Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid

Autor: Garcia-Pavia, Pablo, Aus dem Siepen, Fabian, Donal, Erwan, Lairez, Olivier, van der Meer, Peter, Kristen, Arnt V, Mercuri, Michele F, Michalon, Aubin, Frost, Robert J A, Grimm, Jan, Nitsch, Roger M, Hock, Christoph, Kahr, Peter C, Damy, Thibaud
Přispěvatelé: Université Francisco de Vitoria = Universidad Francisco de Vitoria (UFV), UniversitätsKlinikum Heidelberg, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University Medical Center Groningen [Groningen] (UMCG), AstraZeneca [Cambridge, UK], CHU Henri Mondor [Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Neurimmune, University of Zurich
Rok vydání: 2023
Předmět:
Zdroj: New England Journal of Medicine
New England Journal of Medicine, 2023, ⟨10.1056/NEJMoa2303765⟩
ISSN: 1533-4406
0028-4793
Popis: International audience; BACKGROUND Transthyretin amyloid (ATTR) cardiomyopathy is a progressive and fatal disease caused by misfolded transthyretin. Despite advances in slowing disease progression, there is no available treatment that depletes ATTR from the heart for the amelioration of cardiac dysfunction. NI006 is a recombinant human anti-ATTR antibody that was developed for the removal of ATTR by phagocytic immune cells. METHODS In this phase 1, double-blind trial, we randomly assigned (in a 2:1 ratio) 40 patients with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive intravenous infusions of either NI006 or placebo every 4 weeks for 4 months. Patients were sequentially enrolled in six cohorts that received ascending doses (ranging from 0.3 to 60 mg per kilogram of body weight). After four infusions, patients were enrolled in an open-label extension phase in which they received eight infusions of NI006 with stepwise increases in the dose. The safety and pharmacokinetic profiles of NI006 were assessed, and cardiac imaging studies were performed. RESULTS The use of NI006 was associated with no apparent drug-related serious adverse events. The pharmacokinetic profile of NI006 was consistent with that of an IgG antibody, and no antidrug antibodies were detected. At doses of at least 10 mg per kilogram, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac magnetic resonance imaging, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over a period of 12 months. The median N-terminal pro-B-type natriuretic peptide and troponin T levels also seemed to be reduced. CONCLUSIONS In this phase 1 trial of the recombinant human antibody NI006 for the treatment of patients with ATTR cardiomyopathy and heart failure, the use of NI006 was associated with no apparent drug-related serious adverse events.
Databáze: OpenAIRE
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