Study Description
To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with
relapsing multiple sclerosis (RMS) The study CLOU064C12301 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 (CLOU064C12302) will be conducted simultaneously. Both
studies will be conducted globally and data from the two studies will be pooled for some
of the endpoints.
Interventions
Remibrutinib
Teriflunomide
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 (including all Child-Pugh classes) or hepatic
failure 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 as per central
ECG reading at screening visit
- 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
Novartis Investigative Site
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Caba,Buenos Aires,C1122aak,Argentina
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Capital Federal,Buenos Aires,1424,Argentina
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Rosario,Santa Fe,2000,Argentina
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Buenos Aires,C1012aar,Argentina
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Caba,C1424byd,Argentina
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Capital Federal,C1023aab,Argentina
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Santiago del Estero,4200,Argentina
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Linz,Oberoesterreich,A 4020,Austria
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Graz,A-8036,Austria
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Klagenfurt,9020,Austria
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Linz,4020,Austria
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Brasschaat,2930,Belgium
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Brugge,8000,Belgium
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Bruxelles,1070,Belgium
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Melsbroek,1820,Belgium
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Pelt,3900,Belgium
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Edegem,Antwerpen,2650,Belgium
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Antwerpen,2018,Belgium
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Sofia,1113,Bulgaria
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Sofia,1431,Bulgaria
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Sofia,1680,Bulgaria
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Pleven,5800,Bulgaria
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Santiago,Region Metropolitana,7650568,Chile
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Santiago,Region Metropolitana,8431657,Chile
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Changchun,Jilin,130021,China
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Beijing,100730,China
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Tianjin,300052,China
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Baotou,Inner Mongolia,014040,China
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Hohhot,Inner Mongolia,010017,China
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Beijing,Beijing,100000,China
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Nanchang,Jiangxi,330006,China
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Guangzhou City,Guangdong,510000,China
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Bogota,110110,Colombia
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Medellin,050001,Colombia
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Puerto Colombia,Atlantico,080012,Colombia
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Cali,Valle Del Cauca,760001,Colombia
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Cali,Valle Del Cauca,760012,Colombia
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Rijeka,HRV,51000,Croatia
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Osijek,31000,Croatia
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Zadar,23000,Croatia
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Zagreb,10000,Croatia
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Slagelse,Dk-4200,Denmark
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Tbilisi,159,Georgia
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Tbilisi,160,Georgia
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Tbilisi,172,Georgia
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Tbilisi,179,Georgia
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Mangalore,575018,India
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Mumbai,Maharashtra,400008,India
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Nashik,Maharashtra,422005,India
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Chandigarh,Punjab,160012,India
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Ludhiana,Punjab,141008,India
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Lucknow,Uttar Pradesh,226014,India
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Haifa,310 9601,Israel
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Rzeszow,35-323,Poland
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Salt,Cataluna,17190,Spain
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Leon,24080,Spain
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Glasgow,G51 4tf,United Kingdom
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Westbruy On Trym,Bristol,Bs10 5nb,United Kingdom
Accel Research Sites St Pete-Largo
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Seminole,Florida,33777,United States
Deborah Burke
Patricia Hanson
Neurology Center of New England PC .
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Foxboro,Massachusetts,02035,United States
Salvatore Napoli
SC3 Research Pasadena
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Pasadena,California,91105,United States
M Lorraine Purino
Neuro Eye Clinical Trials Inc
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Houston,Texas,77074,United States
Rosa Tang
The Neurological Institute PA
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Charlotte,North Carolina,28204,United States
T Hemanth Hemanth Rao
Neurology of Central FL Res Ctr
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Altamonte Springs,Florida,32714,United States
Alicia Cabrera
Advocate Medical Group
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Park Ridge,Illinois,60068,United States
Danielle Rice
Neur Ctr of N Orange County
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Fullerton,California,92835,United States
Anthony Ciabarra
Sheraz Mossa
Reading Hospital Tower Health Med Group Neuro
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Reading,Pennsylvania,19611,United States
Clifford Reed
Comprehensive Neurology Clinic
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Orlando,Florida,32825,United States
Refaat El-Said
International Neurorehab Institute .
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Lutherville,Maryland,21093,United States
Daniel Becker
Conquest Research Research
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Winter Park,Florida,32789,United States
Gilbert Mbeo
Daysi Guerrero
Montefiore Medical Center Research
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Bronx,New York,10467,United States
Lauren Gluck
MS Center of Greater Washington, P.C.
