Abstract: TH-OR025
Effects of Ziltivekimab, an Antibody to IL-6, on Inflammation, Nutritional Markers, and Anemia in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial
Session Information
- Anemia and Iron Metabolism: Clinical Research
November 07, 2019 | Location: 150, Walter E. Washington Convention Center
Abstract Time: 05:18 PM - 05:30 PM
Category: Anemia and Iron Metabolism
- 202 Anemia and Iron Metabolism: Clinical
Authors
- Pergola, Pablo E., Renal Associates, P.A., San Antonio, Texas, United States
- Kakkar, Rahul, Corvidia Therapeutics, Waltham, Massachusetts, United States
- Chonchol, Michel, University of Colorado, Aurora, Colorado, United States
- Smith, Mark T., Nephrology Associates, Augusta, Georgia, United States
- Mathur, Vandana S., Mathur Consulting, Woodside, California, United States
- Lo, Larry, Corvidia Therapeutics, Waltham, Massachusetts, United States
- Davidson, Michael, Corvidia Therapeutics, Waltham, Massachusetts, United States
- Devalaraja, Matt, Corvidia Therapeutics, Waltham, Massachusetts, United States
Background
Patients with chronic kidney disease on hemodialysis (HD) and hyporesponsiveness to erythropoiesis stimulating agents (ESA) exhibit functional blockade in iron release from body stores due to inflammation-induced expression of hepcidin. We assessed the effects of ziltivekimab, a novel antibody against the proinflammatory cytokine interleukin (IL)-6, in HD patients with a genotypic variation in the TMPRSS6 gene, hypothesized to induce a heightened susceptibility to IL-6-induced inflammation.
Methods
After a screening period documenting stable ESA and IV iron dosing, patients with high IL-6 (≥4 pg/mL) received double-blinded placebo or ziltivekimab at 2, 6 or 20 mg every 2 weeks during HD for 12 weeks. ESA dose adjustments were permitted after 4 weeks. Pharmacodynamic endpoints included markers of anemia, malnutrition and inflammation. Differences from placebo in changes from baseline were obtained from analysis of covariance with treatment as factor and baseline as covariate. Trend p-values for ordered dose treatment groups were calculated using Jonckheere-Terpstra test.
Results
61 patients were randomized; 53 were included in the pharmacodynamic analysis population (12 received placebo; 16, 13 and 12 received 2, 6 and 20 mg, respectively). Across the treatment groups, baseline epoetin-equivalent doses ranged from 11,250-15,000 U/L, hemoglobin (Hgb) from 9-8-10.5 g/dL and high-sensitivity C-reactive protein (hsCRP) from 4-13 mg/L. Ziltivekimab significantly reduced hsCRP and increased serum albumin and Hgb while reducing ESA requirements in a dose-dependent manner (Table).
Conclusion
We demonstrated that IL-6 inhibition with ziltivekimab significantly improved markers of malnutrition-inflammation and reduced ESA requirements in hyporesponsive, inflamed dialysis patients.
Change from Baseline in Pharmacodynamic Endpoints by Treatment Group
Funding
- Commercial Support –