Abstract: INFO10-SA
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial of ALXN1920 in Adults with Primary Membranous Nephropathy
Session Information
- Informational Posters - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- No subcategory defined
Authors
- Fervenza, Fernando C., Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, United States
- Norouzi, Sayna, Alexion, AstraZeneca Rare Diseases, Boston, Massachusetts, United States
- Farag, Youssef MK, Alexion, AstraZeneca Rare Diseases, Boston, Massachusetts, United States
- Youssef, Wahid, Alexion, AstraZeneca Rare Diseases, Boston, Massachusetts, United States
- Shanmugam, Surish P, Alexion, AstraZeneca Rare Diseases, Boston, Massachusetts, United States
- Esteghamat, Sahar, Alexion, AstraZeneca Rare Diseases, Boston, Massachusetts, United States
- Yu, Ji, Alexion, AstraZeneca Rare Diseases, Boston, Massachusetts, United States
- Radhakrishnan, Jai, Division of Nephrology, Columbia University Medical Center, New York, New York, United States
Description
Primary membranous nephropathy (PMN) is an autoimmune glomerular disease. Despite supportive care and immunosuppressive therapy, many patients do not achieve sustained remission. Evidence suggests that complement activation contributes to disease pathogenesis. Inhibiting the complement alternative pathway (CAP) in the kidney may reduce proteinuria and tubular injury.
ALXN1920 is a kidney-targeted Factor H fusion protein designed to enhance local CAP regulation at sites of complement activation, aiming to reduce kidney injury while avoiding broad systemic complement blockade.
This Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial (NCT07157787) evaluates the efficacy, safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and immunogenicity of ALXN1920 in adults with anti-PLA2R-positive PMN and persistent nephrotic-range proteinuria despite optimized supportive therapy.
The trial enrolls adults with anti-PLA2R-positive PMN, estimated glomerular filtration rate (eGFR ≥60 mL/min/1.73 m2), proteinuria >3.5 g/day, and ≤50% decrease in proteinuria despite optimal RAASi. Key exclusion criteria include anti-PLA2R–negative PMN, recent life-threatening nephrotic syndrome, rapid kidney function decline, and clinically relevant infection or safety risks. Participants will be randomized to receive weekly subcutaneous ALXN1920 or placebo for 26 weeks plus SoC (Fig.). All participants receive background SoC including RTX, allowing evaluation of ALXN1920 as add-on B-cell–directed therapy.
The primary endpoint is change from baseline in 24-h urine protein creatinine ratio at Week 26. Key secondary endpoints include complete remission (CR), CR or partial remission, changes from baseline in proteinuria, serum albumin, anti-PLA2R antibody levels, peripheral CD19+ B cell counts, and urinary complement activation markers. Safety, PK/PD, and immunogenicity will also be assessed.
This Phase 2a trial will test whether kidney-directed CAP regulation with ALXN1920 provides additional clinical and biomarker benefit when added to RTX-based SoC in high-risk PMN.
Acknowledgment
Medical writing support was provided by Amit Koushik, MSc (Alexion, AstraZeneca Rare Disease, Bangalore India).
Funding
- Alexion, AstraZeneca Rare Disease