POS-048 PHASE 3, RANDOMIZED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PEGCETACOPLAN IN TREATMENT OF C3G OR IC-MPGN

IntroductionComplement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases characterized by excessive deposition of C3 breakdown products in renal glomeruli leading to proteinuria and progressive renal disease. Pegcetacoplan is a targeted C3 investigational therapy for diseases related to complement overactivation. This is a phase 3, randomized, placebo-controlled, double-blind, multicenter study of the efficacy and safety of pegcetacoplan in individuals with C3G or IC-MPGN.MethodsApproximately 90 patients (age, ≥12 years; weight, 20-100 kg) diagnosed with C3G or IC-MPGN, either as primary disease or posttransplant disease recurrence, will be recruited. Inclusion criteria include 2+ staining for C3c, global glomerulosclerosis <50%, urine protein-to-creatinine ratio (uPCR) ≥1000 mg/g, and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2. Exclusion criteria include previous pegcetacoplan exposure, C3G/IC-MPGN secondary to other conditions, and significant infection/malignancy. Patients will be randomized 1:1 to receive subcutaneous infusions of pegcetacoplan (1080 mg/20 mL) or matching volume of placebo twice weekly for 26 weeks (in addition to standard care). Thereafter, in the open-label period, all participants will receive pegcetacoplan twice weekly for 26 weeks. Assessments include first-morning uPCR every 4 weeks and renal biopsies at baseline/screening and weeks 26 and 52. Primary endpoint is proportion of participants with reduction in uPCR ≥50% relative to baseline at week 26. Secondary endpoints include proportion of participants with eGFR scores that are stable or improved from baseline; change in C3G histologic index activity score; and proportion of participants with decreased C3c staining on renal biopsy from baseline at week 26. Safety outcomes will also be monitored throughout the study. Participants may enter a subsequent 8-week follow-up period or long-term extension study.ResultsThis is a study design abstract.ConclusionsC3G and IC-MPGN are rare, progressive renal diseases due to deposition in renal glomeruli. This study will evaluate the safety and efficacy of complement protein C3 inhibitor pegcetacoplan in treating C3G and IC-MPGN.Conflict of interest Corporate sponsored research or other substantive relationships:Giuseppe Remuzzi: Consultancy Agreement with Biocryst Pharmaceuticals Bradley Dixon: Consultant for Apellis, Alexion pharmaceuticals (received honoraria) Fadi Fakhouri: Consultancy and/or speaker honoraria from Roche, Alexion, Apellis, Achillion, Novartis and Alnylam Matthew Pickering: Paid Scientific Advisor: Gyroscope, Apellis, Alexion, Sobi, Silence, Gemini Pharma Terence Cook: Consultancy agreements with Alexion, Novartis and Aurinia David Kavanaugh: Consultancy with Alexion, Novartis, Gyroscope Therapeutics, Idorsia, Sarepta Patrick Walker: Consultant for Travere Pharmaceuticals for study design and histologic data analysis Christoph Licht: Scientific advisory activities for Alexion, Aurin, Catalyst Biosciences, Novartis, Johnson&Johnson Marina Vivarelli: Consulting agreements with Travere, Novartis, Roche, Apellis, Achillion and has ongoing clinical studies with Alexion and Chemocentrix Zhiqun Zhang: employee of Apellis Li Li: employee of Apellis Helen Kocinsky: employee of Apellis IntroductionComplement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases characterized by excessive deposition of C3 breakdown products in renal glomeruli leading to proteinuria and progressive renal disease. Pegcetacoplan is a targeted C3 investigational therapy for diseases related to complement overactivation. This is a phase 3, randomized, placebo-controlled, double-blind, multicenter study of the efficacy and safety of pegcetacoplan in individuals with C3G or IC-MPGN.