Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.
Adult
Aged
Anemia
/ complications
Anti-Inflammatory Agents, Non-Steroidal
/ therapeutic use
Antibodies, Monoclonal, Humanized
/ therapeutic use
Biomarkers
/ metabolism
Cardiovascular Diseases
/ metabolism
Double-Blind Method
Female
Hematinics
/ therapeutic use
Hepcidins
/ metabolism
Humans
Inflammation
/ complications
Interleukin-6
/ antagonists & inhibitors
Kidney Failure, Chronic
/ complications
Ligands
Male
Middle Aged
Renal Dialysis
/ adverse effects
Serum Albumin
/ metabolism
Treatment Outcome
anemia
cardiovascular disease
chronic kidney disease
erythropoietin stimulating agents
hemodialysis
inflammation
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
06
05
2020
accepted:
14
09
2020
pubmed:
5
12
2020
medline:
8
7
2021
entrez:
4
12
2020
Statut:
ppublish
Résumé
Patients with CKD who are on hemodialysis are hyporesponsive to erythropoiesis-stimulating agents (ESAs) because of anemia of inflammation. Interleukin-6 (IL-6) induced hepcidin expression is a key mediator of such inflammation. This phase 1/2, placebo-controlled trial assessed effects of ziltivekimab, a novel anti-IL-6 ligand antibody, in patients on hemodialysis with rs855791, a single nucleotide polymorphism of the No patient experienced dose-limiting toxicity. Four patients (two each in the 6- and 20-mg cohorts) died of a treatment-emergent adverse event. Compared with patients receiving placebo, those receiving ziltivekimab experienced significantly greater reductions of high-sensitivity C-reactive protein, serum amyloid A, and fibrinogen from baseline to end of treatment. Median ESA usage decreased by 15,000, 15,000, or 33,000 IU/wk per patient in the 2-, 6-, and 20-mg ziltivekimab cohorts, respectively, compared with no change in the placebo group. We also noted significant dose responses for decreased ESA resistance index and increased serum iron, total iron binding capacity, transferrin saturation, and serum albumin. Ziltivekimab significantly improved markers of inflammation, reduced ESA requirements, and increased serum albumin in patients on hemodialysis with inflammation and hyporesponsiveness to ESA therapy. Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001, NCT02868229.
Sections du résumé
BACKGROUND
Patients with CKD who are on hemodialysis are hyporesponsive to erythropoiesis-stimulating agents (ESAs) because of anemia of inflammation. Interleukin-6 (IL-6) induced hepcidin expression is a key mediator of such inflammation.
METHODS
This phase 1/2, placebo-controlled trial assessed effects of ziltivekimab, a novel anti-IL-6 ligand antibody, in patients on hemodialysis with rs855791, a single nucleotide polymorphism of the
RESULTS
No patient experienced dose-limiting toxicity. Four patients (two each in the 6- and 20-mg cohorts) died of a treatment-emergent adverse event. Compared with patients receiving placebo, those receiving ziltivekimab experienced significantly greater reductions of high-sensitivity C-reactive protein, serum amyloid A, and fibrinogen from baseline to end of treatment. Median ESA usage decreased by 15,000, 15,000, or 33,000 IU/wk per patient in the 2-, 6-, and 20-mg ziltivekimab cohorts, respectively, compared with no change in the placebo group. We also noted significant dose responses for decreased ESA resistance index and increased serum iron, total iron binding capacity, transferrin saturation, and serum albumin.
CONCLUSIONS
Ziltivekimab significantly improved markers of inflammation, reduced ESA requirements, and increased serum albumin in patients on hemodialysis with inflammation and hyporesponsiveness to ESA therapy.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001, NCT02868229.
Identifiants
pubmed: 33272965
pii: 00001751-202101000-00021
doi: 10.1681/ASN.2020050595
pmc: PMC7894678
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
Hematinics
0
Hepcidins
0
Interleukin-6
0
Ligands
0
Serum Albumin
0
ziltivekimab
0
Banques de données
ClinicalTrials.gov
['NCT02868229']
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
211-222Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 by the American Society of Nephrology.
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