Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous Nephropathy
Introduction: Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk an...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-09-01
|
| Series: | Kidney International Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924017947 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849330213228380160 |
|---|---|
| author | Brad H. Rovin Pierre M. Ronco Jack F.M. Wetzels Sharon G. Adler Isabelle Ayoub Philippe Zaoui Seung Hyeok Han Jaideep S. Dudani Houston N. Gilbert Uptal D. Patel Paul T. Manser Julia Jauch-Lembach Nicola Faulhaber Rainer Boxhammer Stefan Härtle Ben Sprangers |
| author_facet | Brad H. Rovin Pierre M. Ronco Jack F.M. Wetzels Sharon G. Adler Isabelle Ayoub Philippe Zaoui Seung Hyeok Han Jaideep S. Dudani Houston N. Gilbert Uptal D. Patel Paul T. Manser Julia Jauch-Lembach Nicola Faulhaber Rainer Boxhammer Stefan Härtle Ben Sprangers |
| author_sort | Brad H. Rovin |
| collection | DOAJ |
| description | Introduction: Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN. Methods: Patients with newly diagnosed or relapsed PMN (cohort 1 [C1]; n = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; n = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point was the incidence and severity of treatment-emergent adverse events (TEAEs). Results: A total of 31 patients were enrolled and received felzartamab. Twenty-seven patients (87.1%) had TEAEs, including infusion-related reactions (IRRs) (29.0%), hypogammaglobulinemia (25.8%), peripheral edema (19.4%), and nausea (16.1%). Five patients (16.1%) had serious TEAEs that all resolved. Immunologic response (anti-PLA2R titer reduction ≥50%) was achieved by 20 of 26 efficacy-evaluable patients (76.9%) (C1, 13/15 [86.7%]; C2, 7/11 [63.6%]). Anti-PLA2R titer reductions were rapid (week 1 response, 44.0%; response 7 months after last felzartamab dose [end of study, EOS], 53.8%). Partial proteinuria remission (urine protein-to-creatinine ratio [UPCR] reduction ≥50%, UPCR <3.0 g/g, and stable estimated glomerular filtration rate [eGFR]) was achieved by 9 of 26 patients (34.6%) (C1, 7/15 [46.7%]; C2, 2/11 [18.2%]) before or at EOS (median follow-up, 366 days). Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]). Conclusion: In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients. |
| format | Article |
| id | doaj-art-c88b107cd5c848e89b3a51428462e26c |
| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-c88b107cd5c848e89b3a51428462e26c2025-08-20T03:47:02ZengElsevierKidney International Reports2468-02492024-09-01992635264710.1016/j.ekir.2024.06.018Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous NephropathyBrad H. Rovin0Pierre M. Ronco1Jack F.M. Wetzels2Sharon G. Adler3Isabelle Ayoub4Philippe Zaoui5Seung Hyeok Han6Jaideep S. Dudani7Houston N. Gilbert8Uptal D. Patel9Paul T. Manser10Julia Jauch-Lembach11Nicola Faulhaber12Rainer Boxhammer13Stefan Härtle14Ben Sprangers15Department of Medicine and Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA; Correspondence: Brad H. Rovin, Division of Nephrology, The Ohio State University Wexner Medical Center, 1644 Neil Avenue, 4th Floor, Columbus, Ohio 43210, USA.Sorbonne Université and INSERM UMRS 1155, Paris France; Centre Hospitalier Le Mans, Le Mans, FranceDepartment of Nephrology, Radboud University Medical Center, Nijmegen, The NetherlandsLundquist Research Institute at Harbor UCLA, Torrance, California, USADepartment of Medicine and Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USACentre Hospitalier Universitaire Grenoble Alpes, Grenoble, FranceYonsei University College of Medicine, Seoul, South KoreaHuman Immunology Biosciences, Inc., South San Francisco, California, USAHuman Immunology Biosciences, Inc., South San Francisco, California, USAHuman Immunology Biosciences, Inc., South San Francisco, California, USAHuman Immunology Biosciences, Inc., South San Francisco, California, USAMorphoSys AG, Planegg, GermanyMorphoSys AG, Planegg, GermanyMorphoSys AG, Planegg, GermanyMorphoSys AG, Planegg, GermanyKatholieke Universiteit Leuven, Leuven, Belgium; Zlekenhuis Oost Limburg Genk, Genk, BelgiumIntroduction: Primary membranous nephropathy (PMN) is most often caused by autoantibodies to phospholipase A2 receptor (PLA2R). M-PLACE (NCT04145440) is an open-label, phase 1b/2a study that assessed the safety and efficacy of the fully human