Last Update: Apr 24, 2024
A Randomized, Double-blind, Double-dummy, Parallel-group Study, Comparing the Efficacy and Safety of Remibrutinib Versus Teriflunomide in Participants With Relapsing Multiple Sclerosis, Followed by Extended Treatment With Open-label Remibrutinib
ClinicalTrials.gov Identifier:
Novartis Reference Number:CLOU064C12302
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.

Study Description

To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS)

The study CLOU064C12302 consists of an initial Core Part (CP) (maximum duration per participant of up to 30 months), followed by an Extension Part (EP, of up to 5 years duration) for eligible participants.

The Core Part is a randomized, double-blind, double-dummy, active comparator-controlled, fixed-dose, parallel-group, multi-center study in approximately 800 participants with relapsing multiple sclerosis (RMS).

The Extension Part is an open-label, single-arm, fixed-dose design in which eligible participants are treated with remibrutinib for up to 5 years.

A second study of identical design (CLOU064C12301) will be conducted simultaneously. Both studies will be conducted globally and data from the two studies will be pooled for some of the endpoints.

Relapsing Multiple Sclerosis
Phase 3
Recruiting
800
Dec 13, 2021
Oct 30, 2030
All
18 Years - 55 Years (Adult)

Interventions

Drug

Remibrutinib

tablet taken orally
Drug

Teriflunomide

capsule taken orally

Eligibility Criteria

Inclusion Criteria:

18 to 55 years of age
Diagnosis of RMS according to the 2017 McDonald diagnostic criteria
At least: 1 documented relapse within the previous year. OR 2 documented relapses within the previous 2 years, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12 months.
EDSS score of 0 to 5.5 (inclusive)
Neurologically stable within 1 month

Exclusion Criteria:

Diagnosis of primary progressive multiple sclerosis (PPMS)
Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening
History of clinically significant CNS disease other than MS
Ongoing substance abuse (drug or alcohol)
History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer),
Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML
suicidal ideation or behavior
Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary , renal, hepatic, endocrine, metabolic, hematological disorders or gastrointestinal disease that can interfere with interpretation of the study results or protocol adherence
Participants who have had a splenectomy
Active clinically significant systemic bacterial, viral, parasitic or fungal infections
Positive results for syphilis or tuberculosis testing
Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
Active, chronic disease of the immune system (including stable disease treated with immune therapy (e.g. Leflunomide, Methotrexate)) other than MS (e.g. rheumatoid arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled diabetes or thyroid disorder.
Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody
History or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or participants with moderate or severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease.
History of severe renal disease or creatinine level
Participants at risk of developing or having reactivation of hepatitis

Hematology parameters at screening:

Hemoglobin: < 10 g/dl (<100g/L)
Platelets: < 100000/mm3 (<100 x 109/L)
Absolute lymphocyte count < 800/mm3 (<0.8 x 109/L)
White blood cells: <3 000/mm3 (<3.0 x 109/L)
Neutrophils: < 1 500/mm3 (<1.5 x 109/L)
B-cell count < 50% lower limit of normal (LLN) or total IgG & total IgM < LLN (only required for participants who had a history of receiving B-cell therapies, such as rituximab, ocrelizumab or ofatumumab, prior to screening)
History or current diagnosis of significant ECG abnormalities
Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment (prior to randomization)
Use of other investigational drugs
Requirement for anticoagulant medication or use of dual anti-platelet therapy Significant bleeding risk or coagulation disorders,
History of gastrointestinal bleeding
Major surgery within 8 weeks prior to screening
History of hypersensitivity to any of the study drugs or excipients
Pregnant or nursing (lactating) female participants, prior to randomization
Women of childbearing potential not using highly effective contraception
Sexually active males not agreeing to use condom
Have received any live or live-attenuated vaccines within 6 weeks of randomization or requirement to receive these vaccinations during study
Use of strong CYP3A4 inhibitors or use of moderate or strong CYP3A4 inducers within two weeks prior to randomization

Inclusion to Extension part:

• Participants who complete the Core Part of the study on double-blind study treatment and conduct the Accelerated Elimination Procedure (AEP)

Other inclusion and exclusion criteria may apply.

