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

• Halfway Through the Marathon: Clinical Candidates in Development
  October 25, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Glomerular Diseases

• 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

• Barratt, Jonathan, University of Leicester, Leicester, Leicestershire, United Kingdom

Jonathan Barratt, MBChB, PhD



Jon leads the Renal Research Group within the College of Life Sciences, University of Leicester. His research is focussed on a bench to bedside approach to improving our understanding of the pathogenesis of IgA nephropathy a common global cause of kidney failure. Jon is the IgA nephropathy Rare Disease Group lead for the UK National Registry of Rare Kidney Diseases (RaDaR) and a member of the steering committee for the International IgA Nephropathy Network. He works closely with pharmaceutical companies interested in new treatments for IgA nephropathy, and is Chief Investigator for a number of international randomised controlled Phase 2 and 3 clinical trials in IgA nephropathy, and a member of the FDA and American Society of Nephrology Kidney Health Initiative: Identifying Surrogate Endpoints for Clinical Trials in IgA Nephropathy Work group.

• Tumlin, James A., Emory University School of Medicine, Atlanta, Georgia, United States

James A. Tumlin,

• Suzuki, Yusuke, Juntendo University, Tokyo, Japan

Yusuke Suzuki,

• Kao, Amy, EMD Serono Research Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, Massachusetts, United States

Amy Kao,

• Aydemir, Aida, EMD Serono Research Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, Massachusetts, United States

Aida Aydemir,

• Zima, Yulia, EMD Serono Research Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, Massachusetts, United States

Yulia Zima,

• Appel, Gerald B., Columbia University Medical Center, New York, New York, United States

Gerald B. Appel,

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 – EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany)