sclerosis Center-Site Number:8400143
state: California
city: San Francisco
country: United States
facility: University of San Francisco, Sandler Neurosciences Center-Site Number:8400137
state: California
city: Torrance
country: United States
facility: Harbor UCLA-Site Number:8400088
state: California
city: West Hollywood
country: United States
facility: Regina Berkovich, MD, PhD-Site Number:8400059
state: California
city: Basalt
country: United States
facility: Mountain Neurological Research Center, Inc.-Site Number:8400128
state: Colorado
city: Denver
country: United States
facility: University of Colorado-Site Number:8400012
state: Colorado
city: Fort Collins
country: United States
facility: Advanced Neurosciences Research-Site Number:8400025
state: Colorado
city: Boca Raton
country: United States
facility: South Florida Neurology Associates-Site Number:8400029
state: Florida
city: Maitland
country: United States
facility: Neurology Associates, PA-Site Number:8400004
state: Florida
city: Naples
country: United States
facility: Aqualane Clinical Research-Site Number:8400027
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida-Site Number:8400001
state: Florida
city: Tampa
country: United States
facility: University of South Florida-Site Number:8400006
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research-Site Number:8400003
state: Georgia
city: Northbrook
country: United States
facility: Consultants In Neurology-Site Number:8400011
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center-Site Number:8400023
state: Kansas
city: Lexington
country: United States
facility: CHI Saint Joseph Medical Group Neurology-Site Number:8400110
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center-Site Number:8400072
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts-Site Number:8400014
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University-Site Number:8400046
state: Michigan
city: Owosso
country: United States
facility: The Memorial Hospital-Site Number:8400033
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Clinic of Neurology-Site Number:8400051
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic-Site Number:8400111
state: Minnesota
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center-Site Number:8400019
state: Missouri
city: Las Vegas
country: United States
facility: Lou Ruvo Center for Brain Health-Site Number:8400117
state: Nevada
city: Teaneck
country: United States
facility: Holy Name Hospital-Site Number:8400104
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico-Site Number:8400032
state: New Mexico
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai (Department of Endoc-Site Number:8400038
state: New York
city: Stony Brook
country: United States
facility: Neurology Associates of Stony Brook-Site Number:8400042
state: New York
city: Raleigh
country: United States
facility: Meridian Clinical Research, LLC-Site Number:8400005
state: North Carolina
city: Fargo
country: United States
facility: Sanford Brain & Spine Center-Site Number:8400126
state: North Dakota
city: Cleveland
country: United States
facility: University Hospitals CMC-Site Number:8400083
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic-Site Number:8400125
state: Ohio
city: Columbus
country: United States
facility: Optimed Research, LTD-Site Number:8400147
state: Ohio
city: Dayton
country: United States
facility: Neurology Specialists-Site Number:8400002
state: Ohio
city: Westerville
country: United States
facility: Columbus Neuroscience-Site Number:8400010
state: Ohio
city: Portland
country: United States
facility: Providence Multiple Sclerosis Center-Site Number:8400020
state: Oregon
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine-Site Number:8400142
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Neurology Associates-Site Number:8400016
state: Pennsylvania
city: Greer
country: United States
facility: Premier Neurology-Site Number:8400069
state: South Carolina
city: Greer
country: United States
facility: Mountain View Clinical Research-Site Number:8400024
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic, PC-Site Number:8400087
state: Tennessee
city: Franklin
country: United States
facility: Advanced Neuroscience Center-Site Number:8400035
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine-Site Number:8400136
state: Texas
city: San Antonio
country: United States
facility: Neurology Center of San Antonio-Site Number:8400036
state: Texas
city: Burlington
country: United States
facility: University Of Vermont College Of Medicine-Site Number:8400130
state: Vermont
city: Milwaukee
country: United States
facility: Medical College of Wisconsin-Site Number:8400028
state: Wisconsin
city: Capital Federal
country: Argentina
facility: Investigational Site Number :0320002
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number :0320001
state: Ciudad De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Investigational Site Number :0320007
city: Córdoba
country: Argentina
facility: Investigational Site Number :0320006
