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Clinical Trial
. 2009 May;18(6):547-55.
doi: 10.1177/0961203309102803.

An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus

C Pena-Rossi  1 , E Nasonov, M Stanislav, V Yakusevich, O Ershova, N Lomareva, H Saunders, J Hill, I Nestorov
Affiliations
Clinical Trial

An exploratory dose-escalating study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous atacicept in patients with systemic lupus erythematosus

C Pena-Rossi et al. Lupus. 2009 May.

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.

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Conflict of interest statement

CRP and HS are employees of Merck Serono S.A. (Geneva, Switzerland). At the time of the study, JH and IN were employees of ZymoGenetics Inc. (Seattle, WA, USA).

Figures

Figure 1
Figure 1
Patient cohorts and dose-escalation scheme. i.v., intravenous; SRB, safety review board.
Figure 2
Figure 2
Free atacicept serum concentration versus time profiles after administration of (A) a single intravenous dose or (B) multiple intravenous doses of atacicept.
Figure 3
Figure 3
B-lymphocyte stimulator (BLyS) • atacicept complex serum concentration versus time profiles after administration of (A) a single intravenous dose or (B) multiple intravenous doses of atacicept.
Figure 4
Figure 4
Median percentage change from baseline in (A) mature B-cell counts for single doses, (B) mature B-cell counts for a repeat dose, (C) immunoglobulin M (IgM) levels for single doses and (D) IgM, IgA and IgG levels after repeat doses, after intravenous administration of atacicept.
See this image and copyright information in PMC

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