title: Safety, pharmacokinetics, and pharmacodynamics of RSLV-132, an RNase-Fc fusion protein in systemic lupus erythematosus: a randomized, double-blind, placebo-controlled study.
abstract: Blood-borne RNA circulating in association with autoantibodies is a potent stimulator of interferon production and immune system activation. RSLV-132 is a novel fully human biologic Fc fusion protein that is comprised of human RNase fused to the Fc domain of human IgG1. The drug is designed to remain in circulation and digest extracellular RNA with the aim of preventing activation of the immune system via Toll-like receptors and the interferon pathway. The present study describes the first clinical study of nuclease therapy in 32 subjects with systemic lupus erythematosus. The drug was well tolerated with a very favorable safety profile. The approximately 19-day serum half-life potentially supports once monthly dosing. There were no subjects in the study that developed anti-RSLV-132 antibodies. Decreases in B-cell activating factor correlated with decreases in disease activity in a subset of patients.
authors.affiliation: 1 Resolve Therapeutics, LLC, Seattle, WA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Burge
authors.affiliation: 1 Resolve Therapeutics, LLC, Seattle, WA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Eisenman
authors.affiliation: 1 Resolve Therapeutics, LLC, Seattle, WA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Byrnes-Blake
authors.affiliation: 1 Resolve Therapeutics, LLC, Seattle, WA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Smolak
authors.affiliation: 1 Resolve Therapeutics, LLC, Seattle, WA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lau
authors.affiliation: 2 Metroplex Clinical Research Center, Dallas, TX, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Cohen
authors.affiliation: 3 Altoona Center for Clinical Research, Duncansville, PA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Kivitz
authors.affiliation: 4 Clinical Research of West Florida, Clearwater, FL, USA.
authors.forename: R
authors.initials: R
authors.lastname: Levin
authors.affiliation: 5 Michigan State University, East Lansing, MI, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Martin
authors.affiliation: 6 Center for Rheumatology, Immunology, and Arthritis, Ft. Lauderdale, FL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sherrer
authors.affiliation: 1 Resolve Therapeutics, LLC, Seattle, WA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Posada
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D053264:B-Cell Activating Factor / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000097:blood*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012260:Ribonucleases / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D012313:RNA; C000626691:RSLV-132; D012260:Ribonucleases
keywords: RNA immune complex; interferon; nuclease therapy