city: San Miguel de Tucuman
country: Argentina
facility: Investigational Site Number :0320005
city: St Leonards
country: Australia
facility: Investigational Site Number : 0360007
state: New South Wales
city: Woolloongabba
country: Australia
facility: Investigational Site Number :0360003
state: Queensland
city: Kent Town
country: Australia
facility: Investigational Site Number :0360002
state: South Australia
city: Hobart
country: Australia
facility: Investigational Site Number :0360004
state: Tasmania
city: Fitzroy
country: Australia
facility: Investigational Site Number :0360001
state: Victoria
city: Heidelberg West
country: Australia
facility: Investigational Site Number :0360006
state: Victoria
city: Innsbruck
country: Austria
facility: Investigational Site Number :0400003
city: Linz
country: Austria
facility: Investigational Site Number :0400001
city: Linz
country: Austria
facility: Investigational Site Number :0400004
city: Wien
country: Austria
facility: Investigational Site Number :0400002
city: Vitebsk
country: Belarus
facility: Investigational Site Number :1120004
city: Vitebsk
country: Belarus
facility: Investigational Site Number :1120005
city: Bruxelles
country: Belgium
facility: Investigational Site Number : 0560009
city: Bruxelles
country: Belgium
facility: Investigational Site Number :0560007
city: Edegem
country: Belgium
facility: Investigational Site Number :0560003
city: Gent
country: Belgium
facility: Investigational Site Number : 0560004
city: Leuven
country: Belgium
facility: Investigational Site Number :0560006
city: Liège
country: Belgium
facility: Investigational Site Number :0560008
city: Mons
country: Belgium
facility: Investigational Site Number :0560002
city: Pelt
country: Belgium
facility: Investigational Site Number :0560001
city: Pleven
country: Bulgaria
facility: Investigational Site Number :1000002
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number :1000005
city: Sofia
country: Bulgaria
facility: Investigational Site Number :1000004
city: Sofia
country: Bulgaria
facility: Investigational Site Number :1000008
city: Sofia
country: Bulgaria
facility: Investigational Site Number :1000001
city: Sofia
country: Bulgaria
facility: Investigational Site Number :1000006
city: Sofia
country: Bulgaria
facility: Investigational Site Number :1000009
city: Burnaby
country: Canada
facility: Investigational Site Number :1240017
state: British Columbia
city: Halifax
country: Canada
facility: Investigational Site Number :1240011
state: Nova Scotia
city: Ottawa
country: Canada
facility: Investigational Site Number :1240003
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number :1240008
state: Ontario
city: Gatineau
country: Canada
facility: Investigational Site Number :1240006
state: Quebec
city: Greenfield Park
country: Canada
facility: Investigational Site Number :1240005
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number :1240004
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number :1240015
state: Quebec
city: Sherbrooke
country: Canada
facility: Investigational Site Number :1240007
state: Quebec
city: Quebec
country: Canada
facility: Investigational Site Number : 1240001
city: Quebec
country: Canada
facility: Investigational Site Number :1240021
city: Beijing
country: China
facility: Investigational Site Number :1560006
city: Beijing
country: China
facility: Investigational Site Number :1560012
city: Beijing
country: China
facility: Investigational Site Number :1560021
city: Beijing
country: China
facility: Investigational Site Number :1560003
city: Beijing
country: China
facility: Investigational Site Number :1560009
city: Changchun
country: China
facility: Investigational Site Number :1560004
city: Changsha
country: China
facility: Investigational Site Number :1560015
city: Chengdu
country: China
facility: Investigational Site Number :1560005
city: Chongqing
country: China
facility: Investigational Site Number :1560019
city: Fuzhou
country: China
facility: Investigational Site Number :1560035
city: Guangzhou
country: China
facility: Investigational Site Number :1560001
city: Hangzhou
country: China
facility: Investigational Site Number :1560007
city: Shijiazhuang
country: China
facility: Investigational Site Number :1560014
city: Taiyuan
country: China
facility: Investigational Site Number :1560008
city: Xi'an
country: China
facility: Investigational Site Number :1560017
city: Brno
country: Czechia
facility: Investigational Site Number :2030002
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number :2030004
city: Jihlava
country: Czechia
facility: Investigational Site Number :2030001
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number :2030010
city: Praha 2
country: Czechia
facility: Investigational Site Number :2030005
city: Teplice
country: Czechia
facility: Investigational Site Number :2030003
city: Esbjerg
country: Denmark
facility: Investigational Site Number :2080001
city: Holstebro
country: Denmark
facility: Investigational Site Number :2080005
city: Odense
country: Denmark
facility: Investigational Site Number :2080004