Study Location

Novartis Investigative Site

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Rosario,Santa Fe,S2000BZL,Argentina

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Rosario,Santa Fe,S2000DSW,Argentina

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Buenos Aires,C1012AAR,Argentina

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Bombal,Mendoza,M5500DXO,Argentina

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Caba,Buenos Aires,C1181ACH,Argentina

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San Miguel De,Tucuman,T4000,Argentina

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Curitiba,PR,81210-310,Brazil

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Vitoria,ES,29055-450,Brazil

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Joinville,Santa Catarina,89202-165,Brazil

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Sao Paulo,01240-020,Brazil

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Porto Alegre,Rio Grande Do Sul,90035-001,Brazil

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Brasilia,DF,70200-730,Brazil

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Porto Alegre,RS,90110-000,Brazil

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Porto Alegre,RS,90430-001,Brazil

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Sofia,1407,Bulgaria

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Sofia,1413,Bulgaria

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Plovdiv,4002,Bulgaria

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Sofia,1309,Bulgaria

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Halifax,Nova Scotia,B3H 4K4,Canada

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Edmonton,Alberta,T6G 2B7,Canada

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Burnaby,British Columbia,V5G 2X6,Canada

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St Jerome,Quebec,J7Z 5T3,Canada

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Ottawa,Ontario,K1H 8L6,Canada

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Montreal,Quebec,H4A 3T2,Canada

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Levis,Quebec,G6W 0M5,Canada

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Quebec,G1J 1Z4,Canada

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Yinchuan,Ningxia,100039,China

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Fuzhou,Fujian,350025,China

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Nanjing,Jiangsu,210029,China

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Hangzhou,Zhejiang,310006,China

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Shanghai,200025,China

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Taiyuan,Shanxi,030001,China

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Hangzhou,Zhejiang,310016,China

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Shanghai,200040,China

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Wenzhou,Zhejiang,325000,China

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Wuhan,Hubei,430030,China

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Beijing,100034,China

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Wuhan,Hubei,430060,China

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Vukovar,32000,Croatia

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Split,HRV,21000,Croatia

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Zagreb,10000,Croatia

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Varazdin,HRV,42000,Croatia

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Tallinn,11315,Estonia

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Tartu,50406,Estonia

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Lille,59037,France

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Nimes,30029,France

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Dijon,21034,France

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Limoges,87042,France

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Toulon Cedex 9,Val De Marne,83800,France

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Clermont-Ferrand Cedex 1,63003,France

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Nantes,Cedex 1,44093,France

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Poissy,78303,France

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Toulouse Cedex 9,31059,France

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Gonesse,95500,France

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Nice,06202,France

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Caen,14033,France

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Contamine Sur Arve,74130,France

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Lille,59000,France

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Grenoble,38042,France

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Marseille,13003,France

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Ioannina,GR,455 00,Greece

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Larissa,GR,411 10,Greece

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Athens,Attica,11526,Greece

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Athens,115 28,Greece

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Greece,53246,Greece

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Athens,12462,Greece

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Thessaloniki,GR 54636,Greece

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Lucknow,Uttar Pradesh,226007,India

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Amritsar,Punjab,143006,India

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Pune,Maharashtra,411004,India

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Kochi,Kerala,682025,India

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Pune,Maharashtra,411013,India

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New Delhi,Delhi,110 060,India

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Kolkata,West Bengal,700017,India

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Hyderabad,Telangana,500082,India

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Brindisi,BR,72100,Italy

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Pozzilli,IS,86077,Italy

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Messina,ME,98121,Italy

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Orbassano,TO,10043,Italy

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Napoli,80131,Italy

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Firenze,FI,50134,Italy

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Modena,MO,41126,Italy

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Foggia,FG,71100,Italy

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Pavia,PV,27100,Italy

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Koriyama city,Fukushima,963-8052,Japan

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Fukuoka,810-0022,Japan

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Ichihara-city,Chiba,299-0111,Japan

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Nagoya,Aichi,466 8560,Japan

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Suita,Osaka,565 0871,Japan

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Kobe-shi,Hyogo,650-0017,Japan

