Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial

Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied. We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, saf...

Full description

Saved in:

Bibliographic Details
Published in:	PloS one Vol. 19; no. 2; p. e0299197
Main Authors:	Tomazini, Bruno Martins, Tramujas, Lucas, Medrado, Junior, Fernando Azevedo, Gomes, Samara Pinheiro do Carmo, Negrelli, Karina Leal, Murinize, Gabriela Souza, Santos, Renato Hideo Nakagawa, Vianna, Bruna Martins Pereira, Piotto, Bruna Fornazieri, Veiga, Thabata Silva, Santos, Bianca Rodrigues do, Peneluppi Horak, Ana Clara, Lemos, Olivia Mora Cavalcante, Lopes, Marcela de Almeida, Olicheski, Beatriz Baptista, Campones, Diego Lurentt, Peixoto, Luiz Angelo Alencar, Basilio, Aline Dos Anjos Chaves, Gebara, Otavio Celso Eluf, Lopes, Ana Tarina Alvarez, Saconato, Humberto, Valeis, Nanci, Miranda, Tamiris Abait, Laranjeira, Ligia Nasi, Santucci, Eliana Vieira, Carlin, Aaron Foster, Esko, Jeffrey David, Gordts, Phillip Leo Stephan Marie, Tsimikas, Sotirios, Cavalcanti, Alexandre Biasi
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 23-02-2024 Public Library of Science (PLoS)
Subjects:	Antimitotic agents Antineoplastic agents Antiviral agents Clinical trials Complications and side effects Evaluation Health aspects Hospital patients Ligases Medical research Medicine, Experimental Patient outcomes Product development Transfer RNA Brazil
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied. We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization. From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days. Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0299197