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Vienna,Virginia,22182,United States
Heidi Crayton
Alpine Clinical Research Center
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Boulder,Colorado,80301,United States
Sidarth Dasari
Center for Neurosciences
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Tucson,Arizona,85718,United States
Francisco Valdivia
Providence St Vincent Med Center
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Portland,Oregon,97225,United States
Stanley Cohan
Neurological Services of Orlando PA
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Orlando,Florida,32806,United States
Daniel H Jacobs
Amparo Gutierrez
College Park Family Care Center
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Overland Park,Kansas,66210,United States
Jeffrey Kaplan
The MS Center for Innovation in Care .
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Saint Louis,Missouri,63131,United States
Barry A Singer
Homestead Assoc In Research Inc
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Homestead,Florida,33033,United States
Angel Carrasco
Palmetto Clinical Research .
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Summerville,South Carolina,29485,United States
Robert Carlile
Beth Israel Deaconess Medical Cente
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Boston,Massachusetts,02215,United States
Jacob Sloane
Velocity Clinical Research
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Savannah,Georgia,31406,United States
J Michael Hemphill
NYU Langone Health Research
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Brooklyn,New York,11201,United States
Josef Gutman
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Seattle,Washington,98122,United States
Christiana Care Health Services
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Newark,Delaware,19713,United States
Jason M Silversteen
Thomas Jefferson University Hospital Dept. of Neurology
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Philadelphia,Pennsylvania,19107-5098,United States
Thomas Leist
Norton Neurology MS Services
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Louisville,Kentucky,40207,United States
Geeta Ganesh
Neuro Center
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Pomona,California,91767,United States
Sadiq Altamimi
Axiom Clinical Research of Florida
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Tampa,Florida,33609,United States
Mark Cascione
DHR Health Institute .
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McAllen,Texas,78503,United States
Roberto Alejandro Cruz
Velocity Clinical Research Drug Shipment
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Raleigh,North Carolina,27607,United States
Casey Jeffreys
Springfield Clinic Research
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Springfield,Illinois,62703,United States
Reuben Valenzuela
Sue Sutherland
Glendale Adventist Medical Center Research
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Glendale,California,91206,United States
Artin Minaeian
Neurology Associates of Ormond Beach
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Ormond Beach,Florida,32174,United States
James Scott
Rush University Medical Center CFTY720D2312
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Chicago,Illinois,60612,United States
Thomas Shoemaker
Neurological Associates of Long Island PC
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Lake Success,New York,11042,United States
Teresa DeAngelis
University of Wisconsin Madison
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Madison,Wisconsin,53792,United States
Natasha Frost
The Research and Education Inst. of Alta Bates Summit Med. Grp
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Berkeley,California,94705,United States
Deepak Soneji
SCL Health
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Billings,Montana,59101,United States
Amanda Klein
Kristian French
Reliant Medical Research
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Miami,Florida,33165,United States
Carlos Ramirez-Calderon
AZ Integrated Neuro and Spine Integrated MS Center
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Phoenix,Arizona,85037,United States
Barry Hendin
Brandon Mc Cravey
John Peter Smith Hospital
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Fort Worth,Texas,76104,United States
Anna Diaz
Horacio Chiong-Rivero
Lahey Clinic
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Burlington,Massachusetts,01805,United States
Dan Michael Pineda
Washington Hospital Center Research Site Shipment
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Washington,District of Columbia,20010,United States
Brian Barry
Mid Atlantic Epilepsy and Sleep Ctr
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Bethesda,Maryland,20817,United States
Jonathan Ross
University Of Pittsburgh Medical Ctr Magee-Womens Hospital
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Pittsburgh,Pennsylvania,15213,United States
Ingrid Loma-Miller
North TX Inst of Neuro and Headache
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Plano,Texas,75024,United States
Annette Okai
Mountain Neuro Research Center PC .
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Basalt,Colorado,81621,United States
Alison Brooke Allen
Leslia Serrano
University Of South Florida .
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Tampa,Florida,33612,United States
Derrick Robertson
Allied Physicians Inc .
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Fort Wayne,Indiana,46845,United States
Ajay Gupta
Olivia Vincent
Multiple Sclerosis Center of Excellence of OMRF
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Oklahoma City,Oklahoma,73104,United States
Gabriel Pardo
Hoag Health System
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Newport Beach,California,92663,United States
Yasir Jassam
Neuroscience Group
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Neenah,Wisconsin,54956,United States
Daniel Long
Insight Hospital and Medical Center
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Chicago,Illinois,60616,United States
Agatha Ngwueke
Rany A Aburashed
NYU Langone Med Center CV Research .
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New York,New York,10016,United States
Nada Abou-Fayssal
The Neuron Clinic .
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Chula Vista,California,91910,United States
Jose Soria
Jersey Shore University Medical Ctr
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Neptune,New Jersey,07753,United States
Lana Zhovtis Ryerson
Honor Health Research Institute .
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Scottsdale,Arizona,85258,United States
Marissa Bielecki
Suraj Muley
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