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Nishinomiya,Hyogo,663 8501,Japan

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Kyoto-city,Kyoto,616-8255,Japan

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Kashihara city,Nara,634 8522,Japan

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Isehara,Kanagawa,259-1193,Japan

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Higashimatsuyama,Saitama,355-0005,Japan

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Sagamihara,Kanagawa,252-0375,Japan

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Shinjuku-ku,Tokyo,160 8582,Japan

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Chiba,2608677,Japan

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Sapporo city,Hokkaido,063-0005,Japan

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Kodaira,Tokyo,187-8551,Japan

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Shinjuku-ku,Tokyo,160-0023,Japan

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Sendai city,Miyagi,983 8512,Japan

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Fukuoka city,Fukuoka,812-8582,Japan

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Moriguchi,Osaka,570-8507,Japan

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Itabashi-ku,Tokyo,173-8610,Japan

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Niigata,951 8520,Japan

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Ciudad De Mexico,14050,Mexico

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Chihuahua,31203,Mexico

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Queretaro,76070,Mexico

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Ciudad de Mexico,Distrito Federal,06700,Mexico

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Bialystok,15-704,Poland

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Plewiska,Poznan,62-064,Poland

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Krakow,31-637,Poland

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Zabrze,41-800,Poland

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Glogow,36-060,Poland

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Katowice,40 571,Poland

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Wroclaw,51-685,Poland

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Katowice,40-081,Poland

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Katowice,40-123,Poland

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Matosinhos,Porto,4454509,Portugal

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Santa Maria da Feira,4520 211,Portugal

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Lisboa,1169 050,Portugal

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Coimbra,3000 075,Portugal

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Braga,4710243,Portugal

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Lisboa,1649 035,Portugal

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Leiria,2410-104,Portugal

Caribbean Center for Clinical Research, Inc. .

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Guaynabo,Vivian Martinez-Maldonado (+1 787 793 7984) email: [email protected] -- Angel R Chinea Martinez,00968,Puerto Rico

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Suceava,727525,Romania

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Campulung Muscel,ROM,115100,Romania

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Constanta,900591,Romania

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Targu Mures,540136,Romania

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Constanta,ROM,900123,Romania

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Brasov,ROM,500123,Romania

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Banska Bystrica,974 04,Slovakia

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Banska Bystrica,975 17,Slovakia

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Bratislava,83305,Slovakia

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Celje,3000,Slovenia

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Ljubljana,1000,Slovenia

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Maribor,2000,Slovenia

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Bloemfontein,Free State,9301,South Africa

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Pretoria,0041,South Africa

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Rosebank,2196,South Africa

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Pozuelo de Alarcon,Madrid,28223,Spain

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Vitoria Gasteiz,Pais Vasco,01009,Spain

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Badalona,Catalunya,08916,Spain

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Torrejon de Ardoz,Madrid,28850,Spain

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Sevilla,Andalucia,41009,Spain

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Albacete,Castilla La Mancha,02006,Spain

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Gijon,Asturias,33394,Spain

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Madrid,28009,Spain

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Santiago De Compostela,Galicia,15706,Spain

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Madrid,28040,Spain

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Barcelona,Catalunya,08003,Spain

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Valencia,Comunidad Valenciana,46017,Spain

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Malaga,29016,Spain

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Barcelona,08041,Spain

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Valencia,46026,Spain

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Hospitalet de Llobregat,Barcelona,08907,Spain

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Logrono,La Rioja,26006,Spain

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Stockholm,102 35,Sweden

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Stockholm,141 86,Sweden

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Sancaktepe,Istanbul,34785,Turkey

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Kayseri,38280,Turkey

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Izmir,35620,Turkey

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Meram,42005,Turkey

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Kocaeli,41380,Turkey

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Bursa,16140,Turkey

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Istanbul,34093,Turkey

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Samsun,55139,Turkey

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Istanbul,TUR,34098,Turkey

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Pendik Istanbul,34899,Turkey

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London,W1G 9JF,United Kingdom

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Inverness,Invernesshire,IV2 3RE,United Kingdom

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Canterbury,Kent,CT1 3NG,United Kingdom

Elligo Health Research

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Crab Orchard,Annie Reardon (704-451-5466) email: [email protected] -- Barry Vaught,25827 - West Virginia,United States

Univ of Florida College of Medicine Norman Fixel Institute

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Gainesville,Brianna Nordelo (352-733-2422) email: [email protected] -- Torge Rempe,32610 - Florida,United States

Memorial Hospital .