city: Helsinki
country: Finland
facility: Investigational Site Number :2460003
city: Tampere
country: Finland
facility: Investigational Site Number :2460001
city: Turku
country: Finland
facility: Investigational Site Number :2460002
city: Bron
country: France
facility: Investigational Site Number :2500011
city: Clermont Ferrand
country: France
facility: Investigational Site Number :2500005
city: Gonesse
country: France
facility: Investigational Site Number :2500015
city: Lille
country: France
facility: Investigational Site Number :2500009
city: Montpellier
country: France
facility: Investigational Site Number :2500006
city: Nancy
country: France
facility: Investigational Site Number :2500008
city: Nantes
country: France
facility: Investigational Site Number :2500010
city: Nimes
country: France
facility: Investigational Site Number :2500017
city: Paris
country: France
facility: Investigational Site Number :2500016
city: Paris
country: France
facility: Investigational Site Number :2500014
city: Paris
country: France
facility: Investigational Site Number :2500007
city: Rennes
country: France
facility: Investigational Site Number :2500003
city: Strasbourg
country: France
facility: Investigational Site Number :2500001
city: Toulouse
country: France
facility: Investigational Site Number :2500012
city: Bayreuth
country: Germany
facility: Investigational Site Number :2760005
city: Berlin
country: Germany
facility: Investigational Site Number :2760009
city: Dresden
country: Germany
facility: Investigational Site Number :2760001
city: Essen
country: Germany
facility: Investigational Site Number :2760012
city: Gießen
country: Germany
facility: Investigational Site Number :2760002
city: Halle (Saale)
country: Germany
facility: Investigational Site Number :2760010
city: Hannover
country: Germany
facility: Investigational Site Number :2760006
city: Münster
country: Germany
facility: Investigational Site Number :2760008
city: Rostock
country: Germany
facility: Investigational Site Number :2760004
city: Ulm
country: Germany
facility: Investigational Site Number :2760011
city: Athens
country: Greece
facility: Investigational Site Number :3000001
city: Athens
country: Greece
facility: Investigational Site Number :3000006
city: Athens
country: Greece
facility: Investigational Site Number :3000002
city: Athens
country: Greece
facility: Investigational Site Number :3000007
city: Larissa
country: Greece
facility: Investigational Site Number :3000004
city: Thessaloniki
country: Greece
facility: Investigational Site Number :3000003
city: Thessaloniki
country: Greece
facility: Investigational Site Number :3000005
city: Budapest
country: Hungary
facility: Investigational Site Number :3480008
city: Budapest
country: Hungary
facility: Investigational Site Number :3480004
city: Budapest
country: Hungary
facility: Investigational Site Number :3480007
city: Pécs
country: Hungary
facility: Investigational Site Number :3480002
city: Szeged
country: Hungary
facility: Investigational Site Number :3480001
city: Tatabánya
country: Hungary
facility: Investigational Site Number :3480006
city: Gurgaon
country: India
facility: Investigational Site Number :3560007
city: Gurgaon
country: India
facility: Investigational Site Number :3560003
city: India
country: India
facility: Investigational Site Number :3560005
city: Mangaluru
country: India
facility: Investigational Site Number :3560004
city: Nagpur
country: India
facility: Investigational Site Number : 3560009
city: New Delhi
country: India
facility: Investigational Site Number :3560006
city: New Delhi
country: India
facility: Investigational Site Number :3560002
city: Ashkelon
country: Israel
facility: Investigational Site Number :3760002
city: Haifa
country: Israel
facility: Investigational Site Number :3760003
city: Jerusalem
country: Israel
facility: Investigational Site Number :3760008
city: Tel HaShomer
country: Israel
facility: Investigational Site Number :3760001
city: Zefat
country: Israel
facility: Investigational Site Number :3760004
city: Bergamo
country: Italy
facility: Investigational Site Number :3800011
city: Cagliari
country: Italy
facility: Investigational Site Number :3800007
city: Firenze
country: Italy
facility: Investigational Site Number :3800012
city: Firenze
country: Italy
facility: Investigational Site Number :3800016
city: Genova
country: Italy
facility: Investigational Site Number :3800014
city: L'Aquila
country: Italy
facility: Investigational Site Number :3800013
city: Milano
country: Italy
facility: Investigational Site Number :3800004
city: Milano
country: Italy
facility: Investigational Site Number :3800001
city: Milano
country: Italy
facility: Investigational Site Number :3800010
city: Pavia
country: Italy
facility: Investigational Site Number :3800008
city: Roma
country: Italy
facility: Investigational Site Number :3800005
city: Roma
country: Italy
facility: Investigational Site Number :3800009
city: Chiba-shi
country: Japan
facility: Investigational Site Number :3920016
state: Chiba
city: Morioka-shi
country: Japan
