Abstract
IgAN (IgA nephropathy) is the most common primary glomerulonephritis in the world. There are currently no approved treatments and limited off-label treatment options consist largely of supportive measures which do not directly address the underlying immunologic pathogenesis of disease. APRIL (A proliferation-inducing ligand) is critical for IgA class switching, maturation and survival of IgA secreting plasma cells, and production of gd-IgA1 (galactose—deficient IgA1) which is recognized as an auto-antigen leading to the formation of pathogenic IgA immune complexes. BION-1301 is a novel humanized monoclonal antibody that neutralizes APRIL and is currently in Phase 1 development in healthy volunteers and patients with IgAN. In prior Phase 1 studies, BION-1301 was well-tolerated in healthy volunteers and reduced serum levels of free APRIL, IgA, IgM, and to a lesser extent IgG at single doses up to 1350 mg IV and multiple doses up to 450 mg IV every 2 weeks. This study compares pharmacokinetic (PK) and pharmacodynamic (PD) profiles following the administration of BION-1301 300 mg by IV and SC routes in healthy volunteers. Up to 34 healthy volunteers were randomized 1:1 to receive BION-1301 300mg either by IV or SC administration. The primary endpoint was an estimate of the bioavailability of BION-1301 with secondary endpoints of safety, tolerability, PK, PD, and immunogenicity. Subjects were closely monitored during the in-clinic stay through day 8, with in-clinic follow-up visits occurring through the end of study at day 57. PK, PD, and immunogenicity samples were collected periodically throughout the course of the study. BION-1301 continues to be well tolerated with no Grade 3 treatment emergent adverse events or serious adverse event to date. Serum PK profiles; PD profiles including free APRIL, IgA, IgG, and IgM levels; and anti-drug antibody levels will be presented and compared between IV and SC routes. Blockade of APRIL by BION-1301 remains a promising therapeutic approach for the treatment of IgAN. PK and PD data comparing IV and SC administration of BION-1301 will be used to refine the SC dose selection for future global clinical studies of BION-1301 in IgAN.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.