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Hollywood,Jean Norma Barton email: [email protected] -- Buse Sengul,33021 - Florida,United States

Colorado Neurological Research PC

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Denver,(303-715-9024) -- Adam Wolff,80210 - Colorado,United States

Regina Berkovich MD PhD Inc

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West Hollywood,(310-493-4715) -- Regina Berkovich,90048 - California,United States

Vladimir Royter MD APMC

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Hanford,Noelle Cagle (559-584-9000) email: [email protected] -- Vladimir Royter,93230 - California,United States

Kansas City VA Medical Center

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Kansas City,Shannon Cornell (+18168614700#57492) email: [email protected] -- Vikas Singh,64128 - Missouri,United States

Advent Health Orlando

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Orlando,Shaun McFerren (407-303-5600) email: [email protected] -- Ryan Mizell,32803 - Florida,United States

Nova Clinical Research LLC .

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Bradenton,Camila Vera (615-775-5102) email: [email protected] -- Sanjay Yathiraj,34209 - Florida,United States

Emerald Coast Neurology .

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Pensacola,Aysha McGrath (850-438-1136) email: [email protected] -- David Bear,32514 - Florida,United States

University of Kansas Medical Center CFTY720D2399E1

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Kansas City,Nicholas LeVine (913-588-3968) email: [email protected] -- Sharon Lynch,66160-7330 - Kansas,United States

Methodist Neuroscience Institute

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Merrillville,Michelle Ham (727-744-1580) email: [email protected] -- William Conte,46410 - Indiana,United States

Colorado Springs Neurological Associates

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Colorado Springs,Aspen Beck (719-473-3272) email: [email protected] -- Kimberly Wagner,80907 - Colorado,United States

SFM Clinical Research LLC

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Boca Raton,(561-939-0300) -- Marc Feinberg,33487 - Florida,United States

Lone Star Neurology

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Frisco,Alex Bannister (214-619-1910) email: [email protected] -- Ramin Ansari,75035 - Texas,United States

Aqualane Clinical Research .

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Naples,Mayve Santos (239-434-0332) email: [email protected] -- Matthew J Baker,34102 - Florida,United States

Gables Neurology

Recruiting

Miami,Dayana Cabrera (786-655-8010) email: [email protected] -- Andrew Lerman,33133 - Florida,United States

University of Miami Miller School of Medicine .

Recruiting

Miami,Cesar Rodriguez Suero (305-243-7424) email: [email protected] -- Silvia R Delgado,33136 - Florida,United States

Metrolina Neurological Associates PA .

Recruiting

Indian Land,Alisha Proffitt (803-366-6135) email: [email protected] -- Howard Mandell,29707 - South Carolina,United States

Comprehensive Neurology

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Frederick,(240-566-3130) -- Shahid Rafiq,21702 - Maryland,United States

South Shore Neurologic Associates CFTY720D2403

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Patchogue,Joanna Weller email: [email protected] -- Mark Gudesblatt,11772 - New York,United States

Med Research Inc

Recruiting

El Paso,Paola Cifuentes (+1 915 307 4669) email: [email protected] -- Javier Alejandro Vasallo,79935 - Texas,United States

Aurora BayCare Medical Center

Recruiting

Green Bay,Laura Thoreson (920-288-8310) email: [email protected] -- James Napier,54311 - Wisconsin,United States

Georgetown University Hospital Research

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Washington,Aastha Bhatnagar (202-444-8525) email: [email protected] -- Faria Amjad,20007 - District of Columbia,United States

University of Texas Health Science Center San Antonio COMB157G2301

Recruiting

San Antonio,Charlotte Rhodes email: [email protected] -- Rebecca Romero,78229 - Texas,United States

