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 Genders
- 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
Vladimir Royter MD APMC
Hanford, California 93230
Hanford, California 93230
VA Greater LA Healthcare System
Los Angeles, California 90073
Los Angeles, California 90073
Contact:
+1 3104783711#47091
+1 3104783711#47091
Regina Berkovich MD PhD Inc
West Hollywood, California 90048
West Hollywood, California 90048
Contact:
310-493-4715
310-493-4715
CU Anschutz Med Campus
Aurora, Colorado 80045
Aurora, Colorado 80045
Colorado Neurological Research PC
Denver, Colorado 80210
Denver, Colorado 80210
Contact:
303-715-9024
303-715-9024
New England Institute for Clinical Research
Stamford, Connecticut 06905
Stamford, Connecticut 06905
Georgetown University Hospital Research
Washington, District of Columbia 20007
Washington, District of Columbia 20007
Nova Clinical Research LLC
Bradenton, Florida 34209
Bradenton, Florida 34209
Univ of Florida College of Medicine
Gainesville, Florida 32610
Gainesville, Florida 32610
Memorial Hospital
Hollywood, Florida 33021
Hollywood, Florida 33021
Mayo Clinic Jacksonville
Jacksonville, Florida 32224
Jacksonville, Florida 32224
Neurology Associates PA
Maitland, Florida 32751
Maitland, Florida 32751
UM Department Of Neurology
Miami, Florida 33136
Miami, Florida 33136
Contact:
305-243-7424
305-243-7424
Aqualane Clinical Research
Naples, Florida 34105
Naples, Florida 34105
Advent Health Orlando
Orlando, Florida 32803
Orlando, Florida 32803
Humanity Clinical Research
Pembroke Pines, Florida 33024
Pembroke Pines, Florida 33024
Emerald Coast Neurology
Pensacola, Florida 32514
Pensacola, Florida 32514
Brain and Spine Institute
Port Orange, Florida 32127
Port Orange, Florida 32127
Vero Beach Neurology
Vero Beach, Florida 32960
Vero Beach, Florida 32960
Conquest Research
Winter Park, Florida 32789
Winter Park, Florida 32789
Methodist Neuroscience Institute
Merrillville, Indiana 46410
Merrillville, Indiana 46410
University of Kansas Hospital
Kansas City, Kansas 66160
Kansas City, Kansas 66160
Baptist Physicians Lexington
Nicholasville, Kentucky 40356
Nicholasville, Kentucky 40356
Ochsner Clinic Foundation
New Orleans, Louisiana 70121
New Orleans, Louisiana 70121
Comprehensive Neurology
Frederick, Maryland 21702
Frederick, Maryland 21702
Tufts Medical Center
Boston, Massachusetts 02111
Boston, Massachusetts 02111
Kansas City VA Medical Center
Kansas City, Missouri 64128
Kansas City, Missouri 64128
South Shore Neurologic Associates
Patchogue, New York 11772
Patchogue, New York 11772
True North Neurology
Port Jefferson Station, New York 11776
Port Jefferson Station, New York 11776
University Of NC At Chapel Hill
Chapel Hill, North Carolina 27599 9500
Chapel Hill, North Carolina 27599 9500
Piedmont HealthCare
Charlotte, North Carolina 28210
Charlotte, North Carolina 28210
Contact:
704-664-8060
704-664-8060
The Boster Ctr for MS
Columbus, Ohio 43235
Columbus, Ohio 43235
Neurology Diagnostics Inc
Dayton, Ohio 45408
Dayton, Ohio 45408
Penn State Hershey Medical Center
Hershey, Pennsylvania 17033
Hershey, Pennsylvania 17033
Medical Uni of South Carolina
Charleston, South Carolina 29425
Charleston, South Carolina 29425
Premier Neurology
Greenville, South Carolina 29605
Greenville, South Carolina 29605
Metrolina Neurological Associates PA
Indian Land, South Carolina 29707
Indian Land, South Carolina 29707
Sibyl Wray MD Neurology PC
Knoxville, Tennessee 37922
Knoxville, Tennessee 37922
Neurology Consultants Of Dallas PA
Dallas, Texas 75231
Dallas, Texas 75231
Med Research Inc
El Paso, Texas 79935
El Paso, Texas 79935
Lone Star Neurology
Frisco, Texas 75035
Frisco, Texas 75035
University of Texas Health Science Center San Antonio
San Antonio, Texas 78229
San Antonio, Texas 78229
Lonestar Neurology of San Antonio
San Antonio, Texas 78258
San Antonio, Texas 78258
Texas Institute for Neurological Disorders
Sherman, Texas 75092
Sherman, Texas 75092
Contact:
+1 903 893 5141#4334
+1 903 893 5141#4334
Baylor Scott and White
Temple, Texas 76508
Temple, Texas 76508
Virginia Mason Medical Centre
Seattle, Washington 98101
Seattle, Washington 98101
University of Washington MS Clinic
Seattle, Washington 98133
Seattle, Washington 98133
Contact:
206-598-3344
206-598-3344
Elligo Health Research
Crab Orchard, West Virginia 25827
Crab Orchard, West Virginia 25827
Ascension St Francis Center
Milwaukee, Wisconsin 53215
Milwaukee, Wisconsin 53215
Medical College of Wisconsin
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
Caribbean Center for Clinical Research, Inc
Guaynabo, Puerto Rico 00968
Guaynabo, Puerto Rico 00968
More Details
- NCT ID
- NCT05156281
- Status
- Recruiting
- Sponsor
- Novartis Pharmaceuticals
Detailed Description
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.