Resumen

To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS)

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 55 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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)

Ubicaciones

Novartis Investigative Site

Capital Federal, Buenos Aires, Argentina

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

Novartis Investigative Site

Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, Argentina

Novartis Investigative Site

Caba, Argentina

Novartis Investigative Site

Capital Federal, Argentina

Novartis Investigative Site

Santiago del Estero, Argentina

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

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Remibrutinib

Teriflunomide

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores