Study Description
To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis
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 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 strong CYP3A4 inducers within two weeks prior to randomization
Inclusion to Extension part:
• patient 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
Recruiting
Rosario,Santa Fe,2000,Argentina
Novartis Investigative Site
Recruiting
Buenos Aires,C1012AAR,Argentina
Novartis Investigative Site
Recruiting
Capital Federal,C1023AAB,Argentina
Novartis Investigative Site
Recruiting
Capital Federal,Buenos Aires,1424,Argentina
Novartis Investigative Site
Recruiting
Caba,C1424BYD,Argentina
Novartis Investigative Site
Recruiting
Caba,Buenos Aires,C1122AAK,Argentina
Novartis Investigative Site
Recruiting
Antwerpen,2018,Belgium
Novartis Investigative Site
Recruiting
Jette,Brussel,1090,Belgium
Novartis Investigative Site
Recruiting
Brugge,8000,Belgium
Novartis Investigative Site
Recruiting
Ath,7800,Belgium
Novartis Investigative Site
Recruiting
Melsbroek,1820,Belgium
Novartis Investigative Site
Recruiting
Lier,2500,Belgium
Novartis Investigative Site
Recruiting
Pelt,3900,Belgium
Novartis Investigative Site
Recruiting
Brasschaat,2930,Belgium
Novartis Investigative Site
Recruiting
Edegem,Antwerpen,2650,Belgium
Novartis Investigative Site
Recruiting
Sofia,1113,Bulgaria
Novartis Investigative Site
Recruiting
Sofia,1431,Bulgaria
Novartis Investigative Site
Recruiting
Pleven,5800,Bulgaria
Novartis Investigative Site
Recruiting
Santiago,Region Metropolitana,7650568,Chile
Novartis Investigative Site
Recruiting
Santiago,Region Metropolitana,8431657,Chile
Novartis Investigative Site
Recruiting
Changsha,Hunan,410008,China
Novartis Investigative Site
Recruiting
Zhengzhou,Henan,450052,China
Novartis Investigative Site
Recruiting
Beijing,Beijing,100000,China
Novartis Investigative Site
Recruiting
Guangzhou City,Guangdong,510000,China
Novartis Investigative Site
Recruiting
Nanchang,Jiangxi,330006,China
Novartis Investigative Site
Recruiting
Beijing,100029,China
Novartis Investigative Site
Recruiting
Guangzhou,Guangdong,510080,China
Novartis Investigative Site
Recruiting
Baotou,Inner Mongolia,014040,China
Novartis Investigative Site
Recruiting
Beijing,100730,China
Novartis Investigative Site
Recruiting
Tianjin,300052,China
Novartis Investigative Site
Recruiting
Hohhot,Inner Mongolia,010017,China
Novartis Investigative Site
Recruiting
Chongqing,400016,China
Novartis Investigative Site
Recruiting
Changchun,Jilin,130021,China
Novartis Investigative Site
Recruiting
Cali,Valle Del Cauca,760001,Colombia
Novartis Investigative Site
Recruiting
Cali,Valle Del Cauca,760012,Colombia
Novartis Investigative Site
Recruiting
Bogota,110110,Colombia
Novartis Investigative Site
Recruiting
Puerto Colombia,Atlantico,080012,Colombia
Novartis Investigative Site
Recruiting
Osijek,31000,Croatia
Novartis Investigative Site
Recruiting
Rijeka,HRV,51000,Croatia
Novartis Investigative Site
Recruiting
Zadar,23000,Croatia
Novartis Investigative Site
Recruiting
Zagreb,10000,Croatia
Novartis Investigative Site
Recruiting
Slagelse,DK-4200,Denmark
Novartis Investigative Site
Recruiting
Guatemala,01015,Guatemala
Novartis Investigative Site
Recruiting
Sha Tin,Hong Kong
Novartis Investigative Site
Recruiting
DehraDun,Uttarakhand,248001,India
Novartis Investigative Site
Recruiting
Nashik,Maharashtra,422005,India
Novartis Investigative Site
Recruiting
Chandigarh,Punjab,160012,India
Novartis Investigative Site
Recruiting
New Delhi,Delhi,110017,India
Novartis Investigative Site
Recruiting
Lucknow,Uttar Pradesh,226014,India
