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


BACKGROUND
ClinicalTrials.gov: NCT00573157.
SUNY Downstate Medical Center, 450 Clarkson Avenue, Box 42, Brooklyn, NY 11203, USA. ellen.ginzler@downstate.edu
Ellen M
EM
Ginzler
Stephen
S
Wax
Anand
A
Rajeswaran
Samuel
S
Copt
Jan
J
Hillson
Eleanor
E
Ramos
Nora G
NG
Singer
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007239:Infections / Q000139:chemically induced; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000305:Adrenal Cortex Hormones; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D009173:Mycophenolic Acid; C524618:TACI receptor-IgG Fc fragment fusion protein; D011241:Prednisone