Efficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS)
Purpose
To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS)
Condition
- Relapsing Multiple Sclerosis
Eligibility
- Eligible Ages
- Between 18 Years and 55 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Eligible participants will be randomized in a 1:1 ratio
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
- Masking Description
- In order to maintain blinding, a double-dummy design will be used
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Remibrutinib - Core |
Remibrutinib tablet and matching placebo of teriflunomide capsule |
|
|
Active Comparator Teriflunomide - Core |
Teriflunomide capsule and matching placebo remibrutinib tablet |
|
|
Experimental Remibrutinib - Extension |
Participants on remibrutinib in Core will continue on remibrutinib tablet |
|
|
Experimental Remibrutinib - Extension (on teriflunomide in Core) |
Participants on teriflunomide in Core will switch to remibrutinib tablet |
|
Recruiting Locations
Honor Health Research Institute
Scottsdale, Arizona 85258
Scottsdale, Arizona 85258
Center for Neurosciences
Tucson, Arizona 85718
Tucson, Arizona 85718
The Research and Education Inst. of Alta Bates Summit Med. Grp
Berkeley, California 94705
Berkeley, California 94705
The Neuron Clinic
Chula Vista, California 91910
Chula Vista, California 91910
Glendale Adventist Medical Center
Glendale, California 91206
Glendale, California 91206
Hoag Health System
Newport Beach, California 92663
Newport Beach, California 92663
Alpine Clinical Research Center
Boulder, Colorado 80301
Boulder, Colorado 80301
Christiana Care Health Services
Newark, Delaware 19713
Newark, Delaware 19713
Washington Hospital Center
Washington, District of Columbia 20010
Washington, District of Columbia 20010
Neurology of Central FL Res Ctr
Altamonte Springs, Florida 32714
Altamonte Springs, Florida 32714
Homestead Assoc In Research Inc
Homestead, Florida 33033
Homestead, Florida 33033
Reliant Medical Research
Miami, Florida 33165
Miami, Florida 33165
Neurological Services of Orlando PA
Orlando, Florida 32806
Orlando, Florida 32806
Contact:
941-400-4578
941-400-4578
Orlando Health Clinical Trials
Orlando, Florida 32806
Orlando, Florida 32806
Comprehensive Neurology Clinic
Orlando, Florida 32825
Orlando, Florida 32825
Neurology Associates of Ormond Beach
Ormond Beach, Florida 32174
Ormond Beach, Florida 32174
Neurostudies Inc
Port Charlotte, Florida 33952
Port Charlotte, Florida 33952
University Of South Florida
Tampa, Florida 33612
Tampa, Florida 33612
Conquest Research
Winter Park, Florida 32789
Winter Park, Florida 32789
Velocity Clinical Research
Savannah, Georgia 31406
Savannah, Georgia 31406
Contact:
912-790-4837
912-790-4837
Rush University Medical Center
Chicago, Illinois 60612
Chicago, Illinois 60612
Norton Neurology MS Services
Louisville, Kentucky 40207
Louisville, Kentucky 40207
Contact:
502-899-6782
502-899-6782
Mid Atlantic Epilepsy and Sleep Ctr
Bethesda, Maryland 20817
Bethesda, Maryland 20817
International Neurorehab Institute
Lutherville, Maryland 21093
Lutherville, Maryland 21093
Beth Israel Deaconess Medical Cente
Boston, Massachusetts 02215
Boston, Massachusetts 02215
Wayne State University Multiple Sclerosis Clinic
Detroit, Michigan 48201
Detroit, Michigan 48201
The MS Center for Innovation in Care
Saint Louis, Missouri 63131
Saint Louis, Missouri 63131
Contact:
314-996-7960
314-996-7960
Jersey Shore University Medical Ctr
Neptune, New Jersey 07753
Neptune, New Jersey 07753
Montefiore Medical Center
Bronx, New York 10467
Bronx, New York 10467
Neurological Associates of Long Island PC
Lake Success, New York 11042
Lake Success, New York 11042
NYU Langone Med Center CV Research
New York, New York 10016
New York, New York 10016
The Neurological Institute PA
Charlotte, North Carolina 28204
Charlotte, North Carolina 28204
Velocity Clinical Research
Raleigh, North Carolina 27607
Raleigh, North Carolina 27607
Providence St Vincent Med Center
Portland, Oregon 97225
Portland, Oregon 97225
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107-5098
Philadelphia, Pennsylvania 19107-5098
Contact:
215-955-6939
215-955-6939
University Of Pittsburgh Medical Ctr Magee-Womens Hospital
Pittsburgh, Pennsylvania 15213
Pittsburgh, Pennsylvania 15213
Palmetto Clinical Research
Summerville, South Carolina 29485
Summerville, South Carolina 29485
Neuro Eye Clinical Trials Inc
Houston, Texas 77074
Houston, Texas 77074
DHR Health Institute
McAllen, Texas 78503
McAllen, Texas 78503
North TX Inst of Neuro and Headache
Plano, Texas 75024
Plano, Texas 75024
MS Center of Greater Washington, P.C.
Vienna, Virginia 22182
Vienna, Virginia 22182
Neuroscience Group
Neenah, Wisconsin 54956
Neenah, Wisconsin 54956
More Details
- NCT ID
- NCT05147220
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
Detailed Description
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.