Clinical Safety and Efficacy of Pegcetacoplan in a Phase 2 Study of Patients with C3 Glomerulopathy and Other Complement-Mediated Glomerular Diseases.
In an early-phase study, the complement-blocking drug pegcetacoplan roughly halved protein leakage in the urine over 48 weeks in people with C3 glomerulopathy, a rare disease with no proven treatment. Kidney function stayed stable and no serious drug-related side effects were reported.
Background
Dysregulated complement activation is likely the primary driver of disease in C3 glomerulopathy and contributes to other complement-mediated diseases including IgA nephropathy, lupus nephritis and primary membranous nephropathy. No complement inhibitor has been proven to halt disease progression in these conditions.
Study design
This open-label, phase 2, 48-week study evaluated subcutaneous pegcetacoplan, a targeted C3 and C3b inhibitor, in 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, change in eGFR and pharmacodynamic biomarkers.
Key findings
In the C3 glomerulopathy cohort, mean proteinuria reduction from baseline to week 48 was 50.9% in the intent-to-treat population (n = 7) and 65.4% in the per-protocol population (n = 4). Mean serum albumin normalised 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.
Safety
The most common adverse events were upper respiratory tract infection, injection site erythema, nausea and headache. No cases of meningitis or sepsis were reported, and no serious treatment-related adverse events were observed across the four glomerular diseases studied.
Category
Research
Source
Kidney International Reports
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