A Phase III Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel-Group Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Ocrelizumab In Adult Patients With Primary Progressive Multiple Sclerosis
Posted Date: Aug 25, 2020
- Investigator: Aram Zabeti
- Type of Study: Drug
Fenebrutinib is a small-molecule reversible antagonist of Bruton's tyrosine kinase (BTK) being developed by Genentech, Inc. as an investigational agent for the treatment of autoimmune diseases, such rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and chronic spontaneous urticaria (CSU). Fenebrutinib is being planned to be evaluated as a treatment for patients with multiple sclerosis (MS). Fenebrutinib is also undergoing limited evaluation as a targeted investigational agent for B cell malignancies. Specifically, fenebrutinib is a potent, selective, orally administered, reversible, and adenosine triphosphate (ATP) competitive inhibitor of BTK. BTK is a key mediator of B-cell receptor (BCR) signaling in B cells and Fc receptor signaling in myeloid cells. Accordingly, fenebrutinib effectively blocks B-cell activation and proliferation as well as myeloid effector functions, including tumor necrosis factor alpha (TNF-alpha) production triggered by immune complexes in vitro. Increasing evidence suggests that B cells (Hauser et al, 2017; Montalban et al, 2017) and myeloid cells/microglia (Howell et al. 2010) are central to the immunopathology of MS, a chronic, inflammatory and degenerative demyelinating disease of the human central nervous system (CNS) leading to a health-related loss of quality of life due to accumulating neurological disability. In addition, fenebrutinib also effectively blocks IgE receptor (FcRI) signaling in human mast cells and basophils, resulting in decreased inflammatory mediator release. Consistent with its in vitro activity, fenebrutinib demonstrates dose-dependent efficacy in nonclinical autoimmune models.
Ppms Patient Age 18-65 Years With Edss 3.0 To 6.5 Who Can Give Consent And Able To Comply With Study Protocol.
Fenebrutinib, Ocrelizumab, Primary Progressive Multiple Sclerosis
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