PMID- 38025230
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 8
IP  - 11
DP  - 2023 Nov
TI  - Clinical Safety and Efficacy of Pegcetacoplan in a Phase 2 Study of Patients with 
      C3 Glomerulopathy and Other Complement-Mediated Glomerular Diseases.
PG  - 2284-2293
LID - 10.1016/j.ekir.2023.08.033 [doi]
AB  - INTRODUCTION: Dysregulated complement activation is likely the primary driver of 
      disease in C3 glomerulopathy (C3G) and contributes to other complement-mediated 
      diseases, including immunoglobulin A nephropathy (IgAN), lupus nephritis (LN), 
      and primary membranous nephropathy (PMN). No complement inhibitors are proven to 
      halt disease progression in these diseases. Pegcetacoplan, a targeted C3 and C3b 
      inhibitor, may mitigate complement-mediated kidney damage in C3G and other 
      glomerular diseases in which complement may have a pathogenic role. METHODS: This 
      open-label, phase 2, 48-week study evaluated the preliminary efficacy and safety 
      of subcutaneous pegcetacoplan for patients with complement-mediated glomerular 
      diseases. The primary end point was proteinuria reduction, measured as 24-hour 
      urine protein-to-creatinine ratio. Secondary end points included remission 
      status, changes in estimated glomerular filtration rate (eGFR), and 
      pharmacodynamic biomarkers. Treatment-emergent adverse events (TEAEs) were 
      monitored. RESULTS: Efficacy results for the C3G cohort are reported herein, 
      along with safety results for the study population. In the C3G cohort, mean 
      proteinuria reduction from baseline to week 48 was 50.9% in the intent-to-treat 
      (ITT) population (n = 7) and 65.4% in the per-protocol (PP) population (n = 4). 
      Mean serum albumin normalized and mean eGFR was stable over 48 weeks. Mean serum 
      C3 levels increased 6-fold and mean soluble C5b-9 levels decreased by 57.3% at 
      week 48. The most common adverse events (AEs) were upper respiratory tract 
      infection, injection site erythema, nausea, and headache. No meningitis or sepsis 
      cases were reported, and no serious treatment-related AEs were observed. 
      CONCLUSION: Pegcetacoplan may provide therapeutic benefit for C3G and has a 
      favorable safety profile across the 4 glomerular diseases studied.
CI  - (c) 2023 International Society of Nephrology. Published by Elsevier Inc.
FAU - Dixon, Bradley P
AU  - Dixon BP
AD  - Renal Section, Department of Pediatrics, University of Colorado School of 
      Medicine, Aurora, Colorado, USA.
FAU - Greenbaum, Larry A
AU  - Greenbaum LA
AD  - Emory University and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
FAU - Huang, Liwei
AU  - Huang L
AD  - Tidewater Kidney Specialists, Inc, Chesapeake, Virginia, USA.
FAU - Rajan, Sandeep
AU  - Rajan S
AD  - Vanderbilt University Medical Center, Nashville, Tennessee, USA.
FAU - Ke, Chunlei
AU  - Ke C
AD  - Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, USA.
FAU - Zhang, Yiwei
AU  - Zhang Y
AD  - Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, USA.
FAU - Li, Li
AU  - Li L
AD  - Apellis Pharmaceuticals, Inc., Waltham, Massachusetts, USA.
LA  - eng
PT  - Journal Article
DEP - 20230825
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC10658235
OTO - NOTNLM
OT  - C3 glomerulopathy
OT  - complement
OT  - end-stage kidney disease
OT  - glomerulonephritis
OT  - pegcetacoplan
OT  - proteinuria
EDAT- 2023/11/29 18:42
MHDA- 2023/11/29 18:43
PMCR- 2023/08/25
CRDT- 2023/11/29 16:25
PHST- 2023/06/23 00:00 [received]
PHST- 2023/08/15 00:00 [revised]
PHST- 2023/08/21 00:00 [accepted]
PHST- 2023/11/29 18:43 [medline]
PHST- 2023/11/29 18:42 [pubmed]
PHST- 2023/11/29 16:25 [entrez]
PHST- 2023/08/25 00:00 [pmc-release]
AID - S2468-0249(23)01470-5 [pii]
AID - 10.1016/j.ekir.2023.08.033 [doi]
PST - epublish
SO  - Kidney Int Rep. 2023 Aug 25;8(11):2284-2293. doi: 10.1016/j.ekir.2023.08.033. 
      eCollection 2023 Nov.