A randomized, double-blind, double-dummy, parallel-group study, comparing the efficacy and safety of remibrutinib versus teriflunomide in participants with relapsing multiple

JRCT ID: jRCT2071220034

Registered date:03/08/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Relapsing Multiple Sclerosis
• Date of first enrollment: 27/02/2023
• Target sample size: 30
• Countries of recruitment: US,Japan,Italy,Japan,Portugal,Japan,South Africa,Japan,France,Japan,Poland,Japan,Slovakia,Japan,Slovenia,Japan,Spain,Japan,Sweden,Japan,Turkey,Japan
• Study type: Interventional

Intervention(s)

Core Part
-Remibrutinib(LOU064) tablet and matching placebo of teriflunomide capsule
-Teriflunomide capsule and matching placebo LOU064 tablet

Extension part
LOU064 tablet

Outcome(s)

Primary Outcome

Annualized relapse rate (ARR) of confirmed relapses [Core Part] [ Time Frame: From Baseline, up to 30 month ]
ARR is the average number of confirmed MS relapses in a year

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 55age old
• Gender: Both

Include 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

Exclude 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

Related Information

• Primary Sponsor: Iwasaki Ryohei
• Secondary ID(s): NCT05156281