facility: Investigational Site Number :3920022
state: Iwate
city: Kyoto-shi
country: Japan
facility: Investigational Site Number :3920011
state: Kyoto
city: Sendai-shi
country: Japan
facility: Investigational Site Number :3920020
state: Miyagi
city: Niigata-shi
country: Japan
facility: Investigational Site Number :3920005
state: Niigata
city: Moriguchi-shi
country: Japan
facility: Investigational Site Number :3920004
state: Osaka
city: Osaka-shi
country: Japan
facility: Investigational Site Number :3920001
state: Osaka
city: Kawagoe-shi
country: Japan
facility: Investigational Site Number :3920018
state: Saitama
city: Kodaira-shi
country: Japan
facility: Investigational Site Number :3920003
state: Tokyo
city: Ota-ku
country: Japan
facility: Investigational Site Number :3920010
state: Tokyo
city: Ube-shi
country: Japan
facility: Investigational Site Number :3920009
state: Yamaguchi
city: Sagamihara-shi
country: Japan
facility: Investigational Site Number :3920023
city: Kaunas
country: Lithuania
facility: Investigational Site Number :4400003
city: Klaipeda
country: Lithuania
facility: Investigational Site Number :4400002
city: Vilnius
country: Lithuania
facility: Investigational Site Number :4400001
city: Amsterdam
country: Netherlands
facility: Investigational Site Number :5280001
city: Breda
country: Netherlands
facility: Investigational Site Number :5280003
city: Groningen
country: Netherlands
facility: Investigational Site Number :5280006
city: Sittard-Geleen
country: Netherlands
facility: Investigational Site Number :5280002
city: Bergen
country: Norway
facility: Investigational Site Number :5780003
city: Namsos
country: Norway
facility: Investigational Site Number :5780002
city: Oslo
country: Norway
facility: Investigational Site Number :5780001
city: Bydgoszcz
country: Poland
facility: Investigational Site Number :6160003
state: Kujawsko-pomorskie
city: Warszawa
country: Poland
facility: Investigational Site Number :6160005
state: Mazowieckie
city: Warszawa
country: Poland
facility: Investigational Site Number :6160006
state: Mazowieckie
city: Katowice
country: Poland
facility: Investigational Site Number :6160002
state: Slaskie
city: Katowice
country: Poland
facility: Investigational Site Number :6160007
state: Slaskie
city: Katowice
country: Poland
facility: Investigational Site Number :6160004
state: Slaskie
city: Plewiska
country: Poland
facility: Investigational Site Number :6160008
state: Wielkopolskie
city: Lodz
country: Poland
facility: Investigational Site Number :6160001
city: Lublin
country: Poland
facility: Investigational Site Number :6160012
city: Zabrze
country: Poland
facility: Investigational Site Number :6160011
city: Braga
country: Portugal
facility: Investigational Site Number :6200001
city: Lisboa
country: Portugal
facility: Investigational Site Number :6200011
city: Lisboa
country: Portugal
facility: Investigational Site Number :6200007
city: Lisboa
country: Portugal
facility: Investigational Site Number :6200006
city: Matosinhos
country: Portugal
facility: Investigational Site Number :6200002
city: Porto
country: Portugal
facility: Investigational Site Number :6200010
city: Bucuresti
country: Romania
facility: Investigational Site Number :6420008
city: Campulung
country: Romania
facility: Investigational Site Number :6420004
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number :6420006
city: Constanta
country: Romania
facility: Investigational Site Number :6420003
city: Oradea
country: Romania
facility: Investigational Site Number :6420013
city: Sibiu
country: Romania
facility: Investigational Site Number :6420005
city: Targu Mures
country: Romania
facility: Investigational Site Number :6420001
city: Timisoara
country: Romania
facility: Investigational Site Number :6420002
city: Barnaul
country: Russian Federation
facility: Investigational Site Number :6430018
city: Ekaterinburg
country: Russian Federation
facility: Investigational Site Number :6430023
city: Kaliningrad
country: Russian Federation
facility: Investigational Site Number :6430025
city: Kazan
country: Russian Federation
facility: Investigational Site Number :6430003
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number :6430022
city: Kirov
country: Russian Federation
facility: Investigational Site Number :6430017
city: Krasnoyarsk
country: Russian Federation
facility: Investigational Site Number :6430024
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430020
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430002
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430013
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number :6430008
city: Nizhny Novgorod
country: Russian Federation
facility: Investigational Site Number :6430021
city: Nizhny Novgorod
country: Russian Federation
facility: Investigational Site Number :6430006
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number :6430005
city: Perm
country: Russian Federation
facility: Investigational Site Number :6430026
city: Pyatigorsk
country: Russian Federation
facility: Investigational Site Number :6430007
