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Kidney Week

Abstract: SU-OR35

24-Week Interim Analysis of a Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Atacicept in Patients with IgA Nephropathy and Persistent Proteinuria

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom
  • Tumlin, James A., Emory University School of Medicine, Atlanta, Georgia, United States
  • Suzuki, Yusuke, Juntendo University, Tokyo, Japan
  • Kao, Amy, EMD Serono Research Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, Massachusetts, United States
  • Aydemir, Aida, EMD Serono Research Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, Massachusetts, United States
  • Zima, Yulia, EMD Serono Research Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, Massachusetts, United States
  • Appel, Gerald B., Columbia University Medical Center, New York, New York, United States
Background

IgA nephropathy (IgAN) is the most common primary glomerulonephritis and currently has no approved therapy. Its central pathogenic feature is circulating immune complexes of poorly O-galactosylated polymeric IgA1 (Gd-IgA1) that often deposit in the kidneys (causing inflammation and scarring) and trigger formation of IgA/G autoantibodies. Atacicept, a human TACI-Ig fusion protein, inhibits B cell-stimulating factors BLyS and APRIL and is associated with reduced serum IgA/G, mature B cells and plasma cells. This Phase II study (NCT02808429) examines atacicept safety and efficacy in reducing Gd-IgA1 and renal activity in IgAN.

Methods

Patients with IgAN and proteinuria ≥1 g/day or 0.75 mg/mg on 24-hr urine protein-creatinine ratio (UPCR) despite maximal standard of care (ACE inhibitor and/or ARB) were enrolled. Patients were randomized to subcutaneous placebo, atacicept 25mg or 75mg weekly. Primary endpoint: change in proteinuria at Week 48; secondary endpoints: changes in eGFR, serum IgA, IgG, and IgM, and Gd-IgA1.

Results


This interim analysis showed that, at Week 24, IgAN patients (placebo=5; atacicept 25mg=6; 75mg=5) had a consistent, dose-dependent reduction in IgA, IgG and IgM, and in Gd-IgA1 (Fig 1A), and a higher median % reduction from baseline in UPCR with atacicept than with placebo (Fig 1B); eGFR remained stable. TEAEs were reported by 81% of patients (mild/moderate, none severe), with no serious related events, severe hypogammaglobulinemia, or fatal outcomes.

Conclusion

These results provide proof of concept for the potential treatment of patients with IgAN and persistent proteinuria with atacicept.

Figure 1. Median changes from baseline to Week 24 in a) serum Gd-IgA1 and b) 24-hour UPCR

Funding

  • Commercial Support