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Kidney Week

Abstract: SA-PO923

Efficacy of 12-Week Pegcetacoplan in Kidney Transplant Recipients with Recurrent C3 Glomerulopathy (C3G) or Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials


  • Bomback, Andrew S., Columbia University Irving Medical Center, New York, New York, United States
  • Daina, Erica, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy
  • Kanellis, John, Monash Medical Centre Clayton, Clayton, Victoria, Australia
  • Kavanagh, David, National Renal Complement Therapeutics Centre, Newcastle University, Newcastle upon Tyne, United Kingdom
  • Pickering, Matthew C., Imperial College London, London, London, United Kingdom
  • Sunder-Plassmann, Gere, Medizinische Universitat Wien, Wien, Wien, Austria
  • Walker, Patrick D., Arkana Laboratories, Little Rock, Arkansas, United States
  • Wang, Zhongshen, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
  • Ahmad, Zurish, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States
  • Fakhouri, Fadi, Centre Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland

Pegcetacoplan (PEG; C3 inhibitor) may prevent C3G or IC-MPGN progression. NOBLE (NCT04572854) is the first prospective randomized controlled trial of PEG vs standard of care (SOC) in kidney transplant recipients (KTRs) with primary C3G or IC-MPGN recurrence.


Adult patients (pts) were randomized 3:1 to subcutaneous PEG 1080 mg twice weekly plus SOC (n=10) or SOC only (n=3). Primary endpoint: reduction in renal biopsy C3c staining (≥2 orders of magnitude [OOM]) from baseline to Week 12 (W12). Additional W12 endpoints: changes in eGFR, uPCR, C3G activity score, serum C3, and serum sC5b-9.


9 (69.2%) pts had C3G and 4 (30.8%) had IC-MPGN. At W12, 5 (50%) PEG pts had ≥2 OOM reduction in C3c staining (4 had 0 intensity); 8 (80%) had ≥1 OOM reduction (Figure). 9 (90%) PEG pts had reduced C3G activity score at W12. In subgroup (≥1000 mg/g), uPCR decreased with PEG (–39.2%) at W12. eGFR remained stable, serum C3 increased, and sC5b-9 decreased with PEG (Table). There were no discontinuations/deaths due to treatment-emergent adverse events.


As early as W12, pegcetacoplan reduced C3c staining and proteinuria with stable eGFR, targeted the pathophysiology of C3 dysregulation, and was well tolerated in KTRs with recurrent C3G or IC-MPGN.

Table. Clinical and biomarker changes in C3G and IC-MPGN
  uPCR (mg/g)uPCR (mg/g)a
(Patients with ≥1000 mg/g at Baseline)
Serum C3 (mg/dL)Serum sC5b-9 (ng/mL)eGFR (mL/min/1.73m2)
BaselineMeand (SD)1506.7 (1097.23)2314.8 (2170.68)2349.3 (595.15)3217.3 (2129.81)56.1 (33.83)103.0 (67.88)651.4 (1024.68)145.3 (41.28)51.8 (13.18)53.3 (11.37)
Week 12Meand (SD)1048.7 (1293.10)2412.9 (1980.32)1582.9 (1559.20)3150.3 (2140.18)291.1 (92.11)89.5 (53.03)123.4 (82.26)228.7 (162.54)53.7 (23.11)47.3 (11.85)
Change from baselineMeand (SD)–458.0 (956.06)98.1 (286.08)–766.4 (1182.82)–67.0 (10.37)235.0 (83.71)–13.5 (14.85)–528.0 (955.19)83.3 (121.33)1.9 (21.74)–6.0 (2.65)
C3G, C3 glomerulopathy; eGFR, estimated glomerular filtration rate; IC-MPGN, immune complex membranoproliferative glomerulonephritis; PEG, pegcetacoplan; SD, standard deviation; SOC, standard of care; uPCR, urinary protein-to-creatinine ratio.
aMeasured by triplicate first-morning spot urine.
bPatients received subcutaneous pegcetacoplan 1080 mg twice weekly plus standard of care. Of 10 patients, 8 (80%) had C3G, and 2 (20%) had IC-MPGN. The mean (SD) age of the patients was 39.8 (12.59) years.
cPatients received standard of care only (SOC). Of 3 patients, 1 (33%) had C3G and 2 (67%) had IC-MPGN. The mean (SD) age of the patients was 44.3 (24.03) years.
dMeans were calculated only using non-missing values.