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Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial.
Di Rocco, Maja; Forleo-Neto, Eduardo; Pignolo, Robert J; Keen, Richard; Orcel, Philippe; Funck-Brentano, Thomas; Roux, Christian; Kolta, Sami; Madeo, Annalisa; Bubbear, Judith S; Tabarkiewicz, Jacek; Szczepanek, Malgorzata; Bachiller-Corral, Javier; Cheung, Angela M; Dahir, Kathryn M; Botman, Esmée; Raijmakers, Pieter G; Al Mukaddam, Mona; Tile, Lianne; Portal-Celhay, Cynthia; Sarkar, Neena; Hou, Peijie; Musser, Bret J; Boyapati, Anita; Mohammadi, Kusha; Mellis, Scott J; Rankin, Andrew J; Economides, Aris N; Trotter, Dinko Gonzalez; Herman, Gary A; O'Meara, Sarah J; DelGizzi, Richard; Weinreich, David M; Yancopoulos, George D; Eekhoff, E Marelise W; Kaplan, Frederick S.
Afiliación
  • Di Rocco M; Department of Pediatrics, Unit of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
  • Forleo-Neto E; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Pignolo RJ; Department of Medicine, Mayo Clinic, Rochester, MN, USA.
  • Keen R; Centre for Metabolic Bone Disease Royal National Orthopaedic Hospital NHS Trust, London, UK.
  • Orcel P; Department of Rheumatology - DMU Locomotion, Assistance Publique - Hôpitaux de Paris, Paris, France.
  • Funck-Brentano T; INSERM Université Paris Cité, Paris, France.
  • Roux C; Department of Rheumatology - DMU Locomotion, Assistance Publique - Hôpitaux de Paris, Paris, France.
  • Kolta S; INSERM Université Paris Cité, Paris, France.
  • Madeo A; Department of Rheumatology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
  • Bubbear JS; Department of Rheumatology, Cochin Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
  • Tabarkiewicz J; Department of Pediatrics, Unit of Rare Diseases, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
  • Szczepanek M; Centre for Metabolic Bone Disease Royal National Orthopaedic Hospital NHS Trust, London, UK.
  • Bachiller-Corral J; Institute of Medical Sciences, Medical College of Rzeszów University, Rzeszów University, Rzeszów, Poland.
  • Cheung AM; Institute of Medical Sciences, Medical College of Rzeszów University, Rzeszów University, Rzeszów, Poland.
  • Dahir KM; Department of Rheumatology, Hospital Universitario Ramón y Cajal, Madrid, Spain.
  • Botman E; University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Raijmakers PG; Vanderbilt University Medical Center, Program for Metabolic Bone Disorders, Nashville, TN, USA.
  • Al Mukaddam M; Department of Endocrinology and Metabolism, Amsterdam University Medical Centers (UMC), Vrije Universiteit, Amsterdam UMC Expert Center in Rare Bone Disease, Amsterdam Movement Sciences, Amsterdam, The Netherlands.
  • Tile L; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.
  • Portal-Celhay C; Departments of Orthopaedics, Medicine and the Center for Research in FOP & Related Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Sarkar N; University Health Network, University of Toronto, Toronto, Ontario, Canada.
  • Hou P; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Musser BJ; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Boyapati A; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Mohammadi K; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Mellis SJ; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Rankin AJ; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Economides AN; Regeneron Pharmaceuticals, Tarrytown, NY, USA. Scott.Mellis@regeneron.com.
  • Trotter DG; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Herman GA; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • O'Meara SJ; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • DelGizzi R; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Weinreich DM; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Yancopoulos GD; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Eekhoff EMW; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
  • Kaplan FS; Regeneron Pharmaceuticals, Tarrytown, NY, USA.
Nat Med ; 29(10): 2615-2624, 2023 10.
Article en En | MEDLINE | ID: mdl-37770652
Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths (5 of 44; 11.4%) occurred in the open-label period and, while considered unlikely to be related, causality cannot be ruled out. The primary efficacy end point in period 1 (total lesion activity by PET-CT) was not met (P = 0.0741). As the development of new HO lesions was suppressed in period 1, the primary efficacy end point in period 2 was prospectively changed to the number of new HO lesions versus period 1. No placebo patients crossing over to garetosmab developed new HO lesions (0% in period 2 versus 40.9% in period 1; P = 0.0027). Further investigation of garetosmab in FOP is ongoing. ClinicalTrials.gov identifier NCT03188666 .
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osificación Heterotópica / Miositis Osificante Tipo de estudio: Clinical_trials Límite: Adult / Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osificación Heterotópica / Miositis Osificante Tipo de estudio: Clinical_trials Límite: Adult / Humans Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos