A Randomized, Double-blind, Double-dummy, Parallel-group Study, Comparing the Efficacy and Safety of Remibrutinib Versus Teriflunomide in Participants With Relapsing Multiple Sclerosis, Followed by Extended Treatment With Open-label Remibrutinib
Study on Investigational Medication for Relapsing Multiple Sclerosis
Ajay Gupta
Primary Investigator
Brief description of study
The purpose of the study is to provide efficacy, safety and tolerability data for remibrutinib to support regulatory approval worldwide as a treatment for relapsing multiple sclerosis (RMS). Two identical Phase III trials (CLOU064C12301 and CLOU064C12302) will be conducted simultaneously.
THIS STUDY IS ENROLLING BY INVITATION ONLY
Detailed description of study
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.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Relapsing Multiple Sclerosis, RMS
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Age: 18 years - 55 years
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Gender: All
Inclusion Criteria:
- 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
The purpose of this study is to investigate an investigational medication for people with relapsing multiple sclerosis (RMS). RMS is a condition where the immune system mistakenly attacks the protective covering of nerves, causing symptoms like fatigue, vision problems, and difficulty with coordination. This study will compare the investigational medication to another treatment to understand its effectiveness and safety.
Participants will be randomly assigned to different study arms to receive either the investigational medication or a comparator. The study will be conducted in two parts: a Core Part, where participants are assigned treatments without knowing which one they receive, and an Extension Part, where all participants will receive the investigational medication. The study involves regular health checks and monitoring to ensure participant safety.
- Who can participate: Individuals aged 18 and older with a diagnosis of relapsing multiple sclerosis may qualify if they have had at least one documented relapse in the past year or specific MRI findings. Participants must be neurologically stable with an EDSS score between 0 and 5.5.
- Study details: Participants will take part in a randomized study, receiving either the investigational medication or a comparator. In the Extension Part, all participants will receive the investigational medication. Regular health assessments will be conducted to monitor safety and effectiveness.
- Study timelines: The study will last up to 30 months for the Core Part, followed by an Extension Part of up to 5 years.