Novartis Investigative Site
Recruiting
Hyderabad,Telangana,500082,India
Novartis Investigative Site
Recruiting
Ludhiana,Punjab,141008,India
Novartis Investigative Site
Recruiting
Mumbai,Maharashtra,400008,India
Novartis Investigative Site
Recruiting
Dublin 4,DO4,Ireland
Novartis Investigative Site
Recruiting
Dublin,DUBLIN 8,Ireland
Novartis Investigative Site
Recruiting
Verona,VR,37134,Italy
Novartis Investigative Site
Recruiting
Roma,RM,00168,Italy
Novartis Investigative Site
Recruiting
Napoli,80131,Italy
Novartis Investigative Site
Recruiting
Milano,MI,20132,Italy
Novartis Investigative Site
Recruiting
Montichiari,BS,25018,Italy
Novartis Investigative Site
Recruiting
Roma,RM,00133,Italy
Novartis Investigative Site
Recruiting
Riga,LV,LV-1005,Latvia
Novartis Investigative Site
Recruiting
Riga,LV 1002,Latvia
Novartis Investigative Site
Recruiting
Beirut,6301,Lebanon
Novartis Investigative Site
Recruiting
El Chouf,LBN,1503201002,Lebanon
Novartis Investigative Site
Recruiting
Kuala Lumpur,50589,Malaysia
Novartis Investigative Site
Recruiting
Kuala Terengganu,Terengganu,20400,Malaysia
Novartis Investigative Site
Recruiting
Seberang Jaya,Pulau Pinang,13700,Malaysia
Novartis Investigative Site
Recruiting
Rotterdam,3079 DZ,Netherlands
Novartis Investigative Site
Recruiting
Hertogenbosch,5200,Netherlands
Novartis Investigative Site
Recruiting
Breda,4818 CK,Netherlands
Novartis Investigative Site
Recruiting
Szczecin,70111,Poland
Novartis Investigative Site
Recruiting
Kielce,25 726,Poland
Novartis Investigative Site
Recruiting
Poznan,60-693,Poland
Novartis Investigative Site
Recruiting
Bydgoszcz,Woj Kujawsko-pomorskie,85-796,Poland
Novartis Investigative Site
Recruiting
Lodz,90 324,Poland
Novartis Investigative Site
Recruiting
Rzeszow,35-323,Poland
Novartis Investigative Site
Recruiting
Lodz,93-113,Poland
Novartis Investigative Site
Recruiting
Wroclaw,Dolnoslaskie,52 416,Poland
Novartis Investigative Site
Recruiting
Piotrkow Trybunalski,97300,Poland
Novartis Investigative Site
Recruiting
Nitra,94901,Slovakia
Novartis Investigative Site
Recruiting
Kosice,Slovak Republic,04066,Slovakia
Novartis Investigative Site
Recruiting
Trnava,917 75,Slovakia
Novartis Investigative Site
Recruiting
Bratislava,82606,Slovakia
Novartis Investigative Site
Recruiting
Las Palmas de Gran Canaria,35010,Spain
Novartis Investigative Site
Recruiting
El Palmar,Murcia,30120,Spain
Novartis Investigative Site
Recruiting
Sant Joan Despi,Barcelona,08970,Spain
Novartis Investigative Site
Recruiting
Leon,24080,Spain
Novartis Investigative Site
Recruiting
Madrid,28034,Spain
Novartis Investigative Site
Recruiting
Baracaldo,Vizcaya,48903,Spain
Novartis Investigative Site
Recruiting
Madrid,28040,Spain
Novartis Investigative Site
Recruiting
Barcelona,08035,Spain
Novartis Investigative Site
Recruiting
Alcorcon,Madrid,28922,Spain
Novartis Investigative Site
Recruiting
Madrid,28222,Spain
Novartis Investigative Site
Recruiting
Getafe,Madrid,28905,Spain
Novartis Investigative Site
Recruiting
La Coruna,Galicia,15006,Spain
Novartis Investigative Site
Recruiting
Salt,Cataluna,17190,Spain
Novartis Investigative Site
Recruiting
Malaga,Andalucia,29010,Spain
Novartis Investigative Site
Recruiting
Cadiz,Andalucia,11009,Spain
Novartis Investigative Site
Recruiting
Cordoba,Andalucia,14004,Spain
Novartis Investigative Site
Recruiting
Bern,3010,Switzerland
Novartis Investigative Site
Recruiting
Basel,4031,Switzerland
Novartis Investigative Site
Recruiting
Westbruy On Trym,Bristol,BS10 5NB,United Kingdom
Novartis Investigative Site
Recruiting
Winchester,Hampshire,SO21 1HU,United Kingdom
Novartis Investigative Site
Recruiting