Neurology Associates, PA

Recruiting

Maitland,Nicole Perovic (+1 407 647 5996) email: [email protected] -- William David Honeycutt,32751 - Florida,United States

Conquest Research

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Winter Park,Shivani Patel (407-353-2402) email: [email protected] -- Rekha Gandhi,32789 - Florida,United States

Texas Institute for Neurological Disorders

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Sherman,(+1 903 893 5141#4334) -- Bharathy Sundaram,75092 - Texas,United States

Medical College of Wisconsin

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Milwaukee,Alexis Micale (414-805-5249) email: [email protected] -- Sam Hooshmand,53226 - Wisconsin,United States

Ochsner Clinic Foundation .

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New Orleans,Ra Janae Morris (504-842-3088) email: [email protected] -- Jenny Feng,70121 - Louisiana,United States

Baptist Physicians Lexington .

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Nicholasville,Franklin Echevarria (859-260-4330) email: [email protected] -- James Winkley,40356 - Kentucky,United States

Georgia Neurology and Sleep Medicine Assoc

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Suwanee,Trista Grant (770-814-9455) email: [email protected] -- David Lesch,30024 - Georgia,United States

University of Washington MS Clinic

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Seattle,(206-598-3344) -- Gloria Von Geldern,98133 - Washington,United States

Neurology Center of San Antonio P.A.

Recruiting

San Antonio,Sofia Sacco (+1 210 490 0016 #23) email: [email protected] -- Ann Bass,78258 - Texas,United States

The Boster Ctr for MS

Recruiting

Columbus,Roger Faubel (614-304-3444) email: [email protected] -- Aaron Boster,43235 - Ohio,United States

Ctr for Neurology and Spine

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Phoenix,Emily Trejo (602-482-2116) email: [email protected] -- Leslie Zuniga,85018 - Arizona,United States

Medical Uni of South Carolina Medical Univ of SC

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Charleston,Robin Bulgarino (843-876-8614) email: [email protected] -- Andrew P Keegan,29425 - South Carolina,United States

Piedmont HealthCare

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Charlotte,(704-664-8060) -- Matthew Carraro,28210 - North Carolina,United States

Brain and Spine Institute

Recruiting

Port Orange,Vanessa Bell email: [email protected] -- Timothy Wierzbicki,32127 - Florida,United States

Vero Beach Neurology .

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Vero Beach,Christopher Stevens (772-569-7039) email: [email protected] -- Stuart Shafer,32960 - Florida,United States

Hope Neurology

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Knoxville,Jada Thomas (865-218-6222) email: [email protected] -- Sibyl Wray,37922 - Tennessee,United States

Neurology Consultants Of Dallas PA Research

Recruiting

Dallas,Melissa Cardoza email: [email protected] -- Adnan Subei,75231 - Texas,United States

Tufts Medical Center .

Recruiting

Boston,(617-636-5848) -- Kristen Babinski,02111 - Massachusetts,United States

CU Anschutz Med Campus

Recruiting

Aurora,Taylor Knox (303-724-0183) email: [email protected] -- Enrique Alvarez,80045 - Colorado,United States

Memorial Healthcare .

Recruiting

Owosso,Jordan Brooks email: [email protected] -- Robert Joseph Pace,48867 - Michigan,United States

Premier Neurology

Recruiting

Greenville,Leann Putman (+1 864 655 4005) email: [email protected] -- Mary Denise Hughes,29650 - South Carolina,United States

Virginia Mason Medical Centre Benaroya Research Institute-2

Recruiting

Seattle,Yeojin Yoon email: [email protected] -- Mariko Kita,98101 - Washington,United States

Humanity Clinical Research .

Recruiting

Pembroke Pines,Gloria Esperanza Laverde (+1 305 705 3441) email: [email protected] -- Linda S Dolin,33024 - Florida,United States

Neurology Diagnostics Inc .

Recruiting

Dayton,Nita Miller (+1 937 224 8200#136) email: [email protected] -- Joel Vandersluis,45408 - Ohio,United States

Worldwide Contacts

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Novartis Pharmaceuticals

Novartis Pharmaceuticals