Kidney Week

Abstract: SA-OR92

VALIANT: A Randomized, Multicenter, Double-Blind, Placebo (PBO)-Controlled, Phase 3 Trial of Pegcetacoplan for Patients with Native or Post-transplant Recurrent Glomerulopathy (C3G) or Primary Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)

Session Information

• High-Impact Clinical Trials - 2
  October 26, 2024 | Location: Hall D, Convention Center
  Abstract Time: 11:00 AM - 11:15 AM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Nester, Carla M., University of Iowa, Stead Family Children’s Hospital, Iowa City, Iowa, United States

Carla M. Nester, MD, MS, FASN

• Bomback, Andrew S., New York-Presbyterian/Columbia University Irving Medical Center, New York, New York, United States

Andrew S. Bomback, MD, MPH

• Ariceta Iraola, María Gema, Hospital Universitari Vall d'Hebron, Barcelona, Catalunya, Spain

María Gema Ariceta Iraola, MD, PhD

• Delmas, Yahsou, Centre Hospitalier Universitaire de Bordeaux Groupe hospitalier Pellegrin, Bordeaux, Aquitaine, France

Yahsou Delmas, MD, PhD

• Dixon, Bradley P., University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, United States

Bradley P. Dixon, MD, FASN

• Gale, Daniel P., University College London, London, United Kingdom

Daniel P. Gale, MA, MBChB, PhD

• Greenbaum, Larry A., Emory University School of Medicine, Atlanta, Georgia, United States

Larry A. Greenbaum, MD, PhD

• Han, Seung Hyeok, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)

Seung Hyeok Han, MD, PhD

• Isbel, Nicole, Princess Alexandra Hospital, Brisbane, Queensland, Australia

Nicole Isbel, MBBS, PhD

• Licht, Christoph, The Hospital for Sick Children, Toronto, Ontario, Canada

Christoph Licht, MD, FASN

• Mastrangelo, Antonio, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy

Antonio Mastrangelo

• Mizuno, Masashi, Nagoya Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Nagoya, Aichi, Japan

Masashi Mizuno, MD, PhD

• de Holanda, Maria Izabel Neves, Hospital Federal de Bonsucesso, Ruschel Medicina, Rio de Janeiro, Brazil

Maria Izabel Neves de Holanda, MD, PhD

• Pickering, Matthew C., Imperial College London, London, United Kingdom

Matthew C. Pickering, MD, PhD

• Remuzzi, Giuseppe, Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Lombardia, Italy

Giuseppe Remuzzi, MD

• Van De Kar, Nicole, Radboudumc Amalia Children's Hospital, Nijmegen, Netherlands

Nicole Van De Kar, MD, PhD

• Vivarelli, Marina, Ospedale Pediatrico Bambino Gesu IRCCS, Rome, Italy

Marina Vivarelli, MD

• Walker, Patrick D., Arkana Laboratories, Little Rock, Arkansas, United States

Patrick D. Walker, MD, FASN

• Wallace, Dean, Royal Manchester Children's Hospital, Manchester, Manchester, United Kingdom

Dean Wallace, MD, MBBS

• Zecher, Daniel, Krankenhaus Barmherzige Bruder Regensburg, Regensburg, Bayern, Germany

Daniel Zecher, MD

• Li, Li, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States

Li Li, MD

• Wang, Zhongshen, Apellis Pharmaceuticals Inc, Waltham, Massachusetts, United States

Zhongshen Wang, PhD

• López Lázaro, Luis, Swedish Orphan Biovitrum AB, Stockholm, Stockholm, Sweden

Luis López Lázaro, MD, PhD

• Szamosi, Johan, Swedish Orphan Biovitrum AB, Stockholm, Stockholm, Sweden

Johan Szamosi, MSc

• Fakhouri, Fadi, Centre Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland

Fadi Fakhouri, MD

Background

VALIANT (NCT05067127) is a double-blind, PBO-controlled trial investigating the efficacy/safety of pegcetacoplan (PEG), a C3/C3b inhibitor, in adolescents (≥12 yrs) and adults with native or post-transplant recurrent C3G or primary IC-MPGN.

Methods

Patients (pts) received PEG (SC infusion 2x/wk) or PBO (randomized 1:1) for 26 wks. The primary endpoint was log-transformed ratio of uPCR at wk 26 vs. baseline to measure proteinuria reduction vs. PBO.

Results

124 pts were randomized to PEG (n=63) or PBO (n=61). The primary endpoint was met:68.3% (95% CI –76.3, –57.7) uPCR reduction in PEG vs. PBO arms at wk 26 (p<0.0001; Table). Results were consistent across all subgroups (disease type, age, and transplant status). Robust reductions in C3c staining and clinically meaningful eGFR stabilization were observed with PEG vs. PBO (Table). Treatment-emergent AE frequency and severity were similar between arms. None of the 4 serious infections (3 PEG; 1 PBO) were attributed to encapsulated bacteria. 1 death occurred in the PEG arm due to COVID-19 pneumonia (unrelated to PEG).

Conclusion

PEG, a C3/C3b inhibitor, is the first therapy to achieve significant and clinically meaningful reductions in proteinuria (68.3% vs. PBO) and C3c staining and eGFR stabilization, compared with PBO in pts ≥12 yrs with C3G or primary IC-MPGN and was well tolerated.