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
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Capital Federal,Buenos Aires,1424,Argentina
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Rosario,Santa Fe Province,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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Ciudad Autonoma de Bs As,Buenos Aires,C1055aaf,Argentina
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Linz,Upper Austria,A 4020,Austria
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Klagenfurt,9020,Austria
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Graz,8036,Austria
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Antwerp,2018,Belgium
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Brasschaat,2930,Belgium
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Bruges,8000,Belgium
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Brussels,1070,Belgium
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Overpelt,3900,Belgium
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Edegem,2650,Belgium
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Pleven,5800,Bulgaria
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Beirut,166378,Lebanon
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Westbruy on Trym,Bristol,Bs10 5nb,United Kingdom
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Winchester,Hampshire,So21 1hu,United Kingdom
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Glasgow,G51 4tf,United Kingdom
Center for Neurosciences
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Tucson,Arizona,85718,United States
Francisco Valdivia
The Research and Education Inst. of Alta Bates Summit Med. Grp
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Berkeley,California,94705,United States
Deepak Soneji
Hoag Health System
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Newport Beach,California,92663,United States
Yasir Jassam
SC3 Research Pasadena
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Pasadena,California,91105,United States
Ana Diego
M Lorraine Purino
Neuro Center
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Pomona,California,91767,United States
Sadiq Altamimi
Alpine Clinical Research Center
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Boulder,Colorado,80301,United States
Sidarth Dasari
Christiana Care Health Services
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Newark,Delaware,19713,United States
Jason M Silversteen
Neurology of Central FL Res Ctr
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Altamonte Springs,Florida,32714,United States
Alicia Cabrera
Homestead Assoc In Research Inc
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Homestead,Florida,33033,United States
Angel Carrasco
Reliant Medical Research
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Miami,Florida,33165,United States
Carlos Ramirez-Calderon
Orlando Health Clinical Trials
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Orlando,Florida,32806,United States
Amparo Gutierrez
Daniel H Jacobs
Comprehensive Neurology Clinic
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Orlando,Florida,32825,United States
Refaat El-Said
Neurology Associates of Ormond Beach
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Ormond Beach,Florida,32174,United States
James Scott
Neurostudies Inc
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Port Charlotte,Florida,33952,United States
Liliana Montoya
Norton Neurology MS Services
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Louisville,Kentucky,40207,United States
Geeta Ganesh
Mid Atlantic Epilepsy and Sleep Ctr
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Bethesda,Maryland,20817,United States
Jonathan Ross
Beth Israel Deaconess Medical Cente
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Boston,Massachusetts,02215,United States
Jacob Sloane
SCL Health
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Billings,Montana,59101,United States
Heather Duyck
Kristian French
Jersey Shore University Medical Ctr
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Neptune City,New Jersey,07753,United States
Lana Zhovtis Ryerson
Lana Zhovtis Ryerson
Neurological Associates of Long Island PC
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Lake Success,New York,11042,United States
Teresa DeAngelis
The Neurological Institute PA
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Charlotte,North Carolina,28204,United States
T Hemanth Hemanth Rao
Providence St Vincent Med Center
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Portland,Oregon,97225,United States
Stanley Cohan
University Of Pittsburgh Medical Ctr Magee-Womens Hospital
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Pittsburgh,Pennsylvania,15213,United States
Ingrid Loma-Miller
John Peter Smith Hospital
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Fort Worth,Texas,76104,United States
Anna Diaz
Horacio Chiong-Rivero
Neuro Eye Clinical Trials Inc
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Houston,Texas,77074,United States
Rosa Tang
North TX Inst of Neuro and Headache
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Plano,Texas,75024,United States
Annette Okai
MS Center of Greater Washington, P.C.
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Vienna,Virginia,22182,United States
Heidi Crayton
Neuroscience Group
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Neenah,Wisconsin,54956,United States
Daniel Long
Honor Health Research Institute
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Scottsdale,Arizona,85258,United States
The Neuron Clinic
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Chula Vista,California,91910,United States
Jose Soria
Glendale Adventist Medical Center
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Glendale,California,91206,United States
Artin Minaeian
Washington Hospital Center
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Washington D.C.,District of Columbia,20010,United States
Brian Barry
Brian Barry
Arrow Clinical Trials
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Daytona Beach,Florida,32117,United States
David Billmeier
Nicole Davis
University Of South Florida
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Tampa,Florida,33612,United States
Derrick Robertson
Conquest Research
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Winter Park,Florida,32789,United States
Daysi Guerrero
Gilbert Mbeo
Rush University Medical Center
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Chicago,Illinois,60612,United States
Thomas Shoemaker
IU Health Inc
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Fort Wayne,Indiana,46815,United States
Ajay Gupta
Olivia Vincent
International Neurorehab Institute
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Lutherville,Maryland,21093,United States
Daniel Becker
Wayne State University Multiple Sclerosis Clinic
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Detroit,Michigan,48201,United States
Jacob Rube
The MS Center for Innovation in Care
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St Louis,Missouri,63131,United States
Barry A Singer
Barry A Singer
Montefiore Medical Center
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The Bronx,New York,10467,United States
Lauren Gluck
Lauren Gluck
NYU Langone Med Center CV Research
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New York,New York,10016,United States
Nada Abou-Fayssal
Velocity Clinical Research
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Raleigh,North Carolina,27607,United States
Casey Jeffreys
Thomas Jefferson University Hospital
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Philadelphia,Pennsylvania,19107-5098,United States
Thomas Leist
Palmetto Clinical Research
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Summerville,South Carolina,29485,United States
Robert Carlile
DHR Health Institute
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McAllen,Texas,78503,United States
Roberto Alejandro Cruz
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