학술논문
Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial
Document Type
Academic Journal
Author
Barratt, Jonathan; Liew, Adrian; Yeo, See Cheng; Fernström, Anders; Barbour, Sean J.; Sperati, C. John; Villanueva, Russell; Wu, Ming-Ju; Wang, Dazhe; Borodovsky, Anna; Badri, Prajakta; Yureneva, Elena; Bhan, Ishir; Cattran, Daniel; Achanti, Anand; Budisavljevic, Milos; Walker, Linda; Aggarwal, Naresh; Andres, Stephanie; Navarro, Marie Stella; Gabuay, Haydee; Barany, Peter; Heimbürger, Olof; Durgé, Ulrika Jensen; Barbour, Sean; Sheriff, Zainab; MacLeod, Paula; Barratt, Jonathan; Cheung, Chee Kay; Selvaskandan, Haresh; Sklarzewicz, Justyna; Cattran, Daniel; Reich, Heather N.; Ling, Paul; Jauhal, Arenn; Chantrel, Francois; Grellier, Jimmy; Alzina, Camille; Chen, Jin Bor; Chen, Kuan-Hsing; Hsu, Hsiang-Hao; Yang, Huang-Yu; Tu, Kun-Hua; Encarnacion, Montserrat Diaz; Rusiñol, Helena Marco; San Miguel Amigo, Luz; Bardaju de Quixano, Beatriz; Torres, Irene Silva; Espinosa, Mario; López-López, Isabel; Regalado, Rocío; Fernström, Anders; Gylling, Micael; Uhlin, Fredrik; Fervenza, Fernando; Goh, Bak Leong; Ibrahim, Fairol H.; Alias, Aida Azlin; Lian, Tay Li; Hour, Billy; Rosales, Tyrone; Macias, Veronica; Kaskas, Marwan; Lanot, Antoine; Gueutin, Victor; Brucato, Sylvie; Legrand, Eric; Cabantous, Julie; Martin, Nadia; Barros, Xoana; Martínez, Cristina; Capdevila, Montserrat; Rovira, Irene; Mohamad Nor, Fariz Safhan; Ahmad, Mohd Kamil; Syahril Rozli Wan Ali, Wan Ahmad; Ng, Tze Jian; Atira Hisham, ‘Izzah’; Kamaronzaman, Nur Liyana; Mohamed Asri, Nadia Shahirah; Abu Othman, Mohamad Haziq; Mohd, Mohd Shahril; Moranne, Olivier; Ng, Kok Peng; Ooi, Shok Hoon; Ambros, Joan Torras; Coloma, Ana; Draibe, Juliana; Galofre, Claudia; Troyanov, Stephan; Marcotte, Guylaine; Villanueva, Russell; De Leon, Donnah Franceska; Wu, Ming-Ju; Lee, Shan; Yahya, Rosnawati; Yee, Seow Yeing; Wan Mohamad, Wan Hazlina; Nordin, Nurul Zaynah; Abdul Wahab, Muhamad Zaimi; Rohani, Zurina Che; Mod Baharuddin, Mohd Alfaisal; Asswad Kassim, Muhamad Nur; Zuhafifah Mohd Zaki, Siti Nur; Yeo, See Cheng; Lim, Ru Sin; Soh, Siew Hwa; Lee, Felicia; Jiao, Hongli; Lim, Rosa; Lin, Kai Yan; Zaoui, Philippe; Carron, Pierre-Louis; Tartry, David; Bugnazet, Mathilde; Imerzoukene, Farida; Theo, Florence; Dhion, Séverine; Argoud, Meryll; Vial, Gaëlle; Lehman, Audrey; Romanet, Thierry
Source
Clinical Journal of the American Society of Nephrology. Apr 01, 2024 19(4):452-462
Subject
Language
English
ISSN
1555-9041
Abstract
BACKGROUND: IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression. METHODS: In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein ≥1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments. RESULTS: Thirty-one patients were randomized (cemdisiran, N=22; placebo, N=9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of –37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of –45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was –98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%). CONCLUSIONS: These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.