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Clinical Trial
. 2024 Feb 23;19(2):e0299197.
doi: 10.1371/journal.pone.0299197. eCollection 2024.

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

Bruno Martins Tomazini  1   2   3 , Lucas Tramujas  1 , Fernando Azevedo Medrado Junior  1 , Samara Pinheiro do Carmo Gomes  1 , Karina Leal Negrelli  1 , Gabriela Souza Murinize  1 , Renato Hideo Nakagawa Santos  1 , Bruna Martins Pereira Vianna  1 , Bruna Fornazieri Piotto  1 , Thabata Silva Veiga  1 , Bianca Rodrigues do Santos  1 , Ana Clara Peneluppi Horak  1 , Olivia Mora Cavalcante Lemos  4 , Marcela de Almeida Lopes  1 , Beatriz Baptista Olicheski  4 , Diego Lurentt Campones  4 , Luiz Angelo Alencar Peixoto  4 , Aline Dos Anjos Chaves Basilio  4 , Otavio Celso Eluf Gebara  5 , Ana Tarina Alvarez Lopes  5 , Humberto Saconato  5 , Nanci Valeis  1 , Tamiris Abait Miranda  1 , Ligia Nasi Laranjeira  1 , Eliana Vieira Santucci  1 , Aaron Foster Carlin  6 , Jeffrey David Esko  7 , Phillip Leo Stephan Marie Gordts  8 , Sotirios Tsimikas  9 , Alexandre Biasi Cavalcanti  1   2
Affiliations
Clinical Trial

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

Bruno Martins Tomazini et al. PLoS One. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Conflict of interest statement

S.T is a co-inventor and receives royalties from patents owned by University of California San Diego (UCSD) and is a co-founder and has an equity interest in Oxitope, LLC and its affiliates, Kleanthi Diagnostics, LLC and Covicept Therapeutics, Inc and has a dual appointment at UCSD and Ionis Pharmaceuticals; A.F.C has received contract payments from Nurix Therapeutics, Inc. and has options in Covicept Therapeutics; J.D.E is a cofounder, consultant and shareholder in Covicept Therapeutics (San Diego, CA) and TEGA Therapeutics (La Jolla, CA); P.L.S.M.G. is a cofounder, consultant and shareholder in Covicept Therapeutics (San Diego, CA). All remaining authors: No conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials, although some restrictions might apply as stated in the submission.

Figures

Fig 1
Fig 1. Flow of patients in Halos trial.
Fig 2
Fig 2. Symptoms free-days up to day 10.
Fig 3
Fig 3. Mean SARS-CoV-2 viral load log 10 between groups.
See this image and copyright information in PMC

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