An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus
Open Access
- 1 May 2009
- journal article
- research article
- Published by SAGE Publications in Lupus
- Vol. 18 (6), 547-555
- https://doi.org/10.1177/0961203309102803
Abstract
Atacicept, a recombinant fusion protein containing the extracellular, ligand-binding portion of the transmembrane activator and calcium modulator and cyclophilin-ligand interactor receptor, and the Fc portion of human immunoglobulin (Ig) G, is designed to block the activity of B-lymphocyte stimulator and a proliferation-inducing ligand, and may have utility as a treatment for B-cell-mediated diseases, such as systemic lupus erythematosus (SLE). This Phase Ib study investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of intravenous (i.v.) atacicept in patients with mild-to-moderate SLE. Patients (n = 24) were randomised (5:1) to receive atacicept (single dose: 3, 9 or 18 mg/kg; or multiple dose: 2 x 9 mg/kg) or matching placebo. Patients were followed for 6 weeks after dosing (9 weeks in the 2 x 9 mg/kg cohort). Local tolerability of atacicept was comparable with that of placebo, with only mild injection-site reactions reported with atacicept. Atacicept i.v. was generally well tolerated, both systemically and locally, in patients with mild-to-moderate SLE. Atacicept displayed non-linear PK, which was predictable across doses and between single and repeat doses. The biological activity of atacicept was demonstrated by its marked effect in reducing B-cells and Ig levels in patients with SLE. This supports the utility of this therapeutic approach in the treatment of autoimmune diseases, such as SLE.This publication has 39 references indexed in Scilit:
- Emerging drug therapies for systemic lupus erythematosusEmerging Drugs, 2006
- B cell receptor signaling in human systemic lupus erythematosusCurrent Opinion in Rheumatology, 2006
- Systemic lupus erythematosus—2005 annus mirabilis?Nature Clinical Practice Rheumatology, 2006
- B-Cell-Targeted Therapy for Systemic Lupus ErythematosusDrugs, 2006
- Prevalence and correlates of perceived unmet needs of people with systemic lupus erythematosusPatient Education and Counseling, 2005
- Identification of proteoglycans as the APRIL-specific binding partnersThe Journal of Experimental Medicine, 2005
- Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferationCell Death & Differentiation, 2005
- Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseasesArthritis & Rheumatism, 2001
- Clinical features of systemic lupus erythematosusCurrent Opinion in Rheumatology, 1995
- Derivation of the sledai. A disease activity index for lupus patientsArthritis & Rheumatism, 1992