Abstract: INFO32
A Phase 1/2, Multicenter Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BION-1301 in Healthy Volunteers and Adults With IgA Nephropathy
Session Information
- Informational Posters
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
- Schwartz, Brian S., Chinook Therapeutics Inc, Seattle, Washington, United States
- Sorensen, Bess, Chinook Therapeutics Inc, Seattle, Washington, United States
- Roy, Suzanne E., Chinook Therapeutics Inc, Seattle, Washington, United States
- Stromatt, Colleen L., Chinook Therapeutics Inc, Seattle, Washington, United States
- MacDonald, Margaret, Chinook Therapeutics Inc, Seattle, Washington, United States
- Endsley, Aaron N., Certara LP, Princeton, New Jersey, United States
- Lo, Jeannette, Chinook Therapeutics Inc, Seattle, Washington, United States
- Glicklich, Alan, Chinook Therapeutics Inc, Seattle, Washington, United States
Description
Background and Aims: IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally, with up to 45% of IgAN patients at risk of progressing to ESKD. There are currently no approved treatments specifically for IgA nephropathy. The initiating step in IgAN pathogenesis is the excess production of galactose-deficient IgA1 (Gd-IgA1) resulting in formation of pathogenic immune complexes that cause kidney inflammation and damage. A Proliferation-Inducing Ligand (APRIL), a TNF-superfamily cytokine, is elevated in IgAN patients and correlated with higher levels of Gd-IgA1 and proteinuria, and lower eGFR. BION-1301 is a novel monoclonal antibody which binds and blocks APRIL.
The primary objective of Study ADU-CL-19 is to assess the safety and tolerability of BION-1301 in Healthy Volunteers (HV) and IgAN patients and to secondarily assess the PK, PD, immunogenicity, and preliminary clinical activity.
Methods: The Phase 1/2 study (NCT03945318) comprises 3 parts. Parts 1 and 2 were blinded, placebo-controlled single and multiple ascending dose designs in HV and have been completed. Part 3 is a multicenter (US, UK, South Korea), multicohort, open-label study in up to 40 patients with IgAN. Patients in Cohort 1 receive BION-1301 at 450mg IV every 2 weeks for up to 1 year. Subsequent cohorts will be given BION-1301 via SC injection. Key eligibility criteria: (1) urine protein ≥0.5 g/24h, (2) stable/optimized dose of ACE-I/ARB (or intolerant), (3) biopsy-verified diagnosis of IgAN within 10 years.
Results: Final HV data from Parts 1 and 2 were presented at ASN in 2020. Part 3 is ongoing, and interim data from Cohort 1 with IV dosing are being presented at ASN in 2021.
Conclusion: The current design of the Phase 1/2 study, incorporating SC dosing, provides for an improved patient experience, and will enable the generation of long-term safety, PK, PD, immunogenicity, and preliminary activity data for use of BION-1301 in IgAN patients.
Funding
- Chinook Therapeutics