anti-CD38 monoclonal antibody felzartamab in high-risk anti-PLA2R+ PMN. Methods: Patients with newly diagnosed or relapsed PMN (cohort 1 [C1]; n = 18) or PMN refractory to immunosuppressive therapy (IST) (cohort 2 [C2]; n = 13) received 9 infusions of felzartamab 16 mg/kg in the 24-week treatment period, followed by a 28-week follow-up. The primary end point was the incidence and severity of treatment-emergent adverse events (TEAEs). Results: A total of 31 patients were enrolled and received felzartamab. Twenty-seven patients (87.1%) had TEAEs, including infusion-related reactions (IRRs) (29.0%), hypogammaglobulinemia (25.8%), peripheral edema (19.4%), and nausea (16.1%). Five patients (16.1%) had serious TEAEs that all resolved. Immunologic response (anti-PLA2R titer reduction ≥50%) was achieved by 20 of 26 efficacy-evaluable patients (76.9%) (C1, 13/15 [86.7%]; C2, 7/11 [63.6%]). Anti-PLA2R titer reductions were rapid (week 1 response, 44.0%; response 7 months after last felzartamab dose [end of study, EOS], 53.8%). Partial proteinuria remission (urine protein-to-creatinine ratio [UPCR] reduction ≥50%, UPCR <3.0 g/g, and stable estimated glomerular filtration rate [eGFR]) was achieved by 9 of 26 patients (34.6%) (C1, 7/15 [46.7%]; C2, 2/11 [18.2%]) before or at EOS (median follow-up, 366 days). Serum albumin increased from baseline to EOS in 20 of 26 patients (76.9%) (C1, 12/15 [80.0%]; C2, 8/11 [72.7%]). Conclusion: In this population with high-risk anti-PLA2R+ PMN, felzartamab was tolerated and resulted in rapid partial and complete immunologic responses and partial improvements in proteinuria and serum albumin in some patients.http://www.sciencedirect.com/science/article/pii/S2468024924017947clinical trialfelzartamabMOR202phase 2phospholipase A2 receptorprimary membranous nephropathy |
| spellingShingle | Brad H. Rovin Pierre M. Ronco Jack F.M. Wetzels Sharon G. Adler Isabelle Ayoub Philippe Zaoui Seung Hyeok Han Jaideep S. Dudani Houston N. Gilbert Uptal D. Patel Paul T. Manser Julia Jauch-Lembach Nicola Faulhaber Rainer Boxhammer Stefan Härtle Ben Sprangers Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous Nephropathy Kidney International Reports clinical trial felzartamab MOR202 phase 2 phospholipase A2 receptor primary membranous nephropathy |
| title | Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous Nephropathy |
| title_full | Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous Nephropathy |
| title_fullStr | Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous Nephropathy |
| title_full_unstemmed | Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous Nephropathy |
| title_short | Phase 1b/2a Study Assessing the Safety and Efficacy of Felzartamab in Anti-Phospholipase A2 Receptor Autoantibody–Positive Primary Membranous Nephropathy |
| title_sort | phase 1b 2a study assessing the safety and efficacy of felzartamab in anti phospholipase a2 receptor autoantibody positive primary membranous nephropathy |
| topic | clinical trial felzartamab MOR202 phase 2 phospholipase A2 receptor primary membranous nephropathy |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924017947 |
| work_keys_str_mv | AT bradhrovin phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT pierremronco phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT jackfmwetzels phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT sharongadler phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT isabelleayoub phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT philippezaoui phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT seunghyeokhan phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT jaideepsdudani phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT houstonngilbert phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT uptaldpatel phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT paultmanser phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT juliajauchlembach phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT nicolafaulhaber phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT rainerboxhammer phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT stefanhartle phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy AT bensprangers phase1b2astudyassessingthesafetyandefficacyoffelzartamabinantiphospholipasea2receptorautoantibodypositiveprimarymembranousnephropathy |