Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19
Abstract
Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 10, 2022
- Source ID
- 10.26508/lsa.202101200
Entities
People
- Adolfo García-Sastre
- Alfonso Monereo
- Alvaro Belgrano
- Ann-kathrin Reuschl
- Antonio Nieto
- Beatriz De Rivas
- Belen Sopesen
- Bonaventura Clotet
- Briana L. McGovern
- Clare Jolly
- Daniel Abad
- Daniel Carnevali
- Greg J Towers
- Isabel Sola
- Javier Gomez
- Jesús Fortun
- Jordi Rodon
- Jose A. Lopez-Martin
- Jose Barberan
- Jose M Fernandez-sousa
- Jose M Jimeno
- José F. Varona
- Julia Vergara-alert
- Julio Ancochea
- Kirsten Obernier
- Kris M White
- Lorena Zuliani-alvarez
- Lourdes Porras
- Lucia Fernandez De Orueta
- Lucy Thorne
- Luis Enjuanes
- M. Luis Rodriguez
- Maria Jose Pontes
- Mehdi Bouhaddou
- Miguel Torralba
- Nevan Krogan
- Noemi Cabello
- Nuria Izquierdo-Useros
- Pablo Aviles
- Pablo Guisado-vasco
- Paloma Gijon
- Patricia Giron De Velasco
- Pedro Landete
- Roberto Vates
- Roger Paredes
- Romel Rosales
- Rubin Lubomirov
- Salvador Fudio
- Soner Yildiz
- Sonia Zúñiga
- Vicente Estrada
Organizations
- Autonomous University of Barcelona
- Autonomous University of Madrid
- Carlos III Health Institute
- Complutense University of Madrid
- Defense Advanced Research Projects Agency
- Germans Trias i Pujol Research Institute
- Gladstone Institutes
- Hospital Clínico San Carlos
- Hospital General Universitario Gregorio Marañón
- Hospital Universitario
- Hospital Universitario Ramón y Cajal
- Hospital Universitario de Getafe
- Icahn School of Medicine at Mount Sinai
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- PharmaMar
- Spanish National Center for Biotechnology
- United States Department of Defense
- Universidad Europea
- University College London
- University of Alcalá
- University of California, San Francisco
- University of Guadalajara
- University of Vic - Central University of Catalonia