Abstract: INFO29
A Phase 2 Study to Evaluate the Efficacy and Safety of Pegcetacoplan in the Treatment of Patients With Post-Transplant Recurrence of C3G or IC-MPGN
Session Information
- Informational Posters
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Fakhouri, Fadi, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Dixon, Bradley P., Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, United States
- Walker, Patrick D., Arkana Laboratories, Little Rock, Arkansas, United States
- Soomro, Irfana, New York University, New York, New York, United States
- Pickering, Matthew C., Imperial College London, London, London, United Kingdom
- Cook, H. Terence, Imperial College London, London, London, United Kingdom
- Zhang, Zhiqun, Former Employee of Apellis Pharmaceuticals, Waltham, Massachusetts, United States
- Kocinsky, Hetal S., Apellis Pharmaceuticals, Waltham, Massachusetts, United States
Description
Introduction: Complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are rare but devastating kidney diseases. There are no approved therapies for these diseases, and 50% of patients develop recurrence of disease and graft loss after transplant. Uncontrolled complement activation at the level of C3 leads to excessive production of C3 breakdown products and deposition in the kidney. As an investigational C3 and C3b inhibitor, pegcetacoplan has the potential to address this underlying pathophysiology. This is a phase 2, open-label, randomized, controlled study of the efficacy and safety of pegcetacoplan in renal transplant recipients with recurrence of C3G or IC-MPGN (ClinicalTrials.gov identifier: NCT04572854).
Methods: This study is recruiting up to 12 patients aged ≥18 years with posttransplant recurrence of C3G or IC-MPGN, with proteinuria ≥1 g/d and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2. The diagnosis of C3G or IC-MPGN must be confirmed by a central pathologist based on a renal allograft biopsy. Exclusion criteria include secondary C3G or IC-MPGN (eg, due to malignancy, infection, or graft rejection). Patients will be randomized 3:1 to receive either pegcetacoplan (1080 mg/20 mL twice weekly subcutaneous injection) or no drug intervention for 12 weeks (with continuation of standard-of-care therapy for both groups). Following the randomized 12-week period, all patients will receive pegcetacoplan until week 52. Patients will undergo renal allograft biopsy during screening and at weeks 12 and 52. The primary endpoint is the proportion of patients with reduction in C3c staining on renal biopsy at week 12. Secondary endpoints include changes in C3c staining, proteinuria, and eGFR. Safety outcomes, including treatment-related adverse events and discontinuations, will be monitored throughout the study.
Conclusion: This study will assess how pegcetacoplan could address the underlying disease pathophysiology of C3G/IC-MPGN in patients with posttransplant disease recurrence, a group with particularly high risk for allograft loss.