Trial results for pegcetacoplan in patients with C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) were posted on ClinicalTrials.gov on 2025-08-06. The Phase 3 study demonstrated that pegcetacoplan significantly reduced proteinuria, with a least squares mean change of -1.114 log (uPCR) from baseline compared to 0.029 log (uPCR) for placebo at Week 26. Additionally, 49.21% of patients on pegcetacoplan achieved the composite renal endpoint versus 3.28% on placebo.
Background
The study aimed to assess the efficacy and safety of pegcetacoplan in patients with C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN), focusing on proteinuria reduction. These are rare and severe kidney diseases.
Trial design
The study (NCT05067127) was a Phase 3, randomized, placebo-controlled trial. It enrolled 124 participants diagnosed with either C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN). Participants received twice-weekly subcutaneous (SC) doses of pegcetacoplan or placebo. The trial assessed efficacy and safety based on a reduction in proteinuria.
Key results
The trial results demonstrated significant improvements in key renal outcomes for patients treated with pegcetacoplan compared to placebo.
- For the outcome 'Change From Baseline in Log-Transformed Urine Protein-to-Creatinine Ratio (uPCR) at Week 26': The pegcetacoplan group showed a least squares mean change of -1.114 log (uPCR), while the placebo group showed a least squares mean change of 0.029 log (uPCR). Analysis (MMRM) showed a difference in least squares (LS) mean of -1.143 (95.0% CI: -1.436 to -0.85) with a p-value of 0.0001.
- For the outcome 'Percentage of Subjects Who Achieved the Composite Renal Endpoint at Week 26': 49.21% of subjects in the pegcetacoplan group achieved this endpoint, compared to 3.28% in the placebo group. Logistic regression analysis yielded an Odds Ratio (OR) of 27.516 (95.0% CI: 6.105 to 124.026) with a p-value of 0.0001.
- For the outcome 'Percentage of Subjects With a Reduction of At Least 50% From Baseline in Urine Protein-to-Creatinine Ratio at Week 26': 60.32% of subjects in the pegcetacoplan group achieved this reduction, versus 4.92% in the placebo group. Logistic regression analysis showed an Odds Ratio (OR) of 30.932 (95.0% CI: 8.401 to 113.897) with a p-value of 0.0001.
- Regarding renal biopsy findings, for 'Percentage of Subjects Who Showed Decrease in C3c Staining on Renal Biopsy From Baseline at Week 26': 74.29% for pegcetacoplan versus 11.76% for placebo. Logistic regression analysis showed an Odds Ratio (OR) of 27.392 (95.0% CI: 6.477 to 115.852) with a p-value of 0.0001.
- For 'Change From Baseline in Estimated Glomerular Filtration Rate at Week 26': The pegcetacoplan group showed a least squares mean change of -1.497 mL/minute/1.73 m^2, while the placebo group showed a least squares mean change of -7.808 mL/minute/1.73 m^2. Analysis (MMRM) showed a difference in LS mean of 6.312 (95.0% CI: 0.501 to 12.122) with a p-value of 0.0333, indicating a more favorable eGFR change with pegcetacoplan.
- The change from baseline in the C3 Glomerulopathy (C3G) Histologic Index Activity Score at Week 26 was -3.482 units on a scale for pegcetacoplan and -2.480 units on a scale for placebo. ANCOVA analysis showed a difference in LS mean of -1.002 (95.0% CI: -2.803 to 0.798) with a p-value of 0.2753.
What this means
The results from this Phase 3 trial indicate that pegcetacoplan significantly reduced proteinuria and improved several key renal endpoints in patients with C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis. The substantial reduction in uPCR, higher rates of achieving the composite renal endpoint, and favorable impact on eGFR compared to placebo suggest that pegcetacoplan could offer a meaningful therapeutic option for these severe kidney conditions. The observed decrease in C3c staining also supports its potential role in modulating disease pathology.
Source
The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05067127, titled 'Phase III Study Assessing the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis,' were posted on 2025-08-06 on clinicaltrials.gov.