Abstract: TH-OR92
MAJESTY: A Phase 3, Randomized, Open-Label, Active Comparator-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Obinutuzumab in Patients with Primary Membranous Nephropathy
Session Information
- Podocytopathies and Membranous Nephropathy: Clinical Advances
October 24, 2024 | Location: Room 1, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Fervenza, Fernando C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
- Gesualdo, Loreto, Universita degli Studi di Bari Aldo Moro, Bari, Puglia, Italy
- Mastroianni-Kirsztajn, Gianna, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
- Hou, Fan Fan, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China
- Appel, Gerald B., Columbia University Irving Medical Center, New York, New York, United States
- Prot, Sylvie, F Hoffmann-La Roche AG, Basel, Switzerland
- Berisha, Eriola, Hoffmann-La Roche Limited, Mississauga, Ontario, Canada
- Khatri, Leena, Roche UK Ltd, Welwyn Garden City, United Kingdom
- Parsons, Tom, Hoffmann-La Roche Limited, Mississauga, Ontario, Canada
- Spinks, Ed, Roche UK Ltd, Welwyn Garden City, United Kingdom
- Boston, Heather, Roche UK Ltd, Welwyn Garden City, United Kingdom
- Riboulet, William, F Hoffmann-La Roche AG, Basel, Switzerland
- Han, Xiaoyan, Roche (China) Holding Ltd, Shanghai, China
- Chen, Debbie, Genentech Inc, South San Francisco, California, United States
- Bomback, Andrew S., Columbia University Irving Medical Center, New York, New York, United States
Background
The MENTOR study demonstrated that rituximab was superior to cyclosporine in maintaining long-term remission in primary membranous nephropathy (pMN). Obinutuzumab, a type II anti-CD20 monoclonal antibody, depletes B cells more effectively than rituximab. The MAJESTY study (NCT04629248) assesses the efficacy and safety of obinutuzumab versus tacrolimus among patients with pMN.
Methods
Participants were randomized 1:1 to receive obinutuzumab or tacrolimus (Figure 1). Obinutuzumab (1000 mg) is dosed on Day 1 and Weeks (Wks) 2, 24, and 26; tacrolimus (0.5 mg/kg) is given twice daily. Participants enter escape treatment with obinutuzumab if any of the following criteria are met: 1) Wk 24 urine protein-to-creatinine ratio (UPCR) >3.5 g/g and <25% decrease from baseline; 2) Wk 52 UPCR>3.5 g/g and <50% decrease from baseline; 3) Wk 52-104 UPCR >3.5 g/g after previously achieving proteinuric complete or partial remission (CR/PR); 4) tacrolimus discontinuation criteria. The primary endpoint is the proportion of patients with CR, defined as UPCR ≤0.3 g/g with a stable estimated glomerular filtration rate (eGFR) at Wk 104. Secondary endpoints include the proportion of participants who achieve CR or PR (UPCR >0.3 and ≤3.5 g/g and ≥50% decrease from baseline) at Wk 104 and the proportion who achieve CR at Wk 76.
Results
MAJESTY is fully enrolled with 142 participants across 86 sites and 11 countries. The study population comprises 31% women, and 25% Asian, 3% Black and 70% White participants; 29% received prior immunosuppressive therapy. At baseline, mean (SD) age was 51.2 (11.1) years and albumin was 2.9 (0.6) g/dL; median (IQR) eGFR was 87.0 (62.5-104.5) mL/min/1.73 m2 and 24 hours UPCR was 6.8 (5.2-9.0) g/g. Among 110 (78%) participants with anti-PLA2R antibody >14 RU/mL, median (IQR) titer was 147 (52-287) RU/mL.
Conclusion
Full results of the MAJESTY study will be available upon completion.
Funding
- Commercial Support – F. Hoffmann-La Roche Ltd.