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Open Access Highly Accessed Research article

Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial

Ellen M Ginzler1*, Stephen Wax2, Anand Rajeswaran3, Samuel Copt3, Jan Hillson4, Eleanor Ramos4 and Nora G Singer5

Author Affiliations

1 SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 42, Brooklyn, NY 11203, USA

2 EMD Serono Inc., 1 Technology Place, Rockland, MA 02370, USA

3 Merck Serono S.A., Chemin des Mines 9, 1202 Geneva, Switzerland

4 ZymoGenetics Inc., 1201 Eastlake Avenue, East Seattle, Washington 98102-3702, USA

5 Case Western Reserve University, 2040 Adelbert Rd, Cleveland, OH 44106-7060, USA

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Arthritis Research & Therapy 2012, 14:R33  doi:10.1186/ar3738

Published: 7 February 2012

Abstract

Introduction

Atacicept is a soluble, fully human, recombinant fusion protein that inhibits B cell-stimulating factors APRIL (a proliferation-inducing ligand) and BLyS (B-lymphocyte stimulator). The APRIL- LN study aimed to evaluate the efficacy and safety of atacicept in patients with active lupus nephritis (LN), receiving newly initiated corticosteroids (CS) and mycophenolate mofetil (MMF).

Methods

This was a randomized, double-blind, placebo-controlled Phase II/III, 52-week study. At screening (Day -14), patients initiated high-dose CS (the lesser of 0.8 mg/kg/day or 60 mg/day prednisone) and MMF (1 g daily, increased by 1 g/day each week to 3 g daily). From Day 1, atacicept (150 mg, subcutaneously, twice weekly for 4 weeks, then weekly) was initiated with MMF along with a tapered dose of CS.

Results

The trial was terminated after the enrollment of six patients, due to an unexpected decline in serum immunoglobulin G (IgG) and the occurrence of serious infections. Efficacy was thus not evaluated. By Day 1, serum IgG levels had declined substantially in patients then randomized to atacicept (n = 4) compared with placebo (n = 2). Patients receiving atacicept also had more severe proteinuria on Day -14 than those on placebo. Lymphocyte counts were low at screening in all patients. IgG decline continued following initiation (Day 1) of atacicept. Three atacicept-treated patients developed serum IgG below the protocol-defined discontinuation threshold of 3 g/l, two of whom developed serious pneumonia.

Conclusions

Future studies are needed to characterize the safety, efficacy, and pharmacodynamic response of atacicept in LN patients.

Trial Registration

ClinicalTrials.gov: NCT00573157

Keywords:
atacicept; clinical trial; immunoglobulin; lupus nephritis; mycophenolate mofetil; nephrotic-range proteinuria