Bethesda,Maryland,20817,United States
Novartis Investigative Site
Recruiting
McAllen,Texas,78503,United States
Novartis Investigative Site
Recruiting
Newport Beach,California,92663,United States
Novartis Investigative Site
Recruiting
Lutherville,Maryland,21093,United States
Novartis Investigative Site
Recruiting
Dallas,Texas,75206,United States
Novartis Investigative Site
Recruiting
Port Charlotte,Florida,33952,United States
Novartis Investigative Site
Recruiting
Seminole,Florida,33777,United States
Novartis Investigative Site
Recruiting
Vienna,Virginia,22182,United States
Novartis Investigative Site
Recruiting
Charlotte,North Carolina,28204,United States
Novartis Investigative Site
Recruiting
Overland Park,Kansas,66210,United States
Novartis Investigative Site
Recruiting
Fort Smith,Arkansas,72916,United States
Novartis Investigative Site
Recruiting
Billings,Montana,59101,United States
Novartis Investigative Site
Recruiting
Tampa,Florida,33609,United States
Novartis Investigative Site
Recruiting
Madison,Wisconsin,53792,United States
Novartis Investigative Site
Recruiting
Chicago,Illinois,60612,United States
Novartis Investigative Site
Recruiting
Park Ridge,Illinois,60068,United States
Novartis Investigative Site
Recruiting
Miami,Florida,33032,United States
Novartis Investigative Site
Recruiting
Fort Wayne,Indiana,46845,United States
Novartis Investigative Site
Recruiting
Oklahoma City,Oklahoma,73104,United States
Novartis Investigative Site
Recruiting
Tampa,Florida,33612,United States
Novartis Investigative Site
Recruiting
Chicago,Illinois,60616,United States
Novartis Investigative Site
Recruiting
Savannah,Georgia,31406,United States
Novartis Investigative Site
Recruiting
Boulder,Colorado,80301,United States
Novartis Investigative Site
Recruiting
Miami,Florida,33175,United States
Novartis Investigative Site
Recruiting
Foxboro,Massachusetts,02035,United States
Novartis Investigative Site
Recruiting
Orlando,Florida,32806,United States
Novartis Investigative Site
Recruiting
Raleigh,North Carolina,27607,United States
Novartis Investigative Site
Recruiting
Neenah,Wisconsin,54956,United States
Novartis Investigative Site
Recruiting
Philadelphia,Pennsylvania,19107-5098,United States
Novartis Investigative Site
Recruiting
Scottsdale,Arizona,85258,United States
Novartis Investigative Site
Recruiting
Fullerton,California,92835,United States
Novartis Investigative Site
Recruiting
Orlando,Florida,32825,United States
Novartis Investigative Site
Recruiting
Reading,Pennsylvania,19611,United States
Novartis Investigative Site
Recruiting
Saint Louis,Missouri,63131,United States
Novartis Investigative Site
Recruiting
Berkeley,California,94705,United States
Novartis Investigative Site
Recruiting
Houston,Texas,77074,United States
Novartis Investigative Site
Recruiting
Chula Vista,California,91910,United States
Novartis Investigative Site
Recruiting
Basalt,Colorado,81621,United States
Novartis Investigative Site
Recruiting
Seattle,Washington,98122,United States
Novartis Investigative Site
Recruiting
Tucson,Arizona,85718,United States
Novartis Investigative Site
Recruiting
Ormond Beach,Florida,32174,United States
Novartis Investigative Site
Recruiting
Altamonte Springs,Florida,32714,United States
Novartis Investigative Site
Recruiting
Summerville,South Carolina,29485,United States
Novartis Investigative Site
Recruiting
Newark,Delaware,19713,United States
Novartis Investigative Site
Recruiting
Glendale,California,91206,United States
Worldwide Contacts
If the location of your choosing does not feature any contact detail, please reach out using the information below.