city: Rostov-on-Don
country: Russian Federation
facility: Investigational Site Number :6430016
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number :6430004
city: Samara
country: Russian Federation
facility: Investigational Site Number :6430009
city: Saransk
country: Russian Federation
facility: Investigational Site Number :6430019
city: Smolensk
country: Russian Federation
facility: Investigational Site Number :6430014
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number :6430011
city: Tyumen
country: Russian Federation
facility: Investigational Site Number :6430012
city: Ufa
country: Russian Federation
facility: Investigational Site Number :6430010
city: Sevilla
country: Spain
facility: Investigational Site Number :7240007
state: Andalucia
city: Barcelona
country: Spain
facility: Investigational Site Number :7240013
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number :7240016
state: Barcelona [Barcelona]
city: Salt
country: Spain
facility: Investigational Site Number :7240014
state: Girona [Gerona]
city: Las Palmas de Gran Canaria
country: Spain
facility: Investigational Site Number :7240017
state: Las Palmas
city: Majadahonda
country: Spain
facility: Investigational Site Number :7240004
state: Madrid
city: Pozuelo De Alarcón
country: Spain
facility: Investigational Site Number :7240001
state: Madrid
city: Donostia
country: Spain
facility: Investigational Site Number :7240012
state: Pais Vasco
city: Córdoba
country: Spain
facility: Investigational Site Number :7240008
city: Lleida
country: Spain
facility: Investigational Site Number :7240015
city: Madrid
country: Spain
facility: Investigational Site Number :7240005
city: Madrid
country: Spain
facility: Investigational Site Number :7240002
city: Madrid
country: Spain
facility: Investigational Site Number :7240003
city: Murcia
country: Spain
facility: Investigational Site Number :7240010
city: Málaga
country: Spain
facility: Investigational Site Number :7240009
city: Valencia
country: Spain
facility: Investigational Site Number :7240011
city: Eskisehir
country: Turkey
facility: Investigational Site Number :7920005
city: Hatay
country: Turkey
facility: Investigational Site Number :7920010
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920002
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920009
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920007
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920006
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920003
city: Izmir
country: Turkey
facility: Investigational Site Number :7920013
city: Izmit
country: Turkey
facility: Investigational Site Number :7920001
city: Kütahya
country: Turkey
facility: Investigational Site Number :7920011
city: Mersin
country: Turkey
facility: Investigational Site Number :7920012
city: Trabzon
country: Turkey
facility: Investigational Site Number :7920008
city: Chernivtsi
country: Ukraine
facility: Investigational Site Number :8040008
city: Chernivtsi
country: Ukraine
facility: Investigational Site Number :8040016
city: Dnipro
country: Ukraine
facility: Investigational Site Number :8040003
city: Ivano-Frankivsk
country: Ukraine
facility: Investigational Site Number :8040010
city: Kharkiv
country: Ukraine
facility: Investigational Site Number :8040007
city: Kharkiv
country: Ukraine
facility: Investigational Site Number :8040011
city: Kharkiv
country: Ukraine
facility: Investigational Site Number :8040012
city: Kyiv
country: Ukraine
facility: Investigational Site Number :8040013
city: Lutsk
country: Ukraine
facility: Investigational Site Number :8040005
city: Lviv
country: Ukraine
facility: Investigational Site Number :8040009
city: Lviv
country: Ukraine
facility: Investigational Site Number :8040004
city: Odesa
country: Ukraine
facility: Investigational Site Number :8040002
city: Vinnytsia
country: Ukraine
facility: Investigational Site Number :8040006
city: Zhytomyr
country: Ukraine
facility: Investigational Site Number :8040014
city: Exeter
country: United Kingdom
facility: Investigational Site Number :8260003
state: Devon
city: Plymouth
country: United Kingdom
facility: Investigational Site Number :8260008
state: Devon
city: Swansea
country: United Kingdom
facility: Investigational Site Number :8260010
state: Neath Port Talbot
city: Nottingham
country: United Kingdom
facility: Investigational Site Number :8260012
state: Nottinghamshire
city: Oxford
country: United Kingdom
facility: Investigational Site Number :8260013
state: Oxfordshire
city: Bristol
country: United Kingdom
facility: Investigational Site Number :8260009
city: Cardiff
country: United Kingdom
facility: Investigational Site Number :8260001
city: London
country: United Kingdom
facility: Investigational Site Number :8260005
city: London
country: United Kingdom
facility: Investigational Site Number :8260018
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigational Site Number :8260014
city: Salford
country: United Kingdom
facility: Investigational Site Number :8260019
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: